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Biomedical subjects

S Pal

Publications and source records attributed to S Pal.

At least 91 records · Page 5Linked to original sources
PubMed1999

A murine model for the study of Chlamydia trachomatis genital infections during pregnancy.

Pregnant BALB/c mice were inoculated intravaginally on day 5 of gestation with the Chlamydia trachomatis mouse pneumonitis biovar. Animals that received 10(5), 10(6), or 10(7) inclusion-forming units (IFU) of C. trachomatis delivered prematurely on days 15 to 16 of gestation. A focal inflammatory infiltrate was observed in the wall of the uterus on the day 14 of gestation in animals inoculated with 10(5) IFU. In this group of mice, immunohistochemical analysis showed chlamydial inclusions in the endometrium and fetal membranes.

Animals↗
PubMed1999

Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract.

Neuropharmacological studies were conducted in experimental animals (rats and mice) with the methanolic fraction of Bryophyllum pinnatum leaf extract. The fraction produced alteration of behaviour pattern, caused dose-dependent potentiation of pentobarbitone sleeping time and had significant analgesic activity. Significant reduction of exploratory behaviour and loss of residual curiosity were among the effects observed with the fraction. The observations suggest that the methanolic fraction of Bryophyllum pinnatum possesses a potent CNS depressant action.

Analgesia↗
PubMed1998

Prolonged activation of the N-methyl-D-aspartate receptor-Ca2+ transduction pathway causes spontaneous recurrent epileptiform discharges in hippocampal neurons in culture.

The molecular basis for developing symptomatic epilepsy (epileptogenesis) remains ill defined. We show here in a well characterized hippocampal culture model of epilepsy that the induction of epileptogenesis is Ca2+-dependent. The concentration of intracellular free Ca2+ ([Ca2+]i) was monitored during the induction of epileptogenesis by prolonged electrographic seizure activity induced through low-Mg2+ treatment by confocal laser-scanning fluorescent microscopy to directly correlate changes in [Ca2+]i with alterations in membrane excitability measured by intracellular recording using whole-cell current-clamp techniques. The induction of long-lasting spontaneous recurrent epileptiform discharges, but not the Mg2+-induced spike discharges, was prevented in low-Ca2+ solutions and was dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. The results provide direct evidence that prolonged activation of the NMDA-Ca2+ transduction pathway causes a long-lasting plasticity change in hippocampal neurons causing increased excitability leading to the occurrence of spontaneous, recurrent epileptiform discharges.

2-Amino-5-phosphonovalerate↗
PubMed1998

Activation of Sp1-mediated vascular permeability factor/vascular endothelial growth factor transcription requires specific interaction with protein kinase C zeta.

The transcription factor Sp1 is ubiquitously expressed and plays a significant role in the constitutive and induced expression of a variety of mammalian genes and may even contribute to tumorigenesis. Here, we describe a novel pathway whereby Sp1 promotes the transcription of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent angiogenic factor, by interacting directly and specifically with protein kinase C zeta (PKC zeta) isoform in renal cell carcinoma. PKC zeta binds and phosphorylates the zinc finger region of Sp1. Moreover, in the presence of the wild type von Hippel-Lindau gene product, the interaction of Sp1 with PKC zeta is inhibited, and in this manner steady state levels of Sp1 phosphorylation are decreased significantly. Co-transfection of renal cell carcinoma cells and human fibrosarcoma cells with a plasmid overexpressing PKC zeta and VPF/VEGF promoter luciferase constructs results in activation of Sp1-mediated transcription, whereas expression of a dominant-negative mutant of PKC zeta repressed this activation. Taken together, our results suggest a new pathway of cell signaling through PKC zeta and provide an insight into PKC zeta and Sp1-dependent transcriptional regulation of VPF/VEGF expression and thus tumor angiogenesis.

Carcinoma, Renal Cell↗
PubMed1998

The solution structure of the DNA-binding domain of Skn-1.

Skn-1 is a maternally expressed transcription factor that specifies the fate of certain blastomeres early in the development of Caenorhabditis elegans. It has been reported that the DNA-binding domain is a molten globule and that the structure cannot be defined because there are no long-range nuclear Overhauser effects (NOEs). Working with short Skn domain fragments and using 13C-labeled proteins, we have been able to identify 28 long-range NOEs that establish a tertiary fold for the Skn domain. The internal region of the Skn domain consists of three stable helices and one conformationally labile helix organized into a nascent helix-turn-helix-turn-helix-turn-helix motif. The N and C termini of the Skn domain are unstructured and emerge from the same end of the folded domain. This structure is consistent with biochemical data on binding of the Skn domain to DNA, which shows that the N and C termini bind in the adjacent minor and major grooves from the same face of the DNA helix. The NMR solution structure of the Skn domain should be useful for developing a complete understanding of the DNA recognition event, including any conformational changes that take place upon binding.

