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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 181 records · Page 10Linked to original sources
PubMed1998

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Animals↗
PubMed1998

A depsipeptide fungal metabolite inhibitor of cholesteryl ester transfer protein.

The organic extract of the fermentation broth of a fungus was found to contain a depsipeptide SCH 58149 (1), containing three amino acids and a beta-hydroxy acid, by spectroscopic studies. The amino acids were phenyl alanine, alanine and leucine and the beta-hydroxy acid is 3-hydroxy-4-methyl octanoic acid. SCH 58149 exhibited weak activity against cholesterol ester transfer protein (CETP) with an IC50 of 50 microM.

Acremonium↗
PubMed1998

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors.

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.

Binding Sites↗
PubMed1998

HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle.

Several important and possibly interrelated functions have been identified for the HIV-1 accessory gene product Vpr. These include import of the HIV reverse transcription complex into the nucleus of nondividing cells, cellular differentiation including cell cycle arrest at the G2/M phase border, immune suppression, and enhancement of virus replication. We have cloned a candidate Vpr ligand, termed human Vpr interacting protein (hVIP/MOV34), by using a yeast two-hybrid assay. This gene is homologous to a simultaneously identified 34-kDa human mov34 homologue. The MOV34 family includes proteins that function as transcriptional and proteolytic regulators of cell growth and differentiation. We demonstrate direct interactions between the putative ligand hVIP/MOV34 and Vpr in vitro and in vivo. hVIP/MOV34 localizes to the nucleus and appears to function as a component of the cell cycle cascade. We observe an association between the induction of cell cycle arrest at the G2/M phase border by Vpr and a change in the subcellular localization of hVIP/MOV34 from a nuclear to a perinuclear localization. This was further associated with the inhibition of maturation promoting factor-associated histone H1 kinase activity. We conclude that hVIP/MOV34 is involved in the regulation of the cell cycle and a likely cellular cofactor for HIV-1 Vpr.

Amino Acid Sequence↗
PubMed1998

Development of a CD28 receptor binding-based screen and identification of a biologically active inhibitor.

CD28 is a T-cell costimulatory receptor which plays a pivotal role in antigen-induced T-cell response. We have developed a cell-free and scintillation-proximity assay-based screen to search for molecules that inhibit ligand binding to CD28. The assay was shown to be versatile and adaptable to automation for high-throughput screening. Using this assay, we identified an inhibitor of CD28, NP2214. The inhibitor was shown to be active in vitro by suppressing IL-2 synthesis and proliferation of peripheral blood mononuclear cells in response to CD28 costimulation. We also demonstrated the additive effects of NP2214 and cyclosporine A which act mechanistically distinctly in inhibiting costimulation-induced IL-2 synthesis.

Abatacept↗
PubMed1998

Upper extremity radionuclide bone imaging: shoulder, arm, elbow, and forearm.

Along with resurgence of physical activity during these fitness conscious times, there is increasing participation by people of all ages in sporting activities. Enrollment in organized and recreational sports among young adults and children has increased with as many as 30% of adolescents participating in competitive high school athletics. Despite improvements in equipment, the number of sports-related injuries presenting for medical attention has increased. Injuries to the upper extremities account for more than 25% of all sports-related injuries, but receive disproportionately less attention compared to lower extremity injuries. If neglected, upper extremity injuries can end the career of a professional athlete and cause sufficient damage to hinder daily activities in a recreational participant. Overuse syndromes, brought on by repetitive microtrauma are sports-specific, and often challenging to diagnose. Accurate diagnosis requires a thorough understanding about mechanism of injury, site of pain, and knowledge of the sport. After a thorough physical exam, a variety of radiographic testing is often necessary to promptly diagnose and manage the injury so athletes can return to competition as soon as possible.

Adolescent↗
PubMed1998

Reattempting failed external cephalic version under epidural anesthesia.

