What's your diagnosis? I'll tell you in advance, that the cause isn't infectious. I'll post the correct answer in a day or three!
I try : sickle cell ulcers (I exclude the more frequent venous ulcers because the patient doesn't seem to have superficial venous insufficiency of lower extremities, 'cause there are neither teleangectasias nor varicose veins. Moreover, I think it's a sickle cell anemia because of patient's ethnicity (considering that this disease is very common in Africa).
I'll try as well: chronic iron overload with cutaneous ulcers (e.g. patient suffering from beta thalassemia not adequately supported with iron chelation therapy)
Correct answer: Ulcers due to sickle cell disease. Leg ulcers are not uncommon in sickle cell disease. Progressive blood vessle narrowing can also cause a stroke and infarction in other areas, e.g. the penis. Mesenteric ischemia and painful vaso-occlusive crises are also common.
A Challenging MCQ on Sickle cell anemia Here is a challenging question on Sickle cell anemia for Step 1 takers A 24-year-old African American mountain climber in excellent physical condition suffers shortness of breath and low oxygen (hypoxia) at high altitude in Nepal. After transport to base camp and oxygen treatment, a family history reveals that his mother has sickle cell anemia. With reference to the upper portion (A) of the figure below, laboratory studies of his -beta globin gene structure and expression would be expected to show which of the following results? (Note that the same MstII restriction and β-globin probe in the figure is used for Southern blotting.) click on the image to enlarge it [FONT=&]A. MstII DNA cleavage segment of 515 and 165 bp by Southern blot, RNA segment of ~550 and 700 bp by Northern blot, normal and abnormal proteins by hemoglobin electrophoresis[/FONT] [FONT=&]B. MstII DNA cleavage segments of 680, 515, and 165 bp by Southern blot, RNA segment of ~550 and 700 bp by Northern blot, normal and abnormal proteins by hemoglobin electrophoresis[/FONT] [FONT=&]C. MstII DNA cleavage segments of 515 and 165 bp by Southern blot, RNA segment of ~1400 bp by Northern blot, single abnormal protein by hemoglobin electrophoresis[/FONT] [FONT=&]D. MstII DNA cleavage segment of 680 bp by Southern blot, RNA segment of ~700 bp by Northern blot, single normal protein band by hemoglobin electrophoresis[/FONT] [FONT=&]E. MstII DNA cleavage segments of 680, 515, and 165 bp by Southern blot, RNA segment of ~1400 and 700 bp by Northern blot, single abnormal protein by hemoglobin electrophoresis[/FONT] EXPLANATION: The offspring of a female with sickle cell anemia must receive one of her abnormal B-globin alleles and be a heterozygote or carrier known as sickle cell trait. Those with sickle trait will have one B-globin gene with a sickle mutation that ablates the sixth codon MstII site, yielding a 680 bp fragment by Southern blot in addition to the 515 and 165 bp fragments yielded by the normal B-globin gene (eliminating incorrect answers a, c, and d). RNA transcription and processing will not be affected, yielding a B-globin mRNA of about 550 bp (eliminating incorrect answer e). The sickle hemoglobin will have a different charge and conformation due to its glutamic acid to valine substitution, migrating differently by electrophoresis and yielding a second, abnormal hemoglobin band in addition to that of normal hemoglobin. Approximately 1 in 12 African Americans will have sickle trait, justifying its inclusion in American neonatal screening protocols. Caucasians, especially those of Mediterranean origin, can also be affected. Individuals with sickle trait will be asymptomatic under normal conditions, but may show symptoms under conditions of low oxygen tension (high altitudes, diving, etc) due to the lower oxygen-binding capacity of their red blood cells (half normal, half sickle cell hemoglobin). B = Beta The answer is B Hint - when u r faced with such a question, it's quite possible that u will be intimidated by all the jagron and the supporting image. So logic is the way to go...It's clear from the case that this is a Sickle cell trait as the patient was asymptomatic this far. Which means 2 types of m-RNA (one normal and one abnormal) on northern blot and 2 types of protein ( one normal and one the abnormal sickle protein ) on electrophoresis, which is option B I hope this helps at least one of you (-: Hats off to Dupuytren and fantastic differentials by both RedNoise and Walkov !