Amino Acid Sequence↗
PubMed1998

Decreased membrane permeability in a polymyxin B-resistant Escherichia coli mutant exhibiting multiple resistance to beta-lactams as well as aminoglycosides.

A laboratory mutant of Escherichia coli stably resistant to more than 36,000 U ml-1 of polymyxin B was isolated. The mutant exhibited moderate increases in minimum inhibitory concentration to fluoroquinolones and bacitracin but high levels of cross-resistance to beta-lactams and aminoglycosides. However, it remained susceptible to tetracycline, nalidixic acid and novobiocin. Changes were observed in the outer membrane proteins and lipopolysaccharide profile leading to a decrease in permeability as evident from reduction in the following: (i) minimum inhibitory concentration values in the presence of Tween 80, (ii) uptake of 1-N-phenyl naphthylamine and norfloxacin, (iii) hydrolysis of beta-lactams and (iv) diffusion of lactose and cefazolin into proteoliposomes reconstituted with outer membrane proteins. We therefore suggest that the novel pattern of cross-resistance of our isolate is due to the decrease in its permeability.

Anti-Bacterial Agents↗
PubMed1998

Erythroderma: a clinico-etiologic study of 90 cases.

BACKGROUND: The difficulty with erythroderma lies in finding the underlying cause. Almost all the published original clinical series of erythroderma originate from western countries. Our aim was to evaluate various causes of exfoliative dermatitis in our community and compare the findings with previous studies. METHODS: Ninety patients with erythroderma of either sex and any age, were studied at the Dermatology Department, Mayo Hospital, Lahore, Pakistan, between April 1992 and May 1995. A through clinical examination and relevant laboratory investigations, including skin biopsies, were performed. RESULTS: The mean age of onset was 41.6 years with a male:female ratio of 2.8:1. The onset was acute in 69% of patients. The salient features included nail changes (80%), mucosal involvement (36.6%), alopecia (30%), islands of normal skin (14.4%), and the "deck chair sign" (5.5%). The most frequent cause of erythroderma was pre-existing dermatoses (74.4%), including psoriasis (37.8%), dermatitis (12.2%), ichthyoses (7.8%), and pemphigus foliaceus (5.6%). Drugs and malignancy each induced erythroderma in 5.5% of cases. No cause could be found in 14.6% of cases. CONCLUSIONS: Etiologically, pre-existing dermatoses showed the highest incidence and drugs the lowest compared with previous studies. Dermatitis was less common. There was a greater variety of causes of erythroderma in our series. Hair and nails were more frequently involved. Mucosal involvement, not mentioned in other studies, was present in 36.6% of our cases. The "deck chair sign" and islands of normal skin were seen in dermatoses not reported previously.

Adolescent↗
PubMed1998

Giant cell phlebitis as a cause of large intestinal stricture.

Although arteritis of the gastrointestinal tract is well known, an isolated phlebitis without associated arteritis of the colon and cecum is rare. We describe a distinct form of giant cell phlebitis in a 16-year-old girl causing ischemic stricture of the large intestine. She presented with subacute intestinal obstruction and was suspected of suffering from tuberculosis. However, histopathologic examination showed giant cell phlebitis, the arterioles and arteries being spared. Although this is an extremely rare form of nonprogressive vasculitis, it should be considered in the differential diagnosis of strictures in the large intestine, especially in the young.

Adolescent↗
PubMed1998

Factors influencing the induction of infertility in a mouse model of Chlamydia trachomatis ascending genital tract infection.

In women, infections due to Chlamydia trachomatis frequently result in long-term sequelae including chronic abdominal pain, ectopic pregnancy and infertility. In an attempt to characterise the pathogenesis of the infection, female C3H (H-2k) mice were inoculated intravaginally with different doses of C. trachomatis and then mated with proven male breeder mice. The inoculated mice developed a broad spectrum of clinical manifestations ranging from infertility to asymptomatic shedding. The dose inducing infertility in 50% of the mice was c. 10(5) inclusion-forming units of C. trachomatis. In another group of mice sampled at intervals after intravaginal inoculation, C. trachomatis was recovered from the upper genital tract starting at 24 h after infection. A higher percentage of animals infected during the luteal phase of the oestrous cycle had positive cultures from the middle and upper genital tract than when mice were inoculated during the follicular phase. These results indicate that rapid therapeutic intervention is required to avoid the sequelae resulting from C. trachomatis genital infection, and suggest that hormonal factors play a role in the pathogenesis of the disease.

