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Biomedical subjects

A Das

Publications and source records attributed to A Das.

At least 19 recordsLinked to original sources
PubMed1999

Topography of contextual modulations mediated by short-range interactions in primary visual cortex.

Neurons in primary visual cortex (V1) respond differently to a simple visual element presented in isolation from when it is embedded within a complex image. This difference, a specific modulation by surrounding elements in the image, is mediated by short- and long-range connections within V1 and by feedback from other areas. Here we study the role of short-range connections in this process, and relate it to the layout of local inhomogeneities in the cortical maps of orientation and space. By measuring correlation between neuron pairs located in optically imaged maps of V1 orientation columns we show that the strength of local connections between cells is a graded function of lateral separation across cortex, largely radially symmetrical and relatively independent of orientation preferences. We then show the contextual influence of flanking visual elements on neuronal responses varies systematically with a neuron's position within the cortical orientation map. The strength of this contextual influence on a neuron can be predicted from a model of local connections based on simple overlap with particular features of the orientation map. This indicates that local intracortical circuitry could endow neurons with a graded specialization for processing angular visual features such as corners and T junctions, and this specialization could have its own functional cortical map, linked with the orientation map.

Animals↗
PubMed1999

Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor.

OBJECTIVES: To determine the role of extracellular proteinases in ischemia-induced retinal neovascularization in an animal model and to examine the effect of proteinase inhibitors on retinal neovascularization. METHODS: Retinal neovascularization was induced in newborn mice exposed to 75% oxygen for 5 days, followed by room air. Retinal extracts underwent zymographic analysis to measure the activity of urokinase and matrix metalloproteinases (MMPs). Some animals under the same conditions also received intraperitoneal injections of an MMP inhibitor. Histological analysis was done to quantitate the neovascular response in these animals. RESULTS: Levels of urokinase and MMPs (MMP-2 and MMP-9) in retinas were significantly increased in animals with induced retinal neovascularization. Neovascularization was significantly inhibited with intraperitoneal administration of an MMP inhibitor. CONCLUSION: Systemic inhibition of MMPs may have therapeutic potential in preventing retinopathy associated with retinal neovascularization. CLINICAL RELEVANCE: Because up-regulation and activation of proteinases represents a final common pathway in the process of retinal neovascularization, pharmacological intervention of this pathway may be an alternative therapeutic approach to proliferative retinopathy.

Animals↗
PubMed1999

An economic analysis of different strategies of immunization against hepatitis A virus in developed countries.

Acute hepatitis A is a major public health problem in developed countries, and because a large proportion of patients with acute hepatitis A do not have any identifiable risk factors, current practice of targeting the high-risk groups for vaccination against hepatitis A virus (HAV) is unlikely to have a significant impact on the overall incidence of acute hepatitis A. No economic analysis of strategies of mass immunization against HAV is available. Three different strategies of immunization against HAV using commercially available inactivated vaccine were compared in a Markov model analysis of a cohort of 2-year-old healthy children in a developed country. In strategy I, universal vaccination was pursued. In strategy II, children were initially screened for antibody and, if susceptible, they were vaccinated. In strategy III, no vaccination was offered. Cost per person and quality adjusted life-years (QALY) gained in each strategy were the outcome measures compared. The baseline analysis showed that strategy II is more cost-effective than strategy I, with marginal cost-effectiveness ratios of $7,267. 67 and $12,833.34, respectively, compared with a strategy of no intervention. Sensitivity analysis showed that if the cost of the two-dose vaccine could be reduced to less than $57, the strategy of universal vaccination would be the preferred immunization strategy. Different strategies of mass immunization against HAV in the developed countries are cost-effective by current standards of health care interventions and should be considered for incorporation into current childhood immunization programs.

Adolescent↗
PubMed1999

The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.

OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.

Case-Control Studies↗
PubMed1999

Reactivity of guanine at m5CpG steps in DNA: evidence for electronic effects transmitted through the base pairs.

BACKGROUND: Mitomycin C (MC), a DNA cross-linking and alkylating agent, targets guanines in the m5CpG sequence with 2-3-fold preference over guanines in unmethylated CpG. Benzo[a]pyrenediolepoxide (BPDE) and several other aromatic carcinogens form guanine adducts with an identical selectivity for m5CpG, and in certain cancers G to T transversion mutation 'hotspots' in the p53 tumor suppressor gene are more frequent at this sequence than at guanines in other sequences. MC appears suitable to probe the general mechanism of this selectivity. RESULTS: A 162-bp DNA fragment containing C, m5C or f5C (5-fluoro cytosine) at all cytosine positions was cross-linked by MC at guanines in CpG steps. The extent of cross-linking increased in the order f5C < C < m5C. Monoalkylation or cross-linking of duplex 12-mer oligonucleotides containing a single CpG, f5CpG or m5CpG step gave yields of adducts that increased in the same order. The rates showed a correlation with the Hammett sigma constant of the methyl and fluoro substituents of the cytosine. Only the base-pair cytosine substituent influenced reactivity of guanine. CONCLUSIONS: The 2-amino group of guanine in the m5CpG sequence of DNA has a greater nucleophilic reactivity with mitomycin than CpG. Evidence is presented for a novel mechanism: transmission of the electron-donating effect of the 5-methyl substituent of the cytosine to guanine through H-bonding of the m5C.G base pair. The results explain the enhanced reaction of BPDE at m5CpG in DNA and the origin of G-T mutational hotspots in the p53 gene in cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Cleogynol, a novel dammarane triterpenoid from Cleome gynandra.

