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Biomedical subjects

B Patel

Publications and source records attributed to B Patel.

At least 145 records · Page 8Linked to original sources

The laminar distribution and postnatal development of serotonin-immunoreactive axons in the cat primary visual cortex.

The laminar distribution and postnatal development of profiles immunoreactive to antibodies directed against serotonin (5-hydroxytryptamine, 5-HT) have been investigated in the primary visual cortex (striate cortex, area 17) of cats. In the adult cat, profiles with serotonin-like immunoreactivity consist exclusively of fibers which exhibit laminar differences in density and predominant orientation. Immunoreactive fibers are dense in layers I-III, less dense in layer V, and sparse in layers IV and VI. In layers I and VI the trajectories of these fibers are mainly tangential to the pial surface; in layers II-V they are predominantly radial and more irregular. The vast majority of immunoreactive fibers consists of fine axons with frequent small varicosities. In addition, there are a few thick axons. In 2-week-old cats, immunoreactive fibers are sparsely distributed through layers II-V. By 4 weeks, fiber density has decreased still further in layer IV and increased in layers I-III. By 6 weeks, the laminar pattern resembles that of adult cats except that fiber density is still lower than in adults. At three months of age, the mature pattern is established.

Aging↗

Hydralazine dose-response curve analysis.

A multicenter, parallel, double-blind, 181-patient study compared the safety and antihypertensive efficacy of immediate-release (IR) and extended-release (ER) hydralazine. After 2 to 4 weeks on diuretic, patients were maintained on diuretic and randomized to a hydralazine treatment regimen: IR thrice daily, ER twice daily, or ER once daily. Daily doses of hydralazine were 75, 150, or 300 mg. Although designed as a titration study, important dose-response data were available for analysis with nonlinear mixed effect modeling (NONMEM). Sitting diastolic blood pressure (BP) was selected as the response variable. Several factors were tested for importance, including body weight, time (week) effects, concomitant beta-blocker (BB) therapy, acetylator class, and treatment regimen. All factors were important (p less than 0.05) except treatment regimen (p greater than 0.30). The maximum antihypertensive response (Emax) to hydralazine was 9.4 mm Hg. The daily dose that elicited 50% of the maximum response (D50) was 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators. BP fell 0.52 mm Hg per week independent of other effects, and concomitant BB therapy induced a drop of 6.6 mm Hg in addition to hydralazine, diuretic and week effects. NONMEM's use assisted in evaluations and provided information not obtainable through traditional means.

Administration, Oral↗

Complete sequence of human vinculin and assignment of the gene to chromosome 10.

We have determined the complete sequence of human vinculin, a cytoskeletal protein associated with cell-cell and cell-matrix junctions. Comparison of human and chicken embryo vinculin sequences shows that both proteins contain 1066 amino acids and exhibit a high level of sequence identity (greater than 95%). The region of greatest divergence falls within three 112-amino acid repeats spanning residues 259-589. Interestingly, nematode vinculin lacks one of these central repeats. The regions of human vinculin that are N- and C-terminal to the repeats show 54% and 61% sequence identity, respectively, to nematode vinculin. Southern blots of human genomic DNA hybridized with short vinculin cDNA fragments indicate that there is a single vinculin gene. By using a panel of human-rodent somatic cell hybrids, the human vinculin gene was mapped to chromosome 10q11.2-qter.

Amino Acid Sequence↗

A case of necrobacillosis.

A case of empyema due to Fusobacterium necrophorum infection is described. A history of sore throat followed by metastatic abscesses may alert the clinician to the possibility of this unusual infection.

Adolescent↗

Primary sequence and domain structure of chicken vinculin.

