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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 145 records · Page 8Linked to original sources

Integration of local orientation in strabismic amblyopia.

In order to investigate the processes which integrate local orientation information in observers with strabismic amblyopia, we measured contrast thresholds for discriminating the global orientation of a pattern (3 "bars") comprised of Gabor patches. We found that in both eyes of amblyopic observers, as has been reported for normal observers [Saarinen, Levi & Shen (1997) Proceedings of the National Academy of Sciences USA, 94, 8267-8271], there is an approximately two-fold enhancement of contrast sensitivity when the global and local orientations are aligned (relative to mixed orientations), and a smaller enhancement when the global and local orientations are orthogonal. This orientation dependent enhancement occurs despite substantial losses of contrast sensitivity. These results suggest that the integration processes in the amblyopic eye that operate to enhance detection are essentially intact.

Adult↗

A closer look at inpatient suicide.

BACKGROUND: We examined the risk factors for suicide among inpatients in an Ontario provincial psychiatric hospital. METHODS: Forty-four inpatients who had committed suicide during their hospital stay from 1969 to 1995 were compared with a group of inpatient controls matched for sex, age and date of admission. The diagnosis for each patient was reviewed by the authors. RESULTS: Suicide victims were more likely to have had a mood disorder, family history of psychiatric problems, mention of suicide risk in chart notes and a previous suicide attempt. Two findings necessitated further scrutiny: The most common diagnosis among inpatients who committed suicide in this study was a mood disorder and not schizophrenia as previously reported. A large proportion of patients (24) had experienced a rapidly fluctuating clinical course prior to the time of suicide. CONCLUSIONS: The implications of these findings, including the possible role of antidepressants in the induction of cycling prior to suicide, are discussed.

Adult↗

Serotonin function and risk for alcoholism in boys with attention-deficit hyperactivity disorder.

Data in animals and adults indicate that central serotonergic (5-HT) function may be involved in the development of alcohol abuse. Despite this, studies exploring this mechanism in individuals at risk for alcoholism are scant. This study used a fenfluramine (FEN) challenge procedure to investigate the relationship between risk for alcoholism and 5-HT function in 7- to 11-year-old boys with attention-deficit hyperactivity disorder (ADHD). The prolactin (PRL) and cortisol (CORT) responses to FEN were examined in 10 sons of alcoholic fathers (FA+) and 30 sons of nonalcoholic fathers (FA-). The FA+ group had a significantly greater CORT, but not PRL, response to FEN relative to the FA- group. The discrepancy between the CORT and PRL responses may be due to the different mechanisms that underlie their 5-HT stimulated release. This suggests that, among ADHD boys, those at familial risk for alcohol abuse may differ from those who are not at risk in 5-HT function.

Alcoholism↗

Identification of antibodies directed against O-acetylated sialic acids in visceral leishmaniasis: its diagnostic and prognostic role.

A significantly increased O-acetylated sialic acid (O-AcSA) binding fraction was purified from serum of visceral leishmaniasis (VL) patients by affinity chromatography on immobilized bovine submaxillary mucin (BSM) and found to be immunoglobulin in origin. The serodiagnostic and prognostic potential of BSM as a capture antigen was established by ELISA with no cross reactivity with coendemic diseases like malaria, tuberculosis, leprosy, chagas disease and cutaneous leishmaniasis; however, a strong cross reactivity was present with trypanosomiasis patients. In 56 clinically diagnosed VL patients, the BSM-ELISA was compared with diagnosis by microscopy using Giemsa stained tissue smears and direct ELISA using crude parasite antigen (parasite-ELISA); 49/56(87.5%) and 5/56(9.0%) were positive and negative respectively by all 3 methods. The BSM-ELISA failed to diagnose 2/56(3.5%) patients which were biopsy and parasite-ELISA positive. The prognostic potential of the BSM-ELISA in 18 longitudinally monitored VL patients before and after conventional antimonial treatment showed a significant decrease in anti O-AcSA titres in drug responsive patients whereas anti O-AcSA levels persisted in drug unresponsive patients. The IgG subclass distribution of antibodies directed against O-AcSA showed increased IgG2 levels in VL patients as compared to healthy controls. The BSM-based ELISA holds great promise as a serodiagnostic and prognostic assay for VL.

