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Biomedical subjects

B B Singh

Publications and source records attributed to B B Singh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains.

Trp1 has been proposed as a component of the store-operated Ca(2+) entry (SOC) channel. However, neither the molecular mechanism of SOC nor the role of Trp in this process is yet understood. We have examined possible molecular interactions involved in the regulation of SOC and Trp1 and report here for the first time that Trp1 is assembled in signaling complex associated with caveolin-scaffolding lipid raft domains. Endogenous hTrp1 and caveolin-1 were present in low density fractions of Triton X-100-extracted human submandibular gland cell membranes. Depletion of plasma membrane cholesterol increased Triton X-100 solubility of Trp1 and inhibited carbachol-stimulated Ca(2+) signaling. Importantly, thapsigargin stimulated Ca(2+) influx, but not internal Ca(2+) release, and inositol 1,4,5-triphosphate (IP(3))-stimulated I(soc) were also attenuated. Furthermore, both anti-Trp1 and anti-caveolin-1 antibodies co-immunoprecipitated hTrp1, caveolin-1, Galpha(q/11), and IP(3) receptor-type 3 (IP(3)R3). These results demonstrate that caveolar microdomains provide a scaffold for (i) assembly of key Ca(2+) signaling proteins into a complex and (ii) coordination of the molecular interactions leading to the activation of SOC. Importantly, we have shown that Trp1 is also localized in this microdomain where it interacts with one or more components of this complex, including IP(3)R3. This finding is potentially important in elucidating the physiological function of Trp.

Calcium↗
PubMed2000

Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells.

The trp gene family has been proposed to encode the store-operated Ca(2+) influx (SOC) channel(s). This study examines the role of Trp1 in the SOC mechanism of salivary gland cells. htrp1, htrp3, and Trp1 were detected in the human submandibular gland cell line (HSG). HSG cells stably transfected with htrp1alpha cDNA displayed (i) a higher level of Trp1, (ii) a 3-5-fold increase in SOC (thapsigargin-stimulated Ca(2+) influx), determined by [Ca(2+)](i) and Ca(2+)-activated K(+) channel current measurements, and (iii) similar basal Ca(2+) permeability, and inhibition of SOC by Gd(3+) but not by Zn(2+), as compared with control cells. Importantly, (i) transfection of HSG cells with antisense trp1alpha cDNA decreased endogenous Trp1 level and significantly attenuated SOC, and (ii) transfection of HSG cells with htrp3 cDNA did not increase SOC. These data demonstrate an association between Trp1 and SOC and strongly suggest that Trp1 is involved in this mechanism in HSG cells. Consistent with this suggestion, Trp1 was detected in the plasma membrane region, the proposed site of SOC, of acinar and ductal cells in intact rat submandibular glands. Based on these aggregate data, we propose Trp1 as a candidate protein for the SOC mechanism in salivary gland cells.

Animals↗
PubMed2000

Molecular cloning and functional characterisation of a glucose transporter, CaHGT1, of Candida albicans.

We have cloned the first glucose transporter CaHGT1 (Candida albicans high-affinity glucose transporter) of a pathogenic yeast, Candida albicans. The DNA sequence (GenBank accession number Y16834) analysis revealed an ORF encoding a novel protein of 545 amino acids with a predicted molecular mass of 60.67 kDa. The putative protein with 12 transmembrane domains has 51% identity with Kluyveromyces lactis high-affinity glucose transporter, HGT1. The protein signatures which are conserved and distinctive of the sugar transporters belonging to the major facilitator superfamily (MFS) were also found in CaHgt1p. When heterologously expressed, the ORF functionally complemented a mutant strain of Saccharomyces cerevisiae RE700A which was deleted in seven hexose transporter genes and thus was unable to grow or transport glucose. The expression of CaHGT1 in C. albicans showed a transcript of 1.6 kb which was enhanced in response to the human steroid hormone progesterone. Interestingly, the transcript levels were also enhanced in the presence of drugs, e.g. cycloheximide, chloramphenicol and benomyl. The results suggest that CaHGT1, which encodes a MFS protein, could be linked to the drug resistance phenomenon in C. albicans.

