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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

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

Analysis of pilus adhesins from Haemophilus influenzae biotype IV strains.

A subset of nontypeable Haemophilus influenzae (NTHI) biotype IV isolates from the human genital tract or from infected newborn infants forms a cryptic genospecies characterized by, among other features, the presence of peritrichous pili. The objective of this study was to determine the similarity of these pili to hemagglutinating, HifA- and HifE-containing pili expressed by respiratory H. influenzae isolates. For this analysis, the presence of hifA and hifE and their gene products in NTHI biotype IV strains was assessed, the binding of H. influenzae biotype IV strains to human epithelial cells was characterized, possible genital tissue tropism of these isolates was explored, and the role of HifA- and HifE-possessing pili in the adhesion of NTHI biotype IV strains to human epithelial cells was determined. None of the six biotype IV NTHI isolates tested agglutinated human red blood cells, nor could they be enriched for hemagglutinating variants. Although hifA, which encodes the major structural subunit of hemagglutinating pili, and hifE, which encodes the tip adhesin of hemagglutinating pili, were detected by PCR from six and five, respectively, of the six biotype IV strains tested, neither HifA nor HifE (the gene products of hifA and hifE) were detected in any of these strains by Western blot analysis using antisera that recognize HifA and HifE of respiratory strains. Transmission electron microscopy showed no surface pili on the two biotype IV H. influenzae isolates examined; strain 4162 containing an insertional mutation in hifA also showed no surface pili, whereas strain 1595 containing an insertional mutation in hifB showed pilus-like structures that were shorter and thicker than hemagglutinating pili of the respiratory strains AAr176 and M43. In enzyme-linked immunosorbent assays, biotype IV strains adhered to 16HBE14o(-) and HEp-2 cells of respiratory origin as well as to ME180 and HeLa cells of genital origin. This adherence was not pilus specific, however, as GM-1, a known pilus receptor analog, did not inhibit binding of biotype IV strains to ME180, HEp-2, or HeLa cells, and GM-1 inhibition of binding to 16HBE14o(-) cells did not correlate with the presence of hifE. While both nonpiliated variants and hifA and hifB (encoding the pilus chaperone) mutants of respiratory strain AAr176 showed reduced binding (64 to 87% of that of piliated AAr176) to 16HBE14o(-) and ME180 cells, hifA and hifB mutants of the biotype IV strains showed minimal reduction in binding to these cell lines (91 to 98% of that of wild-type strains). Thus, although biotype IV H. influenzae isolates of the cryptic genospecies possess the genes that code for HifA- and HifE-containing hemagglutinating pili, epithelial cell adherence exhibited by these strains is not mediated by expression of hemagglutinating pili.

Adhesins, Bacterial↗
PubMed2001

Natural history and effects on 2-year outcomes of urinary incontinence after stroke.

BACKGROUND AND PURPOSE: We sought to describe the natural history of poststroke incontinence and estimate its effect on survival and 2-year outcomes in stroke survivors. METHODS: Two hundred thirty-five incident cases of stroke in 1995 were classified by continence status at 10 days after stroke. Age, sex, ethnicity, diabetes, hypertension, atrial fibrillation, premorbid disability, and Oxfordshire Community Stroke Project classification were recorded. Outcome data collected at 3 months and at 1 and 2 years included disability, case-fatality rates, and institutionalization rates. Disability was classified as severe, moderate, mild, or independent using the Barthel Index (without its "continence" component: 0-9, 10-14, 15-17, and 18, respectively) and Frenchay Activity Index (0-15, 16-30, and 31-45). RESULTS: Of 235 cases, 95 were initially incontinent (group 1); 140 were continent (group 2). At the initial, 3-month, and 1- and 2-year assessments, incontinence was recorded in 95 patients (40%), 34 (19%), 23 (15%), and 12 (10%), respectively. In univariate analyses, the 2 groups were not different in terms of demographic factors and risk factors. Compared with group 2, group 1 patients were more likely to have atrial fibrillation (28% versus 16%; P:=0.02). Multivariate analyses showed that age >75 years (OR 15.9; CI 2.2 to 116.2), dysphagia (OR 4.03; CI 1.85 to 8.73), motor weakness (OR 5.41; CI 1.38 to 21.1) and visual field defects (OR 4.78; CI 1.78 to 12.9) were all significantly associated with incontinence. Incontinence was less common in lacunar infarctions (OR 0.12; CI 0.02 to 0.62). At 2 years, compared with group 2, group 1 had higher case-fatality rates (67% versus 20%; P:<0.001), higher institutionalization rates (39% versus 16%; P:=0.007), and greater disability (Barthel [0-9]: 39% versus 5%; P:<0.001; Frenchay [0-15]: 75% versus 37%; P:=0.001). Death or disability at 2 years was worse in subjects with initial incontinence(OR 4.43; CI 1.76 to 11.2). CONCLUSIONS: Incontinence remains a prevalent condition 2 years after stroke. Initial incontinence was associated with age >75 years, dysphagia, visual field defect, and motor weakness. Poststroke incontinence adversely affected 2-year stroke survival, disability, and institutionalization rates.

