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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 73 records · Page 4Linked to original sources
PubMed2004

A novel method for estimating ancestral amino acid composition and its application to proteins of the Last Universal Ancestor.

MOTIVATION: Knowledge of how proteomic amino acid composition has changed over time is important for constructing realistic models of protein evolution and increasing our understanding of molecular evolutionary history. The proteomic amino acid composition of the Last Universal Ancestor (LUA) of life is of particular interest, since that might provide insight into the early evolution of proteins and the nature of the LUA itself. RESULTS: We introduce a method to estimate ancestral amino acid composition that is based on expectation-maximization. On simulated data, the approach was found to be very effective in estimating ancestral amino acid composition, with accuracy improving as the number of residues in the dataset was increased. The method was then used to infer the amino acid composition of a set of proteins in the LUA. In general, as compared with the modern protein set, LUA proteins were found to be richer in amino acids that are believed to have been most abundant in the prebiotic environment and poorer in those believed to have been unavailable or scarce. Additionally, we found the inferred amino acid composition of this protein set in the LUA to be more similar to the observed composition of the same set in extant thermophilic species than in extant mesophilic species, supporting the idea that the LUA lived in a thermophilic environment. AVAILABILITY: The program is available at http://compbio.cs.princeton.edu/ancestralaa

Algorithms↗
PubMed2004

Biodegradation of acid blue-15, a textile dye, by an up-flow immobilized cell bioreactor.

Acid blue-15, a complex and resonance-stabilized triphenylmethane (TPM) textile dye, resistant to transformation, was decolorized/degraded in an up-flow immobilized cell bioreactor. A consortium comprised of isolates belonging to Bacillus sp., Alcaligenes sp. and Aeromonas sp. formed a multispecies biofilm on refractory brick pieces used as support material. The TPM dye was degraded to simple metabolic intermediates in the bioreactor with 94% decolorization at a flow rate of 4 ml h(-1).

Bacteria↗
PubMed2004

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air is used by common cold sufferers since the invention of the steam kettle. There is scientific literature available investigating this mode of therapy using a rhinotherm. The present reviews addresses to the use of hot, humid air in common cold. OBJECTIVES: To assess the effects of inhaling heated water vapour with the help of a rhinotherm (an equipment designed to deliver heated water vapour to a person's nasal cavity), in the treatment of the common cold by comparing: a. symptoms b. viral shedding c. nasal resistance after a natural or experimentally induced common cold. SEARCH STRATEGY: In the initial review published in issue 3, 1999 of The Cochrane Library, we searched MEDLINE with MeSH headings: common cold, rhinopharyngitis, inhalation, steam, heated vapour, rhinothermy (January 1966 to July 1999). EMBASE, Current Contents, review articles, cross references were also searched. Attempts were also made to contact the manufacturers for any unpublished data. In this updated review, we have searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2003), MEDLINE (January 1966 to November Week 2, 2003), EMBASE (January 1990 to November 2003), and Current Contents (current five years). SELECTION CRITERIA: Randomized trials using heated water vapour in a standardized way in patients with the common cold or volunteers with experimental induction of rhinovirus infection were included in the review. DATA COLLECTION AND ANALYSIS: All the articles retrieved were initially subjected to a review for inclusion / exclusion criteria. Review articles, editorials, abstracts with inadequate outcome description were excluded. Studies selected for inclusion were subjected to a methodological assessment. MAIN RESULTS: The results of a systematic review of six trials with 319 participants, support the use of warm vapour inhalations in the common cold in terms of relief of symptoms (Odds Ratio with 95 % CI 0.31, 0.16-0.60, Relative risk 0.56, 0.4-0.79). Results on symptom score indices were equivocal. None of the studies demonstrated a worsening of clinical symptom scores. One study demonstrated increased nasal resistance one week after steam inhalation in contrast to an earlier study which showed improvement in the nasal resistance. There was no evidence of decreased viral shedding measured by virus isolation in the nasal secretions (Tyrrell 1989a) or measurement of viral titres in nasal washings among treatment group. The rhinovirus titres in the nasal washings from the treatment group were the same as those of the placebo group on day one prior to the treatment and on all four days after the treatment. The area under curve (Hendley 1994) was also similar in the placebo and treatment groups for titres of virus in the nasal washings as were the average viral titres across five days of follow up, the maximum values after treatment, and viral shedding velocity i.e. amount of virus shed per day (Hendley 1994). Minor side effects due to thermal stress were reported in all the studies. REVIEWERS' CONCLUSIONS: Three trials demonstrated beneficial effects on the symptoms of the common cold. One study from Israel showed a decrease in nasal resistance measured by peak nasal expiratory and inspiratory flow rate. Studies done in North America failed to show any objective improvement in outcome measures with the study intervention. A multi-centre double blind randomised controlled trial testing this therapy with uniform outcome measures is recommended.

