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Biomedical subjects

P Bandyopadhyay

Publications and source records attributed to P Bandyopadhyay.

At least 19 recordsLinked to original sources
PubMed2003

Parathyroid hormone-related protein in pancreatic exocrine cancer associated with hypercalcaemia.

Hypercalcaemia is a common complication of malignancy seen in about 10% of cases of advanced cancer. Although hypercalcaemia is not uncommon with endocrine tumour of the pancreas, hypercalcaemia with cancer of the exocrine pancreas unrelated to bone metastasis has been rarely reported. We report a case of undifferentiated pancreatic cancer with severe hypercalcaemia due to parathyroid hormone-related protein produced by the tumour cells that did not respond to medical management.

Fatal Outcome↗
PubMed2002

Adverse cutaneous reaction to naproxen: a missed diagnosis fortuitously resolved.

A 91-year-old man presented with a one-month history of swollen legs and dyspnoea. He also complained of a 16-year chronic rash that had caused him considerable morbidity and cosmetic problems. He had been taking naproxen for several years for osteoarthritis. Clinical examination demonstrated bilateral pitting oedema of the leg and a widespread excoriated rash that affected most of his body. A clinical diagnosis of fluid retention secondary to naproxen was made. Stopping naproxen led not only to the resolution of his leg oedema and dyspnoea, but also to the prompt and complete remission of the rash. Reviewing the patient's history revealed that the rash had almost certainly first appeared when naproxen was started many years previously.

Aged↗
PubMed2001

Ion conductors derived from cholic acid and spermine: importance of facial hydrophilicity on NA(+) transport and membrane selectivity.

A series of ion conductors have been synthesized in which the degree of facial hydrophilicity has been systematically varied. Specifically, conjugates have been prepared from cholic acid and spermine in which the hydrophilic face of each sterol bears methoxy (1), hydroxy (2), carbamate (3), or sulfate groups (4). The ability of these conjugates to promote the transport of Na(+) across phosphatidylcholine membranes of varying thickness has been investigated by (23)Na NMR spectroscopy. Examination of observed activities in three different phosphatidylcholine membranes has provided evidence for membrane-spanning dimers as the transport-active species. In the thinnest membranes investigated, made from 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine (C14), Na(+)-transport activity was found to increase, substantially, with increasing facial hydrophilicity. In thicker membranes, made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (C18), observed activities were found to decrease with increasing facial hydrophilicity; with a membrane of intermediate thickness, prepared from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (C16), ion-conducting activity increased and then decreased, with continuous increases in facial hydrophilicity. The possible origins for these variations in activity are briefly discussed.

Cholic Acid↗
PubMed2001

Identification of a vibrational frequency corresponding to H-atom translocation in hypericin.

Using time-resolved infrared spectroscopy, ab initio quantum mechanical calculations and synthetic organic chemistry a region in the infrared spectrum of triplet hypericin has been found between 1400 and 1500 cm-1 corresponding to the translocation of the hydrogen atom between the enol and the keto oxygens, O...H...O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.

Anthracenes↗
PubMed2001

Spontaneous intramural dissection of the oesophagus.

Spontaneous intramural dissection or intramural haematoma of the oesophagus is an unusual condition and has been recognised as a separate clinical entity. The commonest presenting symptoms are chest pain, dysphagia and haematemesis usually affecting women in their sixties and seventies. Conservative management is usually thought to be adequate. We present a case of spontaneous intramural dissection in an elderly male who did not respond to conservative management and died.

Aged↗
PubMed2000

The spasmodic peptide defines a new conotoxin superfamily.

We purified and characterized a peptide from the venom of Conus textile that makes normal mice assume the phenotype of a well-known mutant, the spasmodic mouse. This "spasmodic" peptide has 27 amino acids, including two gamma-carboxyglutamate (Gla) residues. A cDNA clone encoding the precursor for the peptide was identified; a gamma-carboxylation recognition signal sequence (gamma-CRS) is present in the -1 --> -20 region of the peptide precursor. Both the gamma-CRS and the position of the Gla residues in the mature toxin are notably different from other Gla-containing conopeptides. The spasmodic peptide has a novel disulfide framework and distinct signal sequence which together define a new P-superfamily of conopeptides. A cDNA encoding another member of the P-superfamily was identified from a different species, Conus gloriamaris.

