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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 361 records · Page 20Linked to original sources
PubMed1997

Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer.

BACKGROUND: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. OBJECTIVE: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. DESIGN: Phase I and II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. INTERVENTION: A single intravenous dose of thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before chemotherapy. MEASUREMENTS: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. RESULTS: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. CONCLUSIONS: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.

Antibodies↗
PubMed1997

Mutational analysis of a plant defensin from radish (Raphanus sativus L.) reveals two adjacent sites important for antifungal activity.

Mutational analysis of Rs-AFP2, a radish antifungal peptide belonging to a family of peptides referred to as plant defensins, was performed using polymerase chain reaction-based site-directed mutagenesis and yeast as a system for heterologous expression. The strategy followed to select candidate amino acid residues for substitution was based on sequence comparison of Rs-AFP2 with other plant defensins exhibiting differential antifungal properties. Several mutations giving rise to peptide variants with reduced antifungal activity against Fusarium culmorum were identified. In parallel, an attempt was made to construct variants with enhanced antifungal activity by substituting single amino acids by arginine. Two arginine substitution variants were found to be more active than wild-type Rs-AFP2 in media with high ionic strength. Our data suggest that Rs-AFP2 possesses two adjacent sites that appear to be important for antifungal activity, namely the region around the type VI beta-turn connecting beta-strands 2 and 3, on the one hand, and the region formed by residues on the loop connecting beta-strand 1 and the alpha-helix and contiguous residues on the alpha-helix and beta-strand 3, on the other hand. When added to F. culmorum in a high ionic strength medium, Rs-AFP2 stimulated Ca2+ uptake by up to 20-fold. An arginine substitution variant with enhanced antifungal activity caused increased Ca2+ uptake by up to 50-fold, whereas a variant that was virtually devoid of antifungal activity did not stimulate Ca2+ uptake.

Amino Acid Sequence↗
PubMed1997

Protein phosphatase-2A association with microtubules and its role in restricting the invasiveness of human head and neck squamous cell carcinoma cells.

The role of protein phosphatase-2A (PP-2A) in regulating the motility and adhesion of human head and neck squamous cell carcinomas (HNSCC) was investigated. Immunofluorescent staining of these HNSCC cells showed PP-2A can co-localize with microtubules. That the PP-2A influences motility was shown by the increase in HNSCC cell migration through laminin and vitronectin when PP-2A was selectively inhibited with low dose okadaic acid, and by the reduction in invasion through these same matrix components by elevators of PP-2A activity. Motility of HNSCC cells through collagen I or fibronectin was not modulated by PP-2A. The reduction in HNSCC migration through vitronectin or laminin that resulted from treatment with PP-2A elevators was associated with an increase in cellular adhesiveness to these same ECM components. These studies show the association of PP-2A with the cellular cytoskeleton and its role in restricting the invasiveness of tumor cells through select extracellular matrix components.

Calcitriol↗
PubMed1997

Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats.

Permanent or transient focal cerebral ischemia was induced in spontaneously hypertensive rats (SHR) using the intraluminal filament method. Successful occlusion of the middle cerebral artery (MCA) was achieved using 4/O filaments (terminal diameter 0.20-0.25 mm) coated with poly-L-lysine. The L-type calcium channel blocker isradipine (2.5 mg/kg) administered subcutaneously 30 min following permanent MCA occlusion significantly reduced the volume of ischemic brain damage in the cerebral hemisphere (25%; P = 0.0001), cerebral cortex (18%; P = 0.0034), and caudate nucleus (33%; P = 0.0002) when assessed at 24 h post-MCA occlusion. Isradipine did not affect the functional deficit (measured using a subjective neurological scoring system) induced by MCA occlusion. In SHR undergoing transient (2 h) MCA occlusion isradipine administered 30 min post-MCA occlusion produced a significant reduction (47%; P = 0.001) in hemispheric infarct volume, whereas isradipine administered at the onset of reperfusion did not confer any significant neuroprotection. No change in functional deficit was seen with isradipine with either dosing paradigm at 24 h post-MCA occlusion. These results demonstrate that the intraluminal filament method of MCA occlusion can be used in the SHR strain and also substantiates the neuroprotective efficacy of isradipine in SHR models of permanent and transient focal cerebral ischemia.

