Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 73 records · Page 4Linked to original sources

PubMed1990

Glycosphingolipids in patients with the Rett syndrome.

We have pursued two blind studies on the plasma glycosphingolipids in patients with the Rett syndrome (RS), other disorders and normal individuals from Baltimore, USA, Vienna, Austria, and Rostock, East Germany. We found the presence of an unusual glycosphingolipid in 70% of patients with RS. Approximately 10% of the plasma from patients with other developmental disorders also contained this glycosphingolipid. However, this glycosphingolipid was absent from the plasma of normal individuals and lipid storage disorders. Further work in this area will be necessary to associate the relevance of this finding to RS.

Adolescent↗

PubMed1990

Individual NK cell clones lyse both tumor cell targets and herpes simplex virus-infected fibroblasts in the absence of interferon.

The target specificity of natural killer (NK) cells for either tumor cells or virus-infected cells has been investigated. Lymphocyte clones with the surface phenotype of NK cells (CD3-, CD16+) were obtained by limiting dilution of peripheral blood mononuclear cells stimulated with PHA, Herpes simplex virus type 1 (HSV-1), or Varicella-Zoster antigens. Clones were maintained in media with recombinant interleukin 2 (IL-2). Both NK-sensitive (K562 cells) and NK-resistant (Raji cells) targets were lysed by three cloned lines of NK cells. The ability to lyse NK-resistant target cells was largely lost when the cloned lymphocytes were cultured overnight in the absence of IL-2. Effector cells from all three clones were also capable of specifically lysing HSV-1 infected human fibroblasts in comparison with uninfected fibroblasts. We also showed that lysis of HSV-1 infected targets by NK cloned cells was independent of interferons in the culture system.

Adult↗

PubMed1990

Expression of herpes simplex virus type 1 glycoproteins in interferon-treated human neuroblastoma cells.

Human alpha interferon (IFN) significantly inhibits the replication of herpes simplex virus type 1 in human neuroblastoma cells. This inhibitory effect can be blocked by pretreatment with antiserum to IFN. We observed no significant differences in the expression of major nucleocapsid proteins, including VP5, between IFN-treated and untreated neuroblastoma cells. Electron micrographs demonstrated that there were distinct viral nucleocapsids within IFN-treated neuroblastoma cells. The expression of glycoproteins B and E was significantly reduced in these IFN-treated cells. On the other hand, glycoprotein D, although reduced in quantity, was expressed after IFN treatment. An immunofluorescence assay of the IFN-treated and virus-infected cells detected glycoprotein D in the Golgi complexes and in the nuclear membranes. Our results indicate that human alpha IFN may be useful in the study of gene expression in IFN-treated cells of neuronal origin.

Capsid↗

PubMed1990

Administration of high-dose octreotide (Sandostatin) by continuous subcutaneous infusion for the treatment of acromegaly.

Patients with active acromegaly were treated with octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) given in high dosage by continuous subcutaneous administration (CSI). Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations were rapidly and consistently reduced to the normal range and maintained for up to 14 weeks of study. Maximal inhibition of GH and IGF-1 secretion was obtained at a dose of 600 micrograms/24 h; all except 1 of the 7 patients were able to tolerate a higher dose of 1,600 micrograms/24 h. A single patient failed to show GH suppression at any dosage of octreotide. Computed tomographic evidence of tumour shrinkage was not demonstrated in these 7 patients, although in 2 patients subsequently studied by us definite tumour shrinkage was observed. These data show that the administration of octreotide by CSI is a highly satisfactory method for persistently lowering GH and IGF-1 concentrations in acromegalic patients sensitive to this drug.

Acromegaly↗

PubMed1990

Hypersensitivity to clinically useful alkylating agents and radiation in poly(ADP-ribose) polymerase-deficient cell lines.