Air↗
PubMed2004

Low levels of antibodies against E. coli and mycobacterial 65kDa heat shock proteins in patients with inflammatory bowel disease.

OBJECTIVE AND DESIGN: The aim of the present study was to support and extend our initial observation, where we found low levels of antibodies against mycobacterial 65kD heat shock proteins in patients with inflammatory bowel disease (IBD). For this purpose we tested a new group of 124 patients with IBD, and beside measuring antibodies to Mycobacterium bovis 65kD heat shock protein (Hsp65) and human 60kD heat shock protein (Hsp60) as described previously, we also determined IgG antibody levels to Hsp65 from E. coli, called GroEL. PATIENTS AND CONTROL SUBJECTS: seventy-four patients with Crohn's disease (CD) (30 males, 44 females, 33 (27-45) years old, median (interquartile range)) and 50 patients with ulcerative colitis (UC) (22 males, 28 females, 38 (30-50) years old) were involved in the study. 110 healthy subjects (34 males, 76 females, 47 (37-53) years old) served as controls. Study subjects were consecutive patients referred to an IBD center for complex treatment of the disease. Methods and statistical analysis: The amounts of IgG-type antibodies reacting with proteins of the chaperonin 60 family were assessed by ELISA. Since the antibody levels to heat-shock proteins as variables were not normally distributed, non-parametric Mann-Whitney test and Dunn post hoc test were used for group comparisons. RESULTS: Median levels of anti-GroEL (7,5 (3,5-18,3)) and anti-Hsp65 (4,8 (2,1-7,85)) were significantly (GroEL p = 0,008; and Hsp65 p < 0,001) lower in the IBD patients than in the healthy subjects (GroEL: 10,0 (5,4-31,0); Hsp65: 7,04 (4,66-12,77)). However this difference was found to be restricted to the CD patients (GroEL: 7,5 (3,7-14,2); p < 0,05; Hsp65: 4,35 (1,90-6,94); p < 0,001). We did not find difference in the concentration of anti-human Hsp60 IgG levels between patients (Hsp60: 45,5 (24,9-69,0)) and healthy controls (38,4 (21,6-69,4). Regarding the serum concentrations of each antibody tested there was no significant difference between the active and inactive stage of disease. CONCLUSION: Our present findings support conclusion of our previous work, antibody levels not only for Mycobacterium bovis hsp65 but for E. coli GroEl were found to be decreased as well. In contrast no changes in the concentrations of human anti-hsp60 antibodies were observed. These findings indicate that production of antibodies to 65 kDa bacterial heat shock proteins is selectively impaired in IBD.

Adult↗
PubMed2004

Anatomical variations of occipital bone impressions for dural venous sinuses around the torcular Herophili, with special reference to the consideration of clinical significance.

Venous blood flow through the cerebral dural sinus is variable and clinically significant. It has been investigated by cadaver dissection or radiology; however, we thought that osteology might be informative. A total of 160 dried skulls were macroscopically examined for impressions on the inner surface of the occipital bone in order to interpret the sinus flow around the torcular Herophili. The continuity between the grooves for the superior sagittal sinus (SSS) and the transverse sinuses was categorized into four types. Confluence type was noted in 56 specimens (35%), in which SSS drained into a common pool of venous sinuses. Bifurcation type was noted in 22 cases (14%), in which SSS was divided to drain into the bilateral transverse sinuses. Right dominant type was the most frequent one with 66 cases (41%), in which SSS drained only into the right transverse sinus. Left dominant type was the least frequent one with 16 cases (10%), in which SSS drained to the left, in a mirror image to the right dominant type. Clinical significance is discussed with our preliminary trial for the optimization of the inner skull surface and venous flow using computed tomography and magnetic resonance imaging, and demonstration of cerebrovascular disease.