Animals↗
PubMed1998

Lipoarabinomannan induced cytotoxic effects in human mononuclear cells.

Mycobacteria produce large quantities of lipoarabinomannan, a cell wall associated glycolipid, which confers virulence in many of the disease causing members of the genus. We studied the lipoarabinomannan induced altered signaling mechanism in human peripheral mononuclear cells. Lipoarabinomannan isolated from Mycobacterium smegmatis (a non-pathogenic species) at concentrations of 2, 5 and 10 microg ml(-1) was used for the study. It was found that protein kinase C activity of human mononuclear cells was significantly inhibited by lipoarabinomannan at these concentrations in a dose dependent manner. Calcium, phosphatidyl serine and diglyceride dependent phosphorylation of endogenous proteins (mainly 90-, 80-, 66-, 38-, 36- and 34-kDa proteins) were also inhibited. Potentially cytotoxic superoxide anions generated by peripheral blood mononuclear cells were scavenged by lipoarabinomannan. It was also observed that incubation of peripheral blood mononuclear cells with lipoarabinomannan at concentrations of 5 and 10 microg ml(-1) for 6 h directed the cells towards apoptotic cell death, confirmed by DNA degradation analysis, microscopic observation of Wright-Giemsa as well as DAPI stained nuclei. These results clearly demonstrate that lipoarabinomannan from M. smegmatis may exert its cytotoxic activity via inhibition of protein kinase C, a key signaling molecule inside the mononuclear cells, which ultimately affects the phosphorylation of various proteins imperative for cellular defence and survival.

Adult↗
PubMed1998

Use of monoclonal antibodies to identify phospholipase C as the enterotoxic factor of the bifunctional hemolysin-phospholipase C molecule of Vibrio cholerae O139.

Two hybrid clones producing monoclonal antibodies (MAbs) raised against the purified enterotoxic hemolysin-phospholipase C (HlyPC) bifunctional molecule of a Vibrio cholerae O139 strain were used to study its enterotoxicity in relation to its hemolytic and enzymatic activities. Fab fragments of MAbs from ascites produced by the two hybrids neutralized the hemolytic activity of HlyPC, leaving the enzymatic activity unaffected. In ligated rabbit ileal loop and infant mouse intestine, the Fab fragments of the MAbs were not able to neutralize the enterotoxicity of HlyPC, suggesting that PC rather than Hly is the enterotoxic moiety of the molecule. The enterotoxicity of the purified PC molecule isolated from an Hly- spontaneous mutant of the HlyPC-producing parent strain further confirms this contention. The Hly molecule isolated from a PC- mutant was not diarrheagenic.

Animals↗
PubMed1998

Interaction of the antitumour alkaloid coralyne with duplex deoxyribonucleic acid structures: spectroscopic and viscometric studies.

The interaction of coralyne, an antitumour alkaloid with natural and synthetic duplex DNAs was investigated under conditions where the drug existed fully as a true monomer for the first time using spectrophotometric, spectrofluorimetric, circular dichroic and viscometric techniques. The absorption spectrum of coralyne monomer showed hypochromic and bathochromic effects on binding to duplex DNAs. This effect was used to determine the binding parameters of coralyne. The binding constants for four natural DNAs and four synthetic polynucleotides obtained from spectrophotometric titration, according to an excluded site model, using McGhee-von Hippel analysis, were all in the range of (0.38-9.8) x 10(5) M-1, and showed a relatively high specificity for the GC rich ML DNA and the alternating GC polynucleotide. The binding of coralyne decreased with increasing ionic strength, indicating that the binding affinity has a strong electrostatic component. Coralyne stabilized all the DNAs against thermal strand separation. The intense steady state fluorescence of coralyne was effectively quenched on binding to DNAs and the quantitative data on the Stern-Volmer quenching constant obtained was sequence dependent, being maximum with the GC rich DNA and alternating GC polymer. Circular dichriosm studies further evidenced for a strong perturbation of the B-conformation of DNAs consequent to coralyne binding with the concomitant development of extrinsic circular dichroic bands for the bound drug molecules suggesting their strong intercalated geometry in duplex DNAs. Further tests of intercalation using viscosity measurements on linear and covalently closed plasmid DNA conclusively proved the strong intercalation of coralyne in duplex DNA. Binding of the closely related natural alkaloid, berberine under these conditions showed considerably lower affinity to duplex DNAs in all experiments. Taken together, these results suggest that coralyne binds strongly to duplex DNAs by a mechanism of intercalation with specificity towards alternating GC duplex structure.