Age Factors↗
PubMed2001

A self-assessment program for multidisciplinary mental health teams.

OBJECTIVE: The authors describe a self-assessment training program for multidisciplinary mental health teams that was developed in a public multihospital system, the process of implementing the training at a state psychiatric hospital, and a measurement instrument, the Scale for Leadership Assessment and Team Evaluation (SLATE), which they have used for self-assessment of multidisciplinary teams and which is currently being studied. They assessed whether changes in team self-assessments could be seen after the training program. METHODS: A total of 102 mental health professionals from 12 inpatient units representing the disciplines of psychiatry, psychology, nursing, social work, and occupational and activity therapy completed the SLATE before and after participation in a training program that consisted primarily of team self-assessment in the context of treatment planning sessions. The training program included structured feedback, didactics, consultation, and videotaping of sessions. Aggregate data were used to compare mean item scores for the SLATE overall and for its four subscales (team, psychiatrist, participation, and treatment plan) at baseline and after the training. RESULTS: Scores increased significantly for the overall SLATE and for all four subscales, indicating improved team functioning in the areas addressed. The increase in mean score was greatest for the subscale that assessed the leadership of the psychiatrist. CONCLUSIONS: Treatment planning sessions can be used successfully by multidisciplinary mental health teams to examine team functioning in various areas in a self-assessment model. Participation in a training program that included videotaping of sessions, consultation, and structured attention to team functioning was associated with improved ratings of team functioning.

Case Management↗
PubMed2001

Encouraging pursuit of court-ordered treatment in a state hospital.

The authors discuss a performance improvement project designed to encourage staff psychiatrists at a large state hospital to more assertively pursue the option of court-ordered treatment for severely mentally ill inpatients who refuse medication for more than a week. A campaign was undertaken in 1997 to educate psychiatrists about the importance of using psychotropic medications early in a patient's hospital stay. A monthly report is now circulated to all personnel identifying units on which patients have refused medication for more than a week and psychiatrists who have filed court petitions. The number of petitions filed annually has doubled, from 97 in the year before the project to 192 four years later.

Commitment of Persons with Psychiatric Disorders↗
PubMed2001

One-year outcome of auditory-tactile-visual-vestibular intervention in the neonatal intensive care unit: effects of severe prematurity and central nervous system injury.

Thirty-seven infants with severe central nervous system injury or extreme prematurity were randomly assigned to a multisensory (auditory-tactile-visual-vestibular) intervention or control group. Intervention began in the hospital at 33 weeks' postconceptional age and continued twice daily in the home until 2 months' corrected age. Mother-infant interactions during feedings were videotaped, and the Bayley Scales of Infant Development were administered. Control mothers stimulated their infants more during feeding, but these significant differences dissipated by 4 months. The presence of periventricular leukomalacia was associated with significantly poorer mental development, regardless of group assignment. Experimental infants tended to exhibit better motor and mental performance and had 23% fewer cerebral palsy diagnoses at 1 year, but these trends were not statistically significant. The type of brain injury was more important in determining 1-year developmental outcome than type of postnatal experience, suggesting that periventricular leukomalacia presents a major challenge for infant development.

Birth Injuries↗
PubMed2001

Electronic and resonance effects on the ionization of structural analogues of efavirenz.

The solubility of 4 analogues of efavirenz was studied as a function of pH. The study evaluated the ionization behavior and determined the relative contribution of electronegative substituents versus resonance effects on the pK(a) value of the cyclic carbamate. The most profound lowering effect on the pK(a) was due to the presence of multiple electronegative substituents and in particular the trifluoromethyl and acetylene groups. The presence of chlorine on the benzoxazinone ring was found to have a slight impact on the pK(a), although to a lesser extent. In the absence of any functional groups on the benzoxazinone ring system, the pKa shifted to a value of 13.2, which is 3 pH units above that of efavirenz and more closely correlates with typical literature values for cyclic carbamates.

Alkynes↗
PubMed2001

Osteomyelitis complicating osteopetrosis--a case report.

Osteomyelitis of the jaws is uncommon but can be a complication of extraction or exposure of teeth in patients who are immunosuppressed or have undergone radiotherapy to the head and neck region. We report a case of osteomyelitis in a patient who has osteopetrosis. The initial clinical presentation was that of an infected retained root, secondary to denture trauma to the supporting tissues. Radiological interpretation was difficult owing to the increased bone density and surgical exploration revealed only a dense region of necrotic bone.

