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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 19 recordsLinked to original sources
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↗
PubMed2000

Structure and mechanism of 3-deoxy-D-manno-octulosonate 8-phosphate synthase.

3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase catalyzes the condensation of phosphoenolpyruvate (PEP) with arabinose 5-phosphate (A5P) to form KDO8P and inorganic phosphate. KDO8P is the phosphorylated precursor of 3-deoxy-D-manno-octulosonate, an essential sugar of the lipopolysaccharide of Gram-negative bacteria. The crystal structure of the Escherichia coli KDO8P synthase has been determined by multiple wavelength anomalous diffraction and the model has been refined to 2.4 A (R-factor, 19.9%; R-free, 23.9%). KDO8P synthase is a homotetramer in which each monomer has the fold of a (beta/alpha)(8) barrel. On the basis of the features of the active site, PEP and A5P are predicted to bind with their phosphate moieties 13 A apart such that KDO8P synthesis would proceed via a linear intermediate. A reaction similar to KDO8P synthesis, the condensation of phosphoenolpyruvate, and erythrose 4-phosphate to form 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P), is catalyzed by DAH7P synthase. In the active site of DAH7P synthase the two substrates PEP and erythrose 4-phosphate appear to bind in a configuration similar to that proposed for PEP and A5P in the active site of KDO8P synthase. This observation suggests that KDO8P synthase and DAH7P synthase evolved from a common ancestor and that they adopt the same catalytic strategy.

Aldehyde-Lyases↗
PubMed2000

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis.

BACKGROUND: Controlled trials over two decades ago showed that the polysaccharide vaccine prevented meningococcal meningitis. Subsequent observational studies suggested variations in the level and duration of protection, particularly among young children. OBJECTIVES: To determine the effect of polysaccharide serogroup A vaccine for preventing serogroup A meningococcal meningitis. SEARCH STRATEGY: MEDLINE and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised and other prospective controlled trials. DATA COLLECTION AND ANALYSIS: One reviewer collected data and assessed the methodologic quality of the trials. Data were pooled using the Exact method to assess vaccine efficacy at one, two and three years post-vaccination. MAIN RESULTS: The protective effect within the first year was consistent across all eight trials, including one with participants exclusively under six years of age (in Finland); overall vaccine efficacy was 95% (Exact 95% CI 87%, 99%). The Finnish trial lacked statistical power to assess the effect of a booster dose given to children less than 18 months old. In the three other trials that included children less than six years old (one in Sudan and two in Nigeria), none of the vaccinated children developed meningitis, but the statistical significance of this finding was undetermined. Protection extended into the second (in two studies) and third (in one study) years after vaccination, but these results were also not statistically significant. REVIEWER'S CONCLUSIONS: When compared with current recommendations, the methodological quality and relative incompleteness of the published reports could arguably render the trials invalid for this review. However, it was unlikely that the results of the trials in such diverse settings would have been biased towards a strong and consistent protective effect. Immunogenicity trials were not included in this review. Stage two of the review will assess the vaccine effect from observational studies.

Humans↗
PubMed2000

The high oleate trait in the cultivated peanut [Arachis hypogaea L.]. I. Isolation and characterization of two genes encoding microsomal oleoyl-PC desaturases.

Plant oils rich in oleate are considered superior products compared to oils rich in polyunsaturated fatty acids. Peanut (Arachis hypogaea L.) is one of the major oilseed crops, and high oleate mutant varieties with as much as 85% oleate have been reported. We examined the possibility that this mutant phenotype resulted from reduction in the activity or the transcript level of microsomal oleoyl-PC desaturase. Two independently generated high oleate mutants, M2-225 and 8-2122, and their partially isogenic lines with a normal oleate phenotype were used in this study. Two cDNA sequences coding for microsomal oleoyl-PC desaturases, ahFAD2A and ahFAD2B, have been isolated from the developing peanut seed with a normal oleate phenotype. Cultivated peanut is an allotetraploid, and sequence comparisons with the genes from the putative diploid progenitor species suggested that ahFAD2A and ahFAD2B are non-allelic, but homeologous genes originating from two different diploid species. Northern analysis showed that the transcripts of oleoyl-PC desaturases are highly abundant in both normal and high oleate peanut seeds in the second stage of development. Differential digestion of the RT-PCR products revealed a restriction site polymorphism between ahFAD2A and ahFAD2B, and allowed us to examine the level of transcript expressed from each gene. The results indicate that ahFAD2A is expressed in both normal and high oleate peanut seeds, but the steady state level of the ahFAD2B transcript is severely reduced in the high oleate peanut varieties. These data suggested that the reduction in ahFAD2B transcript level in the developing seeds is correlated with the high oleate trait.

