Day 15. Replication of DNA

Day 14. Structure of nucleic acid

Day 13. Hormones

Day 12. Vitamins

Water soluble

• Metabolic:

1. B1 (thiamin)
2. B2 (riboflavin) FAD(H2)
3. B3 (niacin) NAD(H), NADP(H)
4. B5 (pantothen)
5. Biotin
6. B6 (pyridoxin)

• Blood related

1. B12 (cobalamin)
2. Folate

• Vitamin C

Fat soluble

1. Vitamin D
2. Vitamin A
3. Vitamin K
4. Vitamin E

Day 11. Recombinant DNA. Genetic testing

Day 10. Genetics of Common Diseases

• CHD
• diabetes mellitus
• cancer

Progress

I did a bit of questions of RR Biochemistry today. Well, considering biochemistry, I don't remember much of what I've been reading for a months. And also did some very stupid mistakes. But I mostly knew that if I had memorized the things better, the questions were answerable, the answers had all been in my books.

Day 9. Gene mapping and cloning

Well, I already thought that genetics seems easier, but this subject is tough for me, hard to capture.

Trying to determine where the gene is located and how far apart 2 genes are from one another.

• crossing over (in prophase I of meiosis)
• linked genes - the probability of recombination <>
• syntenic - genes on the same chromosome
• recombination frequency
• LOD scores
• linkage disequilibrium
• polymorhic markers

Gene cloning:

1. find linkage to a known markers;
2. identify protein coding regions (computers - promoter areas, exon-intron boundaries, starting codones, CG islands)
3. compare DNA sequences of these genes in affected and unaffected individuals.

Day 8. Cytogenetics

• Trisomy 21 - Down syndrome
• Trisomy 18 - Edward's syndrome
• Trisomy 13 - Patau syndrome
• Klinefelter's syndrome
• Turner syndrome

Triple screen

SRY gene

Pseudohermophroditism

Day 7. Population Genetics

p + q = 1

pxp +2 pq + qxq = 1

Allpied to autosomal recessive diseases:
pxp - frequency of normal genotype
2pq - frequency of heterozygose carrier
qxq - frequency of mutated genotype

p - frequency of normal allele
q - frequency of mutated allele

Day 6. Genetics. Single-gene Disorders.

Moved to genetics this morning. Metabolsism still needs revising and memorizing, but for the first reading, it's ok, I guess. I read Goljan's high yield notes yesterday and they didn't seem rocket science anymore, started to make sense. I mean, I actually knew something. Questions though seem tricky. The whole picture is still a bit messy. Needs lot of work.

• point mutations
• missense mutations
• nonsense mutations
• deletion/insertion mutations
• framshift mutations

AD - autosome dominant (mostly structural protein defect) (gained/lost). E.g. Achondroplasia.

AR - autosomal recessive (usually ezyme defects) E.g. Cystic fibrosis.

X-linked inheritance. (From mother to son, no father to son) E.g. Hemophilia A.

X-linked dominant inheritance (more women affected).

Mitochondrial inheritance - (all children of a sick woman are affected; men don't transmit) Leber Herditary Optic Neuropathy

Day 5. Lipid Metabolism

It goes slower now, as I've been trying to fit all the different pathways into one whole metabolism picture. But it gets messy as there are huge number of enzymes to remember and how they are controlled.
But as my online study partner said: don't get frustrated and be patient. And I'm trying to do this.
"What is important is to keep learning, to enjoy challenge, and to tolerate ambiguity. In the end there are no certain answers". I like this quota by Martina Horner.

Day 4. Glycogenesis. Glycogenolysis. Glyconeogenesis. PPP.