Aged↗
PubMed2001

A family of depsi-peptide fungal metabolites, as selective and competitive human tachykinin receptor (NK2) antagonists: fermentation, isolation, physico-chemical properties, and biological activity.

Four tachykinin (NK2) receptor inhibitors, SCH 378161 (1), SCH 217048 (2), SCH 378199 (3), and SCH 378167 (4) were isolated from the fermentation broth of a taxonomically unidentified fungus. These compounds were separated from the fermentation broth by ethyl acetate extraction. Purification and separation of the individual compounds were achieved by NK2 assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC. They were identified to be a family of depsipeptides by spectroscopic and degradation studies. Compounds 1 and 3 contain proline and differ as an amide and acid whereas 2 and 4 contain pipecolic acid and differ in being an amide and acid. All of these compounds contain an identical hydroxy acid. They are selective NK2 inhibitors with Ki values ranging from 27-982 nM and demonstrate no activity at 10 microM in the NK1 and NK3 assays. In addition, compounds 1 and 2 inhibited NKA-induced increases in the concentration of intracellular Ca2+, [Ca2+]i, in a CHO cell expressing the human NK2 receptor; this inhibition was competitive in nature with pA2 values of 7.2 and 7.5, respectively. These data demonstrate that these natural products are selective and competitive receptor antagonists of the human NK2 receptor.

Animals↗
PubMed2001

Novel fungal metabolites as cell wall active antifungals: fermentation, isolation, physico-chemical properties, structure and biological activity.

Two novel antifungal compounds, 1 (SCH 466457), and 2 (SCH 466456), active in a "cell wall" assay, were isolated from the fermentation broth of an unidentified fungus. The active compounds were separated from the broth filtrate by adsorption on a macroreticular resin and were purified on reverse phase HPLC. Detailed mass spectrometric and NMR experiments and degradative studies helped in elucidating the structures of these compounds. The compounds were identified to be peptides containing amino acids such as alanine, aminoisobutyric acid, proline, leucine, valine, glycine and a previously identified beta-keto acid, 2-methyl 3-oxotetradecanoic acid. (5) Both compounds were active against Candida, dermatophytes and Aspergillus (Geometric Mean MIC's, 8.9, 20 and 16 microg/ml, and 64, 128 and 23 microg/ml, respectively for 1 and 2).

Anti-Bacterial Agents↗
PubMed2001

Actions of putative chloride channel blocking agents on canine lower esophageal sphincter (LES).

Niflumic acid (NA), a putative Cl(-)-channel blocker, has provided pharmacological evidence that Cl(-)-channel closures mediate hyperpolarization caused by NO in gastrointestinal smooth muscle. However, NA caused concentration-dependent relaxation of canine lower esophageal sphincter (LES) and failed to inhibit NO-mediated relaxations. DIDS also did not inhibit NO-mediated relaxations, but did abolish them when present with 20 mM TEA (tetraethyl ammonium ion), which was also ineffective alone. TEA reversed NA-induced relaxations, but with NA it did not inhibit NO-mediated relaxations. We investigated the modes of action of these agents further. Neither nerve-function block nor block of NOS activity affected the inhibition of LES tone by NA. In patch-clamp studies, NA increased outward currents from -30 to + 90 mV when [Ca2+]pipette was 50 nM. This was prevented by 20 mM TEA, but not by prior inhibition of NOS. At 200 nM [Ca2+]pipette, TEA markedly reduced outward currents, but did not prevent the increase from subsequent NA. In contrast, under similar conditions, application of DIDS after 20 mM TEA further reduced outward currents. When the patch pipette contained CsCl and TEA to block K+ currents, NA had no significant effect on currents between -50 and +90 mV. Thus, NA acted by opening K+ channels: some TEA-sensitive and some not. It had no detectable effect on currents when K+ channels were blocked. We conclude that NA is an unreliable pharmacological tool to evaluate Cl(-)-channel contributions to smooth muscle function. DIDS did not open K+ channels. Decreases in outward currents from DIDS may result from inhibition of K+ currents or currents carried by Cl- at depolarized membrane potentials.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Primate DAX1, SRY, and SOX9: evolutionary stratification of sex-determination pathway.

