Abdominoperineal resection for severe perianal Crohn's disease

Despite the high incidence of involvement of the perianal region in Crohn's disease, excisional surgery seldom is required for perianal disease alone. Nine patients are presented who had severe perianal Crohn's disease, which eventually required abdominoperineal excision of the anorectum. In all nine patients, it was secondary manifestations of anal Crohn's disease that precipitated proctectomy, such as high fistulas, strictures, and rectovaginal fistulas. These secondary phenomena, especially fistulas caused by cavitating ulceration, become self-perpetuating by the mechanical effect of feces being forced into the tract. During the same period, 17 patients required rectal excision by abdominoperineal resection, where perianal disease was incidental to severe colorectal disease. There is a tendency for excessive delay before advising surgery for severe perianal disease. An attempt should be made to identify patients with a poor prognosis to avoid unnecessarily prolonged morbidity. Assessment of the exact nature of the anal lesion and assessment of Crohn's disease activity are important in making this decision.     

A murine model for the switch from fetal to adult hemoglobin during ontogeny

In murine erythroleukemia cells, the minor/major hemoglobin (Hb) ratio depends on the cell line and the inducing agent. To determine whether mouse minor hemoglobin is a "fetal" hemoglobin in vivo, globin chain composition and synthesis rates were determined in DBA/2 mice of various ages ranging from 14-day embryos to > 6-mo adults. Globin chains were separated by electrophoresis on polyacrylamide gels containing urea and Triton X-100. This method separates the embryonic (x,y,z) and the adult (alpha, beta ma, beta mi) globin chains. Fourteen day embryos had only 5%-10% adult globins but approximately 30% of the adult beta chains were beta mi. The % beta mi decreased with age and reached 20% in adult mice. Biosynthetic studies led to more pronounced differences: beta mi synthesis was 45% of total beta chain production in 14-day embryos and declined to 22% in adults. Thus beta minor/total beta globin synthesis declines during mouse ontogeny. This resembles qualitatively the human switch from fetal to adult hemoglobin and provides a murine model for studies of hemoglobin regulation.     

Assessment of cardiovascular risk factors in people with HIV infection treated with ART in rural South Africa: a cross sectional study

Background

The risk of cardiovascular diseases (CVD) in human immunodeficiency virus (HIV) infected people on antiretroviral therapy (ART) from some rural parts of Africa is not well known. We assessed CVD risk factors, the estimated 5-year Data collection on adverse effects of anti-HIV drugs (DA.) risk score and the 10-year Framingham risk score in persons with HIV infection on ART in a rural area in South Africa.

Methods

A cross-sectional study in which the data on demographic, lifestyle, and chronic disease were collected using the World Health Organization Stepwise approach to surveillance questionnaire. Biochemical parameters were tested using standard biochemical methods. CD4 counts were performed using PIMA analyser and viral load was tested using the branched deoxyribonucleic acid technique. Student t test and Chi square test were used on continuous and categorical variables respectively. Bivariate and multivariate logistic regression were used to analyze predictors of CVD risk factors. Estimates of 5 and 10-year CVD risk were calculated using online tools. The Cohen’s kappa coefficient was used to assess the agreement between CVD risk equations.

Results

The mean age of participants was 44.8 ± 11.8 years; 79.9 % were females. Most of the participants (85 %) had an undetectable viral load and a mean CD4 count of 462 ± 235 cell/mm³. The most common CVD risk factors were low high density lipoprotein cholesterol (HDL-C) (43.8 %), hypercholesterolaemia (33.2 %) and a high Apolipoprotein (Apo) B/ApoA ratio (45.4 %).Using the Framingham equation, 6.7 % of participants had a moderate to high 10-year CVD risk while the DAD risk equation showed that 31.1 % of participants had a moderate to high 5-year CVD risk. Most participants had a low CVD risk by both risk equations. The level of agreement between the two risk equations was 73.8 % (k = 0.23; 95 % CI 0.10–0.35; p value 0.001).

Conclusion

CVD risk factors were common among this rural population on ART. The high proportion of participants with a moderate to high CVD risk, observed with the DAD risk equation, clearly represents a considerable health burden that can possibly be reduced by increasing educational programs on CVD prevention for people on ART. There is however a need to develop and evaluate a race/ethnicity-specific CVD risk estimation tool for HIV infected Africans.

