POM Flashcards

Question

What are the different densities of X-ray?

Answer 1

Metal is whitest, then bone, soft tissue (water), fat, and air.

Answer 2

Best spatial resolution Depicts differences in density Different contrast materials can be added to perform more functions BUT Limited contrast resolution Prolonged exposure is harmful

Answer 3

CT scans use radiation to form a computer-generated slice of the body in the transverse plane. They are very expensive and use x rays to work. However, they are very useful for when Ultrasound and X rays won't give a good picture, and can discriminate between soft tissues due to excellent contrast resolution.

Answer 4

MRI scans place the patient in a strong magnetic field, causing the H nuclei in the body to align with the field and then return to their original position, emitting signals detected by the machine. Pros: no radiation, excellent contrast resolution (great for CNS) except for lungs BUT: Expensive, takes a long time to do

Answer 5

Sends pulses of sound and detects echoes from the body tissue, producing a slice of the body from where the sound began. Safe, flexible, cheap BUT: cannot penetrate bone or air-containing structure

Answer 6

It involves the use of X rays, US, CTs or MRIs to place needles and catheters in the body in a moving image. US are used for needle/catheter insertion, CT when the lesion is obscured by gas or bone. These are less disturbing to patients than open surgery and can be done outpatient.

Answer 7

Radioactive isotopes are injected into a vein, or given orally or anally. They may be taken up by a specific organ or tumour, or respond in an antigen/antibody reaction. The contrast these give can then be observed using Xrays or CTs or be detected by a gamma camera. It cannot precisely define organs, but is good for demonstrating early disease and function, and is safe and cheap.

Answer 8

they are a form of nuclear medicine using a chemical with a shorter half life. They are used to show blood flow in the brain, and also for cancers as the chemical is taken up by tumours.

Answer 9

Redness/rubor (due to protein denaturing) Swelling/tumor (due to oedema) Heat/calor Pain/dolor Loss of function/functio laesa (due to damage and other local effects)

Answer 10

Pyrexia/fever (mediated by IL-1 and TNF-a released by endothelium and macrophages) Leukocytosis (increased WBC production) Acute phase proteins (increased proteins involved with inflam. from liver) Endocrine changes (more glucocorticoids)

Answer 11

Produced by macrophage and endothelial cells. Cause fever, slepiness, decreased appetite, increased acute phase proteins, haemodynamic shock and neutrophilia. Increase neutrophil adherence, Increased fibroblast proliferation, collagen synthesis and cytokine secretion from Leukocytes.

Answer 12

If they are not controlled or occur inappropriately, they can cause disease, hypersensitivity and hyperimmune reactions. Repair by fibrosis can lead to scars, intestinal obstruction or limited mobility.

Answer 13

When the cause is prolonged, and other leukocytes (besides neutrophils) enter the tissue. Especially monocytes- they are greater killers and transform from into pacrophages as they enter injured tissue

Answer 14

A focused region of chronic inflammation consisting of a core of necrosis. It involves macrophages fusing into epithelial-esque cells with a collar of lymphocytes surrounding it. This is mainly done to remove foreign bodies.

Answer 15

The body's attempts to restore original structure and function of injured tissue

Answer 16

Cleaning up the mess | Rebuilding structure and function

Answer 17

Ideally, all debris is removed by macrophages If there is too much, repair is set into motion. This is done by organisation, where macrophages secrete FGF and VEGF. These encourage growth of fibroblasts and blood vessels, and once there are many of these the tissue is termed granulation tissue. This is then remodeled as the vessels regress and collagen aligns to form a fibrous scar (fibrosis) However, this may represent loss of functional tissue, and could hinder remaining tissue.

Answer 18

Attempts to replace parenchymal cells are made. , known as regeneration. This involves proliferation of stem cells, both locally and from the bone marrow. It is more commonly done in areas of high tissue turnover (skin and gut).

Answer 19

Anywhere between fibrous scar (function is lost) and complete resolution. The longer the tissue damage and inflammation lasts, the less likely resolution will be.

Answer 20

Mainly used to observe bones Can add barium for enemas, to look at GI tract Iodine compounds for angiography, IVUs Gadolinium to make the pictures useful in MRI scans

Answer 21

Bone scans V/Q scans for pulmonary emboli Thyroid, white cell, liver, renal and brain scans

Answer 22

Examining pain, swelling, mass. Screening for renal dysfunction, cancer. Checking vasculation and abnormal liver function

Answer 23

Head scans | Abdominal pain, trauma, cancer, bowel obstruction, vascular imaging

Answer 24

mainly brain, but can also look at abdominal structures

Answer 25

Cancer staging mainly

Answer 26

``` Viruses: - Particle capsid shapes' antigens - Cells damaged by infection (due to the changes at their surfaces) - Virus-infected cells Bacteria and Fungi: - Bacterial surface antigens - Bacterial/fungal metabolites - Cells damaged by infection Parasites: - Surface shapes - Cells damaged by infection - Life cycle changes within a parasite- as the shapes of the parasites change over their life cycles. ```

Answer 27

Foreign microbe adheres to phagocyte Membrane of phagocyte activated Ridges of cytoplasm extend around microbe, leading to phagosome formation as the microbe is engulfed Fusion and digestion of microbe Release of degraded products Granulocytes (neutrophils, short lived) and monocytes (longer lived)

Answer 28

Complement system stimulates and enhances the processes of inflammation and phagocytosis. This is done by the release of a cascade of blood-derived proteins. - First complement components are able to bind with the membrane antigens of the agents involved, having evolved to recognize most common shapes. When a group of them congregate and form enzymes, they activate other components of the system - Some increase vascular permeability - Some attract granulocytes into tissues by helping with chemotaxis - Some perform opsonisation, where the target is coated with molecule with a high affinity for the phagocyte.

Answer 29

Derived of different macrophage-like cells from the stem cells of bone marrow. These are strategically placed where they will most likely encounter harmful agents.

Answer 30

Fluid drains into the thin-walled vessels perforating the interstitial fluid, and is pumped up the branches by the movement of muscles, held where it is pumped by leaf valves. Afferent vessels take fluid from tissues to lymph nodes Efferent vessels take fluid from the nodes to the thoracic duct, where it is emptied into the bloodstream

Answer 31

Prevent oedema Recycle components of ECM Carry information about infection from the tissues to the lymph nodes

Answer 32

Primary: Lymphocyte formation site. Includes bone marrow, thymus, fetal liver Secondary: Residence of mature lymphocytes. Includes lymph nodes, tonsils, adenoids, peyer's patches, skin.

Answer 33

Physical- mucus, skin Microgial- organisms living on/in us that make it hard for invaders to proliferate Humoral factors: Chemicals (eg. in sweat)

Answer 34

Microscopic entity

Answer 35

Thing capable of generating a disease

Answer 36

Thing found in a place or population

Answer 37

More cases of a thing than you would expect to see

Answer 38

Epidemic spread across a wide area

Answer 39

New presence of a microbe

Answer 40

Symptomatic illness caused by pathogens

Answer 41

Originating within an organism

Answer 42

Present but originated outside an organism

Answer 43

Infectious disease triggering the immune system, but not causing symptoms

Answer 44

Manner of spread of a microbe (can be direct or indirect)

Answer 45

Dynamic process of self-production (ie making your own new cells)

Answer 46

Maintenance of a mutually satisfactory relationship between organism and environment

Answer 47

- To protect against infection - To recover from infection and damage - To maintain the relationship with the environment

Answer 48

Unusual shapes | Familiar shapes in unusual contexts

Answer 49

Blood takes them to spleen Tissues to lymph nodes Gut to peyer's patches

Answer 50

The first line of defense to antigen exposure Includes physical microbial and chemical factors They are effective at preventing invasion or growth of invasion, and act early. Includes lysozyme in secretions from the skin, like tears, sweat and saliva. These break down the cell membranes of some bacteria Also commensal organisms which compete with pathogens for survival

Answer 51

Pluripotent haemopoietic stem cells found in bone marrow - Some mature directly into B lymphocytes - Some migrate to the thymus to become T lymphocytes - Some develop into megakaryocytes and are broken into platelets - Some develop into monocytes and are then converted to macrophages in the tissues - Some develop into basophils, eosinophils, neutrophils or erythrocytes

Answer 52

Susceptibility to infection Low blood counts Inability to clot blood, leading to petechial haemorrhages Large numbers of immature WBCs in the blood due to their overcrowding the RBM

Answer 53

Antibodies- secreted by B-lymphocytes, recognize foreign antigens Cell surface receptors- Attached to lympocyte surface, recognize changes in our own cells that appear on the cell surface.

Answer 54

- Antibodies (soluble, secreted by B cells) Prevent binding of virus to other cells - Cell surface receptors- attached to surfaces of cells, act as hands. See changes in our own cells

Answer 55

Some antibodies may bind to many things with a similar shape- perhaps with low affinity, but enough to bind. This means a single antibody can help to defend against many pathogens

Answer 56

Defence Specificity- response directed against only the agent stimulating disease Diversity- responds to a wide range of substances Adaptivity- unexpected stimuli response provides rapid appropriate response Self/nonself- discrimination between own and foreign antigens Memory- system remembers responding to respond more vigorously next time

Answer 57

Early in development, the immune cells become 'used' to whatever antigens are preexisting within the body- called acquired immunological tolerance

Answer 58

Meet dendritic cells, which collect antigenic information. These then migrate into the lymphatic system, entering the nearest lymph node while presenting the antigen on their surface T Cells cluster around them when they arrive, and those with an appropriate receptor are activated

Answer 59