OBJECTIVES: We hypothesize that the success rate of external cephalic version may be increased by performing a repeat attempt with the patient under epidural anesthesia. STUDY DESIGN: One hundred eight women with term singleton pregnancies in breech presentation underwent attempted external version. When external version failed, we offered them the option of a later attempt under epidural anesthesia. All fetuses who remained in breech position were delivered by elective cesarean section. RESULTS: Fifty (60%) of the 83 attempted external versions performed without anesthesia were successful. Seventeen of the 33 women whose versions were unsuccessful underwent elective cesarean delivery, and 16 elected to undergo repeat version attempts under epidural. Nine (56%) of these 16 procedures were successful, and 7 of these 9 women were delivered vaginally. The overall success rate was 71%, similar to the success rate of versions attempted on 25 women under epidural anesthesia. CONCLUSIONS: When an attempted external version fails, a repeat attempt under epidural anesthesia will usually be successful, resulting in a lower cesarean delivery rate.

Adult↗
PubMed1998

Control of the human cell cycle by a bacterial protein, gapstatin.

The oral gram-negative bacterium Actinobacillus actinomycetemcomitans is a major pathogen in human periodontal disease. Saline extraction releases a range of surface-associated components from this bacterium, including one which exhibits potent anti-proliferative activity as assessed by its capacity to inhibit DNA synthesis by human and other mammalian cells. Cultures incubated with this bacterial fraction for a prolonged period comprise a high proportion of cells containing a 4n level of DNA. Studies using hydroxyurea-synchronized cultures showed that cells treated with the surface-associated fraction were arrested in the G2 phase of the cell cycle and did not enter mitosis. This G2/M blockade was observed only when the bacterial fraction was added to the cells during early S phase. Our data also suggest that the active bacterial component binds to surface receptors expressed by the human cells and may act by a novel mechanism which involves down-regulation of cyclin B1 expression. The anti-proliferative activity of the bacterial fraction, purified by a combination of ammonium sulphate precipitation, HPLC anion exchange and gel filtration, has been shown to be an 8 kDa protein, which we have called gapstatin. Purified gapstatin was shown to be responsible for the the inhibitory effects of the surface-associated fraction on mammalian cells.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

Construction of attenuated HIV-1 accessory gene immunization cassettes.

Delivery of genetic expression cassettes into animals can effectively induce both humoral and cellular immunity to the expressed gene product. Previously, we used this strategy to immunize against HIV-1 structural and enzymatic proteins in mice, non-human primates and in humans. In contrast, the use of the accessory genes including vif, vpr, vpu and nef as immunotherapeutic vaccine targets has not been well characterized. Our goal is to design an effective genetic HIV vaccine, which includes the accessory genes as part of a multi-component immunogen. In order to develop accessory genes as genetic vaccines, we have molecularly cloned and analysed the sequence variation and immunogenic potential present in these genes derived from viral isolates obtained from HIV-1 infected patients and laboratory isolates. Prototype genetic variants were selected and their ability to induce humoral and cellular immune responses was studied in animal models. We observed that attenuated accessory genes can effectively induce both humoral and cellular responses in mice and the resulting immune response is directly correlated with DNA concentrations delivered and the number of boosts. This strategy can be used generally to develop an effective, safe DNA vaccine for any pathogen.

AIDS Vaccines↗
PubMed1998

Glutamate receptor GluR3 antibodies and death of cortical cells.

Rasmussen's encephalitis (RE), a childhood disease characterized by epileptic seizures associated with progressive destruction of a single cerebral hemisphere, is an autoimmune disease in which one of the autoantigens is a glutamate receptor, GluR3. The improvement of some affected children following plasma exchange that removed circulating GluR3 antibodies (anti-GluR3) suggested that anti-GluR3 gained access to the central nervous system where it exerted deleterious effects. Here, we demonstrate that a subset of rabbits immunized with a GluR3 fusion protein develops a neurological disorder mimicking RE. Anti-GluR3 IgG isolated from serum of both ill and healthy GluR3-immunized animals promoted death of cultured cortical cells by a complement-dependent mechanism. IgG immunoreactivity decorated neurons and their processes in neocortex and hippocampus in ill but not in healthy rabbits. Moreover, both IgG and complement membrane attack complex (MAC) immunoreactivity was evident on neurons and their processes in the cortex of a subset of patients with RE. We suggest that access of IgG to epitopes in the central nervous system triggers complement-mediated neuronal damage and contributes to the pathogenesis of both this animal model and RE.

