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Biomedical subjects

A K Chatterjee

Publications and source records attributed to A K Chatterjee.

At least 19 recordsLinked to original sources
PubMed1992

Short- and long-term effects of insulin on tyrosine aminotransferase gene expression.

In the present study the relationship between changes in tyrosine aminotransferase (TAT) enzyme activity, cytoplasmic mRNA levels, and gene transcription in response to both short- and long-term exposure to insulin was investigated. Insulin acutely inhibited transcription of the TAT gene by 50% in serum-deprived rat H4 hepatoma cells. Following this initial 50% decrease in transcription, there was a 2.5-fold induction in TAT activity that could not be accounted for by a concomitant increase in TAT mRNA levels. Insulin had no effect on the half-life of TAT mRNA. Insulin exposure for short periods of time also inhibited the glucocorticoid- and cAMP-induced transcription of the TAT gene. Like insulin, protein synthesis inhibitors acutely inhibited basal and glucocorticoid-induced TAT transcription. TAT activity gradually returned toward basal levels after 8 h of insulin treatment. A second insulin-induced increase in TAT activity (3.5-fold above basal levels) was observed by 24 h of insulin treatment. This second phase of insulin-induced TAT activity was associated with elevated levels of TAT transcription and TAT mRNA levels, and therefore, unlike the earlier stimulation, could be accounted for by changes in gene expression. Thus, the insulin-mediated regulation of the TAT gene in H4 cells is complex. Different transcriptional and post-transcriptional mechanisms are likely to be involved in the biphasic responses to insulin.

Animals↗
PubMed1992

Genetic evidence for an activator required for induction of pectin lyase in Erwinia carotovora subsp. carotovora by DNA-damaging agents.

In Erwinia carotovora subsp. carotovora 71, the induction of pectin lyase (Pnl), the bacteriocin carotovoricin (Ctv), and cellular lysis (Lss) requires a RecA function. We obtained mutants wherein a pleiotropic defect, i.e., the lack of induction with mitomycin C, is not restored by the recA+ DNA. From a genomic library of strain 71, a cosmid (pAKC280) that restored induction of Pnl, Ctv, and Lss by mitomycin C was isolated. The activator function, designated Rdg for regulator of damage-inducible genes, was localized by subcloning and insertional mutagenesis to a 2.6-kb region within a 6.7-kb EcoRI fragment. An rdg-lacZ operon fusion was inducible by mitomycin C in RecA+ but not RecA- derivatives of E. carotovora subsp. carotovora 71 and Escherichia coli. A RecA+ E. coli strain carrying only a PnlA+ plasmid was not inducible for Pnl production; however, when both a PnlA+ plasmid and a Rdg+ plasmid were present, the transcription of pnlA and the production of the enzyme were activated by mitomycin C. The size of the pnlA transcript produced in E. coli was identical to that of the transcript produced by E. carotovora subsp. carotovora 71, suggesting that the same promoter and termination sequences were being utilized in these bacteria.

Bacteriocins↗
PubMed1992

Desmoplastic malignant mesothelioma: a review of 17 cases.

AIMS: To identify the histological features of desmoplastic mesothelioma, and to determine its incidence and prognosis. METHODS: Two hundred and fifty five cases of malignant mesothelioma were examined over seven years (1982-9) to identify the desmoplastic variant. Sections were cut at 5 microns and stained with haemotoxylin and eosin and with CAM 5.2 (Dakopatts). Asbestos fibre counts were carried out by light microscopy in 14 cases using the potash digestion method. RESULTS: Seventeen cases were identified as desmoplastic mesothelioma giving an incidence of 6.6%. In 11 cases the cell type in more cellular areas was sarcomatous and in six others it was biphasic. The mean survival time from onset of symptoms to death was 5.8 months for the sarcomatous variant and 6.8 months for the biphasic variant. Twelve of 16 patients had had previous occupational exposure to asbestos, ranging from five months to 43 years. The diagnosis of desmoplastic mesothelioma was only accepted if acellular connective tissue comprised 50% or more of the tumour bulk. Also seen was collagen necrosis, anastomosing bands of often hyalinised collagen with a prominent storiform pattern, and where cellular detail was present there were hyperchromatic nuclei. CONCLUSIONS: Desmoplastic mesothelioma is a rare variant of malignant mesothelioma with a storiform collagen pattern, collagen necrosis, bland acellular collagen and focal cytological features of malignancy. Though rare, it is important to recognise this variant and distinguish it from a pleural plaque, nonspecific reactive pleural fibrosis, pleurisy, rheumatoid disease, or, rarely, spindle cell sarcomas.