Acetylation↗

Molecular basis of recognition by Gal/GalNAc specific legume lectins: influence of Glu 129 on the specificity of peanut agglutinin (PNA) towards C2-substituents of galactose.

The ability to discriminate between galactose and N- acetylgalactosamine, observed in some lectins, is crucial for their biological activity as well as their usefulness as tools in biology and medicine. However, the molecular basis of differential binding of lectins to these two sugars is poorly understood. Peanut agglutinin (PNA) is one of the few galactose-specific legume lectins which does not bind N- acetylgalactosamine at all and is, therefore, ideal for the study of the basis of specificity towards C-2 substituted derivatives of galactopyranosides. Examination of the three-dimensional structure of PNA in complex with lactose revealed the presence of both a longer loop and bulkier residues in the region surrounding the C-2 hydroxyl of the galactopyranoside ring, which can sterically prevent the accommodation of a bulky substituent in this position. One such residue, is a glutamic acid at position 129 which protrudes into the binding site and perhaps directly obstructs any substitution at the C-2 position. Two mutants in bacterially expressed PNA were therefore constructed. These were E129D and E129A, in which Glu129 was replaced by Asp and Ala, respectively. The specificity of the mutants for galactose, galactosamine, and N- acetylgalactosamine was examined through observing the inhibition of hemagglutination and binding of the lectin to immobilized asialofetuin. The results showed that the affinity of E129A and E129D for C-2-substituted derivatives of the galactose varies. The mutant E129D showed significant binding towards N- acetylgalactosamine, suggesting that the residue Glu 129 is crucial in imparting exclusive galactose-specificity upon PNA. This study not only attempts to provide an explanation for the inability of PNA to accommodate C-2-substituted derivatives at its primary subsite, but also seeks to present a basis for engineering lectins with altered specificities.

Acetylgalactosamine↗

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor.

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G-CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in-vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.

Adult↗

The relationship between follicular fluid aspirate volume and oocyte maturity in in-vitro fertilization cycles.

As a consequence of multiple follicular growth during ovarian stimulation for in-vitro fertilization (IVF), follicles of varying sizes often yield oocytes that vary in maturity and morphology of the oocyte-cumulus-corona complex. The objective of this prospective study was to explore the relationship between follicular fluid aspirate volume and the oocyte's developmental potential in an IVF treatment cycle. In total 9933 follicles were studied from 400 patients who underwent 535 consecutive IVF treatment cycles at St James's University Hospital, Leeds, UK, between February 1995 and February 1996. The volume of each individual follicle aspirated was recorded and related to the probability of obtaining an oocyte, its fertilizing capacity, the cleavage rate and the quality of embryos derived. We found no statistically significant difference in oocyte recovery rates between follicles with an aspirate volume < or = 1 ml and follicles with a volume > 1 ml. Although oocytes obtained from follicles with an aspirate volume > or = 1 ml showed a significantly lower fertilization rate, they went on to cleave at the same rate as oocytes obtained from larger follicles and resulted in embryos of comparable quality. Furthermore, there was no statistically significant difference in the implantation, clinical pregnancy or live birth rates per cycle between embryos derived from follicles with an aspirate volume < or = 1 ml and those derived from follicles with an aspirate volume > 1 ml. We conclude that follicular size and the oocyte's developmental potential in the stimulated ovary are not closely related and can be independent. This is in contrast to the Graafian follicle and the pre-ovulatory oocyte in the natural cycle.

Adult↗

Rapid diagnosis of Indian visceral leishmaniasis using achatininH, a 9-O-acetylated sialic acid binding lectin.

We have developed a rapid, accurate, and inexpensive hemagglutination assay (HA) for diagnosis of Indian visceral leishmaniasis (VL) using achatininH, a 9-O-acetylated sialic acid binding lectin. The assay is based on the selective binding of achatininH to 9-O-acetylated derivatives of sialic acid (9-O-AcSA), which appears exclusively on the erythrocytes of patients with VL. Blood samples from 35 patients with demonstrable splenic or bone marrow amastigotes were assayed by HA and compared with an ELISA. All cases were correctly diagnosed by HA, and were in concordance with the ELISA. The increase in 9-O-AcSA was corroborated by direct fluorimetric estimation of sialic acid and its 9-O-acetylated derivative. Therefore, 9-O-acetylated derivatives of sialic acid, absent in normal erythrocytes, serve as an important biomarker, and indirectly reflect the presence of the parasite. Accordingly, this assay can be used for detection of active kala-azar cases and merits clinical consideration.