We have determined the complete sequence of chick vinculin from two overlapping cDNA clones. The vinculin mRNA consists of 262 bp of 5' untranslated sequence, an open reading frame of 3195 bp (excluding the initiation codon) and a long 3' untranslated sequence (greater than 2 kb). Chick vinculin contains 1066 amino acid residues, and has a deduced molecular mass of 116,933 Da. Analysis of the domain structure of vinculin shows that the molecule can be cleaved by V8 proteinase into a 90 kDa globular head and a 32 kDa tail region, the latter of which could further be cleaved into a 27 kDa polypeptide. The 90 kDa globular head contains the N-terminus of vinculin, three 112-residue repeats (residues 259-589), and extends to approximately residue 850. Gel overlay experiments show that it also contains a binding site for the cytoskeletal protein talin. The talin-binding domain was further localized to the N-terminal 398 amino acid residues of the protein by expression in vitro of this region from a vinculin cDNA cloned into the Bluescript SK+ vector. The head and tail domains are apparently separated by a proline-rich region that contains V8-proteinase-cleavage sites and a candidate tyrosine (822)-phosphorylation site. Secondary-structure prediction suggests that the head and tail domains contain alpha-helical regions separated by short stretches of turn/coil. Comparison of the chick with a partial human sequence reveals that vinculin is a highly conserved protein. In chickens Southern-blot analysis is consistent with a single vinculin gene, and it is therefore likely that vinculin, and its higher-molecular-mass isoform termed metavinculin, arise through alternative splicing.

Amino Acid Sequence↗

Altered myocardial states. The stunned and hibernating myocardium.

There are several potential outcomes of myocardial ischemia. When ischemia is severe and prolonged, myocyte cell death occurs and there is no recovery of contractile function of these cells. When myocardial ischemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function, which may be a protective mechanism whereby these cells attempt to reduce their oxygen demand in the setting of reduced oxygen supply. The resultant chronic left ventricular dysfunction has been termed "hibernating myocardium." Finally, myocardial ischemia may be reversed with coronary artery reperfusion resulting in salvage of the myocytes. However, the viable myocardium may demonstrate relatively prolonged but transient postischemic contractile dysfunction, the situation termed "stunned myocardium." The concepts of stunned myocardium are reviewed as they apply to both coronary reperfusion during evolving acute myocardial infarction, as well as brief periods of ischemia that may occur during angina pectoris, or coronary vasospasm, or both. The concept of hibernating myocardium is reviewed as it applies to left ventricular function prior to and after coronary artery bypass surgery.

Coronary Circulation↗

Coagulation cascade, fibrinolytic system, antithrombin III, protein C and protein S in patients maintained on continuous ambulatory peritoneal dialysis.

We studied the coagulation cascade, fibrinolytic system and naturally occurring anticoagulants in a group of 14 patients with end-stage renal disease maintained on continuous ambulatory peritoneal dialysis (CAPD). The results were compared with those obtained in a group of ten normal volunteers. Plasma procoagulant activities of factors XII, XI, IX, VIII, VII, X and II were significantly greater in the CAPD group as compared to the normal control group. Likewise plasma concentrations of total and free protein S were increased in the CAPD group. Although the mean value for plasma factor V activity in the CAPD group was higher than that found in the control group the difference did not attain statistical significance. In addition plasma fibrinogen concentration and factor VIII-related antigen level were significantly increased in CAPD patients. No significant difference was found between the CAPD patients and the control group with respect to plasma levels of protein C, antithrombin III, plasminogen or alpha 2-antiplasmin. In summary, the results demonstrate a tendency for increased levels of various coagulation factors and protein S in CAPD patients with no significant alterations in the levels of various fibrinolytic and endogenous anticoagulant agents, i.e. antithrombin III and protein C. The clinical significance and the mechanism responsible for the observed changes require further investigation.

Antithrombin III↗

The clinical syndrome of 5-fluorouracil cardiotoxicity.

5-fluorouracil (FUra) is one of the most frequently used drugs in cancer treatment, particularly in combination with other agents. Its activity when administered as an infusion rather than a bolus has led to a renewed and increased use. A cardiotoxicity that mimics ischemia has been associated with the administration of FUra in cancer patients. This cardiotoxicity may manifest itself as: (a) dysrythmias with and without cardiorespiratory symptoms (b) ECG changes with and without cardiorespiratory symptoms (c) cardiorespiratory symptoms with and without ECG changes (d) acute myocardial infarct; symptoms and ECG changes (e) ventricular dysfunction (f) cardiogenic shock and (g) sudden death. Several case studies which illustrate the cardiotoxic sequelae that may be associated with the use of this drug are discussed. The incidence, contributing factors, risk factors and mechanisms underlying this phenomenon are undetermined. No appropriate recommendations for monitoring patients or for predicting those patients that will develop such toxicity while receiving FUra can be made at present. Prospective studies to determine the true incidence, spectrum and mechanisms causing this syndrome are ongoing and required for its understanding and prevention.

Adult↗

Innocuous gas collections in pancreatic allografts demonstrated by computed tomography.

