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Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 163 records · Page 9Linked to original sources

Case report: aesthetic management of a localised periodontal defect with a gingival veneer prosthesis.

Traditionally acrylic resin gingival veneer prostheses have been used to disguise aesthetic deficiencies of maxillary anterior teeth following successful periodontal therapy and have been retained by engaging horizontal undercuts distal to the canine teeth. They are, however, versatile prostheses with uses in fixed and removable prosthodontics and therapeutic treatment of gingival conditions. In the case presented a small acrylic resin gingival veneer prosthesis retained by a resilient lining material was used to manage a localised periodontal defect of the mandibular central incisor teeth.

Adult↗

HIV/AIDS prevalence among male patients in Kuwait.

OBJECTIVE: To determine the prevalence of human immunodeficiency virus infection among male patients with sexually transmitted disease in Kuwait with emphasis on the type of sexually transmitted diseases and sexual partners. METHODS: A sentinel surveillance was conducted among male sexually transmitted disease patients, randomly selected among all new sexually transmitted disease patients who visited the Family Planning Clinic during June 1996 to June 1997. The patient data was recorded by the attending physician on a specially designed questionnaire. RESULTS: A total of 1984 subjects were screened, out of which not a single human immunodeficiency virus/acquired immunodeficiency syndrome case was found. Among the screened, 69% were non-Kuwaitis. Most of the subjects (76%) belonged to the age group 15-34 years, were married (53%), were illiterate (37.5%) and belonged to the low SES group (70%). The most common sexually transmitted diseases were non-specific urethritis (45%) and gonorrhea (42%). With regard to sexual practices, the majority of the respondents showed preference for female prostitutes, both inside (50%) and outside (48%) Kuwait. CONCLUSION: The absence of any human immuno-deficiency virus positive case was probably due to the mandatory screening for granting residency in Kuwait, facilitating early detection of virus carriers among non-Kuwaitis. We, as researchers, are not sure if this study is true representation of human immunodeficiency virus/acquired immunodeficiency syndrome prevalence among Kuwaiti sexually transmitted disease patients in this country who might seek treatment in private clinics. Moreover, the absence of prostitution as professional trade also tends to show the absence of indigenous circulation of the virus. Nevertheless, continuous surveillance is necessary to maintain and prevent the groups with risky behaviors from contracting the virus through sexual transmission. There is a distinct need to develop public education and awareness programs to serve as measures of prevention and protection.

Acquired Immunodeficiency Syndrome↗

In vitro schizontocidal activity of standard antimalarial drugs on chloroquine-sensitive and chloroquine-resistant isolates of Plasmodium falciparum.

The expanding foci of multiple drug resistant malaria and emergence of different strains requires the reassessment of antimalarial activity with various drugs. In vitro response of a chloroquine sensitive and a chloroquine resistant isolate of P. falciparum to a group of 6 quinine derived and 3 artemisinin derived standard drugs has been screened, to evaluate schizontocidal activity of the drugs. In a conventional test system the IC50s were derived from the log dose response curves and evaluated by a rigorous statistical interpretation. Analysis by Tukey's test was significant for the quinine related drugs (Q < or = 0.01) and excludes the statistical significance of artemisinin related drugs in these isolates. The dose-responses of these two isolates vary with quinine derivatives, with some overlap at lower doses for the sensitive isolate than for the resistant one which manifests at higher doses.

Animals↗

Comparative effectiveness of Tiron (4,5-dihydroxy benzene 1,3-disulphonic acid disodium salt) and CaNa2EDTA with time after beryllium poisoning.

The efficacy of two chelating agents (Tiron and calcium disodium EDTA) in the treatment of beryllium induced blood biochemistry and hepatic histopathological alteration was investigated at different duration in female albino rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (im) showed significant decrease in haemoglobin percentage, blood sugar level, protein contents and activity of alkaline phosphatase. On the contrary significant elevation was found in the activity of transaminases (AST and ALT). Tiron was found to be more effective than CaNa2EDTA in reducing the beryllium induced haematological alterations and histopathological lesions in liver. These findings were further confirmed by AAS thus, in which reduced beryllium body burden was seen in liver and blood with Tiron.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Evaluation of in vitro schizontocidal activity of plant parts of Calotropis procera--an ethnobotanical approach.

Calotropis procera (Ait.) R.Br. commonly known, as 'Arka' is a popular medicinal plant found throughout the tropics of Asia and Africa and is used in many traditional systems of medicine. Important factors of the various parts of this plant have been widely reported. Good record keeping of subjective and objectively recorded cures by practitioners of traditional medicinal system will help in the establishment of the use of C. procera as an antimalarial plant. It has been attempted to see the effect of crude fractions of its flower, bud and roof against a chloroquine sensitive strain, MRC 20 and a chloroquine resistant strain, MRC 76 of Plasmodium falciparum using the Desjardins method and the effectiveness of its fractions compare better with the CQ sensitive strain than the CQ resistant strain in vitro.

Africa↗

Frequency of trisomy 15 and loss of the Y chromosome in adult leukemia.

In the interpretation of the varied and complex cytogenetic counts obtained in analysis of bone marrow (BM) samples for leukemia, loss or gain of certain chromosomes may or may not be significant for prognosis. Loss of the Y chromosome in elderly males is a benign finding. Trisomy 15 is rare and may represent another age-related abnormality, particularly in males, together with -Y. We reviewed 3,242 routine referrals sent to our laboratory for BM cytogenetics, over a period of 34 months. We detected 5 cases with uncomplicated trisomy 15, 3 in males and 2 in females. Three of these patients had the diagnosis of myelodysplastic syndrome (MDS). All 3 males showed a -Y cell line, although the 2 females did not have an X chromosome loss. All 5 patients were alive and well at times varying from 12 months to 4 years post-diagnosis. In the further analysis of our referral cohort, there were 62 males with loss of the Y chromosome as the sole abnormality, and of these 47 (76%), were referred with myeloid disease. The frequency of trisomy 15 in our laboratory was 1/475 referrals, but 1/292 in successful cultures from new patients. This is the first report providing frequency data for trisomy 15. Further data with longer term follow-up is required to establish the significance of trisomy 15 in elderly leukemic patients.

Adult↗

Two children with acute lymphoblastic leukemia and "jumping" translocations: both involve 1q23 as the donor breakpoint.

"Jumping" translocations (JT) are relatively rare and are associated with poor prognosis. We report two male patients with childhood acute lymphoblastic leukemia (ALL) and abnormal cell lines detected on bone marrow cytogenetics. Diagnostic marrow cytogenetics were not available for either patient. In patient 1, approximately 11 years after diagnosis, cytogenetics revealed a single translocation, t(1;2)(q23;q32), which was followed by translocations t(1;22)(q23;p11) and t(1;1)(q23;q21.3). In patient 2, two translocations were present together, t(1;6)(q23;p21.3) and t(1;11)(q23;q21), 12 years after diagnosis. The unbalanced JTs in both patients resulted in partial trisomy for (1)(q23-->qter). Both died within 1-2 years after the appearance of the JT. Our patients provide additional support for chromosome 1q preferential involvement in JTs, and that their appearance is associated with a poor prognosis.

Child, Preschool↗

Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation.

Cyclin-dependent kinase 5 (cdk5) is found in an active form only in neuronal cells. Activation by virtue of association with the cyclin-like neuronal proteins p35 (or its truncated form p25) and p39 is the only mechanism currently shown to regulate cdk5 catalytic activity. In addition to cyclin binding, other members of the cdk family require for maximal activation phosphorylation of a Ser/Thr residue (Thr(160) in the case of cdk-2) that is conserved in all cdks except cdk8. This site is phosphorylated by cdk-activating kinases, which, however, do not phosphorylate cdk5. To examine the possible existence of a phosphorylation-dependent regulatory mechanism in the case of cdk5, we have metabolically labeled PC12 cells with (32)P(i) and shown that the endogenous cdk5 is phosphorylated. Bacterially expressed cdk5 also can be phosphorylated by PC12 cell lysates. Phosphorylation of cdk5 by a PC12 cell lysate results in a significant increase in cdk5/p25 catalytic activity. Ser(159) in cdk5 is homologous to the regulatory Thr(160) in cdk2. A Ser(159)-to-Ala (S159A) cdk5 mutant did not show similar activation, which suggests that cdk5 is also regulated by phosphorylation at this site. Like other members of the cdk family, cdk5 catalytic activity is influenced by both p25 binding and phosphorylation. We show that the cdk5-activating kinase (cdk5AK) is distinct from the cdk-activating kinase (cyclin H/cdk7) that was reported previously to neither phosphorylate cdk5 nor affect its activity. We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro.

Amino Acid Sequence↗

Mouse models of prostate cancer.

The pathogenetic basis of prostate cancer remains highly elusive; its clarification could be facilitated greatly by laboratory and clinical models of the disease. Although the genetically manipulated mouse has been invaluable for the modeling of other human cancer types, it has fared less well with respect to prostate cancer. Nevertheless, several highly valuable transgenic models exist and are highlighted in this review. Emerging reagents and strategies may allow us to use the mouse more effectively to define the molecular, cellular and physiological events that lead to prostate cancer initiation and progression.

Animals↗

Leishmania donovani: cellular and humoral immune responses in Indian langur monkeys, Presbytis entellus.