Animals↗
PubMed1998

Biosocial factors affecting vitamin D status of women of childbearing age in the United Arab Emirates.

Low serum 25-OHD in female Arab subjects, which may predispose their infants to hypocalcaemia, has been suggested to be due to inadequate sunshine exposure, but may include other sociobiological factors. The effects of duration of sunshine exposure--weighted against the magnitude of clothing (UV exposure) and other sociobiological variables such as age, education and living accommodation--on serum 25-OHD and mineral status of 33 UAE national women of childbearing age were compared with those of 25 non-Gulf Arabs and seventeen Europeans. Serum concentrations of calcium, phosphorus, alkaline phosphatase and intact parathyroid hormone among the groups were not significantly different. The serum concentration of 25-OHD in UAE nationals was 8.6 ng/ml (4.5-17.4), mean +/- 1 SD, and in non-Gulf Arabs 12.6 ng/ml (6.0-26.4); both these values were significantly lower (p = < 0.0001) than the 64.3 ng/ml (49-84.3) found in Europeans. Compared with Europeans, the UAE and non-Gulf Arabs in this study were younger, had fewer years of education and had significantly lower clothing and UV scores (p < 0.0001). Furthermore, there was a positive correlation (r = 0.59425) between serum 25-OHD and UV score, but not with length of exposure. After adjusting for other confounding variables, nationality, clothing and UV scores remained major determinants of serum 25-OHD (p < 0.0001). Therefore, limited skin exposure to sunlight appears to be an important determinant of vitamin D status in our subjects. Strategies to increase vitamin D stores should include vitamin D supplementation or advice on effective sunlight exposure.

Adult↗
PubMed1998

A cluster of meningococcal disease in western Sydney, Australia initially associated with a nightclub.

Fourteen cases of meningococcal disease (MD) occurred in August September 1996 in western Sydney, Australia. Seven of the 10 young adults affected had a direct or indirect link with a local nightclub. Ten of 11 systemic meningococcal isolates had the phenotype C:2a:P1.5 and showed close genetic relationship by pulsed-field gel electrophoresis (PFGE). Organisms of this phenotype have not previously caused outbreaks in Australia, but have been associated with outbreaks and hyperendemic serogroup C MD in Europe, Canada, and the United States. This is the largest cluster of serogroup C MD reported in urban Australia, and the first involving a nightclub. The strain differentiation results were available rapidly enough to augment epidemiological investigations on a daily basis. Public health staff could thus establish links between cases quickly, follow the spread of new cases in the community, give accurate information to health officials and the press, and utilize existing knowledge about the characteristics of this phenotype to predict likely developments during the outbreak and afterwards. The strain differentiation data was also very helpful when the role of vaccination was considered, and existing guidelines on the management of outbreaks of MD could be used effectively for the first time in western Sydney.

Adolescent↗
PubMed1998

Inhibition of neuronal apoptosis by a metalloporphyrin superoxide dismutase mimic.

The objective of this study was to determine whether free radicals play a pathogenic role in neuronal apoptosis. The ability of Mn(III) tetrakis(benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimic, to inhibit staurosporine-induced neuronal apoptosis was tested in mixed cerebrocortical cultures. Staurosporine produced concentration-dependent cell death that was markedly inhibited by MnTBAP. Immunocytochemical analyses of cultures for neuron- and astrocyte-specific markers revealed that high concentrations of staurosporine induced the death of both neurons and astrocytes; both cell types were protected by MnTBAP. A less active congener of MnTBAP failed to protect cells against staurosporine-induced apoptosis. MnTBAP also protected cortical cultures against ceramide-induced apoptosis. These results support a role for oxidative stress in neuronal apoptosis.

Animals↗