Animals↗
PubMed1997

Asymmetry of respiratory sounds and thoracic transmission.

Breath sounds heard with a stethoscope over homologous sites of both lungs in healthy subjects are presumed to have similar characteristics. Passively transmitted sounds introduced at the mouth, however, are known to lateralise, with right-over-left dominance in power at the anterior upper chest. Both spontaneous breath sounds and passively transmitted sounds are studied in four healthy adults, using contact sensors at homologous sites on the anterior upper and posterior lower chest. At standardised air flow, breath sound intensity shows a right-over-left dominance at the anterior upper chest, similar to passively transmitted sounds. At the posterior lung base, breath sounds are louder on the left, with a trend to similar lateralisation in transmitted sounds. It is likely that the observed asymmetries are related to the effects of cardiovascular structures and airway geometry on sound generation and transmission.

Adult↗
PubMed1997

The cortisol response to psychological challenge is preceded by a transient rise in endogenous inhibitor of monoamine oxidase.

The salivary cortisol response to an acute psychological stress challenge was investigated in normal male undergraduate students. A modified version of the Trier Social Stress Test (TSST) was used and saliva collected on 6 occasions before during and after the stress challenge. Control subjects were allowed to read quietly. As expected the cortisol response in experimental subjects was robust and peaked 12 minutes after the end of the stress. Endogenous monoamine oxidase A inhibitory activity (MAO-AI) was measured in the same saliva samples. MAO-AI also changed in response to the stress challenge, peaking in the saliva sample collected immediately after the stress challenge, 12 minutes prior to the cortisol peak sample. Furthermore the degree of increase in salivary MAO-AI was found to predict the degree of cortisol increase in the test subjects (r=0.76; n=14; p<0.001). These results are consistent with the hypothesis that elevated central monoamines, driven by inhibition of their main metabolic enzyme, can activate the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This finding lends further support to the notion that endogenous generation of MAO-AI is a normal homeostatic regulatory mechanism.

Adult↗
PubMed1997

Investigation of an outbreak of multidrug resistant tuberculosis among renal patients using rpo B gene sequencing and IS6110 inverse PCR.

A cluster of cases of tuberculosis among five patients receiving treatment for renal failure was investigated. Insertion sequence (IS6110) fingerprinting and antibiotic resistance profiling of the Mycobacterium tuberculosis isolates from four of the patients (A-D), who had been on the same ward, showed that three of these cases (A-C) were related, but that the fourth (D) was distinct. An isolate from the fifth patient (E), who had been on a separate ward, was indistinguishable from the outbreak strain by IS6110 profile. However, the isolate from patient E and a second isolate from patient A differed from the previous strains in being rifampicin resistant. Sequence analysis of the rpo B genes of the two rifampicin-resistant strains demonstrated the presence of different mutations, showing that they had evolved independently from the same source strain. IS6110 and rpo B gene analyses are invaluable for the accurate investigation of outbreaks of multidrug resistant tuberculosis.

Cross Infection↗
PubMed1997

Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist.

The discovery of a novel high-affinity and selective dopamine D4 receptor antagonist, L-745,870, and the results of clinical trials with this compound are reviewed. Despite several lines of evidence which suggest that a selective D4 receptor antagonist may be an effective antipsychotic agent with a lower propensity to induce extrapyramidal side-effects, L-745,870 was ineffective as an antipsychotic in humans.

Animals↗
PubMed1997

A system for isolation, transport and storage of herpes simplex viruses.

A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 degrees C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.

Animals↗
PubMed1997

Molecular and structural differences between rat brain D-1 and renal DA-1 dopamine receptors.