1-Carboxyglutamic Acid↗
PubMed2000

Catalase-peroxidases of Legionella pneumophila: cloning of the katA gene and studies of KatA function.

Legionella pneumophila, the causative organism of Legionnaires' pneumonia, contains two enzymes with catalatic and peroxidatic activity, KatA and KatB. To address the issue of redundant, overlapping, or discrete in vivo functions of highly homologous catalase-peroxidases, the gene for katA was cloned and its function was studied in L. pneumophila and Escherichia coli and compared with prior studies of katB in this laboratory. katA is induced during exponential growth and is the predominant peroxidase in stationary phase. When katA is inactivated, L. pneumophila is more sensitive to exogenous hydrogen peroxide and less virulent in the THP-1 macrophage cell line, similar to katB. Catalatic-peroxidatic activity with different peroxidatic cosubstrates is comparable for KatA and KatB, but KatA is five times more active towards dianisidine. In contrast with these examples of redundant or overlapping function, stationary-phase survival is decreased by 100- to 10,000-fold when katA is inactivated, while no change from wild type is seen for the katB null. The principal clue for understanding this discrete in vivo function was the demonstration that KatA is periplasmic and KatB is cytosolic. This stationary-phase phenotype suggests that targets sensitive to hydrogen peroxide are present outside the cytosol in stationary phase or that the peroxidatic activity of KatA is critical for stationary-phase redox reactions in the periplasm, perhaps disulfide bond formation. Since starvation-induced stationary phase is a prerequisite to acquisition of virulence by L. pneumophila, further studies on the function and regulation of katA in stationary phase may give insights on the mechanisms of infectivity of this pathogen.

Aerobiosis↗
PubMed1999

The T-superfamily of conotoxins.

We report the discovery and initial characterization of the T-superfamily of conotoxins. Eight different T-superfamily peptides from five Conus species were identified; they share a consensus signal sequence, and a conserved arrangement of cysteine residues (- -CC- -CC-). T-superfamily peptides were found expressed in venom ducts of all major feeding types of Conus; the results suggest that the T-superfamily will be a large and diverse group of peptides, widely distributed in the 500 different Conus species. These peptides are likely to be functionally diverse; although the peptides are small (11-17 amino acids), their sequences are strikingly divergent, with different peptides of the superfamily exhibiting varying extents of post-translational modification. Of the three peptides tested for in vivo biological activity, only one was active on mice but all three had effects on fish. The peptides that have been extensively characterized are as follows: p5a, GCCPKQMRCCTL*; tx5a, gammaCCgammaDGW(+)CCT( section sign)AAO; and au5a, FCCPFIRYCCW (where gamma = gamma-carboxyglutamate, W(+) = bromotryptophan, O = hydroxyproline, T( section sign) = glycosylated threonine, and * = COOH-terminal amidation). We also demonstrate that the precursor of tx5a contains a functional gamma-carboxylation recognition signal in the -1 to -20 propeptide region, consistent with the presence of gamma-carboxyglutamate residues in this peptide.

Amino Acid Sequence↗
PubMed1999

Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of crigler-najjar syndrome type I with a chimeric oligonucleotide.

Crigler-Najjar syndrome type I is characterized by unconjugated hyperbilirubinemia resulting from an autosomal recessive inherited deficiency of hepatic UDP-glucuronosyltransferase (UGT) 1A1 activity. The enzyme is essential for glucuronidation and biliary excretion of bilirubin, and its absence can be fatal. The Gunn rat is an excellent animal model of this disease, exhibiting a single guanosine (G) base deletion within the UGT1A1 gene. The defect results in a frameshift and a premature stop codon, absence of enzyme activity, and hyperbilirubinemia. Here, we show permanent correction of the UGT1A1 genetic defect in Gunn rat liver with site-specific replacement of the absent G residue at nucleotide 1206 by using an RNA/DNA oligonucleotide designed to promote endogenous repair of genomic DNA. The chimeric oligonucleotide was either complexed with polyethylenimine or encapsulated in anionic liposomes, administered i.v., and targeted to the hepatocyte via the asialoglycoprotein receptor. G insertion was determined by PCR amplification, colony lift hybridizations, restriction endonuclease digestion, and DNA sequencing, and confirmed by genomic Southern blot analysis. DNA repair was specific, efficient, stable throughout the 6-month observation period, and associated with reduction of serum bilirubin levels. Our results indicate that correction of the UGT1A1 genetic lesion in the Gunn rat restores enzyme expression and bilirubin conjugating activity, with consequent improvement in the metabolic abnormality.