``` Effectors: - B Cells (produce antibodies) - Cytototoxic T cells (actively kill cells) - NK and K cells (kill cells) Regulators: - CD4 T cells - Helper T cells - Regulatory T cells ```

Answer 60

B cells recognize a wide range, T cells only recognize short antigens

Answer 61

B cell: CD79 transduction molecules, Surface Ig receptor with binding sites T Cell: CD3 signal molecules, TCR

Answer 62

Made of 2 light chains and 2 heavy chains. Heavy chains have CH1,2,3 parts and a Variable part at the end Between CH1 and 2 there is a hinge region, which allows the antibody to flex between a T and a Y shape Light chains have a hypervariable area and a constant area. The CH2 and 3 areas are able to be crystallized, and can be sensed by neutrophils, improving their phagocytosis The chains are held together by disulphide bonds

Answer 63

Primary responses occur when we respond to something we had not previously encountered. There is a lag of a few days, and then a small rise in specific antbodies, before decaying to low levels. A secondary response occurs subsequent times we are exposed to things, and consists of a vigorous and lengthy reaction to the pathogen

Answer 64

An antigen matches with a specific receptor of a virgin B cell, causing it do express new receptors which match with signals sent from helper T cells. It does this to determine if the related pathogen is dangerous or not. If dangerous, the B cells proliferate, forming plasma cells which form antibodies, and replacement B cells called memory cells. These are longer lived, there are more of them, they circulate to all nodes rather than staying in one, and react without the help of T helper cells.

Answer 65

B cells' development isn't controlled and they spill over into the blood, as well as their precursors. These precursors smudge due to their fragility when put under the microscope slide, leading to their being named smudge cells

Answer 66

- Direct neutralization: Antibodies block the virus from being able to bind to and infect other cells - Opsonisation: The antibodies bind to the virus, exposing their Fc region, which neutrophils have high adherence for. This increases the efficiency of phagocytosis - ADCC: K cells rely on Fc areas to bind to and kill bacteria using short-range cytotoxicity - Complement activation: Forming an antibody-antigen complex activates the first components of the complement zone.

Answer 67

They bind to the antigen, changing to a Y shape.

Answer 68

Activated by: Antigen-antibody complexes First components recognize the surface of the pathogen Presence of bacterial sugars bind to proteins *Enzymes formed convert C3 to C3a and C3b* Effects: C3a causes vasodilation and chemotaxis C3b causes vasodilation C3b also forms a focus for late component assembly, which punch holes into the membranes of pathogens to cause cell lysis.

Answer 69

Infection with microbe for varying period. Host immune response, but no symptoms. Potentially infectious

Answer 70

Interaction with microbe causing damage to the host

Answer 71

Infectious disease transmitted by a non-human animal host

Answer 72

Immune deficiency (age related, treatment related etc.), other illnesses, risk behaviours

Answer 73

Endogenous are those arising from our own bacteria, microbes and other flora Exogenous are infections coming from animals, the environment (uncommon) and human to human transmission

Answer 74

Community onset/acquired (most common, GP visit) | Hospital onset/acquired/nosocomial (reduced by handwashing)

Answer 75

It must interact with the host cells It must damage or incite an immune response within the host Virulence factors include the avoidance of the immune system, improved adherence, damage and invasion

Answer 76

Tissue invasion, involving multiplication and causing an acute immune response

Answer 77

pathogens may use toxins to change the host physiology or to physically damage tissue They may mimic the antigens on other cells They may also cause the formation of cancerous cells

Answer 78

Uses B lymphocytes to produce antibodies Effective against extracellular antigens including: Viruses & toxins (stop attachment) Extracellular bacteria (enhance phagocytosis)

Answer 79

``` Uses T lymphocytes, but no antibodies Effective against intracellular antigens, including: Virus-infected cells tumour cells Transplanted organs ```

Answer 80

Both: - Contain CD3 - Have T cell receptors (TCRs) - Originate in the thymus - Can bind only to antigens presented to them by MHC determinants on APCs T-Helpers - Contain CD4 - Produce cytokines Cytotoxic T Cells - Contain CD8 - Kill cells outright

Answer 81

T cells made in thymus, B in bone marrow T cells do not make antibodies T cells can only react to antigens presented to them by APCs

Answer 82

Genes coding for surface structures on cells to present antigens to T lymphocytes Class 1: Produces double chained structures, found on all nucleated cells. Expressed co-dominantly, polymorphic (HLA-DP/DQ/DR all code for them) and present only to cytotoxic T cells Class II: Code for structures found only on APCs and B cells. Expressed co-dominantly, polymorphic (HLA-A/B/C all code for them) and present only to helper T cells

Answer 83

``` Way 1: Virus infects cell and replicates, changing the physiology of the cell and the composition of its proteins. A sample of these proteins are expressed on the MHC structures, so the immune system notices any changes Way 2: If the pathogen is phagocytosed, it is broken into small fragments, some of which are presented on MHC class II. ```

Answer 84

Precursors with TCRs matching the antigens on class 1 MHC structures are activated and receive helper signals to divide them into effector cells and memory cells

Answer 85

Antigen binding to TCRs on T lymphocytes cause the cell to express cytokine receptors. A second activation signal from helper cells cause differentiation into cytokine secreting cells or memory cells.