Amino Acid Sequence↗
PubMed2000

Sustained improvement produced by nonpharmacologic intervention in fibromyalgia: results of a pilot study.

OBJECTIVE: The aim of this pilot study was to examine the practicality of delivering a package of nonpharmacologic, behavioral-based treatment, previously found to be effective in chronic back pain, to patients with fibromyalgia (FM) and to assess the efficacy of the intervention using a range of outcome measures up to 4 months posttreatment. METHODS: Participants with FM (n = 28) formed a single group for 8 sessions at weekly intervals. Each session comprised an education/cognitive-behavioral component, formal relaxation/meditation training, and instruction in a Chinese movement therapy (Qi Gong). RESULTS: Twenty of 28 subjects completed at least 5 of the 8 sessions. Significant improvement was seen in the Fibromyalgia Impact Questionnaire and a range of other outcome measures including tender points and pain threshold. Improvement was sustained 4 months after the end of the intervention. CONCLUSION: A simple behavioral intervention using large groups can be administered to subjects with FM and appears to produce sustained benefit in a range of outcomes. Controlled trials are currently being planned.

Aged↗
PubMed2000

The public debate over alternative medicine: the importance of finding a middle ground.

As the use of alternative medical therapies has grown in the United States, so has the controversy surrounding it. Many conventional medicine practitioners and researchers often express strong negative attitudes toward alternative medicine therapies and practitioners. Likewise, many alternative medicine practitioners and activists often express strong negative attitudes toward conventional medicine and its methods. Unfortunately, such highly polarized viewpoints tend to dominate the public debate over alternative medicine in this country, obscuring the empirical evidence. This article discusses the evidence pertaining to some of the major controversies surrounding alternative medicine and why there is a critical need to find a more moderate approach to resolving such controversial issues. A potential model for finding a middle ground in this debate is presented.

Complementary Therapies↗
PubMed2000

Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review.

OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1.

The Ran-binding protein 2 (RanBP2) is a large scaffold cyclophilin-related protein expressed in photoreceptor cells. Red/green opsin, Ran-GTPase, and the 19 S regulatory complex of the proteasome associate with specific RanBP2 structural modules. Some of these play a role in chaperoning the functional expression of opsin. RanBP2 localization at cytoplasmic fibrils emanating from the nuclear pore complex and interaction with the Ran-GTPase support also its role in nucleocytoplasmic transport processes. The degenerate nucleoporin repeat motifs FXFG, GLFG, and XXFG have been proposed to mediate the movement of nucleocytoplasmic transport factors. In particular, RanBP2 has been implicated in nuclear import processes. Here, we show the zinc fingers of RanBP2 associate with high specificity to the nuclear export factor, exportin-1 (CRM1). The bovine RanBP2 transcript contained only five of the eight zinc fingers reported in the human counterpart and are sufficient for exportin-1 association with RanBP2. In contrast to Ran interaction with RanBP2-exportin-1 complex, exportin-1 binding to the zinc finger cluster domain of RanBP2 is insensitive to leptomycin B and nucleotide-bound state of Ran-GTPase. Our results indicate that the zinc finger-rich domain of RanBP2 constitutes a docking site for exportin-1 during nuclear export. Thus, RanBP2 emerges as a key component of the nuclear export pathway.

Amino Acid Sequence↗
PubMed1999

ATP-dependent activation of K(Ca) and ROMK-type K(ATP) channels in human submandibular gland ductal cells.