Mutant V79 Chinese hamster cell lines, deficient in poly(ADP-ribose) polymerase activity, were previously shown to be significantly resistant to etoposide, a topoisomerase II inhibitor, and hypersensitive to camptothecin, a topoisomerase I inhibitor (Chatterjee, S.; Trivedi, D.; Petzold, S.J.; Berler, N.A. Mechanism of epipophyllotoxin-induced cell death in poly(adenosine diphosphate-ribose) synthesis-deficient V79 Chinese hamster cell lines. Cancer Res. 50:2713-2718, 1990 and Chatterjee, S.; Cheng, M.F.; Trivedi, D.; Petzold, S.J.; Berger, N.A. Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines. Cancer Commun. 1:389-394; 1990). We have now demonstrated hypersensitivity of these mutant cell lines, designated ADPRT 54 and ADPRT 351, to a variety of antitumor agents including melphalan, BCNU, mitomycin, and bleomycin. They are also hypersensitive to UV- and x-irradiation. These mutants, however, are significantly resistant to the topoisomerase II-targeted DNA intercalators, Adriamycin and m-AMSA. Our results strongly suggest that inhibition of poly(ADP-ribose) polymerase could be useful to potentiate the cytotoxicity of a variety of currently available antitumor drugs.

Alkylating Agents↗

PubMed1990

Retino-cephalic vascular malformation.

Unilateral vascular malformation of the retina, brain and parts of the face constitute a rare syndrome named after Wyburn-Mason or as Bonnet-Dechaume-Blanc syndrome. We report this case because of its rarity.

Adolescent↗

PubMed1990

Phosphatidylcholine stimulates the activity of UDP-Gal beta 1-4 galactosyltransferase in normal human kidney proximal tumour cells.

Effects of various lipid components of low density lipoproteins (LDL) and serine on the regulation of UDP-Gal-beta 1-4-galactosyltransferase (GalT-2) activity have been investigated in normal proximal tubular (PT) cells. Addition of exogenous serine (0.1-0.75 mM), cholesterol (0-200 micrograms/ml medium), linoleic acid and oleic acid (0.1-0.75 mM) for 4 hr at 37 degrees C did not suppress the activity of GalT-2 in PT cells. Similarly, incubation of cells with glucosylceramide and lactosylceramide (25-50 micrograms/ml medium) did not alter GalT-2 activity in cells as compared to control. In contrast, palmitic acid (0-0.75 mM), phosphatidylethanolamine and sphingomyelin (0-200 micrograms/ml) stimulated GalT-2 activity by 20-36% as compared to control. Incubation of PT cells with D-alpha-dipalmitoyl phosphatidylcholine (0-200 micrograms/ml medium) also stimulated the activity of GalT-2, maximum stimulation (200%) occurring with 25 micrograms phosphatidylcholine/ml medium. However, at a higher concentration (200 micrograms/ml), the stimulation of the activity of GalT-2 was in the order of 27% compared to control. Dioleylphosphatidylcholine did not alter GalT-2 activity in PT cells. Thus, it is concluded that (i) various lipid components, sphingosine and serine present in LDL are not involved in the LDL-mediated suppression of GalT-2 activity in normal PT cells, and (ii) stringent structural requirements in the phosphatidylcholine molecule are necessary to exert a time and concentration dependent stimulation of GalT-2 activity.

Cells, Cultured↗

PubMed1990

Morphological changes in some endocrine organs in rats following chronic lithium treatment.

Chronic prophylactic administration of lithium, a well-known anti-manic drug, has been reported to have a wide number of potential side effects involving metabolic, reproductive and endocrine systems. Since most of the existing literature reports on biochemical changes, the present investigations were undertaken to examine whether chronic lithium treatment could lead to morphological alterations in various endocrine organs. Sexually adult male Fischer rats, acclimatized to standardized laboratory conditions of light (LD 14:10) and temperature (21-23 degrees C) for 2 weeks, were treated with lithium by feeding a specially prepared chow containing 0.4% lithium chloride. The diet was administered for 15 d to one group and for 30 d to the other after which the animals were decapitated and the thyroid, adrenal, pancreas, testis and seminal vesicles were quickly dissected out and fixed in 10% neutral formalin. After routine histological procedures, 5 microns thick paraffin sections were stained by hematoxylin-eosin or Gomori's trichrome stain and examined under light microscope. Definitive morphological alterations were noted in the thyroid gland in that chronic lithium led to significant reduction in the epithelial height of the follicular cells and in an increase in colloidal content, suggesting a hypothyroid condition. Chronic lithium also resulted in decreased epithelial height in the seminal vesicle; the mucosal pseudostratified columnar epithelium regressed to an almost squamous epithelium. No discernible morphological changes were evident in the other endocrine glands studied. These results provide important morphological correlates and support some of the biochemical studies reported earlier on the potential adverse effects of lithium.