     

Tissue-specific alternative splicing of protein 4.1 inserts an exon necessary for formation of the ternary complex with erythrocyte spectrin and F-actin

Erythrocyte protein 4.1 is an 78- to 80-Kd peripheral membrane protein that promotes the interaction of spectrin with actin protofilaments and links the resulting interlocking network to the integral membrane proteins. There are several isoforms of protein 4.1 that appear to be expressed in a restricted group of tissues. These arise from alternative mRNA splicing events that lead to the combinational insertion or deletion of at least 10 blocks of nucleotides (motifs) within the mature mRNA. One of these, motif I, consists of 63 nucleotides encoding 21 amino acids in the N-terminal region of the putative spectrin/actin-binding domain. The expression of the motif U- containing isoform occurs late in erythroid maturation. We generated recombinant isoforms of protein 4.1 and of the putative 10-Kd spectrin/actin-binding fragment that contain or lack this 21 amino acid sequence and examined their ability to form a ternary complex with erythrocyte spectrin and F-actin. The isoforms of the complete protein and of the 10-Kd fragment that contain the sequence encoded by motif I efficiently form the ternary complex. Isoforms that lack this sequence, but are otherwise identical, do not participate in the formation of the ternary complex. These results, in conjunction with the expression of motif I during late erythroid maturation, suggest that interaction with actin and the erythroid form of spectrin is a specialized property of the erythrocyte form of protein 4.1. Alternative mRNA splicing in developing red blood cells thus plays a key adaptive role in the formation of the highly specialized erythrocyte membrane.     

Workshop on Schizophrenia

On November 29–30, 1995, the National Academy of Sciences and the Institute of Medicine brought together experts in schizophrenia and specialists in other areas of the biological sciences in a workshop aimed at promoting the application of the latest biological information to this clinical problem. The workshop paid particular attention to evidence of pathology in the brains of people with schizophrenia, and to the possibility that this reflects an abnormality in brain development that eventually leads to the appearance of symptoms. The participants were impressed with the complexity of the problem, and felt that multiple approaches would be required to understand this disease. They recommended that a major focus should be on the search for predisposing genes, but that there should be parallel research in many other areas.     

Characterization of an endopeptidase involved in pre-protein processing.

Proteolytic removal of the pre-segment from growing nascent chains of pre-human placental lactogen (hPL) occurred during in vitro translation of placental mRNA if crude membranes derived from ascites lysates, dog pancreas, or rat liver rough endoplasmic reticulum were added to the translation mixtures. The cotranslational proteolytic event was inhibited by the peptide protease inhibitor, chymostatin, but not by leupeptin, antipain, or elastatinal. The proteases involved in cleavage were solubilized with detergent and converted completed pre-hPL to hPL (post-translational processing). Direct assay of the solubilized membranes, with synthetic fluorogenic aminocoumarin peptide substrates, revealed no significant tryptic or elastase-like activity, but activity against a chymotrypsin substrate [(succinyl-Ala-Ala-Phe)-7-amino-4-methyl-coumarin] was found. This activity was dependent upon both an endopeptidase and an aminopeptidase. Although bestatin inhibited the aminopeptidase activity, it had no effect on the endopeptidase or on post-translational cleavage. Although this endopeptidase cleaved on the COOH side of an alanine residue, it was not inhibited by elastatinal. However, it was inhibited by high levels of chymostatin and by some serine protease inhibitors.     

Acetyl CoA Carboxylase: The Purified Transcarboxylase Component

Acetyl CoA carboxylase of Escherichia coli has been resolved into three functionally dissimilar proteins: (1) biotin-carboxyl carrier protein (BCCP); (2) a biotin carboxylase component that catalyzes the Mn-ATP-dependent carboxylation of BCCP to form CO(2) (-)-BCCP; and (3) a transcarboxylase component that catalyzes the transfer of the carboxyl group from CO(2) (-)-BCCP to acetyl CoA to form malonyl CoA.The transcarboxylase has been purified 1700-fold. Evidence that this protein catalyzes the transcarboxylase step includes the demonstration that it (a) catalyzes the carboxylation of BCCP, (b) catalyzes the BCCP-dependent exchange between [(14)C]acetyl CoA and malonyl CoA, (c) binds labeled acetyl CoA and malonyl CoA, and (d) catalyzes the decarboxylation of CO(2) (-)-BCCP. On the basis of this evidence, it is concluded that the transcarboxylase component contains sites for the acyl CoA group and for biotin, the covalently bound prosthetic group of BCCP.