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Biomedical subjects

G Gupta

Publications and source records attributed to G Gupta.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cerebral metastases of cutaneous melanoma.

Cerebral metastases of cutaneous melanoma carry a very poor prognosis. We report our experience of 31 patients who presented with cerebral metastasis of cutaneous melanoma in a 5-year period between mid-1991 and mid-1996. Cerebral metastases were diagnosed on computerized tomography (CT) scan after patients became symptomatic. The overall median survival in our series was 4 months. Seventeen patients (55%) received treatment with radiotherapy and dexamethasone with resolution of their symptoms, although median survival remained at 4 months. Six patients (19%) had surgery followed by whole brain radiotherapy, with median survival of 5 months. The remaining eight patients received dexamethasone alone. Data from patients surviving less than 2 months and over 6 months suggest that the poor prognostic factors are the presence of more than one cerebral metastasis and additional extracranial metastases.

Administration, Oral↗
PubMed1997

Toxicity identification of poultry litter aqueous leachate.

Poultry litter is a mixture of excreta, feed, feathers, and bedding material. Poultry litter is useful as a fertilizer due to the presence of nitrogen, phosphorus, and potassium. Litter is commonly used for growing corn, soybeans, potatoes, tomatoes, leafy vegetables, and cover crops. The aqueous leachate of poultry litter has been shown to exhibit toxicity to a variety of indicator organisms. The objective of this research was to identify classes of toxicants in the litter aqueous leachate. The aqueous extract of poultry litter was subjected to toxicity identification tests approved by the United States Environmental Protection Agency that use Ceriodaphnia dubia as the test organism. Tests performed included pH adjustment, filtration, aeration, C18 solid-phase extraction, EDTA addition, sodium thiosulfate addition, and extraction through zeolite. Zeolite extraction, filtration at low pH, and aeration at low pH reduced overall toxicity by 68, 20, and 22%, respectively. The major sources of toxicity appear to be ammonia and anionic organic compounds. Toxicity was apparently not due to the presence of heavy metals or oxidants.

Ammonia↗
PubMed1997

The labial melanotic macule: a review of 79 cases.

Seventy-nine patients presented to the pigmented lesion clinic between 1983 and 1996 with labial melanotic macules. We have followed up these patients for up to 13 years and 3 months (mean 6 years, 3 months). We present evidence that this is a benign entity. The appropriate management is reassurance and discharge, with the advice to return only if the lesion grows or darkens. This did not occur in any of our patients during the time of their follow-up.

Adolescent↗
PubMed1997

Seasonal variations in Sertoli and germ cell marker enzymes in testis of rhesus and bonnet monkeys.

Variations in specific activities of the marker enzymes of Sertoli and germ cells during breeding (November-December) and non-breeding (May-June) seasons were investigated in rhesus and bonnet monkeys maintained under laboratory conditions. The marker enzymes selected for testicular cells were-Sertoli cells: beta-glucuronidase, gamma-glutamyl transpeptidase; pre-meiotic germ cells: glucose 6-phosphate dehydrogenase, malate dehydrogenase, alpha-glycerophosphate dehydrogenase; mature germ cells: LDH-X, sorbitol dehydrogenase. Results have indicated significant seasonal variation in marker enzymes only in rhesus testis. Marker enzymes of Sertoli cell increased while those of germ cell decreased significantly during non-breeding season. Marker enzymes of mature germ cells were affected much more drastically than those of the pre-meiotic germ cells.

Animals↗
PubMed1996

Structure-function correlations of the insulin-linked polymorphic region.