Animals↗

PubMed1989

Continuous infusion of octreotide in acromegaly.

15 patients with acromegaly were treated with continuous subcutaneous infusion of octreotide in increasing dose from 200 to 1600 micrograms per 24 h by 200 micrograms increments each week. Patients were studied during the initial 7 h of infusion, weekly at each dose level, then after 1 and 2 months at maximum dosage. 13 patients responded well, as judged by growth hormone (GH) suppression and return of insulin-like growth factor 1 to normal, although 1 patient withdrew due to adverse effects; 2 patients showed no significant reduction in GH. In the 12 responders GH level fell within the first 3 h of infusion at a mean plasma octreotide level of 0.76 (SE 0.26) micrograms/l, corresponding to 25 micrograms of infused drug. Optimum suppression of GH occurred at a dosage of 600 micrograms per 24 h, a plasma drug level of 3.5 (0.5) micrograms/l. A definite reduction in tumour size was seen on computerised tomographic scan in 2 patients. All responders noted subjective improvement in acromegalic symptoms. Adverse effects comprised gastrointestinal disturbances, which were transient and mild in 14 patients but severe in 1; biliary sludging occurred in 1 patient. No significant deterioration in carbohydrate tolerance was seen in the responders.

Acromegaly↗

PubMed1989

Octreotide.

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Acromegaly↗

PubMed1989

Neutral sphingomyelinase from human urine. Purification and preparation of monospecific antibodies.

A neutral sphingomyelinase which cleaves phosphorylcholine from sphingomyelin at a pH optima of 7.4 was purified 440-fold to apparent homogeneity from normal human urine concentrate employing Sephadex G-75 column chromatography, preparative isoelectric focusing, and sphingosylphospholcholine CH-Sepharose column chromatography. The enzyme is composed of a single polypeptide whose apparent molecular weight is 92,000. Analytical isoelectric focusing revealed that the pI of this enzyme is 6.5. Purified neutral sphingomyelinase was devoid of beta-galactosidase and beta-N-acetylglucosaminidase activity originally present in the urine concentrate. The purified neutral sphingomyelinase (N-SMase) had low levels of phospholipase A1 and A2 activity when phosphatidylcholine was used as a substrate and detergents were included in the assay mixture. However, it had no phospholipase activity toward phosphatidylglycerol and sphingomyelin at pH 4.5 irrespective of the presence or absence of detergents. Monospecific polyclonal antibodies raised against N-SMase immunoprecipitated approximately 70% of N-SMase activity from urine, human kidney proximal tubular cells, and partially purified membrane-bound N-SMase from these cells. Western immunoblot assays revealed that the monospecific polyclonal antibody against urinary N-SMase recognized both the urinary N-SMase and the membrane-bound N-SMase. Because this enzyme is distinct biochemically and immunologically as compared to acid sphingomyelinase (EC 3.1.4.12), we would like to assign it an enzyme catalog number of EC 3.1.4.13. The availability of N-SMase and corresponding antibody will be useful in studying various aspects of this enzyme in biological systems.

Acetylglucosaminidase↗

PubMed1989

Topoisomerase II-dependent and -independent mechanisms of etoposide resistance in Chinese hamster cell lines.