Answer 86

Cytokines are low weight glycoproteins secreted mainly by CD4 T cells They are produced locally and transiently, and are responsible for regulating the quality, amplitude, duration of immune reactions Their action differs depending on concentration, other cytokines, target cell and history of cell They also affect other systems- eg. control sickness behaviour through nervous system

Answer 87

Overreaction to innocuous substances- generate strong IGe antibody responses to harmless things (eg. pollen, fur etc.) This causes hypersensitivity where the substance touches you, or in bad cases, systemic reactions (anyphrylactic) can occur. Immune mediated tissue damage- strength of immune/inflammatory response is so great it can damage other tissues. Eg. immune complexes produced in such high numbers that they lodge in capillaries, activating complement system and starting vasculitis The system can also be destroyed from within, eg. when T helper cells are infected with HIV and cytotoxic T cells kill the majority of them Autoimmunity- results in chronic illnesses as the body treats self-cells like non-self cells Immune system can get confused- eg. strep. Some people have heart antigens similar to strep antigens, so immune responses to this damage heart valves too

Answer 88

Hashimoto's thyroiditis: Antibodies/Cytotoxic T cells against thyroid antigens, destroying thyroid gland Pernicious Anaemia: Immune system targets parietal stomach cells, impacting B12 absorption Systemic Lupus Erythematosus: Antibodies made against DNA from cell nuclei, binding to broken cells throughout the body, activating the complement and damaging tissues throughout the body (particularly kidneys and skin due to immune complexes clogging)

Answer 89

It is a virus that lives in the pharynx, commonly causing pharyngitis and skin infection. Firstly, the immune system is activated as S. Pyogenes colonizes the pharynx and irritates the tissue. Then, the pharynx becomes inflamed, causing pain, swelling, redness and pus. They contain M proteins which the body forms antibodies against, although the M proteins are similar in shape to the cells in other locations. If the antibodies bind to our own proteins, they will form a response against them in places not colonized by the bacteria. This can then cause rheumatic fever, with fever, painful joints, inflammed connective tissue of the heart, rash and chorea (strange movement)

Answer 90

It works by targeting the enzyme responsible for linking the peptide chains within the bacteria's cell wall. If this enzyme is inhibited, cracks in the cell wall can't be repaired and the bacteria explodes. There are different types of penicillin, some administered intravenously and some orally depending on whether they get dissolved in the stomach or not However, the issue is that penicillin (and other antibiotics) are being used for viruses etc. which they have no effect on, which results in bacteria gaining resistance to the drugs

Answer 91

- Direct (sexual, faecal-oral, droplet, airborne) - Indirect (contact, vector borne, healthcare worker, transfusion, airborne) ``` Universal protections (always done): Glove/gown, decontamination of waste, disposal or sharps, waste management, clean environment, hand hygiene Contact precautions (GI infections): Gloves, gowns, eyeware Droplet precautions (flu etc.) masks Airborne precautions (TB, chickenpox): Respiratory masks for patients and staff ```

Answer 92

Viruses are nucleic acid that aims to replicate, enclosed within a caspid. Some have an envelope formed from the host cell

Answer 93

Can be classed by their genetic content- RNA, DNA etec. OR what they cause- hepatitis vs. resp. (this down't predict structure OR how they are transmitted- arbovirus (arthopod borne), enterovirus (faecal-oral) or respiratory virus (droplet/contact)

Answer 94

1. virus attaches to cell 2. Virus enters the cell, host enzymes dissolve the capsid and release the RNA 3. mRNA from the virus is formed, and 4. protein synthesis occurs 5. Genome replicates to 6. form a new clone of the virus so that it can be 7. released from the cell

Answer 95

It is a bacteria with a thick peptidoglycan wall, and is graham +ve as it takes up stain that sticks when the cell is washed It has a circular shape and occurs in bunches It causes food-poisoning symptoms commonly, and skin infection-like symptoms rarely. Currently it's the no. 1 cause of healthcare infections as it lives on the skin and can get into catheters & blood. It has a death rate of about 20% in its serious form, and there is a non-serious form that can cause skin infections needing hospitalization.

Answer 96

It is transmitted person to person, although it can be transmitted to cows too (bovine mastitis) Its transmission is affected by host, bacterial, and environmental factors

Answer 97

About 10-15% of population are persistent carriers, 25% non carriers, and the rest have it intermittently.

Answer 98

Bacteria makes toxins on room temperature foods and it is this pre-produced toxin that gets into the stomach and induces vomiting.

Answer 99

Unlike most bacteria, it is able to multiply within the glands of the skin, where it releases free radicals and causes inflammation due to cell damage

Answer 100

Releases CHIPS which are potent disguisers of cytokines Can coat itself with immunoglobulin, pretending to be a human cell Turns off the complement system Cause lysis of neutrophils or prevent the enzyme's lysosomes from working

Answer 101

It produces enzymes to dissolve penicillin's 'garage group' as well as being resistant to the replacement, methicillin, within the year as it changed its transpeptidase. Now, it is called MRSA.

Answer 102

Caused by mycobacterium genus, most commonly m. tuberculosis. It is associated with poverty, low sanitation and poor access to safe drinking water. If a non-TB causing mycobacterium infects, it comes in rapid, non-rapid or other varieties. While it doesn't cause TB, it can cause lung infections and skin infections.

Answer 103

Transmitted via vigorous coughing from someone with it. It enters the distal lungs, where it binds to the complement receptor of pulmonary macrophages. It gets phagocytosed, resists being lysed and immortalizes the macrophage. Infected WBCs recruit T cells using cytokines, but the bacteria isn't able to be destroyed, so the phagocytes surround the persistent antigens (now a necrotic center) with a layer of T cells bordering them, keeping the macrophage barricade alive- chronic inflammation. Large aggregates of these are called nectrotising granulomas.

Answer 104

- Latent TB infection: immune system jails the TB, although if it is strongly needed elsewhere it can cause the TB to reactivate - Miliary TB: TB disseminates and spreads into many small granulomas - Thoracic/pulmonary TB- standard

Answer 105

- Good immune response- small calcified granuloma on lymph nodes or lungs. - Granuloma on lung surface- dangerous, may erode pulmonary space - Abcess or cavity in lung, if TB not surrounded- large granulomas can impact bronchi, vessels - Pulmonary TB- cause pneumonia - Erosion of granuloma into pericardium - Miliary TB

Answer 106

Recipient: close contact with infected. Immune suppressants, institutional care or healthcare workers Transmission: High TB in infected sputum, pulmonary disease, TB cavitation, coughing, not covering mouth, delayed diagnosis

Answer 107

Sometimes visible using granulomas from chest x rays- cts used more and more. Confirmed by sputum/kidney/csf samples. PCR in specimens. TB holds stain when heated to soften lipids- it's acid fast due to its thick cell wall

Answer 108

1. Treat patient with different drugs | 2. Prevent transmission using isolation, masks.

Answer 109

Sneezing, sore throat, runny nose, chills, muscle aches, lethargy. 1 day incubation period, with symptoms highest on second day, corresponding with IFNa cytokine. Nasal mucus peaks 3rd day. Lasts 1-2 weeks- no chronic inflammation as all symptoms due to immune system, not virus. Can become dangerous if lungs become so inflamed they lose SA and ability to gas exchange. Dangerous for 0-4 and 65+

Answer 110

Haemagglutinin- binds to ENT and bronchial cells- not gut or deep lung. Antibodies can prevent its binding, but the virus can mutate the H proteins to keep infecting Neuraminidase ensures virus can be released after infecting host cells, to transmit more virus. There are inhibitors for this available, but they only work in the early stages of the disease. Different H and N proteins make up the flu vaccine- not the virus itself

Answer 111

A: causes serious illness, epidemics, pandemics. Many H and N. Bird virus that adapts to mammals B: Serious illness, epidemics. Only 1H and 1N C: Minor illness Humans immune to AH1 and AH3, but not AH5 immunity.