Renal DA-1 dopamine receptors in proximal tubules (PTs) of the Wistar-Kyoto (WKY) rat display pharmacological binding properties which are different from central nervous system (CNS) striatal D-1 dopamine receptors. In general, the renal DA-1 receptors display affinity binding values of dopaminergic drugs which are 6-36-fold less than those seen for brain D-1 receptors. The renal and brain DA receptors also displayed differential sensitivity toward the alkylating agent, N-ethylmaleimide (NEM). Inactivation of 50% of DA-1 renal receptors was achieved at lower concentrations of NEM (5.2 microM), relative to brain D-1 receptors (140 microM). Western blot analyses of rat pituitary GH4C1 cells, transfected with human CNS D-1 receptor cDNA, with human anti-D-1 dopamine receptor antiserum, detected a single polypeptide with M(r) of 66 kDa. In PTs, a specific polypeptide of higher molecular weight (M(r) = 72 kDa) was seen. Surprisingly, in rat striatal membranes, the D-1 antiserum failed to detect any proteins within this molecular weight range. Photoaffinity labeling studies with a DA-1 selective photoligand, identified the identical protein by autoradiography and Western blots in kidney, but not in striate. Together, these data indicate that renal DA-1 dopamine receptors have distinct molecular properties relative to brain D-1 dopamine receptors.

Animals↗
PubMed1997

4-Methyl-3-oxo-4-aza-5alpha-androst-1-ene-17beta-N-aryl-carboxamides: an approach to combined androgen blockade [5alpha-reductase inhibition with androgen receptor binding in vitro].

4-Aza-5alpha-androstan-3-one 17beta-(N-substituted carboxamides) are potent human type 2 5alpha-reductase (5aR) inhibitors with generally poor binding to the human androgen receptor (hAR). When the 17-amide N-substituent included an aromatic residue, potent dual inhibitors of both type 1 and 2 5aR are produced, but hAR binding remained poor. Tertiary-substituted-17-amides have reduced inhibition of both 5aR isozymes. The addition of an N4-methyl substitutent to the A-ring profoundly increased hAR affinity and the addition of unsaturation to the A-ring (delta1) modestly augmented hAR binding. The unsubstituted carbanilides in the delta1-N4-methyl series show some selectivity for type 1 5aR over the type 2 isozyme, whereas addition of aryl substituents, particularly at the 2-position, increased type 2 5aR binding to provide dual inhibitors with excellent hAR binding, e.g. N-(2-chlorophenyl)-3-oxo-4-methyl-4-aza-5alpha-androst-1-ene-17bet a-carboxamide (9c). Compounds of this type exhibit low nanomolar IC50s for both human 5aR isozymes as well as the human androgen receptor. Kinetic analysis confirms that the prototype 9c displays reversible, competitive inhibition of both human isozymes of 5aR with K(i) values of less than 10 nM. Furthermore, this compound binds to the androgen receptor with an IC50 equal to 8 nM. Compounds in this series are projected to be powerful antagonists of testosterone and dihydrotestosterone action in vivo, with potential utility in the treatment of prostatic carcinoma (PC).

5-alpha Reductase Inhibitors↗
PubMed1997

Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response.

The patterns of differential gene expression were examined in two primary (A's) and two matched-metastatic (B's) head and neck squamous cell carcinoma (HNSCC) cell lines by differential display of mRNAs and northern blot hybridisation. Three cell lines used (PCI-04A, PCI-04B and PCI-06A) were established independently prior to therapy, whereas one cell line (PCI-06B) was established from a recurrent tumor after radiation therapy. A total of seven differentially displayed mRNA clones were identified, of which six clones were obtained by comparison of PCI-06A cells with PCI-06B cells (SCC-S1a/b, SCC-1c, and SCC-S2, PCI-06B; SCC-S3 to SCC-S5, PCI-06A), and one clone was obtained from the PCI-04A and PCI-04B match (SCC-Sa, PCI-04B). Based on the DNA database search for homology to the known sequences, six of the seven partial cDNA clones (SCC-S1a/b, SCC-1c, SCC-S2 to SCC-S4, and SCC-Sa may represent novel genes, whereas one cDNA clone (SCC-S5) shows significant homology to the HLA class II antigen gene (DPW2 beta chain). Each of the seven clones revealed preferential expression by northern blotting in the cell line of origin as compared to the matched counterpart. The transcripts ranged in size from approximately 7.0 Kb to 0.5 Kb. Interestingly, the SCC-Sa clone was preferentially expressed in both metastatic cell lines compared to the primary tumour-derived cell lines. We conclude that the SCC-Sa gene may be more commonly involved in tumour metastasis, whereas expression of the other genes (SCC-S1a/b, SCC-S1c, SCC-S2-SCC-S5) may be associated with metastasis and/or response of HNSCC to ionising radiation.