Resistance to etoposide (VP-16), amsacrine (mAMSA), and doxorubicin (Adriamycin) was studied in two Chinese hamster cell lines primarily selected for resistance to the epipodophyllotoxin. Both lines demonstrated profound resistance to VP-16, and mAMSA stimulated DNA breakage. However, the resistance to mAMSA cytotoxicity in both lines was less than expected from the level of resistance to the effects of topoisomerase II inhibition. Similarly, resistance to the cytotoxicity of high VP-16 concentrations in one of the lines was less than expected from the resistance to inhibition of topoisomerase II. An analysis of the relation of DNA breaks to drug cytotoxicity suggests that cross-resistance to mAMSA was mainly conferred through loss of mAMSA-stimulated, topoisomerase II-mediated DNA breaks. This mechanism also contributed towards reduced VP-16 cytotoxicity. However, our studies suggest that additional mechanisms, independent of resistance to VP-16-mediated topoisomerase II effects, greatly increased the resistance to this agent. Resistance to VP-16 cytotoxicity, not dependent on resistance to drug-mediated DNA cleavage, could be overcome at high drug concentrations in one of the resistant lines and might be responsible for the greater relative resistance to VP-16 than to mAMSA. These findings suggest the presence of two distinct mechanisms of resistance to VP-16 cytotoxicity, one presumably mediated by topoisomerase II and dependent on resistance to drug-mediated DNA scission, and a second mechanism independent of the effects of the drug on topoisomerase II.

Amsacrine↗

PubMed1989

Simultaneous triple-immunogold staining of virus and host cell antigens with monoclonal antibodies of virus and host cell antigens in ultrathin cryosections.

The mechanism of intracellular maturation and sorting of herpes simplex virus type I glycoproteins is not known in details. To elucidate the intracellular sorting of viral glycoproteins and their possible interaction with the cytoskeleton, a method for simultaneous immunogold staining of three antigens in ultrathin cryosections is described. Each antigen is stained by an indirect technique using mouse monoclonal IgG as first layer, rabbit anti-mouse IgG as second and gold-conjugated goat anti-rabbit IgG as third layer antibody. After each staining cycle the sections are covered by methyl cellulose and exposed to paraformaldehyde vapour at 80 degrees C for 30 min. This destroys the free antigen combining sites of the second and the third layer IgG and abolish contaminating staining. Simultaneous triple-staining is documented with three mouse monoclonal antisera specific for 1) herpes simplex virus type 1 glycoprotein C, 2) glycoprotein D and 3) alpha- and beta-tubulin as primary antibodies. Labelling for virus glycoproteins was found in some Golgi vesicles and close to the cytoplasmic microtubules as well as on the cell surface and on intracytoplasmic and extracellular virus particles.

Animals↗

PubMed1989

Mutant cells defective in poly(ADP-ribose) synthesis due to stable alterations in enzyme activity or substrate availability.

We used two different approaches to develop cell lines deficient in poly(ADP-ribose) synthesis to help determine the role of this reaction in cellular functions. One approach to this problem was to develop cell lines deficient in enzyme activity; the other approach was to develop cell lines capable of growing with such low nicotinamide adenine dinucleotide (NAD) levels so as to effectively limit substrate availability for poly(ADP-ribose) synthesis. The selection strategy for obtaining cells deficient in activity of poly(ADP-ribose) polymerase was based on the ability of this enzyme to deplete cellular NAD in response to high levels of DNA damage. Using this approach, we first obtained cell lines having 37-82% enzyme activity compared to their parental cells. We now report the development and characterization of two cell lines which were obtained from cells having 37% enzyme activity by two additional rounds of further mutagenization and selection procedures. These new cell lines contain 5-11% enzyme activity compared to the parental V79 cells. In pursuit of the second strategy, to obtain cells which limit poly(ADP-ribose) synthesis by substrate restriction, we have now isolated spontaneous mutants from V79 cells which can grow stably in the absence of free nicotinamide or any of its analogs. These cell lines maintain NAD levels in the range of 1.5-3% of that found in their parental V79 cells grown in complete medium. The pathway of NAD biosynthesis in these NAD-deficient cells is not yet known. Further characterization of these lines showed that under conditions that restricted poly(ADP-ribose) synthesis, they all had prolonged doubling times and increased frequencies of sister chromatid exchanges.

Animals↗

PubMed1989

Effect of recombinant hybrid human interferon on replication and morphogenesis of HSV-1 in monkey cells.