Answer 112

- Single gene disorders: Change in a single gene causing a change in phenotype - Chromosomal disorder: change in chromosomes as a whole. Eg. extra chromosome, changes in stoichiometry - Multifactorial genetic disorders: Interaction of multiple changes, can be minor or major in affecting phenotype - Somatic mutations: unable to be passed onto offspring, but can come from genetically inherited predisposing factors

Answer 113

A permanent, heritable change in the base DNA code | Alteration in DNA from its natural state

Answer 114

The presence of multiple alleles for a gene in a population at frequencies to high to be random mutations- means the mutation is sustained.

Answer 115

- Silent mutation- no affect due to degeneracy of code - Missense mutation- changed amino acid but may or may not change phenotype - Nonsense mutation- amino acid changed to stop codon, protein non-functional - Frameshift- insertion/deletion of bases not in multiple of 3 - Splice donor/acceptor- change in sequence of intron splicing

Answer 116

- Missense at important site? - Encoded protein truncated? - RNA splicing affected? - Change segregate with disease in prior generations?

Answer 117

Somatic- mutation occurs in body cells, not passed to offspring Germline- mutation occurs in gamete-forming cells, may be passed to offspring

Answer 118

LOF: Reduced amount or activity of final gene product. Can be totally absent (null allele) or half-active/present (haploinsufficiency) with minor affects on phenotype. Some present a dominant negative effect, where an abnormal product affects the action of the normal- common in conn. tissues due to different shaped proteins GOF: Increased amount or activity of product

Answer 119

- Autosomal dominant - Autosomal recessive - X linked recessive - X linked dominant - Y linked (holandric)

Answer 120

Affects and transmitted by either sex. Presence of dominant allele guarantees expression of corresponding phenotype Child of hetero/unaffected pairing has 50% chance of affected.

Answer 121

In homozygous r form, person is affected. In heterozygotes, person a carrier. Affects either sex, with 25% chance affected when born to carrier parents.

Answer 122

Inactivation of normal parts of a single X chromosome in females, allowing a mutated X chromosome to be expressed- rare and random.

Answer 123

Affects mainly males born to unaffected parents No male to male transmission All daughters of affected males are obligate carriers 50% change of affected son/carrier daughter born to carrier woman

Answer 124

Affects either sex, but more commonly females with more variation due to lyonisation Child of affected female 50% likely affected All daughters but no sons are affected from affected male

Answer 125

Affects only males in a direct father to son progression

Answer 126

- Common recessive conditions can appear pseudo-dominant (blood groups) - Nonpenetrance- failure of dominant condition to manifest phenotypically - Variable expression- phenotype differs among affected individuals - New mutations/germline mosaicism- some cells are genetically different to others in the same body

Answer 127

- Allelic- disease can be caused by many alleles | - Locus- mutations at different gene loci can cause the same disease

Answer 128

80% of sufferers don't inherit the condition (dominant) from their parents, but a spontaneous mutation in paternal speriogenesis causing mutated sperm to divide more quickly- this makes it more likely to affect children born to older parents.

Answer 129

A form of recessive inheritance where individuals are heterozygous for two different mutations affecting the same gene, but whose phenotype expresses the same as if the individual were homozygous

Answer 130

There is a dramatically higher number of carriers than of sufferers

Answer 131

Allows diagnoses to be made based on genetic makeup Allows for facilitation of family screening, prenatal checks Can prevent unnecessary invasive procedures

