INHERITED THROMBOPHILIA

Q. A 27-year-old man develops a deep venous thrombosis in his left lower leg after a 4-hour car ride. His father had a thrombosis in a mesenteric vein 1 yr back, and his mother has had repeated superficial venous thromboses. Which of the following disorders does this patent most likely have?
(A) Factor V Leiden thrombophilia
(B) Familial hypercholesterolemia
(C) Fanconi’s anemia
(D) von Hippel-Lindau disease
(E) von Willebrand’s deficiency

Ans: B.

This patient has factor V Leiden thrombophilia, an inherited condition that predisposes patients to thromboses, especially those in unusual locations (eg., the mesenteric veins), and repeated thrombotic events (superficial and/or deep). Many patientshave their first thrombotic event at <50 years old. Heterozygous patients have a slightly increased risk of thrombotic events, while homozygous individuals are at a significantly increased risk.

Answer B is incorrect. Familial hypercholesterolemia leads to increased levels of low-density lipoprotein cholesterol, thereby increasing the risk of atherosclerosis, myocardial infarction, and stroke.

Answer C is incorrect. People with Fanconi’s anemia have a pancytopenia that causes increased incidence of infections, anemia, fatigue, and bleeding.

Answer D is incorrect. von Hippel-Lindau disease is characterized by abnormal blood vessel growth leading to angiomas and hemangioblastomas in the retina, brain, and spinal cord as well as in other regions of the body.

Answer E is incorrect. von Willebrand’s deficiency causes a prolonged bleeding time, which manifests as increased bleeding after trauma or surgery, nosebleeds, and hematomas.

MLCK

Q. What is the function of the enzyme activated by the calciumcalmodulin complex?
(A) Binding to troponin
(B) Dephosphorylation of actin
(C) Dephosphorylation of myosin
(D) Phosphorylation of actin
(E) Phosphorylation of myosin

Ans: E.

The calcium calmodulin complex activates myosin light chain kinase, which phosphorylates myosin and allows it to bind to actin, leading to contraction and shortening of the muscle fiber.

·         In smooth muscle, unlike skeletal muscle, there is no troponin. Instead, calcium is the regulator of myosin on the thick filament.

·         Actin is not phosphorylated or dephosphorylated in the contraction and relaxation cycle of smooth muscle.

·         The calcium-calmodulin complex activates myosin light chain Kinase which phosphorylates myosin.

·       

Myosin light chain phosphatase removes the phosphate group from myosin

TUBULIN

Q. Which of the following make up the cellular structures involved in axonal transport of vesicles?
(A) Desmin
(B) Keratin
(C) Titin
(D) Tubulin
 (E) Vimentin


Ans: D. Tubulin.


Exp. 

Microtubules are involved in the transport of vesicles down the axons of neurons. Microtubules are made of polymerized tubulin. The microtubule is made up of two subunits, that polymerize to form a hollow tubule. Two attachment proteins, dynein and kinesin, attach to membranous organelles and move along the tubules toward and away from the cell center.

Option  A is incorrect. Intermediate filaments of muscle cells are made up primarily of desmin.

Option  B is incorrect. Intermediate filaments are cytoskeletal elements that are prominent in cells that withstand stress. Intermediate filaments of epithelial cells are composed primarily of keratin.

 Option  C is incorrect. Titin, also known as connectin, is a protein that is important in the contraction of striated muscle tissues. In the sarcomere, titin connects the M line to the Z line.

Option E is incorrect. Vimentin is polymerized to form intermediate filaments that are found in cells of mesodermal origin, such as fibroblasts

CHOLERA

Q. A 50-year-old man develops nonbloody watery diarrhea while working as an aid worker in a refugee camp in Bangladesh. He arrived in the area 2 days ago. A stool smear shows no WBCs.
He subsequently develops dehydration and electrolyte abnormalities leading to cardiac and renal failure. Which of the following organisms is the most likely cause of this man’s enterocolitis?
(A) Clostridium difficile
(B) Giardia lamblia
(C) Helicobacter pylori
(D) Salmonella species
(E) Vibrio cholerae

Ans: E.

Vibrio cholerae causes watery stools, often called rice-water stool.

This illness is not accompanied by abdominal pain, but the symptoms are due to dehydration leading to electrolyte imbalances.

 Cholera toxin causes uncontrolled stimulation of adenylate cyclase; the resulting excess of

  cAMP causes uncontrolled secretion of chloride and water (due to the osmotic gradient),

 resulting in extremely watery diarrhea accompanied by electrolyte imbalances.

 Clostridium difficile causes severe non bloody diarrhea associated with pseudomembranes

Diarrhea may be bloody when very severe mucosal ulceration occurs. C. diffi cile infection is associated with previous antibiotic treatment

 
Giardia lamblia is a protozoan parasite that is a frequent cause of nonbloody diarrhea.

 The stools are usually foul-smelling and contain fat (steatorrhea). It is  less severe than the diarrhea caused by Vibrio cholerae.

 Helicobacter pylori infection causes gastritis and would not cause the symptoms describe by the patient.

Salmonella species invade the mucosa to cause bloody diarrhea and can be acquired from poultye meat & eggs.

CHANCROID

Q. A 30-year-old sexually active woman presents with a painful vesicle on her external genitalia and bilateral inguinal lymphadenopathy. A Tzanck smear from the vesicle fails is negative, and polymerase chain reaction analysis of viral DNA is negative. A VDRL assay is also negative. Which of the following medications would be most helpful to this patient?
(A) Acyclovir
(B) Ceftriaxone
(C) Foscarnet
(D) Ribavirin
(E) Vancomycin


Ans:   B.  
The differential diagnosis of a genital ulcer in a sexually active patient should include primary syphilis (though these ulcers are usually painless), genital herpes, and chancroid. 
Because the Tzanck smear (which looks for multinucleated giant cells typical of herpes infection), viral polymerase chain reaction (used to look for herpesvirus) are both negative, as is the VDRL to test for syphilis, chancroid becomes most likely. 

Chancroid is a bacterial infection caused by Haemophilus ducreyi, which presents typically as a painful genital ulcer with associated inguinal lymphadenopathy. It is typically treated with ceftriaxone, though azithromycin or ciprofl oxacin can be used. Vancomycin is effective only

for gram-positive organisms

 A is incorrect. Acyclovir is used to treat herpes infections. It is activated by viral thymidine kinase, whereupon it inhibits the herpes viral polymerase. It can be used to treat herpes simplex virus (HSV) types 1 and 2, varicella- zoster virus (VSV), and Epstein-Barr virus (EBV) infections. It is not effective for bacterial organisms.

 C is incorrect. Foscarnet inhibits viral DNA polymerase without the need of activation by thymidine kinase. It is used to treat cytomegalovirus (CMV) retinitis, but it can also be used

to treat acyclovir-resistant HSV.

 D is incorrect. Ribavirin is used to treat respiratory syncytial virus. It functions by inhibiting inosine monophosphate dehydrogenase, thus blocking the synthesis of guanine

nucleotides.

 E is incorrect. Vancomycin is a bactericidal antibiotic used for multidrug-resistant gram-positive organisms such as Staphylococcus aureus and Clostridium diffi cile. It functions

by binding to mucopeptide precursors, preventing formation of the bacterial cell wall