Chemical examination of Cleome gynandra (whole plant excluding seeds) led to the isolation and identification of a novel (20S, 24S)-epoxy-19,25-dihydroxydammarane-3-one hemiketal (1). The structure of the new compound, designated cleogynol, was determined using spectral and chemical methods.

Acetylation↗
PubMed1999

Glutaric aciduria type I: pathomechanisms of neurodegeneration.

In organotypic corticostriatal and hippocampal slice cultures from rat brain, 3-hydroxyglutaric acid but not glutaric and glutaconic acids induced neurodegeneration by activation of NMDA receptors. Electrophysiological investigations (Xenopus laevis oocytes expressing glutamate receptors; rat mixed cortex culture) revealed no direct interaction of 3-hydroxyglutaric acid with glutamate receptors. We speculate that 3-hydroxyglutaric acid induces a mild energy deprivation that interferes with the voltage-dependent Mg(2+)-block of NMDA receptors.

Animals↗
PubMed1999

A review of the therapy of paraneoplastic neurologic syndromes.

The therapy of paraneoplastic neurologic syndromes remains unclear and warrants a systematic review of the literature. Reports in English and foreign language literature were abstracted. Data were sorted by the primary paraneoplastic neurologic syndrome, the primary malignancy, and the methods of treatment. Neurologic improvement follows surgical, chemotherapeutic, and radiation treatments. Adjuvant immunosuppressive therapy with steroids, plasmapheresis, or immunoglobulin may help stabilize the progression of neurologic symptoms. Syndromes characterized by inflammation or neurotransmitter production without neuronal loss are most responsive to therapy. While treatment of the underlying cancer with appropriate surgery, chemotherapy, and radiation is recommended, the paraneoplastic syndrome should probably be managed with immunosuppressive therapy.

Humans↗
PubMed1999

A novel mutation in the KH domain of polynucleotide phosphorylase affects autoregulation and mRNA decay in Escherichia coli.

Polynucleotide phosphorylase (PNPase) is a key 3'-5' exonuclease for mRNA decay in bacteria. Here, we report the isolation of a novel mutant of Escherichia coli PNPase that affects autogenous control and mRNA decay. We show that the inactivation of PNPase by a transposon insertion increases the half-life of galactokinase mRNA encoded by a plasmid. When the bacteriophage lambda int gene retroregulator (sib/tI ) is placed between pgal and galK, it severely diminishes galactokinase expression because of transcription termination. The expression of galK from this construct is increased by a single base mutation, sib1, which causes a partial readthrough of transcription at tI. We have used this plasmid system with sib1 to select E. coli mutants that depress galK expression. Genetic and molecular analysis of one such mutant revealed that it contains a mutation in the pnp gene, which encodes the PNPase catalytic subunit alpha. The mutation responsible (pnp-71 ) has substituted a highly conserved glycine residue in the KH domain of PNPase with aspartate. We show that this G-570D substitution causes a higher accumulation of the alpha-subunit as a result of defective autoregulation, thereby increasing the PNPase activity in the cell. The purified mutant alpha-subunit shows the same electrophoretic mobility in denaturing gels as the wild-type subunit, as expected. However, the mutant protein present in crude extracts displays an altered electrophoretic mobility in non-denaturing gels that is indicative of a novel enzyme complex. We present a model for how the pnp-71 mutation might affect autoregulation and mRNA decay based on the postulated role of the KH domain in RNA-protein and protein-protein interactions.

Amino Acid Sequence↗
PubMed1999

Macular amyloidosis: etiological factors.

Macular amyloidosis is the commonest form of primary localized cutaneous amyloidosis; its etiology remains unclear. Various incriminating factors include genetics, sunlight, and friction. Seventy-five patients with a clinical diagnosis of macular amyloidosis (confirmed by at least two observers) were enrolled in the study. A detailed history was elicited in relation to the etiological factors and followed by cutaneous examination. Skin biopsy was performed in 44 patients. Amyloid deposits were demonstrated in 21 (48%) of the biopsies. The female to male ratio was over 3:1. Patients with skin type V had a more delayed onset than those with skin types III and IV. Two patients gave histories of regularly subjecting their skin to friction. There was no correlation between the sites affected and the sites subjected to friction, hair style of the patient, or the use of cosmetics. Family history was present in 7 (9.3%) patients. A majority, 44 (58.7%) of the patients, had involvement of both sun-exposed and sun-protected sites. To conclude, there was no direct correlation between macular amyloidosis and atopy, sunlight, or friction to the skin in our patients. Multiple factors may play a collective role in the genesis of macular amyloidosis to variable degrees. These include racial, familial, and environmental factors, atopy, sunlight, friction, and female gender.