Answer 132

22 pairs autosomal chromosomes, 1 pair sex chromosomes

Answer 133

``` P arm (shorter) Centromere Q arm (longer) ```

Answer 134

Aneuploidy- gain or loss of whole chromosome This usually happens in meiosis 1 or 2, resulting in some gametes with multiple chromosomes, some with none (and some normal if in mII) due to the failure of chromosomes to separate (non-disjunction events) Eg. in down syndrome, there is trisomy as there is an extra chromosome 21, causing characteristic facial features, mental retardation and other abnormalities

Answer 135

Happens when non-disjunction occurs post-fertilization in the embryo's mitosis, meaning genetically different cells can co-exist within one person. It can account for some down syndrome cases

Answer 136

- Reciprocal translocation - Robertsonian translocation - Inversion - Deletion

Answer 137

Two way exchange of material between non-homologous chromosmes (ie not crossing over) Phenotype normal as no gain or loss of material (although balanced translocation parents can have recurrent miscarriages, dysmorphic babies with unbalanced translocations, and oligospermia

Answer 138

Occurs when two separate chromosomes join together into one long one No phenotypic effects a no loss/gain of genetic material

Answer 139

Occurs when a balanced translocation parent passes on a split chromosome, giving the child a net loss/gain of genetic material

Answer 140

Same chromosome breaks in two places, and either middle chromosome or broken off pieces rotate before rejoining Phenotype normal, low risk of abnormal offspring

Answer 141

Terminal: End material is lost Interstitial: two breaks, and middle fragment is lost before others join together again

Answer 142

A way of imaging DNA where a target piece is compared to a control patch- certain sequences can be highlighted with fluorescence if present. Used for any tissue with intact DNA Can detect: microdeletions, marker chromosomes, numbers of chromosmes, gene amplification and rearrangements

Answer 143

A scan coparing normal and target whose genomes for overall gene changes Microarrays simultaneously screen hundreds of regions, allowing it to be used in diagnostics

Answer 144

Syndromes: Groups of anomalies consistently occuring together Sequences: Cascades of effects Associations: Traits coincide more often than by pure chance

Answer 145

Discipline of medicine for identifying, delineating, diagnosing and managing dysmorphic anatomical features

Answer 146

Gp 120 proteins on the cell envelope bind to CD4 on Th cells and other WBCs. When it docks, it squeezes the viral contents into the cell via CCR5. In the cell, the capsid is digested, and reverse transcriptase enzymes make a DNA copy of the RNA. The two are then separated, and DNA is transported into the nucleus. Integrase opens the host DNA and integrates viral DNA into it. This viral DNA is then transcribed into more gp120, caspid proteins etc. These products move to outside the cell, where they assemble into a new virus and protease creates more viral enzymes.

Answer 147

Depletes helper T cells to the point where many more diseases are able to take over. It also causes mild, but chronic activation of the imune system. This results in self-mediated damage including bone loss, CV issues and neurological defecits.

Answer 148

Normal CD4 count is 750-1500, and when this drops below 500 we begin to treat it. We manage it by maintaining health and better lifestyle factors, stopping the virus' replication using drugs. We also reduce transmission by increasing safe sex, awareness etc.

Answer 149

There are 3 drugs used, which target at least 2 different areas- can be integrase, protease, reverse transcriptase etc. They make it possible for a 90% chance of working, safe and durable treatment when diagnosed in 2017

Answer 150

Prenatal testing is the use of special tests during pregnancy. We do this to give reassurance to parents to give health professionals early warning, set up support, and inform parents of their options should they have positive tests Screening tests assess whether a baby has an increased risk of a disorder. They are non invasive, low risk, but not definitive. Diagnostic tests determine whether a baby has or will have a disorder, including chromosomal and gene changes. They are more invasive with increased risk, but have definitive outcomes

Answer 151

- Family history of genetic disorder - Both parents known carriers of autosomal recessive disorders - One or both partners have an autosomal dominant disorder - Family history of sex-linked conditions ONLY for serious conditions- not easily treatable

Answer 152

- Woman having a baby in her mid thirties or older - Exposure to chemical or environmental agents - Results of of screening tests have determined increased risk of certain conditions - Previous child with a serious genetic condition

Answer 153

- Ultrasound: 8-10 weeks (checks dates and number of babies) and 18 weeks (detects physical anomalies). - Nuchal Translucency Ultrasound: 10-13 weeks. Looks at space below baby's neck to calculate risk of constitutional abnormality (eg. downs). - Maternal Serum Testing: Looks at AFP, uE3 and hCG to determine risk of chromosomal issues, neural tube defects. When used together, these tests can detect 85-90% downs cases

Answer 154

- CVS: 11-12 weeks. Cells from placenta taken and tested for cytogenic and single gene abnormalities. Small risk of miscarriage. - Aminocentesis: 15-19 weeks. Fine needle aspirates amniotic fluid to be analyzed. Often needs to be cultured first, as there are fewer cells. Baby's cells removed and DNA examined. Slight risk of miscarriage The CVS is preferable to aminocentesis, but often not an option if people aren't actively monitoring their pregnancy.

Answer 155

It is the analysis of cells in the 6-8 stage embryo before it is implanted in IVF. These can be analyzed for known mutations, markers or disorders.

Answer 156

FISH- scan for abnormal chromosme number DNA analysis using PCR for direct (known) mutation analysis (preferable) or indirect (marker) analysis Karyotyping if possible

Answer 157

Gives parents up to date information about their options regarding both what tests are able to be done, what their pros and cons are and what their options are should the results be positive for a disorder.

Answer 158

- Cordocentesis- analyzing umbilical cord blood's proteins and cellular genetics - Detecting loose fetal DNA in maternal blood and analyzing that, followed by diagnostic testing if positive

Answer 159

- Error rate due to confounders | - Fetal blood samples can lead to late prenatal diagnosis (DNA analysis)

Answer 160

- Can give rise to differing severity to the condition | - Can make it difficult to find the mutation responsible- each family's mutation needs to be found

Answer 161

Direct analysis requires knowledge of the specific mutation responsible, but is accurate and does not require additional family members. It is PCR based, looking for allele-specific oglionucleotides and sequencing the PCR fragments Indirect analysis is used when the mutation is unknown or the gene is uncloned. It uses linked markers and pedigrees to see whether the offspring inherit the mother or father's protein for the condition. However, you need several family members, an informative marker gene, and there is a potential that recombination or non-paternity clouds the results. To find the mutation you can do- southern analysis looking for large structural changes, or mutation scanning strategies like directly scanning the gene.

Answer 162

It is circular DNA inherited by the mother, lacking introns and contained in the mitochondria with a known mutation rate. Mutations tend to affect the respiratory chain, so it affects organs with high energy requirements (brain and muscle)

Answer 163

A trait that is stably heritable through mitosis resulting from changes in a chromosome without altering the actual DNA sequence. Can be caused by DNA methylation of C/G runs, turning off promotors, or of the DNA body, turning expression on. Micro RNA can stop translation by binding to the 3' site Histone methylation and RNA methylation are also factors

Answer 164

The restriction of expression to either the maternal or paternal allele in somatic cells- an epigenetic phenomenon causing different expression from identical alleles. It operates at the transcriptional level.

Answer 165

Prader-Willi syndrome- deletion of parental 15q11-13 or two copies of maternal allele Failure to thrive, hypotonia, obesity and short stature, hypogonadism, small hands and feet, behavioural issues. Angelman syndrome- deletion of maternal 15q11-13 or UPD of paternal copy. Open mouth, tongue thrusting and retardation, ataxia, hypotonia, happy and laugh frequently, absent speech

Answer 166

Occurs at cytosine in CpG dinucleotides- methylationof promoters silences transcription- transmitted via cell divisions using methyltransferase Can be reversed if methyltransferase is inhibited Gamete specific- gamete specific protein factors bind and remain bound to imprinted genes during embryogenesis- may encourage or inhibit synthesis. In females, imprinting occurs when the oocyte matures. In males it is during early embryo formation Primary germ cells are unaffected, so this tends to happen spontaneously.

Answer 167

Progressive expansion of repeat sequences (triplet repeats). Anticipation refers to the occurrence of the disease at an earlier age, resulting in more mutations and a more severe clinical presentation (this means there can be reduced penetrance and full penetrance of the same disease, depending on number of repeats)

Answer 168

A field examining how a one-cell embryo gives way to a complete one- particularly important for cancer treatment, regeneration of diseased organs, etc.

Answer 169

Stem cells are self-renewing progenitor cells- they can be totipotent (all adult cells possible), pleuripotent (can become all germ layers but not all cells) and multipotent (can become several).

Answer 170

Embryonic stem cells are capable of generating all differentiated cell types of the body, and can have genes introduced to them. They allow investigation of biological processes in early development, and the generation of many somatic cell types with the potential for use in tissue engineering. Adult stem cells are present in the adult, and they have been recently discovered to be able to be reprogrammed to contribute to multiple organ cells

Answer 171

The transfer of genetic material into the cells of an organism to treat disease or mark cell populations. This is mainly done via gene augmentation. Usually, engineered nucleases (CRISPR, TALENS, zinc finger nucleases) are used, and genes are delivered either ex or in vivo via physical (eg. microinjection) or viral vectors. At present, only single gene, life threatening, untreatable disorders are considered for this therapy

Answer 172

Proteins needed for a disease are generated by expression cloning in other organisms or transgenic livestock before being harvested and given to humans. However, there are issues- purification process is difficult, contamination may occur, side effects (immune responses, unseen mutations, intergenerational transmission)

