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Biomedical subjects

K Ghosh

Publications and source records attributed to K Ghosh.

At least 199 records · Page 11Linked to original sources
PubMed1994

Epithelial ovarian cancer complicating renal transplantation.

Patients taking immunosuppressive therapy are at substantial risk for malignant disease. We report two cases of epithelial ovarian cancer occurring in women after renal transplantation with subsequent poor clinical outcome. Clinicians are advised to thoroughly investigate adnexal masses in this patient population.

Adult↗
PubMed1994

Perinatal outcome in pregnancies complicated by pulmonary tuberculosis.

OBJECTIVES: To assess the perinatal outcome of pregnancies complicated by active pulmonary tuberculosis. METHODS: The perinatal outcome of 79 gravidas with pulmonary tuberculosis was compared with that of 316 normal gravidas of similar age, parity and socioeconomic status. RESULTS: The mean birthweight of infants (2649 g) born to tuberculous mothers was 215 g less than that of control group (P < 0.001). Pulmonary tuberculosis was associated with an approximate 2-fold increase in prematurity (22.8% vs. 11.1%, P < 0.01), small for gestational age (20.2% vs. 7.9%, P < 0.005) and low birthweight neonates (34.2% vs. 16.5%, P < 0.001), and 6-fold increase in perinatal deaths (10.1% vs. 1.6%, P < 0.001). The adverse perinatal outcome was pronounced in cases with late diagnosis, incomplete and irregular treatment, and advanced pulmonary lesions. CONCLUSIONS: Maternal tuberculosis is a high-risk perinatal condition. The study emphasizes the need for early diagnosis and treatment of tuberculosis, preferably before pregnancy, regular medical supervision and good perinatal care for tuberculous mothers.

Adult↗
PubMed1994

Visual hallucinations following treatment with vincristine.

Peripheral neuropathy is a common side effect of vincristine therapy. However, side effects due to central nervous system (CNS) toxicity following intravenous administration are rare. We report two patients who developed visual hallucinations during treatment with vincristine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Membrane anchoring domain of herpes simplex virus glycoprotein gB is sufficient for nuclear envelope localization.

We have used the glycoprotein gB of herpes simplex virus type 1 (gB-1), which buds from the inner nuclear membrane, as a model protein to study localization of membrane proteins in the nuclear envelope. To determine whether specific domains of gB-1 glycoprotein are involved in localization in the nuclear envelope, we have used deletion mutants of gB-1 protein as well as chimeric proteins constructed by replacing the domains of the cell surface glycoprotein G of vesicular stomatitis virus with the corresponding domains of gB. Mutant and chimeric proteins expressed in COS cells were localized by immunoelectron microscopy. A chimeric protein (gB-G) containing the ectodomain of gB and the transmembrane and cytoplasmic domains of G did not localize in the nuclear envelope. When the ectodomain of G was fused to the transmembrane and cytoplasmic domains of gB, however, the resulting chimeric protein (G-gB) was localized in the nuclear envelope. Substitution of the transmembrane domain of G with the 69 hydrophobic amino acids containing the membrane anchoring domain of gB allowed the hybrid protein (G-tmgB) to be localized in the nuclear envelope, suggesting that residues 721 to 795 of gB can promote retention of proteins in the nuclear envelope. Deletion mutations in the hydrophobic region further showed that a transmembrane segment of 21 hydrophobic amino acids, residues 774 to 795 of gB, was sufficient for localization in the nuclear envelope. Since wild-type gB and the mutant and chimeric proteins that were localized in the nuclear envelope were also retained in the endoplasmic reticulum, the membrane spanning segment of gB could also influence retention in the endoplasmic reticulum.

Animals↗
PubMed1993

Evaluation of some properties of a phosphorodithioate oligodeoxyribonucleotide for antisense application.

An all phosphorodithioate oligodeoxyribonucleotide (PS2; 17-mer) complementary to the coding region of the rabbit beta-globin mRNA was compared with the normal (PO2) and phosphorothioate (POS) oligonucleotide of the same size and sequence with respect to physicochemical properties and antisense activity in cell-free systems. The melting temperature (Tm) of the PS2-cDNA duplex was reduced by 17 degrees C relative to the PO2-cDNA duplex, compared to 11 degrees C for the POS-cDNA duplex, suggesting a decreased stability of the duplex with an increasing sulfur substitution. Like the POS-derivative, the PS2 oligonucleotide is quite stable against exonucleases, but these modified oligonucleotides showed different stability towards endonucleases and also towards different sub-cellular fractions of MCF-7 cells. During in vitro protein binding studies, the PS2 oligonucleotide showed similar binding (10-20%) to that of the PO2 oligonucleotide, while the POS oligonucleotide bound 60%. In cell-free translation, the PS2 oligonucleotide produced slightly higher specific translation inhibition of rabbit beta-globin mRNA compared to that of the PO2 oligonucleotide, and this was true only at concentration below 2 mM. The POS-derivative, except at 10 mM concentration, always showed higher translation arrest of the rabbit beta-globin mRNA compared to that of the other two oligonucleotides. The present study suggests that the PS2 oligonucleotide offers very little advantage over the POS oligonucleotide for use as an antisense analog.

Animals↗
PubMed1993

Characterization of the human L-plastin gene promoter in normal and neoplastic cells.