The insulin minisatellite of the insulin-linked polymorphic region (ILPR), a 14 base-pairs long tandem repeat of: 5'-ACAGGGGTGTGGGG-3' 3'-TGTCCCCACACCCC-5', is located 363 base-pairs upstream of the human insulin gene. A locus for insulin-dependent diabetes mellitus (IDDM) has been mapped to the ILPR. It has been shown that the ILPR is polymorphic in length and this length polymorphism is also related to the transcriptional activity of the insulin gene and the susceptibility to IDDM. Here, we attempt to decipher the role of the ILPR structure in length polymorphism and transcriptional regulation. We show by gel electrophoresis, circular dichroism (CD) and one and two-dimensional nuclear magnetic resonance spectroscopy (1D/2D NMR) that the G-rich strand of the ILPR adopts an intramolecularly folded hairpin G-quartet structure. A detailed analysis of 1D/2D NMR data of d(G4TGTG4) and d(G4TGTG4ACAG4TGTG4) enables us to define the nature of chainfolding, the stacking interaction of the G-tetrads in the stem, and the interactions of the bases in the loops. d(G4TGTG4ACAG4TGTG4) happens to be the smallest unit of the G-rich strand that can form the intramolecular hairpin G-quartet structure. For long ILPR sequences, several such hairpin G-quartet structures can be linked in space. Indeed, by an in vitro replication assay, we show the presence of such multiple hairpin G-quartet structures for the G-rich strand of the ILPR of repeat length 6. This observation suggests that the formation of multiple hairpin G-quartets may explain slippage during replication and the observed length polymorphism. From our high resolution structure, we are able to identify a set of interactions that are critical for the structure and stability of the hairpin G-quartet. Single or double mutations in the ILPR that destabilize these interactions also lower the transcriptional activity of the insulin gene. Therefore, the hairpin G-quartet structure of the ILPR has a direct correlation with the transcriptional activity of the human insulin gene.

DNA↗
PubMed1996

Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo.

Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein-Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine alpha-chemokine interferon-inducible protein-10 (IP-10) was higher in the regressing than in the progressive Burkitt tumors. We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed. Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals. Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice.

Animals↗
PubMed1996

Structure and polymorphism of HIV-1 third variable loops.

The third variable (V3) loop of HIV-1 surface glycoprotein, gp120, has been the target of neutralizing antibodies. However, sequence variation inside the V3 loop diminishes its effectiveness as a potential vaccine against HIV-1. The elusive nature of the V3 loop structure prompted us to carry out a systematic study on different isolates in an attempt to identify a common structural motif in the V3 loop regardless of the amino acid sequence variability. We have previously determined the structural features of two V3 loops: V3 Thailand and V3 MN. In this paper, we present the structure of two other variants: V3 Haiti and V3 RF. Our results show that similar secondary structures are observed in all the four V3 loops: a GPG(R/K/Q) crest in the center of the neutralizing domain, two extended regions flanking the central crest, and a helical region in the C-terminal domain. For the Haitian V3 loop, we also show how the conserved structural features are masked through a conformational switch encoded in the amino acid sequences on the C-terminal side of the GPGK crest.

Amino Acid Sequence↗
PubMed1996

Structure and dynamics of the DNA hairpins formed by tandemly repeated CTG triplets associated with myotonic dystrophy.

Anomalous expansion of the DNA triplet (CTG)n causes myotonic dystrophy. Structural studies have been carried out on (CTG)n repeats in an attempt to better understand the molecular mechanism of repeat expansion. NMR and gel electrophoretic studies demonstrate the presence of hairpin structures for (CTG)5 and (CTG)6 in solution. The monomeric hairpin structure remains invariant over a wide range of salt concentrations (10-200 mM NaCl), DNA concentrations (micromolar to millimolar in DNA strand) and pH (6.0-7.5). The (CTG)n hairpin contains three bases in the loop when n is odd and four bases when n is even. For both odd and even n the stacking and pairing in the stem remain the same, i.e, two hydrogen bond T.T pairs stack with the neighboring G.C pairs. All the nucleotides in (CTG)5 and (CTG)6 adopt C2'-endo, anti conformations. Full-relaxation matrix analysis has been performed to derive the NOE distance constraints from NOESY experiments at seven different mixing times (25, 50, 75, 100, 125, 200 and 500 ms). NOESY-derived distance constraints were subsequently used in restrained molecular dynamics simulations to obtain a family of structures consistent with the NMR data. The theoretical order parameters are computed for H5-H6(cytosines) and H2'-H2" dipolar correlations for both (CTG)5 and (CTG)6 by employing the Lipari-Szabo formalism. Experimental data show that the cytosine in the loop of the (CTG)5 hairpin is slightly more flexible than those in the stem. The cytosine in the loop of the (CTG)6 hairpin is extremely flexible, implying that the dynamics of the four base loop is intrinsically different from that of the three base loop.