Adult↗
PubMed2004

Efficacy of nonhormonal vaginal contraceptives from a hydrogel delivery system.

This investigation describes the synthesis of a biodegradable hydrogel composed of a core surrounded by four concentric sheaths containing dextran, copolymers of polylactide and epsilon-caprolactone. The hydrogel was impregnated with iron (II) d-gluconate dihydrate, which causes complete spermiostasis due to lipid peroxidation, ascorbic acid to increase the viscosity of the cervical mucus and mixtures of polyamino and polycarboxylic acids to sustain vaginal pH close to 4.5. The combined effects of the agents in the daily eluates of the hydrogel were efficacious up to 16 days, within 30 s, as shown by sperm penetration tests. For in vivo studies, rabbits were chosen as the experimental model because they are easy to handle and the female is always in estrus. The anterior vagina of estrous female rabbits was instilled with the hydrogel, and then inseminated with the semen from a fertile male. Postinsemination flush from the female rabbits showed that all of the sperm were dead. These observations demonstrate the potential for the development of a biocompatible, nonhormonal, intravaginal contraceptive device.

Administration, Intravaginal↗
PubMed2004

Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses.

Microbial HSPs (heat-shock proteins) are implicated in the induction of the innate and adaptive arms of the immune response. We set out to determine whether peptides complexed with HSP70 generate efficient CTL (cytolytic T-lymphocyte) responses. Human dendritic cells pulsed with peptide-loaded microbial HSP70 complexes generate potent antigen-specific CTL responses. Using fluorescence anisotropy, we have calculated the peptide-binding affinity of mycobacterial HSP70 (K(D)=14 microM) and show that 120 pM HSP70-bound peptide is sufficient to generate a peptide-specific CTL response that is four orders of magnitude more efficient than the peptide alone. Through the generation of mycobacterial HSP70 truncations, we find that the minimal 136 amino acid, mycobacterial HSP70 peptide-binding domain is sufficient to generate CTL responses. The design of an HSP70 mutant, in which the peptide-binding site of HSP70 is filled with a bulky hydrophobic residue, leads to a large decrease in the peptide-binding affinity. This mutant HSP70 retains stimulatory capacity but is unable to generate CTL and has separated antigen delivery from immunostimulation of dendritic cells.

Amino Acid Sequence↗
PubMed2004

Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity.

Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1-358), followed by an 18 kDa peptide-binding domain (amino acids 359-494) and a C-terminal 10 kDa fragment (amino acids 495-609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359-610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFalpha(tumour necrosis factor alpha), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70-CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against Mycobacterium tuberculosis and in conversion of tolerance to immunity.

Adaptation, Physiological↗
PubMed2004

Evaluation of quality of life in indian children with bronchial asthma using a disease-specific and locally appropriate questionnaire.

AIM: To evaluate quality of life (QOL) in Indian children with bronchial asthma. METHODS: A disease-specific, locally appropriate QOL questionnaire was administered in asthmatic children and compared with FEV1, FVC, PEFR and asthma symptom score, on three occasions. RESULTS: QOL score had strong negative correlation with symptom score and weaker positive correlation with pulmonary function tests. CONCLUSION: Disease-specific QOL score correlates inversely with symptom score in children with bronchial asthma.

Asthma↗
PubMed2004

The Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ): a validation.

