Biomedical subjects
Publications and source records attributed to A Crow.
Numerous bacterial proteins involved in the nitrogen cycle, and other processes, require c-type haem as a cofactor. c-type cytochromes are formed by covalent attachment of haem to the conserved CXXCH motif. Here, we briefly review what is presently known about cytochrome c maturation in Bacillus subtilis with particular emphasis on the crystal structures of ResA.
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BACKGROUND: The incidence of prostate cancer in black men is estimated to be 30% to 50% higher than among age-matched white men, and black men have a twofold higher mortality rate. To determine whether racial differences exist in men with similarly staged disease, we compared clinical and pathologic features in black and white men with clinical stage T1-T2 prostate cancer. METHODS: We retrospectively reviewed the records of all men who had prostate biopsy at our facilities. Men were included in this study if they were of black or white race, if the clinical stage of their prostate cancer was T1-T2, and if detailed information regarding their prostate biopsy was available. RESULTS: Black men were found to have significantly higher serum prostate-specific antigen (PSA) levels, but no other differences were noted in the other clinical or pathologic features studied. CONCLUSION: While racial differences in the incidence and mortality of prostate cancer are well known, differences in the clinical and pathologic features between black and white men with similarly staged disease have been poorly studied. Our results suggest that serum PSA levels are higher in black men, but no other differences were noted. This suggests that early detection programs for prostate cancer in black men can potentially decrease prostate cancer mortality.
BACKGROUND: The reported incidence of prostate cancer is higher among African-American men than among white men. We conducted a study of African-American and white men without prostate cancer to determine whether clinical and histologic findings might be associated with racial differences in serum prostate-specific antigen (PSA) levels. METHODS: From January 1990 through March 1997, 493 (59.5%) of 829 African-American men and 736 (74.1%) of 993 white men who had elevated serum PSA levels (> or = 4.0 ng/mL) and/or abnormal digital rectal examinations and who underwent transrectal ultrasound-guided prostate biopsies were found to be without prostate cancer. Also reviewed were patients' age and race, indication for biopsy, histologic features of the prostate biopsy specimen, ultrasound-measured prostate volume, PSA density (i.e., the PSA level divided by the prostate volume), and (in some cases) serum testosterone levels. RESULTS: Among these men without prostate cancer, there were no statistically significant differences by race in the ages of the patients, their prostate volumes, or their serum testosterone levels; however, the mean serum PSA levels and PSA densities were significantly higher in African-American men than in white men (two-sided P values of .00003 and .000009, respectively). A higher proportion of African-American men than white men had inflammation in their prostate biopsy specimen, and men of both races with prostate inflammation had higher PSA values than those without inflammation. African-American men without inflammation had higher PSA values than white men without inflammation. CONCLUSIONS: In this study, African-American men without histologic evidence of prostate cancer had significantly higher PSA levels and PSA densities than similarly aged white men. This finding was not accounted for by racial differences in patients' age, serum testosterone level, or prostate volume.
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Previous angiographic and radiological studies have suggested that the peroneal artery is the best preserved of the calf vessels in peripheral vascular disease and should be a site of preference for a femorodistal bypass graft. Calf vessel run-off assessed by pulse generated run-off (PGR) provides a more accurate prediction of graft success or failure than angiography and may therefore give a better functional picture of vessel patency than angiography. This study compares the presence and degree of preservation of the three calf vessels in patients with severe peripheral vascular disease using both intra-arterial digital subtraction angiography (IADSA) and PGR. Thirty-four limbs in patients with either ischaemic rest pain, ulceration or gangrene were studied and the results were scored according to the extent and severity of disease in the peroneal, posterior tibial and anterior tibial arteries. On IADSA, the peroneal artery was patent significantly more often (79%) than the posterior tibial artery (47%) or the anterior tibial artery (38%). Conversely, PGR examination showed no difference in patency between the three vessels (peroneal 91%, posterior tibial 88%, anterior tibial 79%). The peroneal artery was also significantly better preserved on IADSA (65%) compared to the posterior tibial artery (38%) and the anterior tibial artery (23%). PGR studies again showed no difference in the best preserved vessel between peroneal (47%), posterior tibial (50%) and anterior tibial (50%) arteries. Thus, the peroneal artery appears the better preserved vessel on angiography but this appearance may be misleading because the more functional PGR studies show no significant difference in the patency or degree of preservation of the three calf vessels.