Base Sequence↗
PubMed1996

Solution structures of the individual single strands of the fragile X DNA triplets (GCC)n.(GGC)n.

Three-dimensional structures of the fragile X triplet repeats (GCC)n and (GGC)n are derived by using one- dimensional/two-dimensional NMR. Under a wide range of solution conditions (10-150 mM NaCl,pH6-7)(GCC)5-7 strands form exclusively slipped hairpins with a 3' overhanging C. The slipped hairpins of (GCC)n strands show the following structural characteristics: (i) maximization of Watson-Crick G.C pairs; (ii) formation of C.C mispairs at the CpG steps in the stem; (iii) C2'-endo, anti conformations for all the nucleotides. The ability of (GCC)n strands to form hairpin structures more readily than complementary (GGC)n strands suggests preferential slippage during replication and subsequent expansion of the (GCC)n strands. In addition, the C.C. mispairs at the CpG site of (GCC)n hairpins account for their exceptional substrate efficiencies for human methyltransferase. Gel electrophoresis data show that (GGC)n strands form both hairpin and mismatched duplex structures in 10-150 mM NaCl (ph 6-7) for n < 10, but for n > or + 11 hairpin structures are exclusively present. However, (GGC)n strands remain predominantly in the duplex state for n=4-11 under NMR solution conditions, which require DNA concentrations 100- to 1000-fold higher than in gel electrophoresis. NMR analyses of [(GGC)n]2 duplexes for n=4-6 show the presence of Watson-Crick G.C and mismatched G anti G syn pairs. The mismatches adjacent to the CpG step introduce local structural flexibility in these duplexes. Similar structural properties are also expected in the stem of the hairpins formed by (GGC)n strands.

DNA↗
PubMed1996

Impact of point and nonpoint source pollution on pore waters of two Chesapeake Bay tributaries.

Chesapeake Bay and its tributaries are contaminated by industrial and municipal point sources and agricultural nonpoint sources of pollution. The objective of this study was to compare the porewater characteristics of two Chesapeake Bay tributaries: Wicomico River (WR) contaminated by point source and Pocomoke River (PR) contaminated by both point and nonpoint sources of pollution. Four study sites (1 mile before, adjacent to, and 1 and 2 miles after the sewage treatment plant) were chosen to collect sediment samples in both the rivers. The sediment-pore waters were analyzed for toxicity using Microtox marine luminescent bacteria-Vibrio fischeri. USEPA toxicity identification evaluation tests on these pore waters confirmed that the contaminants (ammonia and heavy metals) in WR were from municipal point sources, whereas in PR the contamination (metals, pesticides, and PCBs) was from nonpoint sources (agriculture) of pollution. The toxicity (and the concentration of contaminants) decreased both upstream and downstream from the most polluted site in both the rivers.

Analysis of Variance↗
PubMed1996

HMG box proteins interact with multiple tandemly repeated (GCC)n (GGC)m DNA sequences.

A number of tandemly repeated DNA sequences have the ability to form hairpin structures by forming non-standard base pairs. When (GCC)15 and (GGC)15 strands are annealed together, the expected duplex is the only product. However, when (GCC)15 is annealed with (GCC)10, depending on the relative concentrations, up to five complexes can be detected in native gels. Three of these species are susceptible to limited digestion by Exo VII, suggesting they are duplexes containing single stranded tails. The remaining two bands are resistant to the enzyme, and have low mobility on native gels, consistent with branched structures. The latter complexes bind HMG box proteins, members of a highly abundant class of non-histone proteins of the nucleus. These proteins, modeled in this study by the second box fragment from rat HMG1, HMGb, interact strongly with branched or chemically modified DNA, relative to normal duplexes. The expansion of triplet repeats in genomic DNA is associated with tumor formation as well with a variety of heritable neurologiocal disorders. It is our thesis that the stability of branched intermediate structures that arise in replication of these sequences and promote expansion can be influenced directly by the presence of two highly abundant proteins in the cell nucleus: the HMG box proteins, HMG1/2, and the histone H1, which associates with HMG1/2.