Day 3. TCA cycle and Oxidative Phosphorylation

• in mitochondria
• AcetylCoA (acetyl group) is completely oxidized to CO2.
• energy saved as NAHD, FADH2 and GTP
• no hormonal control as energy need doesn't depend on fed-state
• control mechanism - energy status of the cell
• enzymes in the matrix of the mitochondria, except succinate dehydrogenase (inner membrane)
• electron transport chain creates H+ gradient between two sides of the enner membrane of the mitichondra
• the H+ gradient's energy is used for making ATP

Day 2. Glycolysis

• rate-limiting enzyme - phosphofruktokinase-1

Day 1. Overview of Metabolism

• in well-fed state the main source of energy for liver - excess of amino acids.

Updates

I have been studying biochemistry for a while now. Recently found a study partner and we made a schedule which we try to follow.

Random Facts

Embryology

Neural tube - CNS cells, skeletal motor neurons and axons of preganglionic autonomic neurons; neuroglia: oligodendroglia, astrocytes, ependymal cells.

Neural crest cells - sensory neurons, postganglionic autonomic neurons, Cromaffin cells in adrenal medulla; neuroglia: Scwann cells.

Random Facts

• The dystrophin gene is one of the largest known genes. Dystrophin - a large protein which connects the thin actin filaments to the transmembrane protein beeta-dystroglycan in the sarcolemma.

Duchenne's muscular dystrophy (mutations of the dystrohin gene cause the dystrophin be absent from the muscles.

Becker's muscular dystrophy - milder form. Dystrophin is present, but altered or reduced in amount.

Overview

I've finished reviewing cell biology at last - organelles, cell's transport and communication systems. It was quite an interesting subject, I even felt somehow thrilled. I did it rather thoroughly, using different sources. Reading the experience of other's, using too many recources is discouraged, but I just can't do otherwise, I need different approaces to begin to understand the topic fully. I also guess, as I don't feel the pressure of exam, I can enjoy the process of learning more - it's just for myself.
Right now I've started neurophyiology.

Random Facts.

• Active transopr of Na- and K-ions (Na-K-ATPase) is one of the major energy using process in the body. Thus it accounts for a large part of the basal metabolism. On average, it accounts 24% of energy utilized by cells, and in neurons it accounts 70%.

• About 50% of all known drugs work through G-protein-linked receptors.

• Actin is the most abundant protein in the cells. (At times up to 15% of all proteins of a cell). A structural component of microfilaments (thin filaments).

Good online sites

Blue Histology: http://www.lab.anhb.uwa.edu.au/mb140/
Cell Biology (Dr. Gwen V. Childs): http://www.cytochemistry.net/Cell-biology/
Ed's Basic Histology Gallery: http://www.pathguy.com/histo/000.htm
Histology Learning System (Common Confusions): http://www.bu.edu/histology/m/append04.htm
Histology at SIU SOM: http://www.siumed.edu/~dking2/index.htm
Histology Tutorial: http://medinfo.ufl.edu/year1/histo/
Üldine histoloogia: http://raud.ut.ee/~rraid/index/Uldine%20histoloogia/
NCBI Bookshelf: http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books

What have I been doing.

I've gone through cell cytoplasm, epithelium and connective tissue. Made good notes on paper on nucleus, haven't have time to update notes here.
I also found some good histology and cell biology sites online which I will list next time.

2. Cell nucleus

Components:

1. nucleus membrane (envelope)
   
2. nucleolus


3. chromatine

Most of the cells have 1 round-shaped, loosely-packed nucleus.

Variations:

• relatively small nucleus with tightly backed contents (e.g. cells lining the blood spaces (sinusoids) of the liver (you can't see nucleolus in these nuclei);


• extraordinarily large nucleus (megakaryocytes);


• nucleus of distinctive shape (deeply segmented nucleus of neutrophils);


• binucleated (occasionally some hepatocytes and muscle cells of the heart);


• multinucleated (osteoclasts and sceletal muscle cells);


• without nucleus (erythrocytes, platelets).

Nuclear membrane is composed of 2 parallel unit membranes that fuse with each other at certain regions to form perforations knows as nuclear pores. It can be seen in EM.