Animals↗
PubMed1997

The von Hippel-Lindau gene product inhibits vascular permeability factor/vascular endothelial growth factor expression in renal cell carcinoma by blocking protein kinase C pathways.

Mutation or loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is regularly found in sporadic renal cell carcinomas (RCC), well vascularized malignant tumors that characteristically overexpress vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). The wild-type VHL (wt-VHL) gene product acts to suppress VPF/VEGF expression, which is overexpressed when wt-VHL is inactive. The present study investigated the pathways by which VHL regulates VPF/VEGF expression. We found that inhibition of protein kinase C (PKC) represses VPF/VEGF expression in RCC cells that regularly overexpress VPF/VEGF. The wt-VHL expressed by stably transfected RCC cells forms cytoplasmic complexes with two specific PKC isoforms, zeta and delta, and prevents their translocation to the cell membrane where they otherwise would engage in signaling steps that lead to VPF/VEGF overexpression. Other experiments implicated mitogen-activated protein kinase (MAPK) phosphorylation as a downstream step in PKC regulation of VPF/VEGF expression. Taken together, these data demonstrate that wt-VHL, by neutralizing PKC isoforms zeta and delta and thereby inhibiting MAPK activation, plays an important role in preventing aberrant VPF/VEGF overexpression and the angiogenesis that results from such overexpression.

Biological Transport↗
PubMed1997

Skn-1: evidence for a bipartite recognition helix in DNA binding.

Skn-1 is a maternally expressed transcription factor that specifies the fate of certain blastomeres early in the development of Caenorhabditis elegans. This transcription factor contains a basic region, but it binds to DNA as a monomer. Because other transcription factors containing basic regions bind as dimers, this finding implied that Skn represents a new DNA recognition motif. It has been proposed that the basic region helix of Skn is stabilized for binding by tertiary contacts to other parts of the protein. We have tested this proposal by carrying out circular dichroism (CD) and NMR experiments on the Skn domain and five truncated proteins. Our results have shown that the basic region of Skn is unstructured in solution and does not contact other parts of the protein; like other basic region peptides, it folds into a helix only upon binding specifically to DNA. However, there is a stably folded helical module in the Skn domain, and one of the helices in this module terminates immediately before the start of the basic region. This pre-organized helix contains a surface rich in basic amino acids, and we propose that this helix contacts the DNA distal to the basic region proper, providing an extra long helical recognition surface which helps to stabilize monomeric binding. Homology between the Skn domain and several basic-region leucine zipper (bZIP) domains raises the possibility that the affinity and perhaps the specificity of DNA binding by bZIP proteins can be modulated by incorporating a stably folded helical segment that contacts the DNA just below the basic region proper.

Amino Acid Sequence↗
PubMed1997

Purification and characterisation of a hemolysin with phospholipase C activity from Vibrio cholerae O139.

A hemolysin was purified from a Vibrio cholerae O139 strain which moved as a single protein band of 67 kDa in SDS-PAGE. The hemolysin showed high level of phospholipase C activity. The purified phospholipase C-hemolysin demonstrated enterotoxic activity in rabbit ileal loop, suckling mice and enhanced permeability of rabbit skin. The pI of the purified hemolysin was 6.4. Erythrocytes from rabbit, chicken, guinea pig, sheep and horse were sensitive to the purified hemolysin in decreasing order of intensity. Erythrocytes from human and cow were unaffected by purified hemolysin.

Animals↗
PubMed1997

Induction of Encystment and Poly-beta-Hydroxybutyric Acid Production by Azotobacter chroococcum MAL-201

Azotobacter chroococcum MAL-201, when grown under nitrogen-free conditions with excess glucose, accumulated poly-beta-hydroxybutyric acid amounting to 75% of cell dry weight at the late exponential phase. This led to induction of encystment, which increased steadily with concomitant intracellular degradation of the polymer. Increase in encystment and PHB production were parallel up to 0.5% (wt/vol) glucose. Further increase in glucose reduced cyst formation but enhanced PHB accumulation. Replacement of glucose by n-butyl alcohol and metabolically related compounds identified crotonate as the best encystment inducer followed by beta-hydroxybutyrate and butyrate, but PHB production was inhibited in general. Supplementation of medium with these compounds enhanced the onset of encystment, and only beta-hydroxybutyrate increased PHB accumulation significantly.

Journal Article↗