Answer 173

Artificially produced antibodies designed to recognize disease specific antigens, leading to increased killing of disease cells. Targets are cancer, infectious and autoimmune diseases At the moment, animal antibodies are limited due to immune reactions, and human antibodies are hard to generate. Fully human antibodies are being pursued

Answer 174

Vaccines where the nucleic acid, antigen, modified virus or modification of antiviruses are used to produces immunity

Answer 175

I can be useful in cancer, infectious, immune, and dominantly inherited disorders (with a gain-of-function Can target DNA, RNA and protein levels

Answer 176

Non-mendelian inheritance patterns, but still show some heritability. They are caused by an interaction between the environment/pathogen and a genetic predisposer or modifier

Answer 177

Interaction between the environment and a person's genetics causes a disease- all people are susceptible, but a certain threshold must be reached before the disease will develop. Risk is a bell curve, and only those at the upper end will develop it. For people with family histories of the disease, its development is much more likely

Answer 178

Genes not associated with the disease origin, but once susceptibility or the disease itself is present, they regulate the severity of the phenotype

Answer 179

Disorders run in families but without pattern Monozygotic twins more likely to share disease than dizygotic 1st degree relatives more at risk than 2nd degree Recurrence risk proportional to no. of family embers affected, severity of the condition (reflects no. of affected alleles) and relatives of the statistically less susceptible sex (as it means more mutations must be present)

Answer 180

When a disease affects multiple 1st degree relatives, an analysis can determine whether a locus is linked to the phenotype- this is more challenging for multifactorial diseases than for single gene disorders, although affected siblings likely share the same locus so they are more useful

Answer 181

Genome wide association studies- these examine many common variants in individuals to see whether it is associated with a trait- link made between SNPs and multifactorial disease

Answer 182

- Advance disease understanding and classification - Examine gene-environment interactions - Risk and disease prevention strategies - Monitoring progression of disease - Developing new drug targets

Answer 183

Personalised- using individual DNA to make decisions to maintain health, prevent disease or improve health outcomes Precision- creating an infrastructure for patients' health information to be accessible to scientists to be able to inform patient care.

Answer 184

Prevention- identify those at greatest risk Screening- identify and prioritise high risk individuals Diagnosis- presymptomatic Prognosis- identify best approaches for different people's diseases Drug efficacy and tolerance- identify what will work best and what will have the fewest complications

Answer 185

Differentiation inolves cells becoming different from one another- involves inactivation of proliferation genes and activation of specific function genes- like keratin producing etc. De-differentiation involves the reversion back to embryonic, proliferative cells- as occurs in neoplasia.

Answer 186

Disorders in the regulation of cell proliferation or differentiation Malformation: Abnormality in growth and development in utero. In adult: abnormalities of tissue function or mass.

Answer 187

Atrophy- cell nuclei are closer together, cells smaller. Hypertrophy, cells are larger so their nuclei are further apart.

Answer 188

It can be caused by increased functional demand, endocrine stimulation or chronic irritation. It causes increased function in endocrine tissue, increased size and a potential increased risk of malignancy.

Answer 189

Premalignant means that there is an increased chance of developing carcinoma with this tissue disorder than without it. It is not a definite thing. Prostatic (inner hyperplasia, outer atrophy) and thyroid hyperplasias are not premalignant- but breast and cervical hyperplasias are.

Answer 190

Metaplasia- change from one mature tissue type to another. It is caused due to a change in environment, or irritation. It may be normal (eg. glanular epi in cervix changes to squamous during menstruation), or obnormal. Some types (eg. barretts oesophagus) are premalignant, other are not.

Answer 191

Dysplasia is a partial malignant transformation of cells (histologically and genetically). Therefore, they are by definition pre-malignant. Those formed on traditionally 'flat' surfaces don't form a mass, but otherwise a mass is formed, or inflammation is caused. They can be graded as mild (Intraepithelial neoplasia 1), moderate (IN2) or severe (carcinoma in situ/IN3) They are clonal, classing them as neoplastic (autonomous growth of new cells)

Answer 192

Reative atypia occurs when after injury, cells regenerate but look abnormal, with suspicious nuclear changes. Often, this is acute, and disappears over time. However, if the regeneration is chronic (promoter effect), there is a real risk of pre-malignancy.

Answer 193

A dysplastic mass can be benign or dysplastic, so fits in both. Some metaplasias are dysplastic. No hyperplasias are dysplastic Dysplasias are pre-malignant. Genetic abnormalities can cause benign neoplasms, dysplasia or cancer.

Answer 194

In situ hasn't broken through the basement membrane, whereas invasive carcinoma has- it forms a spiky mass, with small metasteses coming off it.

Answer 195

Benign do not metastasize, have differentiated cells, slow growth and are rarely fatal. Malignant types metastasize, have less differentiated cells, and grow infiltratively and rapidly. They are fatal if untreated.

Answer 196

Cells infiltrate and then stimulate angiogenesis. They often also cause immune responses, and promote growth of fibrous tissue surrounding it.

Answer 197

Tumor stroma consists of everything in the tumor apart from the tumor cells themselves. This inclused the fibroblasts, collagen fibres and matrix, as well as new blood vessels and inflammatory cells. When tumors grow, they often grow faster than new blood vessels can be put down, and therefore often get deprived of oxygen. The hypoxic (not dead) tumour cells are resistant to chemo and radiation therapy though, so it can help the cancer to survive.

Answer 198

Disorganised architecture, and invasion of normal tissues Increased nuclear staining and size, with variation in shape Constant mitoses, and decreased cell cohesion.

Answer 199

For a cancer to develop, mutations of cancer-related genes must occur- must commonly acquired, but some inherited. These can be in: - Oncogenes- genes which promote cell growth and proliferation - Tumor suppressor genes- genes which control cell growth - Apoptotic genes- genes which initiate apoptosis - Also DNA repair genes and epigenetic factors.

Answer 200

- Viruses can carry RNA mutations into the host cells. - Proto-oncogenes (inactive form) can be transformed into oncogenes, causing a gain of function mutation. They can cause secretion of growth factor, expression of growth factors not reliant on ligands, they can affect intracellular signalling pathways, and can cause increased proliferation via nuclear transcription factors.

Answer 201

- Gene amplification: more copies of the oncogene, resulting in increased expression and activity- eg. neuroblastoma N-myc, or Her-2 in breast cancer (cokes for t. k. receptor) - Over-expression of gene, or inappropriate expression - Point mutations causing a different amino acid (and different product) - Gene rearrangement / structural translocation- forms a fusion gene, or causes upregulation of expression (eg. putting the gene next to a common promoter) - Epigenetic mechanisms- acetylation, methylation.

Answer 202

They have a loss-of-function mutation where they are no longer able to put the brakes on cell proliferation. Normally they regulate and inhibit growth and repair DNA. - Normally you need both alleles to de-activate. - Commonly caused by loss of heterozygosity (deletions of all/part of an allele) - Sometimes inherited cancer syndromes- eg. inherit one defective gene which only needs one mutation to tip over - Eg. retinoblastoma- has hereditary (early onset, more tumors) and non-hereditary forms

Answer 203

It results in the slow accumulation of malignant cells that can become a tumor. Come about by either: - Loss of apoptosis-mediating gene expression - Up-regulation of genes that block apoptosis.

Answer 204

All cancers start from a single cell and develop from there. They have properties allowing them to proliferate faster. Daughter cells have these same advantages, and may gain additional ones, leading to a mass. The next step comes when enough changes have occured to allow invasion of tissues, angiogenesis and metastases.

Answer 205

It is caused by proliferation of bone marrow cells- radiation exposure is the only known environmental risk. Clinical features are high white count and splenomegaly. It is caused by a chromosomal fusion: Between chromosomes 9 and 22. The BCR-ABL genes are fused, and cause production of a very powerful tyrosine kinase. This chromosomal pattern is called the philadelphia chromosome. The Philadelphia chromosome can be used to diagnose, monitor treatment and develop a target for this cancer. It is treated by a drug that inhibits the BCR-ABL fusion protein by binding to its ATP binding site, preventing further phosphorylation of substrates.

Answer 206

- Many close relatives with cancer - Cancers appear in successive generations - Young age of onset - Multiple cancers in a single patient NB in some familial cancer syndromes, there are more defined criteria

Answer 207

Majority of familial cancers affect tumor suppressor genes. Causes inheritance of one inactivated allele, and if the second allele becomes inactive, it will cause loss of tumor suppressor gene activity and potential cancer.

Answer 208

HNPCC: Associated with other cancers, often right side, increased risk endometrial cancer FAP: Present in adolescence, formation of hundreds of polyps with high incidence of transformation to carcinoma Both are autosomal dominant inheritance

Answer 209

It's a mutation in a DNA repair gene, which recognizes and excises incorrect sequences. In microsatellite regions, it can cause an increase in replication error rate, resulting in many, many repeats in these regions Inheritance of this allele has incomplete penetrance- 85% lifetime risk of cancer Diagnosed using clinical features, finding microsatellite instability in tumor, immunochemistry of tumor and analysis of repair genes (definitive) Managed with genetic testing and screening

Answer 210

Caused by mutation of gene promoting degradation of transcription activator by truncating the protein. Almost 100% penetrant. Managed by identifying and counselling families, cancer screening, and potential colorectomy

Answer 211