Base Sequence↗
PubMed1997

Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis.

We examined the antihypertensive efficacy of: (1) sublingual-oral single doses of captopril (25 mg) and nifedipine-capsules (10 mg) in 9 + 9 white patients and in 9 + 8 black patients with hypertensive crisis; and (2) a single oral dose of the slow-acting preparation of nifedipine-retard (20 mg) in another 10 black patients. Blood pressure (BP) was assessed at 10 min intervals for 6 h after administration. After 6 h, the BP falls induced by these drugs were still significantly lower than the baseline placebo values. Hypotensive effect of nifedipine-capsules was established more rapidly than that of captopril in both white and black patients, and of nifedipine-retard in black patients. Considering the area under the curve of BP values during the 6-h treatment, the overall hypotensive effect of nifedipine-capsules was similar to captopril in white patients, but significantly more pronounced than captopril and nifedipine-retard in black patients. In white patients similar maximal drops of BP (mean+/-s.e.m.) were obtained with nifedipine-capsules (71+/-4/52+/-4 mm Hg) and with captopril (69+/-4/50+/-3 mm Hg). In black patients the maximal drop of BP of nifedipine-capsules (70+/-4/52+/-4 mm Hg) was greater (P < 0.02) than that of captopril (48+/-4/32+/-3 mm Hg) but similar to that of nifedipine-retard (71+/-4/49+/-4 mm Hg). However, in contrast to nifedipine-capsules and captopril, nifedipine-retard produced a slower drop in BP. The time of peak drop in BP of both nifedipine-capsules and captopril occurred within the first 2 h whereas with nifedipine-retard it occurred only between 4 and 6 h after administration. Fewer patients reported side effects with nifedipine-retard as compared with the other two preparations. We conclude that single doses of captopril and nifedipine reduces BP for at least 6 h in both white and black patients with hypertensive crisis, but nifedipine is more potent than captopril in black patients. The slow release form of nifedipine-retard effectively and safely lowers BP while achieving a rapid enough effect without the critical rapid falls in BP that occur with nifedipine-capsules.

Administration, Oral↗
PubMed1997

Isolated choroid plexus cysts and association with fetal aneuploidy in an unselected population.

We sought to determine the relationship between an isolated choroid plexus cyst diagnosed antenatally and fetal aneuploidy in an unselected population at a district general hospital. Over a 5-year period all women attending for a detailed anomaly scan at 18-20 weeks' gestation were screened for evidence of a fetal choroid plexus cyst. All cases of choroid plexus cyst were recorded prospectively. The size, position and number of the cysts were noted and associated abnormalities seen on ultrasound were also recorded. Cases of choroid plexus cyst associated with fetal aneuploidy were noted. A total of 13,690 women were screened, and 84 cases of choroid plexus cyst were identified (0.6%). Of these, 41% underwent prenatal karyotyping by amniocentesis; 78 of 84 cases (93%) were isolated. Six had other markers for aneuploidy, and three of these fetuses had trisomy 18. All cases of isolated choroid plexus cyst resulted in chromosomally normal neonates. This was confirmed by either normal antenatal karyotype or postnatal examination by the pediatricians. The size, position and number of cysts did not appear to influence the risk of aneuploidy. We conclude that the risk of aneuploidy for a case of isolated choroid plexus cyst in an unselected population appears to be very low, and in this series was 0%. In this setting, we suggest detailed ultrasound examination is essential, rather than routine karyotyping.

Adolescent↗
PubMed1997

Survey of ochratoxin A in UK retail coffees.

A new method providing sensitivity to low concentrations was developed for the analysis of ochratoxin A in roast and ground and soluble coffee and a survey has been carried out to determine levels of ochratoxin A (OTA) in 100 samples of retail coffees available in the UK. The survey covered 80 soluble coffees (granulated, powdered, freeze-dried), of which nine products were decaffeinated, and 20 roast and ground retail coffee samples. OTA was detected (> or = 0.1 microgram/kg) in 64 samples of soluble coffee at levels ranging from 0.1 to 8 micrograms/kg. Seventeen samples of roast and ground coffee contained OTA at levels between 0.2 and 2.1 micrograms/kg. These results indicate that coffee products are not a major dietary source of OTA in the UK.

Carcinogens↗