Biomarkers↗

Emergency drugs in dental practice.

An increase in the life expectancy of medically compromised patients has resulted in greater numbers of these individuals within our ageing population. As dental surgeons are increasingly expected to provide care for such patients, the likelihood of a medical emergency occurring within the dental surgery may increase. This article reviews the more common emergency drugs that a dentist may have to administer in the event of a medical emergency. The indications, mode of action, method of administration and dose of each agent are discussed.

Dental Care for Chronically Ill↗

The summer penile syndrome: seasonal acute hypersensitivity reaction caused by chigger bites on the penis.

OBJECTIVE: To describe the seasonal acute hypersensitivity reaction of the penis due to chigger bites, known as the summer penile syndrome. DESIGN: A consecutive series of patients. SETTING: The emergency department of an urban academic children's hospital in the midwestern United States. PARTICIPANTS: Male pediatric patients with an acute hypersensitivity reaction of the penis. RESULTS: Ninety-four patients were treated for summer penile syndrome during the four-month period from June through September. Patients ranged in age from seven months to 11 years (mean = 5.1, SD = 2.5). Twenty-one percent of patients had also experienced a similar prior episode of penile swelling. Symptoms included pruritus in 84% of cases, dysuria in 33%, and decreased strength of urine stream in 8% of patients. Eighty-four percent of patients had recent exposure to the woods, park, lawn, or poison ivy. In addition to edema, findings on physical examination included a papule or bite puncture mark in 50% of patients, erythema in 32%, and excoriation in 6% of patients. Fifty-six percent of patients had bites on other areas of the body. The emergency physician attributed the penile edema to an insect or chigger bite in 98% of cases. Treatment consisted of an oral antihistamine and cold compresses in most cases. The reported duration of penile swelling ranged from one to 18 days with a mean of 4.1 days (SD = 3.5), and the reported duration of pruritus ranged from 0 to 14 days with a mean of 3.0 days (SD = 2.6). CONCLUSION: This study provides an understanding of the summer penile syndrome for pediatric care providers. To our knowledge, this study is the first to describe this seasonal syndrome in the medical literature.

Acute Disease↗

Effect of substituents on the thermodynamics of D-galactopyranoside binding to winged bean (Psophocarpus tetragonolobus) basic lectin.

Isothermal titration calorimetric measurements of the binding of deoxy, fluorodeoxy, and methoxy derivatives of D-galactopyranoside (alpha-D-Gal) to the basic lectin from winged bean Psophocarpus tetragonolobus, WBA I, have been carried out. Each of the ligands binding to WBA I displayed the same stoichiometry of one per subunit (29 kDa) of WBA I. The binding enthalpies for various derivatives are essentially independent of temperature and show complementary changes with respect to binding entropies. Replacement of the hydroxyl group by fluorine or hydrogen on C3 and C4 of the galactopyranoside eliminates binding to the lectin, consistent with C3-OH and C4-OH acting as hydrogen bond donors. The affinity for C2 derivatives of galactose decreases in the order GalNAc > 2MeOGal > 2FGal congruent with Gal > 2HGal, which suggests that both polar and nonpolar residues surround the C2 locus of galactose, consistent with the observed high affinity of WBA I toward GalNAc where the acetamido group at C2 position is probably stabilized by both nonpolar interactions with the methyl group and polar interactions with the carbonyl group. The binding of C6 derivatives follows the order Gal > 6FGal > D-Fuc >> 6MeOGal congruent with L-Ara, indicating the presence of favourable polar interactions with a hydrogen bond donor in the vicinity. On the basis of these results the hydrogen bond donor-acceptor relationship of the complexation of methyl-alpha-D-galactopyranoside with the primary combining site of WBA I is proposed.

Acetylgalactosamine↗

Feature integration in pattern perception.