BACKGROUND: We wished to evaluate the psychometric properties of the Polycystic Ovary Syndrome Questionnaire (PCOSQ), a questionnaire developed to measure the health-related quality of life (HRQoL) of women with polycystic ovary syndrome. METHOD: To assess reliability and validity, women recruited from an outpatient gynaecology clinic at the Jessop Wing, Royal Hallamshire Hospital, Sheffield completed two copies of the PCOSQ and the Short Form-36 (SF-36). Secondary factor analysis was carried out to verify the composition of the dimensions. Semi-structured interviews were conducted to assess face validity. RESULTS: Of the 92 women who consented, 82 women (89%) returned questionnaires at time 1, and 69 women (75%) returned questionnaires at time 2. All five PCOSQ dimensions were internally reliable with Cronbach's alpha scores ranging from 0.70 to 0.97. Intra-class correlation coefficients to evaluate test-retest reliability were high (range 0.89-0.95, P < 0.001). Construct validity was demonstrated by high correlations for all comparisons of similar scales of the SF-36 and PCOSQ (0.49 and 0.54). Acne was identified as an important area of HRQoL missing from the questionnaire. CONCLUSIONS: The PCOSQ is a reliable instrument for measuring the HRQoL in women with PCOS. However, the validity of the questionnaire needs to be improved by incorporating a dimension on acne into the instrument.

Acne Vulgaris↗
PubMed2004

Effect of Mycobacterium tuberculosis chaperonins on bronchial eosinophilia and hyper-responsiveness in a murine model of allergic inflammation.

BACKGROUND: Epidemiological evidence suggests that infection with Mycobacterium tuberculosis protects children against asthma. Several laboratories have shown that, in mouse models of allergic inflammation, administration of the whole live tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), prevents ovalbumin (OVA)-induced pulmonary eosinophilia. OBJECTIVE: The aim of this study was to characterize specific M. tuberculosis molecules that are known to modulate immune responses to see if they affected pulmonary eosinophilia and bronchial hyper-responsiveness. METHODS: C57Bl/6 mice were sensitized to OVA on days 0 and 7 and subsequently challenged with OVA on day 14 over a 3-day period. Pulmonary eosinophilia and bronchial hyper-responsiveness were measured 24 h following the last antigen challenge. In some groups, mice were pre-treated with M. tuberculosis or M. tuberculosis chaperonins (Cpns)60.1, 60.2 and 10, and the effect of this treatment on the allergic inflammatory response to aerosolized OVA was established. RESULTS: We show that M. tuberculosis Cpns inhibit allergen-induced pulmonary eosinophilia in the mouse. Of the three Cpns produced by M. tuberculosis, Cpn60.1, Cpn10 and Cpn60.2, the first two are effective in preventing eosinophilia when administered by the intra-tracheal route. Furthermore, the increase in airways sensitivity to inhaled methacholine following OVA challenge of immunized mice was suppressed following treatment with Cpn60.1. The allergic inflammatory response was also characterized by an increase in Th2 cytokines IL-4 and IL-5 in bronchoalveolar lavage fluid, which was also suppressed following treatment with Cpn60.1. CONCLUSION: These data show that bacterial Cpns can suppress eosinophil recruitment and bronchial hyper-responsiveness in a murine model of allergic inflammation.

Animals↗
PubMed2004

Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu's arteritis.

Expression of heat shock protein (HSP)-65 as well as infiltration of T-cells in arterial lesions and raised levels of circulating antibodies against mycobacterial HSP65 (mHSP65) led us to the concept that mHSP65 or its human homologue (hHSP60) might be involved in the etiopathogenesis of Takayasu's arteritis (TA). Therefore, we investigated mHSP65 and hHSP60 reactive peripheral blood T-cell subsets by BrdU incorporation assay and flow cytometry as well as investigating the different isotypes of anti-mHSP65 and hHSP60 antibodies by ELISA. Eighty-four percent (22/26) of the TA patients were observed to show T-cell proliferation to mHSP65 and hHSP60 whereas only 16% (3/18) healthy controls showed such proliferation (P <0.001). Both HSPs induced proliferation of exclusively CD4+ T-cells and not CD8+ T-cells. We also observed a significantly higher prevalence of only the IgG isotype reactive to mHSP65 and hHSP60 in TA as compared to HC (mHSP65: 92% TA versus 11% HC, P <0.0001 and hHSP60: 84% versus 22%, P <0.001). Our data show a significant correlation between mHSP65 and hHSP60 reactive T-cells (CD3+: r=0.901; CD4+: r=0.968) as well as anti-mHSP65 and anti-hHSP60 IgG antibodies (r=0.814) suggesting an infection induced autoimmunity in TA, possibly induced by molecular mimicry between mHSP65 and hHSP60 or other tissue specific antigens.