Amino Acid Sequence↗
PubMed2000

Laparoscopic nephroureterectomy. A new standard for the surgical management of upper tract transitional cell cancer.

Laparoscopic nephroureterectomy for upper tract TCC still remains somewhat controversial. Unlike laparoscopic radical nephrectomy, which has become widely accepted, LNU is still in its earliest stages. Although there are obvious benefits for the patient who has LNU--less pulmonary complications, less postoperative discomfort, a shorter hospital stay, a better cosmetic result, and a brief convalescence--there are significant concerns. The longer operative time creates a negative financial and professional inducement to learn this technique. Operative times need to fall into the 4-hour range or less to make the procedure cost-effective. Analysis of the efficacy of laparoscopic nephroureterectomy as a curative treatment modality is important. In the short-run, LNU seems to provide similar results to open nephroureterectomy for upper TCC. Although concerns over port site seeding, bladder recurrence, and intraperitoneal seeding have been voiced, these problems have not occurred. The higher incidence of local recurrence noted in the authors' series, however, is of concern and remains an unsettled issue. Despite these local recurrences, the overall cancer survival for a given grade and stage of upper tract TCC seem to be similar to survivals recorded after open nephroureterectomy. Still, the number of LNU cases remains small, and follow-up is brief. These patients need to be monitored closely, with follow-up CT scans over the next decade. The authors believe that there are still several significant hurdles standing in the path of LNU before it can become a widely accepted procedure. Issues of cost, training, and long-term efficacy must be answered definitively. To obtain these types of data, it will be necessary to create a multi-institutional, cooperative study to obtain sufficient numbers of patients with a more than 5-year follow-up on which to base future recommendations.

Carcinoma, Transitional Cell↗
PubMed2000

Chlorhexidine release from room temperature polymerising methacrylate systems.

A series of different methacrylate monomers (with either 1 or 2.5% dimethyl-p-toluidine, DMPT) was gelled with poly(ethyl methacrylate) powder (containing benzoyl peroxide) thus forming a room temperature curing system. When doped with 5.625% chlorhexidine diacetate the release from the tetrahydrofurfuryl methacrylate-based samples was considerably greater than that from other methacrylate monomers. This seems to be due to the formation of channels in the polymer. Nuclear magnetic resonance spectroscopy, of solutions that the samples were immersed in, showed chlorhexidine was indeed being released from the polymer. It also showed that doping the polymer with chlorhexidine hindered the polymerisation, resulting in a higher level of residual monomer and low molecular weight components being leached from the polymer. The DMPT also affected the polymerisation with greater leaching from the 2.5% DMPT sample.

Anti-Infective Agents, Local↗
PubMed2000

Mitochondrial superoxide production in kainate-induced hippocampal damage.

The objective of this study was to determine the role of mitochondrial superoxide radical-mediated oxidative damage in seizure-induced neuronal death. Using aconitase inactivation as an index of superoxide production, we found that systemic administration of kainate in rats increased mitochondrial superoxide production in the hippocampus at times preceding neuronal death. 8-Hydroxy-2-deoxyguanosine, an oxidative lesion of DNA, was also increased in the rat hippocampus following kainate administration. Manganese(III) tetrakis(4-benzoic acid)porphyrin, a catalytic antioxidant, inhibited kainate-induced mitochondrial superoxide production, 8-hydroxy-2-deoxyguanosine formation and neuronal loss in the rat hippocampus. Kainate-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were attenuated in transgenic mice overexpressing mitochondrial superoxide dismutase-2. We propose that these results demonstrate a role for mitochondrial superoxide production in hippocampal pathology produced by kainate seizures.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

High seroprevalence of antibodies to varicella zoster virus in adult women in a tropical climate.