The human visual system is able to effortlessly integrate local features to form our rich perception of patterns, despite the fact that visual information is discretely sampled by the retina and cortex. By using a novel perturbation technique, we show that the mechanisms by which features are integrated into coherent percepts are scale-invariant and nonlinear (phase and contrast polarity independent). They appear to operate by assigning position labels or "place tags" to each feature. Specifically, in the first series of experiments, we show that the positional tolerance of these place tags in foveal, and peripheral vision is about half the separation of the features, suggesting that the neural mechanisms that bind features into forms are quite robust to topographical jitter. In the second series of experiment, we asked how many stimulus samples are required for pattern identification by human and ideal observers. In human foveal vision, only about half the features are needed for reliable pattern interpolation. In this regard, human vision is quite efficient (ratio of ideal to real approximately 0.75). Peripheral vision, on the other hand is rather inefficient, requiring more features, suggesting that the stimulus may be relatively underrepresented at the stage of feature integration.

Contrast Sensitivity↗

Modulation of macrophage inflammatory protein-1alpha and its receptors in human B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma.

Macrophage inflammatory protein-1 alpha (MIP-1alpha) is a member of the -C-C- family of low-molecular weight chemokines. MIP-1alpha is involved in the homeostatic control of stem cell proliferation, in inducing chemotaxis, and also in inflammatory responses in mature cell types. In order to observe modulations of MIP-1alpha secretion and expression along with MIP-1alpha receptor (MIP-1alpha-R) expression for a possible autocrine role in AIDS associated B-cell lines, we studied a wide panel of human B-cell lines. Previous work by us has shown that HIV-1 tat down modulates MIP-1alpha by inducing a novel transcription factor MNP. Our data in this report suggest that HIV down modulates MIP-1alpha as a mechanism to evade suppression by this chemokine in human B-cells. Furthermore, our results strongly suggest MIP-1alpha autocrine loops in a majority of tumor B-cells as evident by MIP-1alpha-R expression, and also secretion of MIP-1alpha.

Acquired Immunodeficiency Syndrome↗

In vivo hyperexpression of transforming growth factor-beta1 in mice: stimulation by cyclosporine.

BACKGROUND: We have demonstrated that cyclosporine (CsA) stimulates transforming growth factor (TGF) beta1 expression in vitro and that growth of mammalian cells can be arrested by CsA via a TGF-beta1-dependent mechanism. Herein, we have explored whether CsA stimulates TGF-beta1 hyperexpression in vivo. METHODS: Four groups of B6AF1 mice were studied: group 1, control; group 2, CsA pretreatment; group 3, anti-CD3 monoclonal antibody pretreatment; and group 4, CsA plus anti-CD3 pretreatment. RESULTS: CsA pretreatment augmented TGF-beta1 protein expression and increased intrarenal display of TGF-beta1 mRNA. This heightened TGF-beta1 expression was associated with an impaired T cell proliferative response. CONCLUSIONS: Our observations, together, advance the hypothesis that CsA might function in vivo as an immunosuppressant not only by inhibiting the expression of proinflammatory cytokines (e.g., interleukin 2), but also by stimulating the expression of TGF-beta1, a potent immunosuppressive cytokine. Moreover, prevention of TGF-beta1 hyperexpression might prevent CsA-associated renal fibrosis, as TGF-beta1 is a fibrogenic cytokine.

Animals↗

Analyses of carbohydrate recognition by legume lectins: size of the combining site loops and their primary specificity.

Recognition of cell-surface carbohydrates by lectins has wide implications in important biological processes. The ability of plant lectins to detect subtle variations in carbohydrate structures found on molecules, cells and organisms have made them a paradigm for protein-carbohydrate recognition. Legume lectins, one of the most well studied family of plant proteins, display a considerable repertoire of carbohydrate specificities owing perhaps to the sequence hypervariability in the loops constituting their combining site. However, lack of a rigorous framework to explain their carbohydrate binding specificities has precluded a rational approach to alter their ligand binding activity in a meaningful manner. This study reports an extensive analysis of sequences and structures of several legume lectins and shows that despite the hypervariability of their combining regions they exhibit within a significant pattern of uniformity. The results show that the size of the binding site loop D is invariant in the Man/Glc specific lectins and is possibly a primary determinant of the monosaccharide specificities of the legume lectins. Analyses of size and sequence variability of loops reveal the existence of a common theme that subserves to define their binding specificities. These results thus provide not only a framework for understanding the molecular basis of carbohydrate recognition by legume lectins but also a rationale for redesign of their ligand binding propensities.

Acetylgalactosamine↗