We have previously reported that disease mimicking human visceral leishmaniasis can be established in Presbytis entellus, the Indian langur monkey, following a single intravenous challenge of 10(8) Leishmania donovani amastigotes. In the present report, infection was assessed in monkeys infected intravenously with a single dose of 10(8) amastigotes (HDA group), three weekly doses of 10(7) amastigotes (LDA group) and three weekly doses of 5 x 10(7) promastigotes (HDP group). Typical clinical infection was established in all three groups with significant parasite load. There was a gradual and sustained rise in anti-leishmania specific immunoglobulin G response, and a severe fall in the lymphoproliferative response to the T cell mitogens PHA and Con A by day 80 post infection (p.i.). The antibody level remained elevated until death in monkeys of the HDA and HDP groups; the T-cell responses showed a recovery prior to death. T-cell responses to leishmania antigen, however, could not be demonstrated in any of these monkeys prior to death. One monkey of the LDA group survived for 155 days and two monkeys spontaneously eradicated the infection. Surprisingly, one monkey of the HDA group also achieved spontaneous cure. In the three monkeys which eradicated infection spontaneously, the antibody level declined to baseline levels on day 180 p.i. with a well demonstrable antigen specific lymphoproliferative response; no parasites could be demonstrated in splenic aspirates by direct examination of culture. These data demonstrate that disease severity may be the function of the total inoculum dose rather than the stage of the parasite and that the immunological responses in the Indian langur model parallel the reported changes in human visceral leishmaniasis. This makes the langur a potentially useful model for the evaluation of candidate anti-leishmanial drugs and vaccines.

Animals↗

Identification of substrate binding site of cyclin-dependent kinase 5.

Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine. Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown. We have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5. The experimental data and computer simulations suggest that Asp86 and Asp91 are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates.

Amino Acid Sequence↗

Characterization of the cloned atlantic cod neuropeptide Y-Yb receptor: peptide-binding requirements distinct from known mammalian Y receptors.

Five members of the neuropeptide Y (NPY) receptor family have been cloned in mammals. The recently cloned NPY receptor in the Atlantic cod seems to be distinct from the mammalian subtypes as it has only 50% identity to Y1, Y4, and y6 and only 30% to Y2 and Y5. In most of the other families of G-protein-coupled receptors, species homologues have 65-90% identity between fishes and mammals. The functional expression and detailed pharmacological characterization of this cod NPY receptor, designated Yb, is reported. Membranes of cells transiently transfected with cod Yb showed saturable [(125)I]PYY binding with a K(d) of 45 pM. The pharmacological profile is similar to those of both the zebrafish Yb and Yc receptors and distinct from those of the mammalian NPY receptors. In competition experiments the cod Yb receptor had the following rank order of potencies: porcine PYY = porcine NPY = p[Leu(31), Pro(34)]NPY > zebrafish PYY > zebrafish NPY >> NPY2-36 = NPY3-36 > NPY18-36 > bovine PP = [D-Trp(32)]NPY > BIBP3226. This is in sharp contrast to the high selectivity of BIBP3226 for the Y1 receptor from all mammalian species. Together with the low amino acid identity of cod Yb with the mammalian Y1, Y4, and y6 receptors, this is further support for the notion that fish Yb constitutes a distinct NPY receptor subtype.

Animals↗

Laser and multipolar electrocoagulation ablation of early Barrett's adenocarcinoma: long-term follow-up.

BACKGROUND: Endoscopic ablation of Barrett's esophagus, including associated dysplasia and adenocarcinoma, can be achieved by various techniques, but few long-term results are available. The aim of our study was ablation of intramucosal adenocarcinoma with a combination of Nd:YAG laser plus multipolar electrocoagulation. METHODS: Patients with documented Barrett's esophagus and adenocarcinoma who either had refused surgery or were poor candidates for surgery because of high risk were offered endoscopic therapy. Patients underwent therapy with Nd:YAG laser and multipolar electrocoagulation. They were treated with omeprazole (20 mg twice daily) as maintenance therapy. RESULTS: Six patients were enrolled in the study over a 7-year period. All were men with a mean age of 78.2 years. The mean length of Barrett's esophagus was 6.0 cm (range, 3 to 10 cm). Seventeen Nd:YAG laser (mean, 2.8/patient) and 20 multipolar electrocoagulation (mean, 3.3/patient) sessions were used during the study period. All patients had a complete initial response to therapy. One patient on chronic immunosuppressive medications had recurrence of the tumor after an initial complete response (36-month follow-up). Two patients have no evidence of Barrett's esophagus, and 3 patients have residual intestinal metaplasia on biopsy of an irregular appearing "neo" Z-line. Mean follow-up in this group is 3.4 years (range, 9 to 86 months). CONCLUSIONS: Laser photocoagulation and multipolar electrocoagulation can be successfully and safely used to ablate intramucosal adenocarcinoma in the setting of Barrett's esophagus. Patients remain functional with normal swallowing.

Adenocarcinoma↗

Durability of new squamous epithelium after endoscopic reversal of Barrett's esophagus.