``` Mostly BRCA 1 & 2. Autosomal dominant inheritance with: - Early onset of breast/ovarian cancer - Premenopausal breast cancer - Multiple family members affected - Both cancers in one patient - Male breast cancer (BRCA2) - Increased prostate cancer risk Not fully penetrant due to environmental factors and where the mutation is ```

Answer 212

- Always consider genetic counselling - Presymptomatic testing of BRCA 1 & 2 mutations Manage by accounting for variable penetrance, screening frequently, potential prophylactic surgery (although there is still some risk)

Answer 213

PROS Gives more options due to early interventions Empowers through information ``` CONS Alienation and discrimination Loss of spiritual integrity Stress Guilt for not being affected/ guilt for being affected and potentially passing it to children ```

Answer 214

Monoclonality is where all cells are the same. This means they are neoplastic, and in some cases are malignant. These cells only produce a single antibody molecule, so on electrophoreisis graphs it shows a single peak of antibody types rather than a whole heap of multiple ones making a flat kind of plateau.

Answer 215

The reactive cells will produce multiple types of antibody, whereas the neoplastic ones will produce only the one.

Answer 216

Tumours differ in cell of origin (and distribution) as well as behaviour. Therefore, their presentation, prognosis and treatment will also be affected.

Answer 217

Grading is a measure of the rate of tumour growth, based on tumour histology. It indicates the aggressiveness- both in growth and invasion. They are graded based on three components: Differentiation, nuclear changes (pleomorphism, enlargement, hyperchromasia) and mitotic activity. Grade 1 tumours show god differentiation, and potential tubular structure in adenocarcinomas. Grade 2 show less differentiation, and grade three show a mass of random structures.

Answer 218

Tumour staging is a measure of the extent of growth, based on clinical, radiological and pathological features. Rate x Duration = Extent. Measures of rate of growth (grading) are histological- looking at lymphocytes, cytogenic changes, proliferation indices, and suppressor/oncogene function. This is all biological. Measures of extent of growth are stage, and serum markers- as well as looking how these change after tumor removal.

Answer 219

There are three categories- T for tumor, N for nodal metastasis, and M for distant metastasis. There can also be a p/c prefix for pathological and clinical. Stage 1 is tumour hasn't penetrated multiple layers of tissue, stage 2 is it has, and stage 3 is nodal metastases (with stage 4 distant)

Answer 220

Can spread locally- growth | - Metastasise through lymph (lung, breast), venously, through the serosal cavities and through nervous tissue.

Answer 221

Breast- can block the lymphatics, causing oedema and dimpling of the skin around hair follicles Bone- Can cause pathological fracture, hypercalcaemia (although this can also be due to hyperparathyroidism) and pain. Sometimes the cancer eats through the bone, sometimes it causes increased deposits.

Answer 222

Cancers can be epithelial, melanocytic, connective tissue, lymph node, bone marrow or CNS types.

Answer 223

Can be adenomas (glandular), papillomas (surface) or cystadenomas (cystic formation) Show regular tightly packed cells similar to normal epithelia, although some can be premalignant.

Answer 224

Most common malignant tumours, which affect the surface epithelium. They start with an in situ growth phase, and are then classed as malignant once they invade. They show cohesive polygonal cells, and test positive for cytokeratin. They are able to spread to bone, lymph nodes and viscera. Treatment is mainly surgical, but can also be done with radiation and chemotherapy/

Answer 225

They can be benign (moles) or malignant. They commonly occur in the skin. They can be defined while still in situ, but can also spread via the lymph and blood vessels. They can appear as spindle, round or pleomorphic cells, and while they are cytokeratin negative, they are S100/SOX10 positive

Answer 226

Sarcomas are rare, but benign tumors are common. They cannot be defined while still in situ, as connective tissue is frequently moving and it will have grown very large by the time it's identified. They spread via the bloodstream (mainly to the lungs). They are treated with a combination of surgery, radiation and chemo. They also show spindle cells, round and pleomorphic cells, and are also cytokeratin negative.

Answer 227

They are common tumors of the lymph nodes and extranodal sites, and are always malignant with no in situ phase. They spread to other lymph nodes. Treatment is with chemo and radiotherapy. They show non-cohesive round cells and are cytokeratin negative, although they are leukocyte common antigen positive (stains their cell membranes). Hodgkins shows reed-sternberg cells, which are multinucleated, while non-hodgkins can be differentiated into small-cell (long life but no cure) and large cell (short timecourse but curable).

Answer 228

An uncommon cancer of the bone marrow, with no in situ phase. It is treated by chemotherapy, with prognosis differing depending on type. They can also cause splenomegaly.

Answer 229

Uncommon tumours, mostly incurable. They are restricted to the CNS and can be treated with a mixture of surgery, radiotherapy and chemotherapy.

Answer 230

- Undifferentiated cells - Anaplastic (de-differentiated) cells - Pleomorphic cells (v. irregular nuclei)

Answer 231

- A complete carcinogen is any agent sufficient to cause cancer. - Initiators are doses of complete carcinogens introduced at doses not high enough to induce cancer. They cause cancer via synergy with promoters: - Promoters are agents that, when administered in repeated doses in close succession, can cause cancer with prior exposure to an initiator

Answer 232

- Initiator has to be applied prior to promoter - Effects of the initiator is reversible as promotion can be delayed - Effects of promoters are also reversible, because promoters are ineffective if doses are widely spaced enough.

Answer 233

Initiators have a permanent effect, while promoters are transient Initiators target the DNA, while promoters target proteins- eg. enzymes and receptors Initiators cause mutations, while promoters affect signalling pathways Initiators alter the gene sequences, while promoters affect gene expression Initiators deliver potentially carcinogenic damage, while promoters stimulate the outgrowth of initiated cells.

Answer 234

- Initiator is UVB, which is a complete carcinogen or initiator. UVA is the promoter. - When adjacent CC pyrimidine bases absorb UV radiation, they form cyclobutane dimers. Polymerase n is a faulty DNA repair enzyme, which inserts an A opposite the C. Then replication proceeds, and the CC is swapped to a TT. This can initiate and cause cancer when it occurs in the P53 gene.

Answer 235

Initially, sun-damaged skin has efficient apoptosis- the cells die off and the sunburn peels When one copy of the P53 gene is knocked out, it causes less efficient apoptosis, and clones of this mutation are allowed to survive. Further damage yields both genes being damaged, and apoptosis is lost, the cell cycle loses control and malignancy forms.

Answer 236

- PAH (from any form of plant smoking) - NNK (from nicotine) - NNK is hydroxylated at its alpha carbon due to immune activation, causing release of a very reactive product, which binds to guanine. This is then methylated, and begins to pair like an A rather than a G, so that T replaces the paired C, the following replication an A replaces the methylated G, and the GC pair changes to A-T (if not repaired). Additionally, NNK binds to receptors on the lung cells responsible for the Ras protein generation, causing increased proliferation, survival and invasion from this gene

Answer 237

In undeveloped countries, Aflatoxin acts and an initiator and alkylates guanine, and if it isn't repaired it causes a GC- TA transition. HBV then acts as a promoter, causing inhibited DNA repair, binding to P53 and deactivating it, Additionally, it activates Ras, and causes cell death, inflammation, regeneration and proliferation.

Answer 238

Chronic inflammation

Answer 239

Normally, cells are adhered with adherens junctions, formed from E-cadherin sticking out from adjacent walls, attaching to beta and then alpha catenins, which is attached to the actin cytoskeleton. When there is a reversible epithelial-mesenchymal transition, the E-cadherin gene is phosphorylated, and growth factors and inflammation causes focal dislocation- the cells maintain local structure, but are essentially unattached- in primary and secondary stages. These are solid tumors, with high metastatic potential. Irreversible EMT occurs due to mutation or silencing of the EMT or a cadherin genes, causing a permanent and loose attachment- or diffuse type cancers, where tumor cells are loose.

Answer 240

Overactive due to: - Overexpression due to altered regulation - Gene amplification - Missense mutations causing constitutive receptor activation - Co-expression with HGF in the same cells, forming autocrine loops Causes activation of ras oncoprogeins, inducing proteins (like snail) that repress E-cadherin Also phosphorylates E cadherin and b-catenin, causing the dissolution of adherens junctions.