Over a 4-year period, 6 pancreatic abscesses were found in 37 patients who had combined renal and segmental pancreatic transplants. An additional 4 patients who were nontoxic at the time of their computed tomographic (CT) examinations had innocuous gas collections, either in the pancreatic allograft or the surrounding peripancreatic tissue. The possible etiology of this gas formation is discussed. These collections do not have the same ominous clinical significance as would be expected in abscess formation. Radiological evaluation should include examination of the gastrointestinal tract and voiding cystograms to detect fistula formation. Simultaneous percutaneous aspiration of this area should be performed to rule out an infective process. If this is negative in a nontoxic transplant patient, the radiologist will be in a position to obviate unnecessary surgical intervention.

Adult↗

Structure and expression of the glycoprotein gene of Chandipura virus.

A cDNA copy of the mRNA for the glycoprotein G of Chandipura virus, a rhabdovirus, has been cloned, sequenced, and expressed in mammalian cells. The deduced amino acid sequence of G shows that the encoded protein is a typical transmembrane glycoprotein of 524 amino acids containing a cleavable amino-terminal signal peptide, two potential N-linked glycosylation sites, a hydrophobic membrane anchor domain near the carboxy terminus, and a cytoplasmic domain at the carboxy terminus. Somewhat unusual is the appearance of two charged amino acid residues, aspartate and arginine, within the putative membrane anchor sequence. Expression of the G gene in COS cells resulted in production of a glycosylated protein of mol wt 71,000 which was recognized by anti-Chandipura antibodies. Like the viral G protein, the expressed G contained covalently linked palmitic acid. However, unlike its vesicular stomatitis virus (Indiana serotype) counterpart, the Chandipura G protein has no potential palmitate-accepting cysteine residue within its cytoplasmic domain. Thus, the covalent attachment of fatty acid to this molecule may occur at one or both of the cysteines within the membrane anchor domain. The G protein was intracellularly transported to the cell surface and could induce cell fusion at low pH, showing that the expressed G protein was biologically active.

Amino Acid Sequence↗

Binding protein, radioreceptor and biological activities of recombinant methionyl insulin-like growth factor-I variants.

Reversed-phase chromatography (RPC) was used to resolve two variants of recombinant amino terminal methionyl residue (N-Met) insulin-like growth factor-I (IGF-I) with the same amino acid constitution but different disulphide linkages. Following radioiodination, equilibration with plasma and size exclusion chromatography at neutral pH the major form on RPC (approximate abundance 60%) demonstrated greater than 80% binding to 150 kDa and 40-50 kDa IGF binding proteins. This peptide has the RPC elution characteristics and disulphide assignment (Cys6-Cys48, Cys18-Cys61, Cys47-Cys52) of authentic with mismatched disulphides (Cys6-Cys47, Cys18-Cys61, Cys48-Cys52; N-Met IGF-I peak 1 peptide) demonstrated less than 15% binding under similar conditions. Potency of the peptides was investigated in competitive IGF-I plasma binding protein and L6 myoblast radioreceptor assays. The peak 2 peptide proved equipotent to purified ovine plasma IGF-I in each system but by contrast the peak 1 peptide was 40-fold and 200-fold less potent in the binding protein and radioreceptor assays respectively. Biological potency was examined in a non-competitive assay based on incorporation of [3H]leucine into confluent cultures of L6 myoblasts. In this system the N-Met IGF-I peak 1 peptide proved 15-fold less potent than the peak 2 peptide with correct disulphide linkages. Refolding variants may prove useful in establishing structure/function relationships for IGF-I.

Amino Acid Sequence↗

Topical corticosteroid compounding: effects on physicochemical stability and skin penetration rate.

Compounding compatibility studies of four corticosteroid cream products and four commonly added chemicals are presented. Physical alteration, chemical stability, micropreservative challenge status, and in vitro skin penetration were evaluated at ambient conditions for 2 months. The study was designed to generate useful, previously unavailable information to aid dispensing pharmacists and dermatologists.

Administration, Topical↗

Identification of a talin binding site in the cytoskeletal protein vinculin.

