Biomedical subjects
Publications and source records attributed to S Chatterjee.
Two patients with mononucleosis, one due to cytomegalovirus (CMV), and the other due to Epstein-Barr virus (EBV), presenting with high fever, malaise and hepatitis, had granulomas in the bone marrow but not in the liver. In patients who have unexplained fever, bone marrow granulomas may be a clue to CMV or EBV infection and need not initially raise the fear of prognostically more severe illness.
The effects of gentamicin, an antibiotic used extensively for antimicrobial therapy on the ultrastructure, binding, internalization, degradation, and cholesterol esterification of low-density lipoproteins, were investigated in cultured human proximal tubular cells. Cells were incubated with 0.3 mM gentamicin for 21 days with the following observations. Cells treated with gentamicin contained numerous "myeloid bodies." The binding, internalization, and degradation of 125I-labeled low-density lipoproteins ([125I]LDL) in cells treated with gentamicin was twofold lower than control cells. Pulse-chase experiments demonstrated that gentamicin did not impair the internalization of receptor-bound LDL and their subsequent transport to the lysosome. The relative amounts of [125I]LDL displaced by increasing concentrations of unlabeled LDL were the same in both gentamicin-treated and control cells. This pattern was reflected in the cell surface binding, internalization, and degradation of [125I]LDL. Gentamicin did not alter the degradation of [125I]LDL in cell homogenates at 4.0. The data suggest that gentamicin decreases the receptor-mediated endocytosis of LDL and subsequent lipid metabolism.
Eighty-four healthy asymptomatic sedentary smokers and 92 healthy sedentary non-smokers of the age range 20-59 years were investigated for their maximum oxygen uptake capacity (VO2max) and related cardiorespiratory parameters at the level of maximal exercise by bicycle ergometry. The subjects were blocked into four age decades of 20-29, 30-39, 40-49, and 50-59 years to show the effect of smoking on VO2max of smokes of different age groups. The physical characteristics of smokers and non-smokers of comparable age groups did not show any significant difference. The smokers of each subsequent age group consumed 5.9 +/- 4.1, 6.3 +/- 5.7, 12.7 +/- 7.1, and 11.5 +/- 9.1 pack years of cigarettes, respectively (pack year = number of packets of cigarettes per day X number of years of smoking). VO2max of smokers (38.9 +/- 4.6 ml.kg-1.min-1) was significantly lower (p less than 0.05) than that of nonsmokers (42.1 +/- 3.2 ml.kg-1.min-1) only in the young age group of 20-29 years. VO2max expressed in per kg of the body weight (VO2max/BW) was found to be significantly (p less than 0.01) and negatively correlated with number of cigarettes smoked per day (-0.36, p less than 0.01), number of years through which smoked (-0.38, p less than 0.01), and pack years (-0.42, p less than 0.01). In other age groups, though non-smokers predominated over smokers in VO2max, the differences were not statistically significant. Also, in these age groups, smoking histories failed to reveal any significant correlation with VO2max. This suggests that smoking impairs VO2max only in the young ages. By increasing age, VO2max was diminished by 13% from 20 to 59 years in non-smokers and 15.5% from 20 to 59 years in smokers. Age also diminished HRmax and VEmax of smokers in the same manner as in the case of non-smokers. The VO2max of Indian sedentary non-smokers was found to be lower than those of Caucasians, Kurds, Yemenites, Europeans, and Africans. Values reported on Asians were found to be comparable with those of the present study.
The effects of passive immunization with specific monoclonal antibodies against herpes simplex virus glycoproteins gB, gC, gD, and gE on the course of herpetic keratitis, survival and the establishment of latency in an outbred mouse model are described. A total of nine monoclonal antibodies were tested in these experiments. Passive immunization at 24 or 48 hours post-inoculation had little effect on the severity of the initial epithelial infection of the cornea, but blocked dissemination of the virus to the central nervous system and periocular tissues and prevented development of blepharitis, iritis and stromal keratitis. Additional studies are needed to characterize these monoclonal antibodies in greater detail, and to define the mechanism of these protective effects.
A new macrolide antibiotic, swalpamycin, has been isolated from the culture broth of Streptomyces sp. Y-84,30967. Taxonomically the producing organism most closely resembles Streptomyces anandii and has therefore been named S. anandii subsp. swalpus. Swalpamycin is a neutral 16-membered macrolide active against Gram-positive bacteria including erythromycin-resistant strains.