Another MCQ testing ur diagnostic acumen U will surely see one question on electrophoresis on Step 1 and this one is a classic. A 35-year-old female with heavy menstrual periods (metrorrhagia) has anemia but does not respond to iron supplementation. Blood is drawn and the red cell hemoglobin is analyzed. Which of the following results is most likely if the patient has an altered hemoglobin molecule (hemoglobinopathy)? [FONT=&]A. Several proteins but only one red protein detected by high-performance liquid chromatography (HPLC)[/FONT] [FONT=&]B. Two proteins detected in normal amounts by Western blotting[/FONT] [FONT=&]C. Several proteins and two red proteins separated by native gel electrophoresis[/FONT] [FONT=&]D. Two labeled bands a slight distance apart after SDS-gel electrophoresis and reaction with labeled antibody to α- and β-globin[/FONT] [FONT=&]E. A reddish mixture of proteins retained within a dialysis membrane[/FONT] [FONT=&]EXPLANATION:[/FONT] [FONT=&]In the technique of polyacrylamide gel electrophoresis (PAGE), the distance that a protein is moved by an electrical current is proportional to its charge and inversely proportional to its size. Patients with normal hemoglobin A have two alpha-globin and two beta[SUB]1[/SUB]-globin chains, each encoded by a pair of normal globin alleles. Mutation in one alpha- or beta-globin allele alters the primary amino acid sequence of the encoded globin peptide. If the amino acid change alters the charge of the peptide, then the hemoglobin tetramer assembled with the mutant globin peptide has a different charge and electrophoretic migration than the normal hemoglobin tetramer. The electrophoresis of native (undenatured) hemoglobin therefore produces two species (two bands) rather than one, each retaining its heme molecule and red color. [/FONT] [FONT=&]If the hemoglobins were first denatured into their alpha- and beta-globin chains as with SDS-polyacrylamide gel electrophoresis, then the similar size of the alpha- or beta-globin peptides would cause them to move closely together as two colorless bands. Identification of these peptides as globin would require use of labeled antibody specific for globin (Western blotting). Because the sodium dodecyl sulfate (SDS) detergent covers the protein surface and causes all proteins to be negatively charged, the distance migrated is solely dependent (inversely proportional) on protein size. [/FONT] [FONT=&]High-performance liquid chromatography (HPLC) uses ionic resins to separate proteins by charge. The columns are run under high pressure, rapidly producing a series of proteins that are separated from most negative to most positive (or vice versa, depending on the charge of the ionic resin). A mutant hemoglobin with altered charge should produce a second red protein in the pattern. [/FONT] [FONT=&]In dialysis, semipermeable membranes allow smaller proteins to diffuse into the outer fluid, but not larger proteins such as hemoglobin. [/FONT] The answer is C Comments - this question tests whether u know how the diff electrophoretic methods work - i.e 1) separation by size alone (SDS-gel) vs seperation by charge and size ( PAGE ) 2) denaturation b4 seperation ( SDS and SDS PAGE ) vs seperation without denaturation ( PAGE aka Native Gel Electrophoresis, HPLC ) in cases where we may be interested in the quaternary structure. SDS vs PAGE vs SDS-PAGE Disambiguation In SDS the gel medium denatures the protein (quartenary structure is lost - ex. hemoglobin will break down into 2 close groups alpha and beta or inabnormal cases into normal components and the abnormal alpha or beta component (Y) )and then coats them uniformly with a negative charge - so seperation is based on size alone. In PAGE the gel medium does not denature the protein and so all proteins will be maintained in their quartenary state and seperated on the basis of charge and size. Note - If the charge to size ratio is the same then seperation will b based on size with smaller particles moving faster. In SDS-PAGE - it's not hard to guess. First denaturation and then denaturation based on both charge and size. Additional Hint: Although we are saying Hemoglobin electrophoresis, there are other proteins in RBC in smaller amounts and so we will always see a mixture. If the method used does not denature the protein then we will see a single red band due to the heme still beinfg attached ( along with other minor bands ) in normal individuals and 2 red bands (along with other minor bands ) in case of a hemoglobinopathy. If we denature, then the normal and abnormal chains will separate out as diff bands (no red color, as the heme will break free). So we will have 2 close bands in normal and at least 3 in abnormal ( remember fetal hemoglobin will also be present in hemoglobinopathies ). These bands can the be identified with specific antibodies (Western Blot ) I hope I have done a decent job P:
