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V Sharma

Publications and source records attributed to V Sharma.

At least 55 records · Page 3Linked to original sources
PubMed2001

Lactoferrin-melanin interaction and its possible implications in melanin polymerization: crystal structure of the complex formed between mare lactoferrin and melanin monomers at 2.7-A resolution.

The concentration of melanin determines the intensity of colors of the skin and hair of animals. Melanin pigments are tyrosine-based polymers formed in melanocytes within specialized organelles called melanosomes. In order to understand the mechanism of melanin polymerization, lactoferrin, a basic protein with a pI value of 9.0, has been used to produce melanin. Lactoferrin is a monomeric iron-binding protein with a molecular weight of 80 kDa. The crystals of lactoferrin were soaked in a solution containing dihydroxyphenylalanine (DOPA) and tyrosinase enzyme. These crystals were used for X-ray intensity data collection. The intensity data were collected to 2.7-A resolution to an overall completeness of 91% with an R(sym) of 0.071. The crystals belong to orthorhombic space group P2(1)2(1)2(1) with cell dimensions: a = 85.0 A, b = 99.8 A, c = 103.4 A. The structure was determined by molecular replacement method, using the model of diferric mare lactoferrin, and refined to an R-factor 0.215 (R(free) = 0.287) for all the data to 2.7-A resolution. The final model comprises 5,281 protein atoms from 689 amino acids, 2Fe(3+), 2CO(2-)(3) ions, 2 indole-5,6-quinone molecules (IQ), and 73 water molecules. Two IQ molecules, one in each lobe, bind to lactoferrin. In the C-lobe, the IQ binds in the iron-binding cleft, whereas in the N-lobe, it is located in the side pocket between two alpha-helices, filled with solvent molecules in the native iron-saturated mare lactoferrin. The IQ molecules interact with protein molecule mainly through glutamic acid in both lobes, without significant perturbation to the protein structure. The orientation of N- and C-lobes in the present structure is similar to that observed in the native iron-saturated protein. However, as a result of the binding of IQ molecules, the orientations of the domains N1, N2 and C1, C2 in the two cases differ slightly.

Animals↗
PubMed2001

Autocrine role of macrophage inflammatory protein-1 beta in human T-cell lymphotropic virus type-I tax-transfected Jurkat T-cells.

The interaction of human T-cell lymphotropic virus I (HTLV-I) tax gene with host cell factors plays an important role in the maintenance of the transformed state. There have been numerous reports that have demonstrated the role of tax in transactivating several cytokines. In this study, we show that upon mitogen stimulation, macrophage inflammatory protein-1 beta (MIP-1beta) is expressed and secreted in tax-transfected Jurkat cells. Furthermore, expression of CC-chemokine receptor-5 (CCR5) mRNA in these cells suggests an autocrine role for MIP-1beta in HTLV-I-infected T-cells. These results, coupled with our earlier observations, demonstrate the influence that extracellular Tax protein might have on modulating host chemokines for proliferation and transformation of uninfected cells.

Autocrine Communication↗
PubMed2001

Mutational analysis at Asn-41 in peanut agglutinin. A residue critical for the binding of the tumor-associated Thomsen-Friedenreich antigen.

Peanut agglutinin is a clinically important lectin due to its application in the screening of mature and immature thymocytes as well as in the detection of cancerous malignancies. The basis for these applications is the remarkably strong affinity of the lectin for the tumor-associated Thomsen-Friedenreich antigen (T-antigen) and more so due to its ability to distinguish T-antigen from its cryptic forms. The crystal structure of the complex of peanut agglutinin with T-antigen reveals the basis of this specificity. Among the contacts involved in providing this specificity toward T-antigen is the water-mediated interaction between the side chain of Asn-41 and the carbonyl oxygen of the acetamido group of the second hexopyranose ring of the sugar molecule. Site-directed mutational changes were introduced at this residue with the objective of probing the role of this residue in T-antigen binding and possibly engineering an altered species with increased specificity for T-antigen. Of the three mutants tested, i.e. N41A, N41D, and N41Q, the last one shows improved potency for recognition of T-antigen. The affinities of the mutants can be readily explained on the basis of the crystal structure of the complex and simple modeling. In particular, the change of asparagine to glutamine could lead to a direct interaction of the side chain with the sugar while at the same time retaining the water bridge. This study strengthens the theory that in lectins the nonprimary contacts generally made through water bridges are involved in imparting exquisite specificity.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2001

Interleukin-8 expression in AIDS-associated lymphoma B-cell lines.