Answer 241

Firstly, podosomes are assembled on the tumor cell surfaces, in response to the presence of growth hormones. The structure involves integrin-associated urokinase Plasminogen Activator receptors (uPARs). This allows uPA to bind, cleaving plasminogen to plasma. This protease then cleaves itself, pro-MMPs and the ECM itself. MMPs degrade the ECM, secreted by fibroblasts, inflammatory and neoplastic cells in an inactive form. They: - Carve a pathway for cell migration through the ECM and release growth factors from the ECM - Release chemotactic chemicals by breaking down laminin 5 - Suppress adhesion of E-cadherin - Degrade latent growth factor proteins to release the growth factor Integrins also signal cells via FAK and ras to stimulate pro-uPA production, proliferation and invasion.

Answer 242

Viable hypoxic cells are resistant to radiotherapy as oxygen is required to kill them. Hypoxia also induces activation of angiogenesis via HIF1a and VEGF. Hypoxia can also increase tumor aggressiveness as any cell with dysfunctional p53 will have a selective advantage Additionally it can activate snail and twist, repressing E-cadherin genes and inducing EMT, resulting in a higher risk of metastases.

Answer 243

- Metabolic stress (hypoxia, pH, gypoglycaemia) - Inflammation - Activation of oncogenes or inactivation of tumor suppressor genes

Answer 244

- Angiogenic sprouting: VEGF is applied, causing endothelial cells to degrade some basement membrane and form a migrating column through it, where proliferating cells follow the leading edge and differentiate. VEGF along however generates immature, heaky, haemorragic vessels, causing inflammation and oedema. It is characterised by an angiogenic switch: hyperplastic ducts --> dysplastic ducts --> angiogenic dysplastic ducts --> invasive ductal carcinomas

Answer 245

Tumors initially grow around blood vessels, but when they become highly malignant, the vasculature regresses, making the tumor secondarily avascular. Angiogenesis is then triggered

Answer 246

Columns of tumors grow against the lumen of a blood vessel and force it to remodel as it grows

Answer 247

Haemangioblasts are stem cells which can be called by tumors from the bone marrow. They differentiate into endothelial cells, smooth muscles and pericytes to form new blood vessels

Answer 248

Some cancer cells can express endothelial characteristics of endothelial cells and form their own capillaries. These are lined by a mosaic of EC and cancer cells. This also increases the chance of distant metastases

Answer 249

- The site, type and stage of cancer - Treatment modalities and possible side effects - Co-morbidities of disease - Age and social circumstances - Swallowing impairment - Effects on digestive mechanisms - Any surgical blockages - Cachexia

Answer 250

Cachexia is the breakdown of skeletal muscles and issues in fat and carbohydrate metabolism despite adequate nutritional intake. It is caused by the tumor releasing acute phase proteins, causing inflammation and cytokines, as well as reducing appetite due to hypothalamic effects. The tumor also releases PIF to directly break down skeletal muscle Finally, it releases LMF to break down fat.

Answer 251

Altered metabolism - Increased protein catabolism and loss - Glucose intolerance and abnormal insulin response - Increased lipolysis and fatty acid turnover - Inefficiency in energy consumption and increase in energy expenditure Altered physiology - Malabsorption and maldigestion - Constipation and dysmotility due to surgery or narcotics Insufficient dietary intake - Appetite suppression, caused by cytokines, depression or loss of taste - Learned aversion Physical impairment - Swallowing - Saliva - Mass of tumor - Mucositis in mouth - Surgical interruption

Answer 252

- Improve quality of life - enhance anti-tumor treatment effects - Reduce adverse effects - Prevent or correct defficiency

Answer 253

- Supplemental feeding- increasing energy/protein content - Advice and information - Enteral feeding- oral sip feeds or NG tube - TPN - Pharmacological agents to combat cachexia - Nutraceutical agents to enhance immunity - Intravenous feeding (but problems with sterility)

Answer 254

These make up 98.5% of our entire RNA pool, with a very important role in the normal development of cells and organs. They can be classes as small (less than 200 nucleotides) or large ( more than 200 nucleotides). They can also be classified by function, size, shape and biogenesis.

Answer 255

- Transfer RNA - Small nucleolar RNA - MicroRNA

Answer 256

- Its job is to carry amino acids to the messenger RNA in order to translate it to protein. It's found in mtDNA. When mutated it causes the maternally inherited disease MELAS, for mitochondiral myopathy, encephalomyopathy, lactic acidosis, and stroke like episodes

Answer 257

- Its job is to modify the ribosomes by coupling amino acids together during tanslation - In diseases where the 11q13 region of chromosome 15 is lost, this is where the snoRNA sits, so it can cause prader willi and angelman syndromes by changing splicing, causing increased energy expenditure and growth retardation.

Answer 258

MicroRNA represses translation of target RNA, and each can regulate about 200 different ones. In disease, it is especially associated with: - Cancer- when damaged, they lose the ability to regulate oncogenes/tumor suppressor genes - Down syndrome- gain of chromosome 21 contains 5 micro-RNAs involved in regulation of MECP2, important for brain development - Alzheimers- loss of miRNA causes increased BACE1 enzyme, causing accumulation of protein plaques in the brain

Answer 259

- XIST - HOTAIR - H19 - snoRNA-incRNA

Answer 260

Its job is to regulate X inactivation by binding to and switching off the whole chromosome. - Errors lead to skewed X inactivation, causing accumulation of X linked diseases

Answer 261

This methylates messenger RNA, and is especially prominent in breast cancer as it methylates metastasis suppressor genes, switching them off

Answer 262

It's an imprinted ncRNA expressed from maternal chromosmes, which regulates insulin growth factor in cells. A loss of H19 causes excess cell growth, and also contains a micro-RNA which switches off tumor suppressor genes.

Answer 263

It is transcribed from the same region as those in prader-willi syndrome. The inc-RNA mops up FOX 2, and so is implicated in Angelmann syndrome too.

Answer 264

They can be used as Biomarkers of disease (due to their being found in higher or lower levels depending on the disease They can act in genome wide association studies, where they can find SNPs associated with disease, which alter the ability of RNA to bind to other RNAs and reduce their functions They can also be used in therapeutics, as their close association with disease progression can mean they are able to be targeted to reduce diseases such as cancer, inflammation and chronic heart disease.

Answer 265

All DNA = genome All RNA = transcriptome All Protein = proteome All Metabolites = metabolome

Answer 266

Originally, DNA was labeled so that when it was read on a computer each nucleotide gives off a color Next generation breaks the genes into small portions, and adds linkers to bind them to the microscope slide. When enzymes run up the side of the DNA, a colored light is emitted each time the base changes. - These fragments are captured using baits (complementary matches) or using PCR

Answer 267

A part of the genome that codes for genes

Answer 268

Some fragments are repeated multiple times throughout the genome, so identifying which chromosme and gene something comes from can be difficult Also difficult to see new mutations from mutations (but can use conservation- if something has been handed through many, many different generations in multiple species, it's likely a polymorphism)

Answer 269

So that medicine which targets a particular gene can be adapted to work on that mutation too

Answer 270

Use of the knowledge of somebody's genetics to personalise disease treatment. This can also be used to assess a person's suitability for tratments like anti cancer trugs.

Answer 271

Tumors can delete the MHC receptors on its cells to prevent antigen presentation- but these cells are picked up by CD335 NK cells. Additionally some tumor DNA is released into the blood- this allows us to know what tumor it is and where by taking this DNA from the blood.

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