Animals↗
PubMed1999

Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns.

All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences among Conus species may be based on the 50-200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in various Conus lineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10-35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of a Conus peptide precursor (signal sequence, pro-region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment-specific rate of divergence of Conus prepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.

Amino Acid Sequence↗
PubMed1999

Nucleotide exchange in genomic DNA of rat hepatocytes using RNA/DNA oligonucleotides. Targeted delivery of liposomes and polyethyleneimine to the asialoglycoprotein receptor.

Chimeric RNA/DNA oligonucleotides have been shown to promote single nucleotide exchange in genomic DNA. A chimeric molecule was designed to introduce an A to C nucleotide conversion at the Ser365 position of the rat factor IX gene. The oligonucleotides were encapsulated in positive, neutral, and negatively charged liposomes containing galactocerebroside or complexed with lactosylated polyethyleneimine. The formulations were evaluated for stability and efficiency in targeting hepatocytes via the asialoglycoprotein receptor. Physical characterization and electron microscopy revealed that the oligonucleotides were efficiently encapsulated within the liposomes, with the positive and negative formulations remaining stable for at least 1 month. Transfection efficiencies in isolated rat hepatocytes approached 100% with each of the formulations. However, the negative liposomes and 25-kDa lactosylated polyethyleneimine provided the most intense nuclear fluorescence with the fluorescein-labeled oligonucleotides. The lactosylated polyethyleneimine and the three different liposomal formulations resulted in A to C conversion efficiencies of 19-24%. In addition, lactosylated polyethyleneimine was also highly effective in transfecting plasmid DNA into isolated hepatocytes. The results suggest that both the liposomal and polyethyleneimine formulations are simple to prepare and stable and give reliable, reproducible results. They provide efficient delivery systems to hepatocytes for the introduction or repair of genetic mutations by the chimeric RNA/DNA oligonucleotides.

Animals↗
PubMed1999

Post-translationally modified neuropeptides from Conus venoms.

Predatory cone snails (genus Conus) comprise what is arguably the largest living genus of marine animals (500 species). All Conus use complex venoms to capture prey and for other biological purposes. Most biologically active components of these venoms are small disulfide-rich peptides, generally 7-35 amino acids in length. There are probably of the order of 100 different peptides expressed in the venom of each of the 500 Conus species [1,2]. Peptide sequences diverge rapidly between Conus species, resulting in a distinct peptide complement for each species. Thus, the genus as a whole has probably generated approximately 50 000 different peptides, which can be organized into families and superfamilies with shared sequence elements [3]. In this minireview, we provide a brief overview of the neuropharmacological, molecular and cell-biological aspects of the Conus peptides. However, the major focus of the review will be the remarkable array of post-translational modifications found in these peptides.

Amino Acid Sequence↗
PubMed1998

In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides.

A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated gene was associated in vivo with significantly reduced factor IX coagulant activity and a marked prolongation of the activated partial thromboplastin time. The results demonstrate that single base-pair alterations can be introduced in hepatocytes in situ by RNA/DNA oligonucleotides, suggesting a potentially powerful strategy for hepatic gene repair without the use of viral vectors.

Animals↗
PubMed1998

Legionella pneumophila catalase-peroxidases: cloning of the katB gene and studies of KatB function.