Interleukin 8 (IL-8), a member of the CXC subfamily of chemokines, is a potent inflammatory cytokine produced by many cell types in response to several stimuli. In an attempt to determine whether human B-cell IL-8 functions as an autocrine growth factor, a wide panel of B-cell lines derived from patients with AIDS-associated B-cell lymphomas (AABCL) (n = 5) and from non-AABCLs (n = 8) was studied for expression of IL-8, IL-8 Receptor type A (IL-8R), and secretion of IL-8 protein. Using RT-PCR and Northern Blot analysis, we were able to observe IL-8 expression ubiquitously. However, IL-8R expression was seen only in EBV negative (4 out of 7) B-cell lines. EBV and HIV-1 activated B-cell line; HBL-1, was the major secretor of IL-8. Our results demonstrate that IL-8 is expressed in malignant B-cell phenotypes that correspond to a narrow window in the B-cell differentiation pathway (pre-B, early-B, and intermediate-B) as well as in normal CD19-enriched B-cells. Furthermore, IL-8 autocrine loops were not evident since IL-8R was detected only in cell lines that did not secrete IL-8 protein.

B-Lymphocytes↗
PubMed2001

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Journal Article↗
PubMed2001

Relationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention-deficit/hyperactivity disorder.

Data indicate that diminished central serotonergic (5-HT) function is related to aggression in adults, but discrepant findings in children suggest that age or the presence of attention-deficit/hyperactivity disorder (ADHD) may influence this relationship. This study examined whether age or ADHD affects the association between 5-HT and aggression in 7-11-year old clinically-referred boys. Forty-six boys were divided into non-aggressive ADHD, aggressive ADHD, and aggressive non-ADHD groups based on responses to interviews and ratings of behavior. Central 5-HT function was assessed by measuring the prolactin response to a 1-mg/kg oral dose of D,L-fenfluramine. There was no significant difference in the prolactin response across the three groups of boys. Furthermore, when examined dimensionally, prolactin response was largely unrelated to ratings of aggression, even after controlling for ADHD. Finally, age was not associated with prolactin response, and had no effect on the relationship between prolactin response and aggression. This study provides further evidence that there is no clear relationship between central 5-HT function and aggression in disruptive boys. Moreover, these data do not confirm the hypothesis that age or the presence of ADHD influence the relationship between 5-HT and childhood aggression.

Age Factors↗
PubMed2001

Crystal structure of Lyme disease antigen outer surface protein C from Borrelia burgdorferi.

The outer surface protein C (OspC) is one of the major host-induced antigens of Borrelia burgdorferi, the causative agent of Lyme disease. We have solved the crystal structure of recombinant OspC to a resolution of 2.5 A. OspC, a largely alpha-helical protein, is a dimer with a characteristic central four-helical bundle formed by association of the two longest helices from each subunit. OspC is very different from OspA and similar to the extracellular domain of the bacterial aspartate receptor and the variant surface glycoprotein from Trypanosoma brucei. Most of the surface-exposed residues of OspC are highly variable among different OspC isolates. The membrane proximal halves of the two long alpha-helices are the only conserved regions that are solvent accessible. As vaccination with recombinant OspC has been shown to elicit a protective immune response in mice, these regions are candidates for peptide-based vaccines.

Amino Acid Sequence↗
PubMed2001

Do hair care practices affect the acquisition of tinea capitis? A case-control study.

OBJECTIVE: To determine the influences of hair-grooming practices and environmental factors as risk factors for the acquisition of tinea capitis (TC) in children. DESIGN: Case-control study comparing children with culture-proved TC with age-, sex-, and race-matched control subjects without scalp disease. SETTING: A multicenter study involving 3 urban referral centers in the United States. PARTICIPANTS: A convenience sample of 66 patients aged 12 years and younger presenting to pediatric dermatology clinics with clinical evidence of TC were enrolled as cases. Matched control subjects (n = 68), without known scalp disease, were enrolled from the outpatient pediatric clinics at the same institutions. RESULTS: Significant associations with TC in the conditional logistic regression model were a prior history of TC (odds ratio, 3.11; 95% confidence interval, 1.02-9.43; P =.04) and exposure to TC (odds ratio, 16.32; 95% confidence interval, 3.55-75.16; P =.001). The use of a hair conditioner was statistically significant in the univariable model but not in the multivariable model (odds ratio, 0.46; 95% confidence interval, 0.20-1.08; P =.07). Hairstyling, frequency of washing, use of oils or grease, and other hair care practices were not shown to be associated with the presence of TC. CONCLUSIONS: Hair-grooming practices do not appear to play a major role in the acquisition of TC. Hair conditioners may be protective in children at risk for TC, but further studies are needed to confirm this finding.

Case-Control Studies↗
PubMed2001

Loss of response to antidepressants and subsequent refractoriness: diagnostic issues in a retrospective case series.

BACKGROUND: The loss of response to antidepressant drugs is not an uncommon phenomenon. While some patients respond to changes in the drug regimen, others develop resistance to various treatment modalities. METHOD: I describe 15 cases who had a loss of response to repeated trials of antidepressants before developing a chronic and severe, refractory depression. RESULTS: These patients had failed to respond to various treatment strategies including substitution with other antidepressant drugs, augmentation with agents such as T3 and lithium; and finally electroconvulsive therapy (ECT). Following discontinuation of antidepressants and treatment with mood stabilizers, there was a sustained improvement. Notably some of the patients who had earlier failed to respond to mood stabilizers in combination with unimodal antidepressants improved upon discontinuation of antidepressants and continued treatment with mood stabilizers. LIMITATIONS: Open trial, retrospective design and small sample size. CONCLUSION: These clinical findings suggest that some refractory depressives represent cryptic bipolar disorders. Prospective validation is necessary to support this conclusion.

Adult↗
PubMed2001

Interaction of melanin with proteins--the importance of an acidic intramelanosomal pH.

Melanin is a highly irregular heteropolymer consisting of monomeric units derived from the enzymatic oxidation of the amino acid tyrosine. The process of melanin formation takes place in specialized acidic organelles (melanosomes) in melanocytes. The process of melanin polymerization requires an alkaline pH in vitro, and therefore, the purpose of an acidic environment in vivo remains a mystery. It is known that melanin is always bound to protein in vivo. It is also seen that polymerization in vitro at an acidic pH necessarily requires the presence of proteins. The effect of various model proteins on melanin synthesis and their interaction with melanin was studied. It was seen that many proteins could increase melanin synthesis at an acidic pH, and that different proteins resulted in the formation of different states of melanin, i.e., a precipitate or a soluble, protein-bound form. We also present evidence to show that soluble protein-bound melanin is present in vivo (in B16 cells as well as in B16 melanoma tissue). An acidic pH appeared to be necessary to ensure the formation of a uniform, very high molecular weight melano-protein complex. The interaction between melanin and proteins appears to be largely charge-dependent as evidenced by zeta potential measurements, and this interaction is also increased in an acidic pH. Thus, it appears that an acidic intramelanosomal pH is essential to ensure maximum interaction between protein and melanin, and also to ensure that all the melanin formed is protein-bound.

Animals↗
PubMed2001

Silver(I) ion-selective membrane based on Schiff base-p-tert-butylcalix[4]arene.

A PVC membrane electrode for silver(I) ion based on Schiff base-p-tert-butylcalix[4]arene is reported. The electrode works well over a wide range of concentration (1.0 x 10(-5)-1.0 x 10(-1) mol dm-3) with a Nernstian slope of 59.7 mV per decade. The electrode shows a fast response time of 20 s and operates in the pH range 1.0-5.6. The sensor can be used for more than 6 months without any divergence in the potential. The selectivity of the electrode was studied and it was found that the electrode exhibits good selectivity for silver ion over some alkali, alkaline earth and transition metal ions. The silver ion-selective electrode was used as an indicator electrode for the potentiometric titration of silver ion in solution using a standard solution of sodium chloride; a sharp potential change occurs at the end-point. The applicability of the sensor to silver(I) ion measurement in water samples spiked with silver nitrate is illustrated.