Adolescent↗
PubMed2004

Lipodystrophy following hepatitis infection: a causative relationship?

Progressive partial lipodystrophy is a clinical syndrome characterized by progressive loss of subcutaneous fat. A 27-year-old female developed progressive loss of fat from the face and upper part of the torso associated with increased bulkiness of the body below the pelvis following an attack of hepatitis. She had been persistently hepatitis B surface antigen positive and her serum was positive for IgG antibodies to hepatitis B core antigen. Although the woman had hypocomplementaemia of the C3 component of complement, there was no evidence of renal involvement.

Adult↗
PubMed2004

Biological treatment of textile dye acid violet-17 by bacterial consortium in an up-flow immobilized cell bioreactor.

AIMS: To develop a cost effective and efficient biological treatment process for small scale textile processing industries (TPI) releasing untreated effluents containing intense coloured Acid violet-17 (AV-17), a triphenyl methane (TPM) group textile dye. METHODS AND RESULTS: The samples collected from effluent disposal sites of TPI were used for selective enrichment of microbial populations capable of degrading/decolourizing AV-17. A consortium of five bacterial isolates was used to develop an up-flow immobilized cell bioreactor for treatment of feed containing AV-17. The bioreactor, operating at a flow rate of 6 ml x h(-1), resulted in 91% decolourization of 30 mg AV-17/l with 94.3 and 95.7% removal of biochemical oxygen demand and chemical oxygen demand of the feed. Comparison of the input and output of the bioreactor by UV-visible, thin layer chromatography and (1)H-nuclear magnetic resonance spectroscopy indicates conversion of the parent dye into unrelated metabolic intermediates. SIGNIFICANCE: These results will form a basis for developing 'on-site' treatment system for TPI effluents to achieve decolourization and degradation of residual dyes.

Bacteria↗
PubMed2004

Transpupillary thermotherapy for the treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Prospective, non-randomized, non-masked, case-selected series. METHODS: All patients with subfoveal CNV due to AMD and initial visual acuity (VA) between 6/9 and 6/60 were offered the opportunity to undergo TTT. Recruited subjects were treated using a diode laser (810 nm) with a beam size of 1.2-3.0 mm and power settings of 460-1200 mW. Treatment was applied for 60 seconds in a subthreshold manner. MAIN OUTCOME MEASURES: Differences in VA and changes in the angiographic appearance of CNV. RESULTS: Thirty-one occult/predominantly occult and five classic/predominantly classic membranes were treated with TTT and were followed-up for a mean of 6.0 +/- 1.2 months. Following an average of 1.5 +/- 0.7 (range 1-4) laser sessions, VA remained stable ( -1 to +1 Snellen line) in 24 (66.7%) eyes, improved by > 1 line in two (5.6%) eyes and decreased significantly (> or = 2 Snellen lines) in 10 (27.8%) eyes. Angiographically confirmed closure of CNV was detected in 22 (61.1%) patients. Membranes persisted in 11 (30.6%) eyes and recurred in three (8.3%) eyes. There was no association between reduction, elimination or persistence of angiographic leakage of CNV and change in VA after treatment (p = 0.347). CONCLUSIONS: Transpupillary thermotherapy may be effective at preserving vision and reducing CNV leakage in a number of patients with exudative AMD. Further studies are required to compare TTT with the natural course of subfoveal CNV and alternative treatment options.

Aged↗
PubMed2004

Randomized controlled trial of intrapleural streptokinase in empyema thoracis in children.

AIM: To compare intrapleural streptokinase and placebo in paediatric empyema. METHODS: Children with empyema greater than stage 5 received intrapleural streptokinase (n = 19) or normal saline (n = 21) along with intercostal drainage. Clinical and serial sonographic outcomes were compared. RESULTS: Although there was no difference in clinical and sonographic outcome, none of the children with stage 7 empyema (multi-loculated empyema) who received streptokinase developed pleural thickening 30 d later. CONCLUSION: There is no short-term clinical benefit of intrapleural streptokinase in paediatric empyema; this therapy may be reserved for those with stage 7 empyema to prevent pleural thickening in the long term.

Anti-Bacterial Agents↗