Legionella pneumophila, the causative organism of Legionnaires' pneumonia, is spread by aerosolization from man-made reservoirs, e.g. , water cooling towers and air conditioning ducts, whose nutrient-poor conditions are conducive to entrance into stationary phase. Exposure to starvation conditions is known to induce several virulence traits in L. pneumophila. Since catalase-peroxidases have been extremely useful markers of the stationary-phase response in many bacterial species and may be an avenue for identifying virulence genes in L. pneumophila, an investigation of these enzymes was initiated. L. pneumophila was shown to contain two bifunctional catalase-peroxidases and to lack monofunctional catalase and peroxidase. The gene encoding the KatB catalase-peroxidase was cloned and sequenced, and lacZ fusion and null mutant strains were constructed. Null mutants in katB are delayed in the infection and lysis of cultured macrophage-like cell lines. KatB is similar to the KatG catalase-peroxidase of Escherichia coli in its 20-fold induction during exponential growth and in playing a role in resistance to hydrogen peroxide. Analysis of the changes in katB expression and in the total catalase and peroxidase activity during growth indicates that the 8- to 10-fold induction of peroxidase activity that occurs in stationary phase is attributable to KatA, the second L. pneumophila catalase-peroxidase.

Amino Acid Sequence↗
PubMed1998

Enhanced gene transfer into HuH-7 cells and primary rat hepatocytes using targeted liposomes and polyethylenimine.

Different ratios of DNA phosphate to polyethylenimine amine were used for encapsulation and delivery to liver cells of chloramphenicol acetyl transferase (CAT) or luciferase expression plasmids in cationic, neutral and anionic liposomes. Positive liposomes consisted of dioleoyl phosphatidylcholine (DOPC): dioleoyl trimethylammonium propane (DOTAP) (6:1 molar ratio); neutral liposomes were composed of DOPC and dioleoyl phosphatidylethanolamine (DOPE) (1:1); and negative liposomes contained dioleoyl phosphatidylserine (DOPS) and DOPC (1:1). All formulations included 8 mol% galatocerebroside for targeting to the hepatocyte asialoglycoprotein receptor. Liposomes were prepared by film hydration followed by sequential extrusion through 0.8-0.2 mumol polycarbonate membranes. Transfection efficiency of HuH-7 human hepatoma cells and isolated rat hepatocytes was determined by CAT enzyme-linked immunosorbent assay (ELISA) or luciferase activity. Uptake of liposomal-encapsulated, fluorescently labeled 68-mer oligonucleotides was assessed by confocal microscopy. All three formulations demonstrated a twofold or greater increase in transfection efficiency and significantly lower toxicity compared to nonencapsulated polyethylenimine complexes. Negative liposomes were most effective, particularly in the rat hepatocytes. Only the cationic and anionic liposomal formulations exhibited significant thermodynamic stability. These formulations are readily characterized for size, phospholipid and DNA content, and they represent feasible systems for optimizing in vivo delivery systems to hepatocytes.

Animals↗
PubMed1997

Human heat tolerance in simulated environment.

The heat tolerance of 11 male volunteers were examined under seven climatic conditions in a climatic chamber. The conditions were 38 to 49 degrees C dry bulb temperature and 45 to 80 per cent relative humidity, i.e., 32.3 to 40 degrees C effective temperature-basic [ET(B)]. The ET(B) values were equated to other heat stress indices, e.g., WBGT (Wet-bulb Globe Temperature Index) and Oxford Index. The subjects did ergometric work at an intensity of 60 per cent VO2max. The exposure durations were decided by the cardiorespiratory, body temperature and sweating responses. Of the climatic conditions studied, at 35.4, 38, 39 and 40 degrees C ET(B), the body core temperature (Tcr) reached over 39 degrees C and heart rates attained 172 to 182 beats/min, which were taken as the tolerance limit. The total oxygen demand significantly varied with the increase in environmental warmth, i.e., increase or decrease of one litre of oxygen demand was equivalent to one minute change in tolerance time. The volunteers were not susceptible to heat; only in extreme hot situations beyond 35.4 degrees C ET(B), were unacceptable levels of physiological and psychophysical reactions seen. The study suggests the acceptable and tolerable limits for human exposure in heat: (i) acceptable at 38 to 38.2 degrees C Tcr for a tolerance time of 80 to 85 min; and (ii) the tolerable limit of short duration (40-45 min) at 39 degrees C Tcr that corresponded to 31.5 and 36.5 degrees C ET(B).

Adolescent↗