Journal Article↗
PubMed2001

Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs.

INTRODUCTION: The question of how a defibrillation shock affects the myocardium far (> approximately 1 mm; the space constant of continuum tissue models) from the electrode is not fully understood. According to a long-standing, yet to be verified, hypothesis, the relatively high-resistance intercellular gap junctions may help in coupling the shock effect to the distant myocardium by redistributing the defibrillation current and creating a sawtooth pattern of polarization in which every cell undergoes hyperpolarization and depolarization. The goal of this study was to conduct an in-depth theoretical and experimental investigation of the sawtooth effect in the simplest coupled system, that of an isolated cell-pair. METHODS AND RESULTS: Theoretically, we present a relationship between sawtooth amplitude (STA) and junctional resistance (Rj), and show that, in a cell-pair with two cells of different lengths, the sawtooth effect may not necessarily appear as a reversal in polarization across the junction when Rj is below a critical value. Experimentally, we optically mapped transmembrane potential responses along the lengths of enzymatically isolated guinea pig cell-pairs at 10- or 17-microm resolution, and estimated STA as the magnitude of discontinuity in responses at the intercellular junction. From 14 cell-pairs, STA was estimated to be approximately 11 mV for a nominal 10 V/cm field. Based on our theoretical results, this value corresponds to an Rj of approximately 18 Mohms. CONCLUSION: The intercellular junction induces a measurable sawtooth effect in the simplest system of an isolated cell-pair. An accounting for the sawtooth effect might be essential for understanding field-tissue interaction far from the electrode and to accurately predict tissue response during field stimulation.

Animals↗
PubMed2001

Self-esteem and performance on word tasks.

The authors investigated word-task performance of 192 postgraduate Indian women, grouped according to high or low self-esteem, after different causal attributions for failure. The subsequent performance of the low-self-esteem (LSE) participants improved after reattribution training. When the LSE participants were induced to attribute their prior failure to external causes, the external attribution not only reduced their natural tendency toward self-blame but also broke the self-defeating cycle, thereby enabling them to improve their subsequent performance.

Adult↗
PubMed2001

Influence of body mass index and self-administration of hCG on the outcome of IVF cycles: a prospective cohort study.

Final maturation of the oocyte in in vitro fertilization (IVF) cycles is achieved through the administration of a timed injection of human chorionic gonadotrophin (hCG). The success of mature oocyte retrieval is dependent on serum concentrations of the hormone reaching values capable of initiating meiosis and triggering the release of the cumulus-oocyte complex into the follicular fluid. The objective of this prospective cohort study was to examine the effect of adiposity, as measured by body mass index (BMI), on serum concentrations of hCG and gonadotrophins and to relate this to IVF outcome. A comparison was also made between professionally and non-professionally administered hCG to assess any possible effect on cycle parameters. A total of 50 patients with a high BMI (> or = 26 kg m(-2)) who underwent IVF treatment at the Assisted Conception Unit, St James's University Hospital, Leeds, was recruited prospectively into the study. They were matched with 50 patients with a normal BMI (18-25 kg m(-2)) who acted as a control group. The two groups were matched for age (mean of 32 years and range of 22-42 years) and cause of infertility. Serum gonadotrophins, oestradiol and hCG concentrations, measured at the time of oocyte retrieval, and the clinical outcome of the two groups were compared. Patients with a high BMI had a significantly lower mean serum hCG concentration compared with controls (63.9 versus 99.6 iu l(-1), P < 0.0003). They also required a higher dosage of gonadotrophin (3660 versus 3007 iu) to achieve follicular maturation than the controls. Similarly, the high BMI group of patients had higher serum concentrations of follicle-stimulating hormone (FSH) (12.3 versus 11.2 iu l(-1)) and lower oestradiol (3499 versus 3506 pmol l(-1)) compared with controls. Patients with a high BMI had significantly fewer oocytes aspirated, resulting in a significant decrease in the oocyte:follicle ratio compared with controls (33.9 versus 41.7, P < 0.05). The fertilization rate (46.2 versus 61.3%, P < 0.05) and clinical pregnancy rate per cycle (26.6 versus 37.1%, P < 0.05) were also lower in the patients with high BMI compared with those with normal BMI. The administration of hCG by the patient or her partner did not have a significant effect on clinical outcome. The mean serum hCG at the time of oocyte recovery was equivalent in both groups (87.1 versus 89.7 iu l(-1)). Furthermore, the oocyte:follicle ratio (0.73 versus 0.72), fertilization rate (46.2 versus 54.2%) and clinical pregnancy rate (38.9 versus 36.5%) were similar. These findings indicate that high BMI is detrimental to the success of IVF treatment and has an important influence on the distribution and metabolism of hCG. The results also indicate that non-professional administration of hCG does not compromise cycle outcome.