Adult↗
PubMed1992

Impact of lead toxicity on brain metabolisms of nucleic acid and catecholamine in protein malnourished rats.

The brain biochemistry in terms of certain key substances of brain were studied in 18% protein and 6% protein-fed rats following lead ingestion at a level of 1% in the diet. Lead ingestion diminished the protein and increased the RNA content of brain, and, consequently reduced the protein/RNA ratio. The RNA/DNA ratio in brain was elevated in lead toxicity, while the protein/DNA ratio remained unaltered. The RNase and DNase activities of brain were decreased. Lead treatment diminished the glutathione (GSH) level of blood but the GSH level of brain was not altered significantly by the lead treatment. The plasma protein level was also diminished after lead treatment. The effects of lead on some of these parameters were found to be more pronounced in rats receiving the 6% protein diet. The serotonin (5-HT) level of brain was reduced, while the norepinephrine (NE) and dopamine (DA) levels of brain were elevated following lead treatment. The monoamine oxidase (MAO) and tryptophan hydroxylase (TPH) activities and 5-hydroxy-indole acetic acid (5-HIAA) content of brain were elevated in lead-ingested rats. The effects of lead on these parameters were found to be potentiated when the rats were fed on a 6% protein diet. These studies suggest that lead at the present dose affects brain biochemistry in terms of both nucleic acids and amine metabolism, and protein deficiency potentiates some of these lead-induced changes.

Animals↗
PubMed1991

Cloned Erwinia chrysanthemi out genes enable Escherichia coli to selectively secrete a diverse family of heterologous proteins to its milieu.

The out genes of the enterobacterial plant pathogen Erwinia chrysanthemi are responsible for the efficient extracellular secretion of multiple plant cell wall-degrading enzymes, including four isozymes of pectate lyase, exo-poly-alpha-D-galacturonosidase, pectin methylesterase, and cellulase. Out- mutants of Er. chrysanthemi are unable to export any of these proteins beyond the periplasm and are severely reduced in virulence. We have cloned out genes from Er. chrysanthemi in the stable, low-copy-number cosmid pCPP19 by complementing several transposon-induced mutations. The cloned out genes were clustered in a 12-kilobase chromosomal DNA region, complemented all existing out mutations in Er. chrysanthemi EC16, and enabled Escherichia coli strains to efficiently secrete the extracellular pectic enzymes produced from cloned Er. chrysanthemi genes, while retaining the periplasmic marker protein beta-lactamase. DNA sequencing of a 2.4-kilobase EcoRI fragment within the out cluster revealed four genes arranged colinearly and sharing substantial similarity with the Klebsiella pneumoniae genes pulH, pulI, pulJ, and pulK, which are necessary for pullulanase secretion. However, K. pneumoniae cells harboring the cloned Er. chrysanthemi pelE gene were unable to secrete the Erwinia pectate lyase. Furthermore, the Er. chrysanthemi Out system was unable to secrete an extracellular pectate lyase encoded by a gene from a closely related plant pathogen. Erwinia carotovora ssp. carotovora. The results suggest that these enterobacteria secrete polysaccharidases by a conserved mechanism whose protein-recognition capacities have diverged.

Amino Acid Sequence↗
PubMed1991

Interactions of diabetogenic compounds: cyproheptadine and alloxan.

Pretreatment with an oral dose (45 mg/kg) of cyproheptadine (CPH), a drug that inhibits secretion and synthesis of insulin. 3 hr before alloxan (100 mg/kg, iv) protects mice from the permanent diabetes produced by alloxan. Pretreated animals at the time of alloxan administration were hyperglycemic. Therefore, the possibility that CPH-induced hyperglycemia protected mice from alloxan was investigated. This was accomplished by giving mannoheptulose (a glucose antagonist) or insulin (to lower blood glucose) after CPH and before alloxan. These interventions eliminated CPH-induced protection from alloxan, indicating a role for CPH-induced hyperglycemia in the protective effect. To confirm that CPH does not protect mice from alloxan-induced diabetes by a direct action, in vitro experiments using isolated pancreatic islets were conducted. Mouse islets were pretreated with CPH, its metabolite desmethylcyproheptadine (DMCPH), or an equal mixture of the two and/or various concentrations of glucose prior to an acute exposure to a toxic concentration of alloxan. Glucose-stimulated insulin release was used as a measure of pancreatic beta-cell function after alloxan exposure. CPH or DMCPH (alone or in combination) pretreatment did not provide protection against alloxan-induced inhibition of insulin release nor did pretreatments potentiate the protective action of glucose against in vitro alloxan toxicity. The results indicate that the protective action of CPH when given to mice before alloxan is due to drug-induced hyperglycemia and not to a direct effect of CPH or its metabolite.