• perinuclear cisterna (a 10 - to 30-nm space between two membranes);
  
• inner nuclear membrane (about 6 nm thick, faces the nuclear contact). It's in the close contact with the nuclear lamina which is made up of three polypeptides, called lamins (lamins A, B and C). It's a meshwork of intermediate filaments, 80 to 100 nm thick. Peripheral chromatin adheres to the inner aspectof the nuclear lamina. Certain integral proteins of the inner nuclear membrane act either directly or via other nuclear matrix proteins as contact sites for the nuclear RNAs and chromosomes.
  
• outer nuclear membrane (about 6 nm thick, is studded with ribosomes and faces the cytoplasm). It's continous with rough endoplasmatic reticulum. Its cytoplasmatic surface is surrounded by a thin, loose meswork of the intermediate filaments, vimentin. Its cytoplasmatic surface usually possesses ribosomes, actively synthesizing transmembrane proteins that are destined for the outer or inner nuclear membrane.
  
• nuclear pores (there are 20 - 3000 in one nucleus). It's surrounded by nonmembranous structures embedded in its rim - nuclear polar complex (NPC). It guards selectively passage through the pore.

Nuclear pore complex is composed of nuclear pore and its associated glycoproteins.

- cytoplasmic ring

- middle ring

- nucleoplasmic ring

1. Introduction to Histology

Covered introduction to histology and started the review of cell nucleus.
Brief notes.


Histology - a science of the tissues.

Basic tissues:
1. epithelial
2. connective
3. nervous
4. muscle
Mõtle, kas tean: For example where do liver belong to?


Three primary components that make up the body tissue:
1.cells
2.intercellular (extracellular) matrix (produced by the cells of connective tissue)
3.body fluids (blood plasma, interstitial fluid, lymph).

• preparation of histologic sections

Routinely prepared by the paraffin technique. If tissues need to be examined without delay, tissue freezing is used (f.e. the course of surgical procedure depends on rapid histological assessment of the nature or spead of a diseased tissue).

• coloring of stains

Histological stains reveal tissue components either by coloring them selectively (LM) or by increasing their optical densities to different extents (EM).

Hematoxylin-eosin stained sections:

a)hematoxylin (basic/cationic stain) colors the acidic components (basophilic) of the cell a bluish-purple color (DNA, RNA);

b)eosin (acid/anionic stain) colors basic (acidophilic) components of the cell a pinkish colors (positive (e.g.NH3) sites on fixed proteins).

• light microscope (LM)

The max magnification about x 1400. The limit of resolution 0,2 mcm (details that are less than 0,2 mcm apart cannot be distinguished as separate entities.)

• elecron microscopy (EM)

Magnification up to x 50000, resolution 1 nm. a)transmission EM (routinely used);

b)scanning EM.

• interpreting histologic sections in three dimensions (transverse, longitudinal, oblique and grazing sections).

Mõtle: microscopic appearance of tubes, partitions, proteins, stored carbohydrates, stored fat.

Recognition of extracellular matrix and bodu fluids in sections.

Artifacts (postmortem degeneration, shrinkage artifact, precipitate, wrinkles or folds, microtome knife nicks, rough handling).

• localization of specific tissue constituents

Mõtle: fluorescence microscope, immunofluorecence staining, confocal microscope, blotting techiques and in situ hybridization (Northern, Southern and Western Blots).

Starting my medical career again?

I have no idea whether I will ever work as a doctor again and if yes whether then in Estonia or in the USA. But I felt that it's still a good idea to refresh my memory on basic medical knowledge.
Anyway, I have 7 books coming from Amazon and yesterday I also took 2 histology and an anatomy book from the collage library.
So here it comes - to track my progress or the lack of progress.... just some notes. I thought that it would be better to keep them in English. Just for the reason of practise and also as all the books, which I'm going to read, are in English. And after all, nobody would ever ask me this stuff in Estonian again. If I'm not going to work as a doctor, then it's just for myself - to broaden my hosrizons. I've really forgotten a lot of all of this which I studied 15 years ago.