Adult↗
PubMed2001

Utero-ovarian blood flow characteristics of pituitary desensitization.

BACKGROUND: Down-regulation in assisted reproduction treatment cycles is monitored by suppression of ovarian/pituitary hormones and/or measurement of endometrial thickness. METHODS: This prospective longitudinal study reports on utero-ovarian characteristics of pituitary desensitization. A total of 75 patients were recruited; 32 had IVF treatment, 20 frozen--thawed embryo transfer cycles and 23 patients were recipients of donated oocytes. All received early follicular-phase down-regulation and had colour flow Doppler velocimetry of the utero-ovarian arteries < or =3 days before the start of menses and after 21 days of gonadotrophin-releasing hormone (GnRH) analogue treatment. Ovarian volume, endometrial thickness, pituitary and ovarian hormone concentrations were recorded at each scan. RESULTS: Significant changes (P < 0.05) were noted in these and utero-ovarian vasculature during the down-regulation period, with good correlation between resistance index and oestradiol estimations. Neither the type of GnRH analogue nor age influenced the changes in utero-ovarian blood flow. Ovarian artery resistance index was the best Doppler predictor for pituitary suppression and a mean discriminatory cut-off value of 0.867 +/- 0.025 was found to have the highest specificity and positive predictive value. CONCLUSIONS: This study has, for the first time, defined cut-off values for satisfactory pituitary suppression with high positive predictive value and specificity in an early follicular phase long protocol of GnRH analogue down-regulation using colour flow Doppler.

Adult↗
PubMed2001

Apolipoprotein E polymorphism and response to electroconvulsive therapy.

The aim of this study was to determine whether the apolipoprotein E genotype differs in patients who respond or do not respond to electroconvulsive therapy (ECT). Inpatients, out-patients, and day-treatment patients who had received ECT comprised the study group. The 34 patients included met DSM-III-R criteria for affective or schizoaffective disorder. Responder or nonresponder status was assessed using the Clinical Global Inventory and Montgomery Asberg Depression Rating Scale. Blood samples were taken and coded when the patients entered the study. DNA extraction and apolipoprotein E genotyping were performed with no knowledge of the clinical classification of the patients. A significant difference in E4 genotype distribution was found between ECT responders and nonresponders (p < 0.02); psychosis was significantly less frequent in this group (p = 0.046), and there was a trend toward older onset of depression among these persons (p = 0.10). Only the E3/3 genotype was found in the patients with early-onset depression. The E4 genotype appears to define a subgroup of patients with late-onset depression who respond to ECT. If confirmed in prospective studies, this may provide a useful marker in the treatment decision-making process for late-onset depression.

Adolescent↗
PubMed2001

Fever with acute arthritis in calcium pyrophosphate dihydrate deposition disease: a missed explanation for altered mental status in elderly patients?

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a relatively common condition primarily affecting the elderly. Various clinical presentations ranging from an acute arthritis resembling gout (pseudogout) to fever of unknown origin have been reported. We describe four elderly patients with fever and altered mental status. Each patient underwent an extensive unrevealing work-up. An acute arthritis missed by the health-care team in their initial evaluation was later identified, leading to rheumatologic consultation and subsequent diagnosis of CPPD disease after joint aspiration and synovial fluid analysis. Defervescence and resolution of mental status changes occurred after improvement of the arthritis. Awareness that CPPD disease may present with systemic symptoms, including fever and altered mental status, may assure careful examination of joints and can prevent unnecessary testing and diagnostic delay.

Journal Article↗