[Ca(2+)](i) and membrane current were measured in human submandibular gland ductal (HSG) cells to determine the regulation of salivary cell function by ATP. 1-10 microM ATP activated internal Ca(2+) release, outward Ca(2+)-dependent K(+) channel (K(Ca)), and inward store-operated Ca(2+) current (I(SOC)). The subsequent addition of 100 microM ATP activated an inwardly rectifying K(+) current, without increasing [Ca(2+)](i). The K(+) current was also stimulated by ATP in cells treated with thapsigargin in a Ca(2+)-free medium and was blocked by glibenclamide and tolbutamide, but not by charybdotoxin. This suggests the involvement of a Ca(2+)-independent, sulfonylurea-sensitive K(+) channel (K(ATP)). UTP mimicked the low [ATP] effects, while benzoyl-ATP activated internal Ca(2+) release, a Ca(2+) influx pathway, and K(Ca). Thus, ATP acts via P(2U) (P2Y(2)) and P(2Z) (P2X(7)) receptors to increase [Ca(2+)](i) and activate K(Ca), but not K(ATP). Importantly, (i) ROMK1 and the cystic fibrosis transmembrane regulator protein (but not SUR1, SUR2A, or SUR2B) and (ii) cAMP-stimulated Cl(-) and K(+) currents were detected in HSG cells. These data demonstrate for the first time that a ROMK-type K(ATP) channel is present in salivary gland duct cells that is regulated by extracellular ATP and possibly by the cystic fibrosis transmembrane regulator. This reveals a potentially novel mechanism for K(+) secretion in these cells.

Adenosine Triphosphate↗
PubMed1999

Identification of amino acids responsible for the oxygen sensitivity of ferredoxins from Anabaena variabilis using site-directed mutagenesis.

The filamentous cyanobacterium Anabaena variabilis (ATCC 29413) possesses two molybdenum dependent nitrogenase systems, nif1 and nif2. The nif1 system is regulated by a developmental program involving heterocyst differentiation; the nif2 system is expressed in all cells only under anaerobic conditions and the expression is controlled environmentally. The genes fdxH1 and fdxH2, encoding two [2Fe-2S] ferredoxins, are part of the these two distinct and differently regulated nif gene clusters. The sensitivity of both ferredoxins to oxygen was different; the half-life of FdxH2 in air was only approximately 1.5 h, while FdxH1 retained 80% of its nitrogenase activity after 24 h. We used site-directed mutagenesis to identify the role of individual amino acid residues responsible for oxygen sensitivity and found out that the FdxH2 double mutant I76A/V77L was much more resistant to oxygen than the wild-type ferredoxin (FdxH2) and similar to FdxH1. By modelling it was shown that the accessibility of the cavity around the iron-sulfur cluster was responsible for that.

Alanine↗
PubMed1999

Sex hormone receptor status of the dental pulp and lesions of pulpal origin.

OBJECTIVE: The purpose of this study was to determine whether the dental pulp and lesions of pulpal origin (eg, pulp polyps, periapical granulomas, and periapical cysts) exhibit receptors for the sex steroid hormones estrogen, progesterone, and androgen. STUDY DESIGN: Staining for the receptors of the hormones estrogen, progesterone, and androgen was accomplished through use of available immunohistochemical detection techniques. Pulpal tissues were obtained from freshly extracted human third molars; the other tissues were obtained from the Oral and Maxillofacial Pathology Laboratory archives. Ten samples of each tissue were processed and immunostained for these specific receptors. RESULTS: Staining for estrogen and androgen receptors was essentially negative for all cell populations examined. However, positive progesterone receptor staining of varying degrees was noted in 8 of 10 pulpal specimens. Primarily, pulpal fibroblasts and odontoblasts exhibited positive immunoreactivity. CONCLUSIONS: The results of this study suggest that although the dental pulp may be a potential target tissue for progesterone, evidence is lacking with respect to the other sex steroid hormones.

Composite Resins↗
PubMed1999

A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to standard care for the relief of pain and dysfunction in elderly patients with osteoarthritis (OA) of the knee. METHODS: Seventy-three patients with symptomatic OA of the knee were randomly assigned to treatment (acupuncture) or standard care (control). Analysis was performed on last score carried forward to account for patients who dropped out before completion. Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne indices at baseline and at 4, 8 and 12 weeks. Patients in the control group were offered acupuncture treatment after 12 weeks. The data for these patients are pooled with those from the original acupuncture group for within-group analysis. RESULTS: Patients randomized to acupuncture improved on both WOMAC and Lequesne indices compared to those who received standard treatment alone. Significant differences on total WOMAC Scale were seen at 4 and 8 weeks. There appears to be a slight decline in effect at 4 weeks after cessation of treatment (12 weeks after first treatment). No adverse effects of acupuncture were reported. CONCLUSION: These data suggest that acupuncture is an effective and safe adjunctive therapy to conventional care for patients with OA of the knee.