OBJECTIVES: To determine whether the seroprevalence of antibodies to varicella zoster virus (VZV) in adults is similar to that reported in tropical populations elsewhere. METHODS: We measured the seroprevalence of VZV IgG antibodies, using an enzyme immunoassay (EIA) in women attending an antenatal clinic in an urban centre in tropical Australia. RESULTS: The overall seroprevalence of VZV antibodies in 298 women was 92% (95% CI 88-95), with no difference between women who spent their childhoods in the tropics and colleagues. None of the overseas-born women was seronegative. CONCLUSION: The seroprevalence of VZV antibodies in this tropical population in Australia is as high as that reported from temperate regions, suggesting that social and cultural factors and population mobility are more important determinants of age distribution of VZV immunity than tropical climate.

Adolescent↗
PubMed2000

A protocol of early spiral computed tomography for the detection of stones in patients with renal colic has reduced the time to diagnosis and overall management costs.

BACKGROUND: The recent use of spiral computed tomography (CT) without contrast for the diagnosis of acute flank pain has been shown to be highly sensitive and specific for the detection of urolithiasis. This method has not, however, been evaluated for its contribution to savings in management costs. The present study aims to evaluate the cost savings gained by instituting a protocol of early spiral CT to investigate these patients. METHODS: The records of 200 patients presenting to the Accident and Emergency Department (A&E) with acute flank pain during two periods were retrospectively reviewed. The first period was before the spiral CT protocol was instituted and the second was after. Cost analyses between the two periods were performed. RESULTS: After the spiral CT protocol, 72 versus 31 patients had a definitive diagnosis prior to discharge from hospital. The time taken to diagnosis was also significantly shorter after the protocol implementation (6.3 vs. 16.8 h). This resulted in a shorter time spent in the A&E, and hence bed cost savings. Radiological costs were reduced by 22%, but the major cost saving was made by a reduction in time spent in A&E (44%). CONCLUSIONS: The implementation of a protocol of early spiral CT for patients with suspected renal colic has led to earlier definitive diagnosis and shorter hospital stays. This is associated with a significant reduction in costs associated with managing this condition.

Adult↗
PubMed2000

High creatinine excretion ratio predicts a good outcome in peritoneal dialysis patients.

The creatinine excretion (CrEx) ratio was first described as a method for detecting noncompliance in peritoneal dialysis (PD) patients. However, a high CrEx ratio is not specific for noncompliance and may also be found in compliant patients with a relatively greater lean body mass (LBM). A cohort of 44 PD patients was followed up for a mean of 13 +/- 8 months after measurement of baseline CrEx ratio to investigate whether greater values were predictive of good or poor clinical outcomes. During this follow-up, 11 patients died, 12 patients transferred to hemodialysis, 4 patients underwent transplantation, 1 patient recovered renal function, and 16 patients continued on PD. The mean CrEx ratio in all patients was 1.14 +/- 0.32. It did not differ between men and women (1.15 versus 1.13, respectively; P = 0.76) but showed a trend toward being less in patients with diabetes (1.03 versus 1.19; P = 0. 19). The mean weekly Kt/V, weekly creatinine clearance, normalized protein equivalent of nitrogen appearance, and serum albumin values were 2.18 +/- 0.57, 73.57 +/- 33.75 L/1.73 m(2), 0.80 +/- 0.22 g/kg/d, and 3.22 +/- 0.59 g/dL, respectively. Technique failure (P < 0.001) and death (P < 0.05) were significantly more common in patients with a CrEx ratio less than 1 compared with those with a CrEx ratio greater than 1. On Cox regression analysis, the CrEx ratio was the only significant predictor of technique failure and was also an independent predictor of death. High CrEx ratio is a predictor of good, rather than poor, outcome in PD patients, perhaps because it is primarily an index of nutrition. This further weakens the argument that it is a reliable or useful marker of noncompliance.

Biomarkers↗