Vascular surgeons are being asked to manage vascular disease in an increasingly elderly population, and advanced age may be considered a relative contraindication to limb salvage surgery with an amputation seeming the preferred option. We present a review of 50 patients over the age of 80 years, presenting with ischaemic rest pain, ulceration or gangrene of the lower extremity. Six patients were treated conservatively, four of whom died during the same admission. Only two patients proved suitable for transluminal angioplasty as the sole curative procedure. Twelve patients (24%) underwent primary amputation with a perioperative mortality of 3/12 (25%). Five patients (10%) had an iliac bypass procedure, and 25 patients (50%) were considered suitable for infrainguinal bypass. Of the latter group 14 had femoropopliteal bypasses, and 11 had femorodistal bypasses with an overall perioperative mortality of 3/25 (12%). Mortality at 6 months was high (33%) and was similar in both the grafted and amputation groups. Patients having reconstruction fared well in terms of independent mobility, use of long-term care, and length of hospital stay. Patients over 80 years of age with critical ischaemia should not be denied the opportunity of vascular reconstruction.
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The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose-dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.
A mammalian splicing commitment complex was functionally defined by using a template commitment assay. This complex was partially purified and shown to be a required intermediate for complex A formation. The productive formation of this commitment complex required both splice sites and the polypyrimidine tract. U1 small nuclear ribonucleoprotein (snRNP) was the only spliceosomal U snRNP required for this formation. A protein factor, very likely U2AF, is probably involved in the formation of the splicing commitment complex. From the kinetics of appearance of complex A and complex B, it was previously postulated that complex A represents a functional intermediate in spliceosome assembly. Complex A was partially purified and shown to be a required intermediate for complex B (spliceosome) formation. Thus, a spliceosome pathway is for the first time supported by direct biochemical evidence: RNA+U1 snRNP+?U2 auxiliary factor+?Y----CC+U2 snRNP+Z----A+U4/6,5 snRNPs+ beta----B.
A panel of 24 IgG2ak monoclonal antibodies was produced against murine hepatitis virus strain 3 (MHV-3)-induced procoagulant activity (PCA) from murine macrophages. The antibodies were specific and did not react in an enzyme-linked immunosorbent assay with purified MHV-3; lipopolysaccharide-induced PCA; crude mouse, human, or rabbit tissue factor, or unstimulated murine macrophages. Sixteen of 24 monoclonal antibodies inhibited functional PCA expression in a one-stage clotting assay. More detailed studies on one monoclonal antibody, 3D4.3, demonstrated that it inhibited prothrombin cleavage at concentrations of greater than or equal to 0.1 microgram/ml, and by Western blot this antibody reacted with proteins of a molecular mass of 140, 74, and 70 kDa on nonreduced gels and 74 and 70 kDa on reduced gels distinct from tissue factor known to have a molecular mass of 47 kDa. Induction of PCA was dependent on both host RNA and protein synthesis. Immunofluorescence studies showed specific binding to MHV-3-stimulated PCA-positive macrophage membranes. Both numbers of positive macrophages and intensity of staining correlated with multiplicity of infection. These monoclonal antibodies will be useful in isolation and characterization of the unique viral-induced PCA as well as in determining its biologic role in MHV infection and other diseases in which the prothrombinase has been implicated.
With real-time ultrasound visualization and an automatic core biopsy system 23 percutaneous renal biopsies were performed with the use of local anesthesia in 22 patients. Adequate tissue for diagnosis was obtained in all 23 cases, with 1 patient undergoing bilateral renal biopsy and 1 requiring repeat biopsy. One patient had an asymptomatic perirenal hematoma and 1 experienced a single episode of transient gross hematuria. There were no major complications. The use of an automatic core biopsy system guided by real-time ultrasound is an important technique that may be added to the urological armamentarium.