Acupuncture Analgesia↗
PubMed1999

Are psychosocial factors related to response to acupuncture among patients with knee osteoarthritis?

CONTEXT: Acupuncture has been found to be beneficial in the treatment of patients with knee osteoarthritis. However, response among such patients is highly variable. Identification of subjects with greater response would facilitate a more rational use of acupuncture. OBJECTIVE: To examine the relationship between demographic and psychosocial variables and response to acupuncture as defined by reduction in pain and disability at the end of an 8-week course of treatment. DESIGN: Retrospective study. SETTING: Outpatients attending rheumatologists or primary care physicians. PATIENTS: 37 patients with symptomatic knee osteoarthritis who had previously participated in a controlled trial using acupuncture were recalled for an interview approximately 1 year later. INTERVENTION: Structured interview, questionnaire completion, and an examination. MAIN OUTCOME MEASURES: Depression, anxiety, helplessness, self-efficacy, and fatigue were measured by standard instruments. Knee examination and assessment of pain threshold were measured by dolorimetry. RESULTS: Response at 8 weeks was significantly related to duration of symptoms. A statistically nonsignificant trend was found for older and more educated subjects to have a better response; anxiety and fatigue were found to be inversely related to response (also statistically nonsignificant). Subjects with localized medial pain had significantly better response in terms of pain and disability than did subjects with generalized knee pain. CONCLUSION: Other than a weak relationship with anxiety (at 8 weeks only), no evidence of a link between psychosocial variables and response to acupuncture was found. Prospective studies are needed to confirm these results.

Acupuncture Therapy↗
PubMed1998

Immunohistochemical evaluation of bcl-2 oncoprotein in oral dysplasia and carcinoma.

The proto-oncogene bcl-2 is associated with follicular lymphoma involving translocation t(14;18)(q32;q21) and is also overexpressed in various neoplasms. We report deregulation of bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein in formalin-fixed paraffin-embedded tissue sections revealed that severe epithelial dysplasias had a higher percentage of immunoreactivity than did mild and moderate dysplasias and squamous cell carcinomas. Expression of this oncoprotein was directly proportional to the degree of epithelial dysplasia, and nondysplastic basal cells contiguous to neoplastic lesions also expressed bcl-2. These findings, along with down-regulation of bcl-2 in differentiating carcinomas, suggest a role for this oncoprotein in relatively early stages of oral tumor progression. Differentiating neoplastic cells with marginal or no bcl-2 reactivity showed heterogeneous cell labeling of varying intensity for differentiation-associated cytokeratin (CK13), indicating their inverse topographic relationship.

Carcinoma, Squamous Cell↗
PubMed1998

Study on lipid peroxidation potential in different tissues induced by ascorbate-Fe2+: possible factors involved in their differential susceptibility.

Susceptibility of four major rat tissues to oxidative damage in terms of lipid peroxidation induced by in vitro by ascorbate-Fe2+ in homogenates and mitochondria has been examined. Lipid peroxidation, as assessed by thiobarbituric acid reactive substances (TBARS) and conjugated dienes was maximum in brain followed by liver, kidney and heart. However, the time course of lipid peroxidation showed different patterns in tissues examined. The higher susceptibilities of brain and liver can be explained by substrate availability and to a lesser extent the level of antioxidants. The differences observed in the tissues studied may reflect their susceptibility to degenerative diseases and xenobiotic toxicity which are considered as a result of oxidative damage to membranes.

Animals↗
PubMed1998

A clinical study to assess chlorpromazine as hypoxic cell sensitizer in head & neck cancer treated with conventional radiation.