Alloxan↗
PubMed1991

Extracellular secretion of pectate lyase by the Erwinia chrysanthemi out pathway is dependent upon Sec-mediated export across the inner membrane.

The plant pathogenic enterobacterium Erwinia chrysanthemi EC16 secretes several extracellular, plant cell wall-degrading enzymes, including pectate lyase isozyme PelE. Secretion kinetics of 35S-labeled PelE indicated that the precursor of PelE was rapidly processed by the removal of the amino-terminal signal peptide and that the resulting mature PelE remained cell bound for less than 60 s before being secreted to the bacterial medium. PelE-PhoA (alkaline phosphatase) hybrid proteins generated in vivo by TnphoA insertions were mostly localized in the periplasm of E. chrysanthemi, and one hybrid protein was observed to be associated with the outer membrane of E. chrysanthemi in an out gene-dependent manner. A gene fusion resulting in the substitution of the beta-lactamase signal peptide for the first six amino acids of the PelE signal peptide did not prevent processing or secretion of PelE in E. chrysanthemi. When pelE was overexpressed, mature PelE protein accumulated in the periplasm rather than the cytoplasm in cells of E. chrysanthemi and Escherichia coli MC4100 (pCPP2006), which harbors a functional cluster of E. chrysanthemi out genes. Removal of the signal peptide from pre-PelE was SecA dependent in E. coli MM52 even in the presence of the out gene cluster. These data indicate that the extracellular secretion of pectic enzymes by E. chrysanthemi is an extension of the Sec-dependent pathway for general export of proteins across the bacterial inner membrane.

Adenosine Triphosphatases↗
PubMed1991

Nucleotide sequence and molecular characterization of pnlA, the structural gene for damage-inducible pectin lyase of Erwinia carotovora subsp. carotovora 71.

In a previous study, pnlA (the DNA damage-inducible structural gene for pectin lyase) of Erwinia carotovora subsp. carotovora 71 was localized to a 1.4-kb DNA segment within a 3.4-kb EcoRI fragment (J. L. McEvoy, H. Murata, and A. K. Chatterjee, J. Bacteriol. 172:3284-3289, 1990). We present here DNA sequence data for a 2.2-kb region revealing an open reading frame of 870 bases, corresponding to a protein (Pnl) of an approximate molecular mass of 32,100 Da and an isoelectric point of 9.92. Although initiation of translation is presumed to occur at the ATG codon, direct protein sequencing revealed alanine as the N-terminal amino acid, probably as a consequence of posttranslational removal of the initiating amino acid. The sequence of the first 20 amino acid residues of Pnl, purified from E. carotovora subsp. carotovora 71, agreed completely with the predicted amino acid sequence of the N-terminal segment. This finding also indicated that Pnl is not subject to processing by a signal peptidase. The transcriptional start site of pnlA was determined to reside 80 bp upstream of the translational start site. Deletion analysis revealed that 218 bp of DNA upstream of the transcriptional start site is sufficient for induction of pnlA by mitomycin C. Within 600 bp upstream of the translational start site, no sequences resembling a LexA binding site (SOS box) or a cyclic AMP receptor protein binding site were found. However, palindromic sequences were detected at -187 and -86 bp relative to the translational start site, and these could be potential sites for the binding of a regulatory protein(s). Comparison of the deduced amino acid sequence for PnlA with that of a Pnl from Aspergillus niger and with those of various pectate lyases of Erwinia species revealed a low degree of homology dispersed throughout the length of the proteins.

Amino Acid Sequence↗
PubMed1991

Rapid alteration of pancreatic proinsulin and preproinsulin messenger ribonucleic acid in rats treated with cyproheptadine.

Cyproheptadine (CPH) appears to be unique among islet beta-cell toxicants by virtue of its ability to rapidly and reversibly inhibit insulin biosynthesis in rats. These studies examined the mechanism of CPH-induced insulin depletion by determining the time course for CPH-induced changes in pancreatic preproinsulin mRNA, proinsulin, and insulin levels. A single oral dose of CPH decreased proinsulin levels to 35% of the control value by 3 h. Proinsulin stayed depressed for up to 24 h. Preproinsulin mRNA declined more slowly, reaching 35% of the control value at 6 h, and increased more rapidly, returning to the control value by 24 h. Pancreatic insulin levels did not decrease significantly until 24 h. Exposure of isolated rat islets to CPH for 30 min in vitro selectively inhibited proinsulin synthesis by 62%, without affecting preproinsulin mRNA levels. The dissociation between changes in proinsulin and preproinsulin mRNA levels suggests that the decrease in preproinsulin mRNA in vivo is associated with but does not cause CPH-induced changes in insulin biosynthesis.