Binding of the cytoskeletal protein vinculin to talin is one of a number of interactions involved in linking F-actin to cell-matrix junctions. To identify the talin binding domain in vinculin, we expressed the NH2-terminal region of the molecule encoded by two closely similar, but distinct vinculin cDNAs, using an in vitro transcription translation system. The 5' Eco RI-Bam HI fragment of a partial 2.89-kb vinculin cDNA encodes a 45-kD polypeptide containing the first 398 amino acids of the molecule. The equivalent restriction enzyme fragment of a second vinculin cDNA (cVin5) lacks nucleotides 746-867, and encodes a 41-kD polypeptide missing amino acids 167-207. The radiolabeled 45-kD vinculin polypeptide bound to microtiter wells coated with talin, but not BSA, and binding was inhibited by unlabeled vinculin. In contrast, the 41-kD vinculin polypeptide was devoid of talin binding activity. The role of residues 167-207 in talin binding was further analyzed by making a series of deletions spanning this region, each deletion of seven amino acids contiguous with the next. Loss of residues 167-173, 174-180, 181-187, 188-194, or 195-201 resulted in a marked reduction in talin binding activity, although loss of residues 202-208 had much less effect. When the 45-kD vinculin polypeptide was expressed in Cos cells, it localized to cell matrix junctions, whereas the 41-kD polypeptide, lacking residues 167-207, was unable to do so. Interestingly, some deletion mutants with reduced ability to bind talin in vitro, were still able to localize to cell matrix junctions.

Amino Acid Sequence↗

Ventricular vulnerability in diabetes and myocardial norepinephrine release.

Previously the authors have observed a reduction of the ventricular fibrillation threshold (VFT) in a mild diabetic model. This investigation examines the role of more severe hyperglycemia in altering the ventricular fibrillation threshold and how the sympathetic nervous system modulates the response. Alloxan diabetes was induced in eight male mongrel dogs 3-5 years of age (Group 2), for comparison with matched controls (Group 1). Hemoglobin A1c rose from 2.9 +/- .4-7.8 +/- .3% and body weight was maintained with daily insulin. After 1 year, anesthesia was induced with chloralose and an electrode catheter placed at the right ventricular apex. VFT was 41.7 +/- 1.8 ma in Group 1 and 27.8 +/- 2.1 ma in the diabetics of Group 2 (p less than .001). There was significantly greater decline of VFT in response to epinephrine infusion in Group 2. The threshold in diabetics rose to normal levels after infusion of the beta-blocking agent, esmolol. Subsequently, the response of the cardiac sympathetic system was assessed during ventricular pacing at 200 beats/minute. Serial paired blood samples were taken from catheters in the aorta and coronary sinus for catecholamine assay by HPLC. Both groups had similar coronary blood flow responses by the thermal method, as well as changes in arterial pressure. While no change occurred in Group 1, a progressive rise of norepinephrine (NE) concentration was observed in coronary venous effluent of Group 2 (p less than .01). The basal arterial-coronary sinus difference was-123 +/- 52 pg/ml, which rose during pacing in Group 2 to a peak of -376 +/- 9.3 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metoclopramide-induced parkinsonism.

Metoclopramide hydrochloride (Reglan) is a widely prescribed drug for treatment of upper gastrointestinal symptoms. Although the drug is relatively safe, a growing body of literature has noted movement disorders after its administration. We have reported six cases of metoclopramide-induced parkinsonism seen in consultation over a two-year period. Five of these six patients had renal failure. Their parkinsonism improved on discontinuation of metoclopramide therapy. Metoclopramide-induced parkinsonism is not rare, and appropriate dose reduction in patients with renal failure will help reduce the incidence of this morbidity.

Adult↗

Pancreatic transplant rejection: assessment with duplex US.

The value of duplex ultrasonography (US) in the assessment of pancreatic transplants was studied in 22 patients over a 1 1/2-year period. Ninety-eight duplex US examinations were performed, and the Doppler arterial resistive indexes (RIs) correlated with clinical events after transplantation. The RI was 0.70 or less in the parenchymal vessels in all instances of normal transplant function and greater than 0.70 in seven of eight clinical episodes of rejection (87.5%). In all studies performed during these eight cases of rejection, the positive predictive value of an RI exceeding 0.70 was 100%. The negative predictive value of an RI of less than 0.70 in excluding rejection was 90%. High RI values were not found in isolated episodes of cyclosporine toxicity, pancreatitis, peripancreatic hemorrhage, or infection. Duplex US may prove to be more accurate in the diagnosis of rejection of pancreatic transplants versus renal transplants because the former cases have fewer causes of increased vascular impedance and diminished perfusion.

Female↗