A randomized prospective study was conducted to evaluate the effectiveness of chlorpromazine as a sensitizer of radiation in advanced head and neck cancers. Patients with unresectable laryngopharyngeal cancers except glottic cancers, with histologically proven squamous cell carcinoma staged III and IV were accrued for the study. Patients received radiation to a total dose of 6000 cGy in six weeks in both the groups except that patients in the study group received 50 mgs Chlorpromazine (CPZ) in divided doses. Fourteen of 20 patients showed complete response in the control group whereas 34 of 38 patients in chlorpromazine treated group had complete regression of the tumour (p = 0.016). The survival was (p = 0.08) better in patients receiving CPZ. This preliminary study shows beneficial effects of chlorpromazine. No adverse effects due to chlorpromazine in conjunction with radiation were documented.

Carcinoma, Squamous Cell↗
PubMed1998

Incidence of premenstrual syndrome and remedy usage: a national probability sample study.

CONTEXT: Premenstrual syndrome is believed to affect 30% to 80% of women. Studies in various cultures have used a variety of methodologies to determine prevalence, symptom profile, and effectiveness of available treatments. This study was designed to provide information on incidence of PMS and therapies used based on a national probability sample of US women. METHOD: In 1996 a national probability sample (N = 1052) of women aged 21 to 64 years was surveyed by telephone using random digit dial methods. The survey included demographic information, questions concerning respondent knowledge of premenstrual syndrome, incidence rates of common premenstrual syndrome symptoms, and any remedies that were used to control the symptoms. RESULTS: Forty-one percent of the women responded "yes" to the question, "Do you suffer from premenstrual syndrome?" An additional 17% indicated that they experienced symptoms prior to their menstrual cycle that are commonly associated with premenstrual syndrome (e.g., pain, bloating, feeling more emotional, weight gain, food cravings), though without associating these symptoms with premenstrual syndrome explicity. The most frequently noted severe symptom was that of "[feeling] more emotional." Of those reporting premenstrual syndrome symptoms, approximately 42% took either prescription or over-the-counter medications to relieve them. Eighty percent of the women taking any type of medication relied on over-the-counter medications. Prescription drug use for premenstrual syndrome symptoms focused on medications to control pain; hormone supplements were the second most frequently prescribed rugs. Fewer than 3% of the respondents used prescription medications. Respondents were asked to indicate whether they had used a complementary medical therapy to control symptoms. Exercise was used most frequently (18%), and acupuncture was the least frequently used. Although only a small percentage of women used complementary therapies, for most of these therapies a near-perfect concordance was found between usage and belief in efficacy. CONCLUSIONS: Women were aware of symptoms related to premenstrual syndrome more frequently than they recognized a formalized medical syndrome. Less than half of the women reporting symptoms had taken either over-the-counter or prescription drugs. Those who tried complementary therapies generally found them to be effective.

Adult↗
PubMed1998

A pilot study of cognitive behavioral therapy in fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by widespread musculoskeletal pain and multiple tender points as well as high levels of self-reported disability and poor quality of life. OBJECTIVES: In this pilot study, a mind-body approach (cognitive-behavioral therapy) was tested that has been successful in treating chronic back pain patients to determine whether it would improve function, decrease perceived pain, and improve mood state for fibromyalgia patients. PARTICIPANTS: 28 patients recruited from the greater Baltimore area. INTERVENTION: Eight weekly sessions, 2 1/2 hours each, with three components: an educational component focusing on the mind-body connection, a portion focusing on relaxation response mechanisms (primarily mindfulness meditation techniques), and a qigong movement therapy session. MAIN OUTCOME MEASURES: Data collection instruments were the Fibromyalgia Impact Questionnaire, the Health Assessment Questionnaire, the Beck Depression Inventory, the Coping Strategies Questionnaire, the helplessness subscale of the Arthritis Attitudes Index, the Medical Outcomes Study Short Form General Health Survey, and a double-anchored 100-mm visual analog scale to assess sleep. RESULTS: Twenty patients completed the study. Standard outcome measures showed significant reduction in pain, fatigue, and sleeplessness; and improved function, mood state, and general health following an 8-week intervention. CONCLUSION: A mind-body intervention including patient education, meditation techniques, and movement therapy appears to be an effective adjunctive therapy for patients with fibromyalgia.

Cognitive Behavioral Therapy↗