Plastins are a family of human actin-binding proteins (isoforms) which are abundantly expressed in all normal replicating mammalian cells. One isoform, L-plastin, is constitutively expressed at high levels in hemopoietic cell types while T-plastin is constitutively expressed in all non-hemopoietic cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). L-plastin is, however, constitutively synthesized in many types of malignant human cells of solid tissues suggesting that its expression is induced during tumorigenesis. The frequency of L-plastin induction in some cancers of the steroid-regulated female reproductive tract (breast, ovary, uterus, and placenta) appears to be especially high (79% in a limited survey). To learn the mechanism of L-plastin gene activation accompanying tumorigenesis, we have begun to characterize the promoter and regulatory elements of the L-plastin gene. Transcription initiation from this promoter was found to occur at multiple sites and as near as 10 base pairs from the 3'-side of the TATAAA box. The promoter and its flanking DNA were cloned and sequenced to identify potential regulatory elements that participate in the induction of the L-plastin gene in neoplastic cells. Examination of upstream sequences revealed the existence of two potential progesterone, one potential estrogen, and four potential Ets-1 responsive elements flanking the promoter. A 315-base pair fragment spanning the TATAAA box and a potential Sp1-binding site exhibited maximum promoter activity using CAT as a reporter while longer promoter fragments extending into upstream flanking sequences spanning the hormone receptor-response elements exhibited reduced promoter activity. An expression vector, pHLPPr-1-neo, was constructed using a 5.1-kilobase pair EcoRI-HindIII fragment of the L-plastin gene that contained the potential upstream regulatory elements, the TATAAA box, and part of the first exon. This promoter could direct the constitutive expression of the reporter beta-galactosidase at high frequency in transfected colonies of transformed cells that express L-plastin constitutively; by contrast, this promoter was virtually inactive in transfected colonies of normal fibroblasts and it exhibited a low frequency of constitutive activation in transfected colonies of in vitro SV40-transformed fibroblasts which did not exhibit L-plastin expression. The utility of this recombinant promoter in determining the mechanism(s) that leads to activation of the L-plastin gene in tumor cells is discussed. The potential significance of regulation of the L-plastin gene by reproductive hormones in cancers arising in hormone-responsive tissues is also discussed.

Base Sequence↗
PubMed1993

An outbreak of echovirus type 4 infections and its implications for diagnosis and management in general practice.

Altogether, 133 patients with Echovirus type 4 infection were studied. Presenting illnesses and reasons for referral to hospital were analyzed. The reason for admission was commonly concern about meningitis, but also an unexplained rash or sore throat. More research is needed in general practice in order to clearly elucidate the spectrum of disease caused by Echoviruses.

Adolescent↗
PubMed1993

Targeting of antisense DNA: comparison of activity of anti-rabbit beta-globin oligodeoxyribonucleoside phosphorothioates with computer predictions of mRNA folding.

To assess the usefulness of computer-assisted modeling of mRNA as an aid in design of antisense DNA, the efficiency of inhibition of translation of rabbit beta-globin mRNA by various antisense sequences was compared with calculated structures of the mRNA. The model obtained by consideration of 30 lowest-energy computer-simulated structures is consistent with the high accessibility of the AUG initiation codon region known from digestion with nucleases and with previous antisense inhibition studies reported in the literature. Additional antisense inhibition data were obtained with 20-mer phosphorothioate oligonucleotides, targeted to regions of beta-globin mRNA differing moderately in their degree of participation in intramolecular folding. The efficiency of translation arrest by the oligonucleotides in cell-free expression systems (wheat germ extract and rabbit reticulocyte lysate) was obtained by measuring incorporation of [35S]methionine into total protein, and corrected for sequence-nonspecific inhibition using brome mosaic virus mRNA. In the presence of RNase H (wheat germ system), the inhibitory activity of the oligonucleotides showed correlation with the calculated secondary structure of mRNA, in particular at low oligonucleotide-to-mRNA ratios (correlation coefficient, 0.95). No correlation was observed in the reticulocyte lysate system, in which the inhibition is mediated by translational arrest.

Animals↗
PubMed1993

Effects of sequence of thioated oligonucleotides on cultured human mammary epithelial cells.

We have compared the effects of a number of different oligonucleotides on the growth and morphology of normal finite life span and immortally transformed human mammary epithelial cells. The oligonucleotide sequences chosen initially for study were based on that of the NB-1 gene, which encodes a calmodulin-like protein of unknown function. We found that certain thioated oligonucleotides 15-20 residues in length altered the morphology and decreased the growth rate of the normal cells in a concentration-dependent manner. These effects were rapid, occurring within 24-48 h of oligonucleotide addition. The effects, which occurred without an accompanying detectable decrease in the levels of NB-1 mRNA or protein, were most pronounced in the normal epithelial cells, less apparent in the immortalized epithelial cells, and unobserved in normal breast fibroblasts. Identical sequences having mixed phosphodiester and phosphorothioate backbones, or phosphodiester backbones alone, had little or no effect on normal epithelial cell morphology or growth. Two out of seven additional thioated oligonucleotides which were not complementary to NB-1 mRNA, also affected normal epithelial cell morphology and growth when used at similar concentrations (10 microM). Taken together, the observed effects on normal epithelial cells indicate that certain thioated oligonucleotides may have pharmacological consequences that do not depend on strict complementarity of their sequences to known mRNAs.

Base Sequence↗