Bacterial Proteins↗
PubMed1996

Colonization by Staphylococcus aureus resistant to methicillin and ciprofloxacin during 20 months' surveillance in a private skilled nursing facility.

OBJECTIVE: To evaluate endemic colonization with Staphylococcus aureus resistant to methicillin, ciprofloxacin, or both among patients of a private skilled nursing facility, with regard to colonization rate and site, and relation to infection and prior antibiotic use. DESIGN: Prospective quarterly culture surveillance of nares and rectal specimens over 20 months' observation. RESULTS: The mean prevalence was 3.8% in new admissions and 5.4% for in-house patients; cumulatively, 7.5% of the patients were colonized during the study period. The colonization rate remained stable during the study period. Screening of rectal, as well as nares, specimens detected substantially more colonized patients than would have been detected by nasal cultures alone. Five to seven percent of the colonized patients developed later infection with methicillin-ciprofloxacin-resistant S aureus. Colonized patients did not differ significantly from the noncolonized group in prior use of quinolones, but the colonized group was exposed significantly more frequently to other antibiotics than the noncolonized group. Eighty-three percent of methicillin-resistant S aureus (MRSA) isolated from infections and 89% from colonization were also ciprofloxacin resistant. CONCLUSION: Although all infecting and most colonizing isolates of MRSA were resistant to quinolones, the overall rate of colonization remained low and stable despite the continued use of quinolones. The findings suggest that good infection control practice has prevented broader spread of such strains in this facility.

Adolescent↗
PubMed1996

Bacterial colonization of indwelling vascular catheters in newborn infants.

OBJECTIVE: To determine the incidence of bacterial colonization of intravascular catheters, to compare the incidence of colonization of intra-arterial (IA), intravenous (IV) and central venous catheters (CVC), and to determine the association, if any, between catheter withdrawal and bacterial sepsis. METHODOLOGY: A prospective observational study was carried out at the neonatal intensive care unit of a university-affiliated regional referral centre. A total of 155 catheters (45 IA, 54 IV and 56 CVC) were obtained from 96 infants admitted to the unit and the distal 0.75 cm studied under the scanning electron microscope. The adjoining 0.75 cm was cultured for bacteria. RESULTS: Scanning electron microscopy revealed that 46% of catheters had bacteria on the internal surface and 13% had bacteria on the outer surface. Greater numbers of CVC were colonized with bacteria compared to IA and IV catheters (P < 0.01). Bacterial colonization of intravascular catheters was not significantly associated with the duration the catheter remained in situ or local reaction at the site of entry of the catheter. Colonization of the external surface of the catheter was significantly associated with bacterial septicaemia (P = 0.0466). Eighty-three per cent of 155 catheters studied had coagulum on the inner or outer surface. Only 53% of these were colonized with bacteria. Bacterial colonization occurred in the absence of a coagulum in only three instances. Catheter withdrawal was not associated with bacterial sepsis. Lack of coagulum on the internal surface of the catheter was strongly associated with septicaemia during the 7 days after catheter withdrawal. CONCLUSIONS: Although significant numbers of intravascular catheters were colonized with bacteria, only colonization with the external surface was associated with catheter-related sepsis.

Analysis of Variance↗
PubMed1995

Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications.

Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC)n.(GCC)n, are correlated with the ability of the individual G- and C-rich single strands to form hairpin structures. Two-dimensional NMR and gel electrophoresis studies show that both the G- and C-rich single strands form hairpins under physiological conditions. This propensity of hairpin formation is more pronounced for the C-rich strand than for the G-rich strand. This observation suggests that the C-rich strand is more likely to form hairpin or "slippage" structure and show asymmetric strand expansion during replication. NMR data also show that the hairpins formed by the C-rich strands fold in such a way that the cytosine at the CpG step of the stem is C.C paired. The presence of a C.C mismatch at the CpG site generates local flexibility, thereby providing analogs of the transition to the methyltransferase. In other words, the hairpins of the C-rich strand act as better substrates for the human methyltransferase than the Watson-Crick duplex or the G-rich strand. Therefore, hairpin formation could account for the specific methylation of the CpG island in the fragile X repeat that occurs during inactivation of the FMR1 gene during the onset of the disease.

Base Sequence↗