The molecular evolution of DAX1, SRY, and SOX9, genes involved in mammalian sex determination, was examined in six primate species. DAX1 and SRY have been added to the X and Y chromosomes, respectively, during mammalian evolution, whereas SOX9 remains autosomal. We determined the genomic sequences of DAX1, SRY, and SOX9 in all six species, and calculated K(a), the number of nonsynonymous substitutions per nonsynonymous site, and compared this with the K(s), the number of synonymous substitutions per synonymous site. Phylogenetic trees were constructed by means of the DAX1, SRY, and SOX9 coding sequences, and phylogenetic analysis was performed using maximum likelihood. Overall measures of gene and protein similarity were closer for DAX1 and SOX9, but DAX1 exhibited nonsynonymous amino acid substitutions at an accelerated frequency relative to synonymous changes, similar to SRY and significantly higher than SOX9. We conclude that, at the protein level, DAX1 and SRY are under less selective pressure to remain conserved than SOX9, and, therefore, diverge more across species than does SOX9. These results are consistent with evolutionary stratification of the mammalian sex determination pathway, analogous to that for sex chromosomes.

Amino Acid Sequence↗
PubMed2000

The spectrum of HIV-1 related cancers in South Africa.

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Charged-particle multiplicity near midrapidity in central Au+Au collisions at sqrt[SNN]=56 and 130 GeV.

We present the first measurement of pseudorapidity densities of primary charged particles near midrapidity in Au+Au collisions at sqrt[s(NN)] = 56 and 130 GeV. For the most central collisions, we find the charged-particle pseudorapidity density to be dN/deta|(|eta|<1) = 408+/-12(stat)+/-30(syst) at 56 GeV and 555+/-12(stat)+/-35(syst) at 130 GeV, values that are higher than any previously observed in nuclear collisions. Compared to proton-antiproton collisions, our data show an increase in the pseudorapidity density per participant by more than 40% at the higher energy.

Journal Article↗
PubMed2000

Discovery of (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity.

Continuing structure-activity studies were performed on the 2,3,4, 5-tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepine farnesyltransferase (FT) inhibitors. These studies demonstrated that a 3(R)-phenylmethyl group, a hydrophilic 7-cyano group, and a 4-sulfonyl group bearing a variety of substituents provide low-nanomolar FT inhibitors with cellular activity at concentrations below 100 nM. Maximal in vivo activity in the mutated K-Ras bearing HCT-116 human colon tumor model was achieved with analogues carrying hydrophobic side chains such as propyl, phenyl, or thienyl attached to the N-4 sulfonyl group. Several such compounds achieved curative efficacy when given orally in this model. On the basis of its excellent preclinical antitumor activity and promising pharmacokinetics, compound 20 (BMS-214662, (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thie nyl sulfonyl)-1H-1,4-benzodiazepine) has been advanced into human clinical trials.

3T3 Cells↗
PubMed2000

Real-time fluorescence assay for O6-alkylguanine-DNA alkyltransferase.

O6-alkylguanine-DNA alkyltransferase (AGT) is a DNA-repair protein that reverses the effects of alkylating agents by removing DNA adducts from the O6-position of guanine. We developed a real-time AGT assay that utilizes a fluorescent guanosine analog (3-methylisoxantopterin, 3-MI). 3-MI fluorescence is quenched in DNA and fluorescence intensity increases substantially with digestion of the oligonucleotide and release of 3-MI. The substrate is a doubled-stranded oligonucleotide with 3'-overhangs on each end and a PvuII recognition site. PvuII is inhibited by O6-methylguanine, positioned within the restriction site. 3-MI is incorporated in the opposite strand just outside of the PvuII restriction site. AGT repairs O6-methylguanine; PvuII cleaves at its restriction site, yielding a blunt-ended double strand, which is then digested by exonuclease III. This releases 3-MI from the oligonucleotide, resulting in an increase in fluorescence intensity. All reaction components (100-microL volume) are monitored in a single microcuvette. Rate of increase in fluorescence intensity is related to the amount of AGT in the reaction mixture. We measured AGT levels in extracts from a leukemia cell line, from leukemic lymphoblasts from patients, and from peripheral blood mononuclear cells from normal controls. This method may prove useful for mechanistic studies of AGT.

Base Sequence↗
PubMed2000

Differing serologic responses to an haemophilus influenzae type b polysaccharide-neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) vaccine in australian aboriginal and caucasian infants - implications for disease epidemiology.

This study compared Hib antibody responses to a single lot of PRP-OMPC vaccine given at 2, 4 and 12 months to 57 Aboriginal infants in rural areas of the Northern Territory and 56 Caucasian infants in Sydney, Australia. The Aboriginal infants had lower levels of antibody in cord blood (P>0.05), which were significantly lower (P<0.02) by 2 months of age. Antibody responses to one or two doses of vaccine, measured at 4 and 12 months of age, were similar but the geometric mean titre following the booster dose in Aboriginal infants was significantly lower (1.98 vs. 6.04 mcg/ml, P = 0.002). Low preimmunisation antibody is consistent with the early onset of Hib disease in Aboriginal infants before immunisation. Lower responses to boosting could correlate with persistence of Hib colonisation in indigenous populations.

Age Factors↗