A new antibiotic swalpamycin (1) has been isolated from the culture broth of Streptomyces sp. Y-84,30967. The antibiotic has the molecular formula of C37H56O14 and belongs to the class of 16-membered neutral macrolide antibiotics. Its structure has been elucidated by an analysis of its spectral properties. It contains a novel aglycone herein called swalpanolide.
Effects produced by caffeine on X-irradiated Chinese hamster V79 cells depended on the growth conditions of the cells. For exponentially growing cells, nontoxic concentrations of caffeine decreased the shoulder width from the survival curve, but the slope remained unchanged. The yield of mutants under the same conditions also remained unaffected. In case of density-inhibited cells, delaying trypsinization for 24 h after X irradiation increased the survival and decreased the yield of mutants. The presence of caffeine during this incubation period inhibited such recovery and significantly increased the yield of X-ray-induced mutants.
We have investigated the effects of lipoproteins on sphingolipid metabolism in proximal renal tubular cells from normal subjects and low density lipoprotein (LDL) receptor-negative homozygous familial hypercholesterolemic subjects employing radioactive precursors, e.g. [3H]serine, [3H]glucose, and [14C]galactose. Compared to cells incubated with lipoprotein-deficient serum, maximum suppression (70-80%) of incorporation of [3H]glucose and [3H]serine into ceramide and LacCer occurred when the LDL concentration in the medium was 25 micrograms/ml medium, and addition of higher amounts of LDL (up to 500 micrograms/ml medium) to normal cells did not produce further suppression. In contrast, high density lipoproteins did not suppress the incorporation of [3H]glucose into lactosylceramide (LacCer) in normal cells. The incorporation of [14C] galactose into LacCer was also suppressed by LDL (50% suppression at a concentration of 100 micrograms/ml medium). In contrast, LDL modified by reductive methylation of lysine residues did not suppress the incorporation of [3H]glucose into LacCer and the incorporation of [3H]serine into ceramide, whereas, native LDL exerted a concentration-dependent suppression of [3H]serine incorporation into ceramide and sphingomyelin in normal cells. At high concentrations of LDL (50-500 micrograms/ml medium), the incorporation of [3H]glucose and [14C]galactose into LacCer in homozygous FH cells was stimulated approximately 2-fold. Maximum stimulation of [3H]serine incorporation into ceramides, LacCer, and sphingomyelin occurred at 100 micrograms LDL/ml medium. Our studies indicate that the endogenous synthesis of sphingolipids in normal renal cells is regulated by the LDL receptor. Modification of the lysine residues in LDL by reductive methylation results in the inability to suppress sphingolipid synthesis in normal cells. Lack of LDL receptors, as in the case of homozygous FH cells, results in the lack of suppression of endogenous sphingolipid synthesis.
The metabolism of low density lipoproteins (LDL), and LDL modified by reductive methylation (M-LDL) of lysine residues, was studied in proximal tubular (PT) cells both from normal human kidney and from urine of patients with homozygous (LDL receptor-negative) familial hypercholesterolemia (FH). LDL and M-LDL was labeled either in the protein moiety with 125I or in the lactosylceramide moiety with 3H. The binding and degradation of 125I-LDL in normal cells was saturable and displaced by unlabeled LDL but not by M-LDL. The uptake of [3H]lactosylceramide (LacCer) low density lipoprotein in normal renal cells was saturable, and time and temperature-dependent. Exogenously derived [3H]LacCer on LDL was rapidly taken up and catabolized to monoglycosylceramide, or it was utilized for the endogenous synthesis of globotriaosylceramide (trihexosylceramide) and globotetraosylceramide (tetraglycosylceramide). [3H]LacCer M-LDL was taken up less avidly and metabolized less extensively than [3H]LacCer-LDL in normal cells. In homozygous FH renal cells the binding of 125I-LDL was not saturable and not displaced by unlabeled LDL. 125I-LDL degradation did not occur in FH cells. The homozygous FH PT cells took up a 2-fold greater amount of exogenously derived [3H]LacCer on LDL than normal cells. Yet, most of the [3H]LacCer taken up by FH PT cells accumulated as LacCer, and only small amounts were metabolized to monoglycosylceramide, globotriaosylceramide (trihexosylceramide), or globotetraosylceramide (tetraglycosylceramide). When normal and FH PT cells were preincubated with LDL (0-100 micrograms/ml medium), there was a 5-fold increase in cellular LacCer levels in FH cells at saturating levels of LDL, whereas there was about a 50% decrease in LacCer levels in normal cells. While the high affinity binding of LDL was not essential for the delivery of LacCer to cells, the data support the conclusion that LDL binding to the LDL receptor facilitates further LacCer processing and metabolism in normal renal cells. We speculate that [3H] LacCer is taken up by FH homozygous cells via a LDL receptor-independent mechanism and accumulates in the cells without significant metabolism. LacCer taken up by this mechanism contributes to the storage of LacCer in FH PT cells.