BACKGROUND: Endoscopic reversal of Barrett's esophagus with multipolar electrocoagulation and high-dose omeprazole has been previously described but long-term results are not available. The aim of this study was to follow patients after endoscopic reversal and to perform a detailed analysis of the "new" squamous mucosa. METHODS: After reversal, patients with Barrett's esophagus were maintained on high-dose omeprazole and underwent interval endoscopy, and large biopsies were obtained of the former Barrett's epithelium. RESULTS: Nine of 11 patients were men; the mean age was 62 years. The mean length of Barrett's mucosa was 4.4 cm; the mean dose of omeprazole used was 49 mg/day. All patients had an initial complete response to treatment-no evidence of Barrett's endoscopically and histologically. Three patients had intestinal metaplasia underlying the new squamous mucosa in the latest follow-up biopsies. In these 3 patients, only 0.4%, 2%, and 8% of the total biopsy area had intestinal metaplasia. All but 4 patients had underlying intestinal metaplasia at variable times during the study period. Patients have been followed for a mean of 36 months (range 19 to 53 months). CONCLUSIONS: New squamous mucosa is durable and resembles normal squamous tissue. Underlying glands of intestinal metaplasia are intermittently found. Because the significance of this residual intestinal metaplasia is unclear, surveillance endoscopy with biopsies of the treated segment is recommended even after reversal therapy.

Aged↗

Novel chromosome 16 abnormality--der(16)del(16) (q13)t(16;21)(p11.2;q22)--associated with acute myeloid leukemia.

Inversion of chromosome 16 is a common feature of acute myeloid leukemia (AML) M4, while t(16;21), although also associated with AML, appears to be a separate entity. We present a patient with myelodysplastic syndrome (MDS) who transformed to AML-M1. The karyotype was normal at diagnosis; at 15 months, hematological evidence of transformation was present, and repeat cytogenetics showed a novel rearrangement of one chromosome 16. Two breaks had occurred; one in the short arm at 16p11, with translocation of the segment distal to this onto chromosome 21q, and the other in the long arm at 16q22 with subsequent deletion of the segment from 16q22-->qter. Fluorescence in situ hybridization (FISH) confirmed the abnormalities detected by cytogenetics and excluded involvement of the AML1 gene on 21q22. While the 16q22 breakpoint was at the usual site for the inv(16), the 16p11 was not. The patient is more characteristic of t(16;21) than inv(16), and adds to the spectrum of chromosome 16 abnormalities in AML.

Aged↗

Impact of diabetes on CNS: role of signal transduction cascade.

Diabetic neuropathy is the most common secondary complication of diabetes mellitus. Several pathogenetic factors have been proposed for diabetic neuropathy. The present investigation was undertaken to study different components of signal transduction from discrete brain regions from streptozotocin-induced diabetic rats. Rats were sacrificed after 1 and 3 months of induction of diabetes, and a control group was also studied in parallel to ascertain the specificity of diabetes-associated changes. Blood glucose level and protein content of discrete brain regions were also estimated. Signal transduction cascade components like protein kinase A, protein kinase C, cAMP, phospholipase C, phospholipase A2, diacylglycerol and inositol phosphate levels were assayed in control and diabetic groups of rats. Significant attenuation in phosphoinositide metabolism along with activation of protein kinase activities were observed. These findings provide evidence to suggest a mechanism linking changes in signal transduction cascade, which is observed in 1- and 3-month diabetic rats, which ultimately leads to development of diabetic neuropathy.

Animals↗

Bio-battery signal predicts myocardial lesion formation and depth in vitro.

AIMS: The aim of this study was to determine if the bio-battery signal can predict myocardial lesion formation and depth. METHODS: Fresh bovine ventricular myocardium was immersed in a temperature-controlled bath of circulating blood. RF energy was delivered with a custom generator to a catheter electrode. RF energy, electrode temperature, bio-battery signal and tissue impedance were displayed and recorded. A copper return plate was placed in the bath. RESULTS: When 50 volts of constant RF energy was terminated at a 20, 40, or 60% decline from the maximum bio-battery signal, the lesion depth was 4 +/- 0.4 mm. When RF energy application was terminated later, at a point characterized by a brief change of slope of the bio-battery signal, the lesions measured 7.8 +/- 1.4 mm in depth. This "bump" occurred before a rapid impedance rise. CONCLUSION: The depth of lesions created at the "bump" point was almost two-fold deeper than those at the termination points of 20, 40 and 60% bio-battery decrease (p = 0.0001). When RF energy was terminated at the rapid impedance rise the lesions were similar in depth, 8.2 +/- 0.9 mm, to those obtained when RF energy was stopped at the "bump" (p = 0.28). The bio-battery signal provides a unique marker that might be useful to obtain maximum lesion depth while avoiding rapid impedance rise.

Animals↗