Adolescent↗
PubMed1999

Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes.

PURPOSE: Retinal neovascularization is one of the leading causes of blindness. A crucial event in this process is the remodeling and penetration of the capillary basement membrane by migrating endothelial cells. This process requires proteolysis of basement membrane components by a variety of proteinases. The objective of the present study was to determine the expression of proteinases in human retinal tissues showing active neovascularization. METHODS: Epiretinal neovascular membranes surgically removed from patients with proliferative diabetic retinopathy were analyzed by zymography, and the types and amounts of proteinases present in the tissues were determined. Retinas from nondiabetic donor eyes served as control specimens. RESULTS: Both the high- (54 kDa) and low- (33 kDa) molecular-weight forms of urokinase were present at significantly higher levels in neovascular membranes than in normal retinas. The pro forms of the matrix metalloproteinases (MMP) MMP-2 and MMP-9 were significantly elevated in the neovascular membranes in comparison with levels in normal retinas. In addition, the active forms of these enzymes were present in the membranes, whereas there was no detectable level of the active forms in normal retinas. CONCLUSIONS: Human diabetic neovascular membranes contain high levels of urokinase and MMP. The increased activity of proteinases in the final common pathway of retinal neovascularization indicates that inhibition of these enzymes may be a useful therapeutic target as an alternative approach in the management of proliferative retinopathies.

Aged↗
PubMed1999

Prevention of visual loss in older adults.

The major causes of visual loss in older adults are cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. Intensive research is ongoing for the prevention of these diseases. The present article updates different research studies and clinical trials aimed at prevention of visual loss in older adults.

Aged↗
PubMed1998

The D arm of tRNATyr is necessary and sufficient for import into Leishmania mitochondria in vitro.

Transfer RNAs are selectively imported from the cytoplasm into mitochondria of kinetoplastid protozoa such as Leishmania . The specific structural features of tRNA which determine selectivity are largely unknown. Using an in organello system from Leishmania , the import signals on tRNATyrand on a synthetic transcript which binds to the same receptor, were studied by deletion and reconstruction analyses. In both cases, short oligoribonucleotides (minihelices) containing the sequence UGGYAGAG were imported with high efficiency in the presence of ATP. This motif is present in the D arm of tRNATyr, as well as in the majority of imported Leishmania tRNAs. Deletion of the D arm, or a point mutation in the conserved motif, reduces importability. The import signal coincides with the binding site for the mitochondrial receptor TAB. tRNAGln, which is not imported, forms non-productive, TAB-independent complexes with the mitochondrial surface. However, the observation that the imported:bound ratio of the D arm minihelix is higher than that of the entire molecule suggests that the post-binding translocation step is constrained in terms of size or structural flexibility. Kinetic studies of minihelix import indicate stepwise insertion of the molecule into import channels.

Animals↗
PubMed1998

Plasma ferritin, premature rupture of membranes, and pregnancy outcome.

OBJECTIVE: The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation. METHODS: Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable. RESULTS: The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days. Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median. CONCLUSIONS: Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis. These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.

Adult↗
PubMed1998

The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

OBJECTIVE: Preterm births occur for many different reasons. Most efforts to identify risk factors for preterm births either ignore cause and consider preterm births as a single entity or examine risk factors for spontaneous preterm births. We performed this study to examine risk factors for indicated preterm births, which constitute more than one quarter of all preterm births. STUDY DESIGN: The study included 2929 women evaluated at 24 weeks' gestation at 10 centers. Information was gathered about demographic factors, socioeconomic status, home and work environments, drug and alcohol use, and medical history. In addition vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and cervical length was measured by transvaginal ultrasonography. Associations with indicated preterm birth were evaluated by univariate tests and by multivariable analysis with logistic regression. RESULTS: Of the women studied at 24 weeks' gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these deliveries, 27.7% were indicated preterm births. Risk factors in the final multivariable model were, in order of decreasing odds ratios, mullerian duct abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio 5.85), history of chronic hypertension (odds ratio 4.06), history of previous indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio 2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors found in this analysis tend to be different from those associated with spontaneous preterm birth.

Adolescent↗
PubMed1998

Study of ethmoid sinus involvement in multibacillary leprosy.

The nasal mucosal involvement in lepromatous leprosy is well recognized. Currently interest has centred around the involvement of paranasal sinuses in leprosy. They act as a reservoir and constant source of reinfection to the nasal mucosa. In the present prospective study 25 untreated patients with multi-bacillary leprosy were included. Clinical examination, computed tomography (CT) scan of paranasal sinuses, ethmoid sinus endoscopy and biopsy were carried out in all patients, to investigate the involvement of the paranasal sinuses in leprosy. Ethmoid sinus involvement was noted in 20 patients on CT scan. Bilateral involvement was more common (65 per cent). Anterior ethmoids were more commonly affected (65 per cent). On ethmoid sinus endoscopy abnormal mucosa was noted in 17 patients (68 per cent). Ethmoid sinus biopsy was confirmative in 16 patients (64 per cent). Statistically significant correlation was found between CT findings, sinus endoscopy and sinus biopsy findings.

Adolescent↗