Monoclonal antibodies against herpes simplex virus type 1 glycoproteins were isolated and utilized to study the synthesis and processing of glycoproteins B, C, and D (gB, gC, gD, respectively). Monoclonal antibodies against both gB and gD had higher virus-neutralizing activity when compared to that of gC. Differences among these glycoproteins were observed in their time of appearance in the virus-infected cells. The presence of gD was detected at a very early stage of infection when compared to gB and gC. The localization of these glycoproteins during their synthesis and processing was studied.
This report provides evidence for the replication of varicella zoster virus (VZV) in Raji cells. Infection was achieved by co-cultivation of Raji cells with VZV-infected human fibroblasts. Replication of VZV, as assessed by immunofluorescence using monoclonal antibodies against VZV-glycoproteins, ranged from 18 to 24% of the cells. Electron microscopy detected complete virions within the membrane-bound cytoplasmic vesicles and free viral particles in the nuclear matrix as late as 12 days post-infection. Western blot analysis of infected Raji cells demonstrated VZV-specific glycoproteins. The availability of a VZV-susceptible cell line growing in suspension culture provides a useful model for future studies.
Deficiency in the lysosomal enzyme responsible for cholesteryl ester hydrolysis, acid cholesteryl ester hydrolase (E.C. 3.1.1.13), leads to two clinically recognized diseases: Wolman disease and cholesteryl ester storage including leukocytes, fibroblasts and liver. Analysis of urinary sediment from well characterized cases of Wolman disease and CESD also revealed the shedding of lipid enriched renal tubular cells. Morphologic, enzymic and lipid compositional studies of these cells indicate that the enzyme deficiency observed in fibroblasts and leukocytes from these individuals are reflected in these cells shed in the urine. These findings in renal tubular cells confirm and extend those made in other cell types. These studies indicate that analysis of urinary sediment in suspected cases of acid cholesteryl ester deficiency may provide a meaningful approach for monitoring therapeutic attempts involving enzyme infusion and gene therapy.
The maximum aerobic capacity (VO2 max) of young untrained Bengali girls aged between 22-24 years after maximum workload as determined by bicycle ergometer, standard step test and a treadmill is studied in 22 subjects. It was found that the VO2 peak in the treadmill exercise was significantly higher than that obtained by the step test and bicycle ergometer, in that order. On each type of ergometer, VO2 max was found to be positively correlated with body weight, body surface area, maximal pulmonary ventilation and maximal oxygen pulse.
The very sensitive and specific method for the detection of beta-lactam antibiotics using DD-carboxypeptidase (DDCase) from Actinomadura strain R39 has been improved to meet the requirements of a high-throughput beta-lactam screening from culture broths of microorganisms. The method is based on a novel chromophor-labeled substrate N alpha-acetyl-N epsilon-4-(7-nitrobenzofurazanyl)-L-lysyl-D-al anyl-D-alanine (ANLA2) which is converted by DDCase into ANLA1 with only one D-alanine residue left. Both compounds are intensely yellow as well as highly fluorescent and can be separated by thin-layer chromatography. This allows easy determination of residual DDCase activity after reaction with beta-lactams by simple visual inspection of chromatograms. Also, many assays can be run at a time without sophisticated instrumentation. Details of the method as well as some results of a beta-lactam screening performed with this type of assay are described.
Three IgG1 monoclonal antibodies derived from BALB/c mice immunized with the Caki-1 human renal cell carcinoma (RCC) line react with antigens present in most human RCCs but restricted in their expression in normal adult tissues. Antibody DAL-K20 reacted with five of six RCCs and the lining epithelium of normal proximal and distal convoluted tubules. Antibody DAL-K29 reacted with eight of nine RCCs, with glomeruli, where it outlined the capillaries, and more weakly with prostatic glandular epithelium and the basal layer of the epidermis. K29 precipitated molecules with molecular weights of 118,000 and 150,000 from extracts of surface-labeled Caki-1 cells. Antibody DAL-K45 reacted with four of six RCCs but not with any normal adult tissue including kidney. It precipitated Mr 177,000 and 150,000 antigens. The three antibodies showed distinct patterns of reactivity with human tumor cell lines.
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