Human recombinant alpha interferon, A/D, significantly reduced the replication and cell fusion induced by herpes simplex virus type 1 in monkey cells. Thin-section electron microscopy of interferon-treated monkey cells showed distinct assembly of nucleocapsids within the nucleus. Analysis of virus-specific proteins by the immunoblot technique confirmed that A/D interferon had no significant effect on the expression of major nucleocapsid proteins, although the expression of glycoproteins B and D was reduced in interferon-treated cells. The possibility of an interferon-induced block at a late stage in virus morphogenesis is discussed.

Animals↗

PubMed1989

Sequences near the termini are required for transposition of the maize transposon Ac in transgenic tobacco plants.

Deletion derivatives of the maize transposable element Activator (Ac) were constructed in vitro and inserted into a kanamycin resistance gene. These constructions were then introduced into tobacco protoplasts derived from plants previously transformed with Ac. The ability of each deletion derivative to excise was measured by whether or not kanamycin-resistant tobacco calli were recovered. This allowed us to determine the length of DNA present at each terminus that is required to respond to the products expressed by the Ac element present in the genome. We show that around 200 base pairs (bp) are required at both ends for excision to occur at wild-type levels. When between 100 and 200 bp were retained at one of the ends, reduced frequencies of excision were detected. With less than 100 bp remaining at either end, no excision was detected. In addition, we show that although similar lengths of DNA are required at each terminus, the termini are not interchangeable. The significance of these data is discussed with respect to the protein(s) which interact(s) with the termini of Ac.

Blotting, Southern↗

PubMed1989

A role for herpes simplex virus type 1 glycoprotein E in induction of cell fusion.

The role of herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) in the induction of multinucleate cell (syncytium) formation was investigated using monoclonal antibodies and a gE deletion mutant, R7023. We found that monoclonal antibodies directed against gE blocked HSV-1-induced syncytium formation in human cells. R7023 also failed to induce syncytium formation in tissue culture cells. The results indicate that gE, in addition to glycoproteins B, D, H and the gene sequence located between 0.732 and 0.745 map units, is involved in cell fusion. Thus, this important biological property appears to be regulated by several HSV-1 gene products.

Animals↗

PubMed1989

Effects of melatonin on the growth of MtT/F4 anterior pituitary tumor: evidence for inhibition of tumor growth dependent upon the time of administration.

In the present report, we have examined the anti-tumor potential of melatonin by utilizing the MtT/F4 anterior pituitary transplantable tumor. The tumor was obtained (Bogden Labs.) in cryopreserved condition and transplanted (in the left rear thigh), and allowed to grow for 8 weeks in adult Fischer 344 rats, maintained under uniform laboratory conditions of light (LD 14:10; lights on at 06:00 h), and temperature (21-23 degrees C). Subsequently, the tumor was dissected out, minced, and washed in Medium 199, and similarly transplanted into groups of adult Fischer 344 rats representing the final tumor recipient groups utilized for the evaluation of melatonin's anti-tumor effects. Melatonin (50 micrograms/0.1 ml/animal) was administered subcutaneously either early in the morning (at 08:00 h), or late in the afternoon (at 18:00 h), for 6 weeks, beginning the day after tumor transplantation. The matched controls were given equal volumes of physiological saline. A careful record of the appearance and growth of the tumor was maintained by examining the animals every morning. At the termination of the experimental schedule, the tumor masses were carefully dissected out, rinsed with normal saline, dried, and weighted on a sensitive Mettler balance. Our results showed that melatonin significantly increased the latency period of the tumor, irrespective of the time of drug administration. Analysis of the final tumor weights showed that afternoon, but not morning, injections of melatonin significantly reduced both the absolute (P less than 0.025) and relative (P less than 0.05) tumor weights in comparison to the saline-injected matched control. These results suggest that a) melatonin exhibits its anti-tumor efficacy on MtT/F4 tumor, by delaying the appearance of the tumor, and b) the anti-tumor potential of melatonin is greatly dependent on the time of administration of the drug within the daily light-dark cycle.

Animals↗