Actins↗
PubMed1991

Protective effect of a high protein diet against the toxicity of some organophosphorus compounds in albino rats.

The present investigation deals with determining the efficacy of a high protein diet (HPD) in combating toxicity in albino rats of some organophosphorus compounds (OPCs) that follow dissimilar metabolic patterns in a living system. As assessed by an increase or decrease in the levels of some biochemical and nutritional parameters, the high protein diet containing 59% protein seems to have a beneficial effect in alleviating toxicity of low but prolonged doses of OPCs over the standard diet (SD) containing 19% protein. OPCs undergoing direct detoxication in a living system like diisopropyl phosphoro-fluoridate (DFP) appear to be more susceptible to HPD than those undergoing biotoxication like EPN (O-ethyl O-p-nitrophenyl phenyl-phosphonothioate) and malathion (S-(1,2-dicarbethoxyethyl) O,O-dimethyldithiophosphate).

Alanine Transaminase↗
PubMed1991

High altitude dives from 7000 to 14,200 feet in the Himalayas.

Indian Navy divers carried out no-decompression dives at altitudes of 7000 to 14,200 ft (2134-4328 m) in the Nilgiris and Himalayas from May to July 1988. Seventy-eight dives on air and 22 dives on oxygen were carried out at various altitudes. The final dives were at Lake Pangong Tso (4328 m) in Ladakh, Himalayas, to a maximum of 140 feet of sea water (fsw) [42.6 meters of sea water (msw)] equivalent ocean depth in minimum water temperature of 2 degrees C. Oxygen diving at 14,200 ft (4328 m) was not successful. Aspects considered were altitude adaptation, diminished air pressure diving, hypothermia, and remote area survival. Depths at altitude were converted to depths at sea level and were applied to the Royal Navy air tables. Altitude-related manifestations, hypoxia, hypothermia, suspected oxygen toxicity, and equipment failure were observed. It is concluded that stress is due to effects of altitude and cold on man and equipment, as well as changes in diving procedures when diving at high altitudes. Equivalent air depths when applied to Royal Navy tables could be considered a safe method for diving at altitudes.

Acclimatization↗
PubMed1990

DNA analysis by flow cytometry in malignant pleural mesothelioma: relationship to histology and survival.

In a retrospective study of 70 patients with malignant pleural mesothelioma, 168 formalin-fixed, paraffin-embedded tumour specimens were examined for DNA content by flow cytometry. In 20 patients where two or more blocks of the same tumour were available, there was considerable agreement between ploidy status and S-phase percentage in the different specimens. There were no significant differences for survival for patients who had been exposed to asbestos and those in whom no exposure could be elicited, nor for aneuploid and diploid tumours. The S-phase content was examined for different areas of the same tumour and the percentages were largely in agreement. However, those patients who had tumours with an S-phase percentage greater than the median (6 per cent) had a significantly shorter survival than those with tumours of lower S-phase percentage. Differences in DNA content and other cell cycle parameters were not associated with the histological subtypes.

Aged↗
PubMed1990

Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody.

The expression of epidermal growth factor receptor (EGF-R) in 34 formalin fixed paraffin embedded specimens of malignant mesothelioma was examined using the F4 antibody. Eight samples of reactive pleura showed homogenous cytoplasmic staining with the antibody. EGF-R positive cells (greater than or equal to 5%) were found in 68% of the mesotheliomas examined. EGF-R positivity was more commonly seen in the epithelial histological subtype than in the sarcomatous or mixed subtypes. Patients with less than 5% of mesothelioma cells staining positive for EGF-R had a significantly shorter survival (median 299 days) compared with patients whose tumours had a greater number of cells positive for EGF-R (median 446 days) (P = 0.04). However, when the histological subgroup was also taken into consideration (epithelial type had a significantly longer survival than the sarcomatous or mixed) the survival difference in relation to EGF-R positivity was no longer significant (P = 0.08). EGF-R could not be used to distinguish between malignant and benign mesothelial tissue and was not an independent prognostic factor for survival.

Adult↗