Human autoantibodies reveal titin as a chromosomal protein

Assembly of the higher-order structure of mitotic chromosomes is a prerequisite for proper chromosome condensation, segregation and integrity. Understanding the details of this process has been limited because very few proteins involved in the assembly of chromosome structure have been discovered. Using a human autoimmune scleroderma serum that identifies a chromosomal protein in human cells and Drosophila embryos, we cloned the corresponding Drosophila gene that encodes the homologue of vertebrate titin based on protein size, sequence similarity, developmental expression and subcellular localization. Titin is a giant sarcomeric protein responsible for the elasticity of striated muscle that may also function as a molecular scaffold for myofibrillar assembly. Molecular analysis and immunostaining with antibodies to multiple titin epitopes indicates that the chromosomal and muscle forms of titin may vary in their NH2 termini. The identification of titin as a chromosomal component provides a molecular basis for chromosome structure and elasticity.     

Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group

The objective of this study is to describe usual medical management and costs associated with recurrent respiratory infections in subjects with chronic obstructive bronchitis in France. A prospective survey was performed in Autumn 1994 on a national sample of private practice pulmonologists (N = 71). Two hundred forty-four patients, presenting at least one infection of the lower respiratory tract, were included. Bronchitis was the most frequent acute exacerbation observed (94%). Pneumonia concerned 9% of the patients. Biological tests, X-rays and pulmonary function tests were prescribed for, respectively, 59, 65 and 45% of the patients. Following the visit, 15 patients were hospitalized (6%). The direct medical cost per acute exacerbation was estimated 3,289 francs (1994 value) of which 60% were hospital-related. An average 10.4 day sick-leave was prescribed to 21% of patients in employment. For those patients, this sick-leave was associated to an extra-cost of 1,264-1,876 francs for Social Security and of 0-2,553 francs out of pocket per episode varying according to their Benefit Regimen.     

Expression of topoisomerase II, bcl-2, and p53 in three human brain tumor cell lines and their possible relationship to intrinsic resistance to etoposide

We characterized three human brain tumor cell lines (D54, HBT-20, and HBT-28) with respect to resistance to etoposide (VP-16), a topoisomerase II-reactive drug. All three cell lines were inherently resistant to VP-16 when compared to other human cell lines, with D54 showing the greatest resistance using colony formation assays. Resistance to VP-16 has been attributed to decreased drug uptake and changes in topoisomerase II; however, drug uptake and topoisomerase II protein levels (immunoblot) were no lower in D54 than in HBT-20 and HBT-28, cell lines relatively more sensitive to VP-16. More to the point, measurement of topoisomerase II-mediated DNA cleavage of cellular DNA after treatment with VP-16 showed that the topoisomerase II in these cells was active. These data indicate mechanisms other than those attributable to decreased drug uptake or altered topoisomerase II exist for clinical resistance to VP-16. VP-16-induced DNA cleavage has been associated with apoptosis in some cell lines; however, neither DNA laddering nor morphological changes characteristic of apoptosis were detected in these cell lines after treatment with VP-16. Bcl-2 and mutant p53 were present in these cells. Either of these conditions can prevent apoptosis and could explain a dissociation between the proximal mediator of VP-16-induced cytotoxicity (topoisomerase II-DNA complex formation) and cellular death.     

Pitfalls and complications of esophageal prosthesis, laser therapy, and dilation

Although often diagnosed and treated by gastroenterologists, thoracic surgeons should be skilled partners in the management of esophageal obstruction. Knowledge of pitfalls and complications of any procedure is a prerequisite to success. This article focuses on problems encountered in dilatation, laser ablation, and stenting of esophageal strictures. Dilatation of both benign and malignant strictures requires knowledge of the different types of dilators and the ability to adapt to different stricture characteristics. Although lower morbidity makes laser ablation of malignant obstruction attractive, this author finds its use to be restrictive. The advent of expandable metal stents offers the potential for fewer early complications when compared with plastic protheses but, as discussed, morbidity may be different rather than less.     

Precision and accuracy of total body bone mass and body composition measurements in the rat using x-ray-based dual photon absorptiometry

Lean body mass (LBM), total body bone mineral mass (BMC), total body bone areal density (BMD), and body fat mass (FM) were measured in rats by dual photon absorptiometry (DXA), using two different instruments. The coefficients of variation for repeated measurements of LBM and FM were about 0.4 and 2.5%, respectively, over an animal body weight range of 150 to 600 g. For BMC and BMD, the coefficients of variation were less than 2%. The correlation coefficients for LBM, FM, BMC, and BMD measured on the two densitometers were all greater than 0.94. The slope of the regression line relating LBM measured by DXA and LBM measured by carcass analysis was 0.999, and the correlation coefficient was 0.99. For FM the slope was 1.05, and the correlation coefficient was 0.98. BMC measures by DXA were falsely low in small animals. For larger animals, the correlation between BMC and ash weight was 0.93, but the slope of the regression line was 0.78. DXA measures of LBM and FM were accurate and reproducible for rats weighing between 150 and 600 g. There was a size-dependent error in BMC, which will be significant in longitudinal measurements of bone mass.     

Focal segmental glomerulosclerosis in primates infected with a simian immunodeficiency virus

Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy. Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15-120 weeks after experimental infection with a simian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury. One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis. All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation. Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections. In contrast, autopsy studies of macaques infected with a type D simian retrovirus (SAIDS-D/Washington, SRV-2) for similar periods of time (n = 40) showed no evidence of FSG. One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy. They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a simian immunodeficiency state that resembles human AIDS.