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Biomedical subjects

B Patel

Publications and source records attributed to B Patel.

At least 73 records · Page 4Linked to original sources
PubMed1995

Magnetic brain stimulation: safety studies.

We describe short-term and long-term safety studies after low repetition rate magnetic brain stimulation in 10 normal subjects. We obtained quantitative EEG data, psychometric test results, serum prolactin and cortisol levels before and after brain stimulation. EEG and psychometric data were also obtained in 5 of these subjects 16-24 months after the initial experiment. Short- and long-term studies did not show any deleterious effects. Randt delayed recalls, however, showed a transient reduction in the score immediately after stimulation which resolved on retesting in 2 weeks. To address the question of fatigue we repeated Randt tests in 4 subjects before and after magnetic brain stimulation but without the other extensive psychometric, EEG and blood tests. Pre- and post-stimulation scores on this occasion showed no significant difference in these 4 subjects suggesting that the transient changes in the previous Randt score were related to fatigue. We conclude that single-pulse magnetic brain stimulation has no deleterious effects after magnetic brain stimulation.

Adult↗
PubMed1995

Oxygen modulates production of bFGF and TGF-beta by retinal cells in vitro.

Vasoproliferative retinopathies result from retinal capillary non-perfusion and consequent inner retinal hypoxia. However, it is not known whether oxygen mediates vasoproliferation directly (at the nuclear level) or indirectly by regulating the production of growth factors. We have investigated the effect of oxygen on the production of basic fibroblast growth factor and transforming-growth-factor-beta by a variety of retinal cell types in culture. Confluent cultures were maintained for 48 hr under varying oxygen tensions ranging from 135 to 18 mmHg. A reduction in basic fibroblast growth factor levels was observed in the cell lysates and extracellular matrix from retinal microvascular endothelial cell, retinal microvascular pericyte and retinal pigment epithelial cell cultures when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Levels of basic fibroblast growth factor in conditioned media from microvascular endothelial and retinal pigment epithelial cell cultures also decreased when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Total transforming-growth-factor-beta (and specifically isoforms 1 and 2) in the conditioned media from all three cell types was similarly modulated by oxygen i.e. it decreased as the oxygen tension of the medium was reduced from 135 to 18 mmHg. In contrast, the steady state messenger RNA levels for both basic fibroblast growth factor and transforming-growth-factor-beta 1 genes in RPE cells increased significantly when the oxygen tension of the medium was reduced from 135 to 18 mmHg. These results support the putative role of oxygen in influencing the balance of growth factors during the development of preretinal new vessels.

Blotting, Northern↗
PubMed1995

Preterm prelabour amniorrhexis: intrauterine infection and interval between membrane rupture and delivery.

This study aimed to determine if fetal bacteraemia and amniotic fluid infection at the time of membrane rupture reduces the interval between membrane rupture and the onset of labour in pregnancies complicated by preterm prelabour amniorrhexis. Sixty nine pregnancies with preterm prelabour amniorrhexis at 12-36 weeks' gestation that were managed expectantly had spontaneous onset of labour. In all cases cordocentesis and amniocentesis were performed and fetal blood and amniotic fluid were cultured for aerobic and anaerobic bacteria. In the group with negative fetal blood and amniotic fluid cultures (group 1) the median interval from amniorrhexis to delivery was 41 days (range 1-161) and there was an inverse correlation between gestational age at amniorrhexis and delivery interval. In the group with negative fetal blood but positive amniotic fluid cultures (group 2) the median amniorrhexis to delivery interval was nine days (range 1-37), and in the group with positive fetal blood cultures (group 3) the interval was two days (range 1-5). These findings suggest that pregnancies complicated by preterm prelabour amniorrhexis and fetal bacteraemia undergo spontaneous labour within five days of membrane rupture, and if labour does not occur then infection is unlikely.

Amniotic Fluid↗
PubMed1995

Management of residual thymic cysts in patients treated for mediastinal Hodgkin's disease.

The pathogenesis of residual thymic cysts after treatment for mediastinal Hodgkin's disease is uncertain. Their presence after adequate treatment often presents the oncologist and the thoracic surgeon with a therapeutic dilemma. Two patients with residual thymic cysts after curative treatment for mediastinal Hodgkin's disease are described and the management discussed.

Adult↗
PubMed1995

Reciprocal regulation of endothelin-1 and endothelial constitutive NOS in proliferating endothelial cells.

The expression of endothelin-1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) was assessed in two independent in vitro models: asynchronously differentially proliferating cultures and wounded endothelial cell monolayers. Northern blot analysis of RNA isolated from preconfluent, confluent, and postconfluent cells revealed a fourfold rise in ET-1 mRNA transcripts, whereas levels of ecNOS mRNA transcripts were reduced twofold in proliferating cells. Nuclear run-off analysis demonstrated that increased steady-state ET-1 mRNA content in proliferating cells was mediated, in part, by increased gene transcription. In contrast, ecNOS transcription rates in proliferating cells were not decreased compared with quiescent nonproliferating cells, indicating that mRNA destabilization mediated the decreased ecNOS mRNA levels in proliferating endothelium. Concordant changes in protein expression were documented for both ET-1 and ecNOS. In injured endothelial cell monolayers, in situ cRNA hybridization demonstrated increased mRNA transcript levels for ET-1 in growth fronts of injured endothelial monolayers. These data are taken to indicate that expression of ET-1 and ecNOS is reciprocally regulated in two different models of endothelial cell proliferation.

Animals↗
PubMed1995

SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole ligand.

UNLABELLED: This investigation evaluates the efficacy of a 99mTc-labeled nitroimidazole (BMS-181321) in identifying oxygen-deprived tissue in two canine models of myocardial ischemia. METHODS: For both models (A and B), epicardial microvascular oxygen pressure (mPO2) was monitored by measuring the oxygen-dependent quenching of phosphorescence lifetime of Palladium mesotetra (4-carboxyphenyl) porphine. In Model A (beagles, n = 5), BMS-181321 was administered intravenously and a distal branch of the left anterior descending coronary artery (LAD) was ligated completely 40 sec later. Ten minutes later, the ligature was released establishing tissue reoxygenation. In Model B, flow through the LAD was reduced until the mPO2 was about 2 Torr. After bolus administration of BMS-181321 (50-60 mCi), coronary ischemia was continued for a residence period of up to 4 hr. RESULTS: With Model A, SPECT reconstructions revealed a small ischemic area in three of five dogs, however, a transmural accumulation of the compound was evident in the autoradiograms from all dogs. In the two animals in which the defect was not observed by SPECT, the ischemic episode had nominal effects on the ratio of +/- dp/dt (< 4% change as compared to baseline values). In Model B, SPECT reconstructions showed positive images of the oxygen-deprived area within the mid- to apical regions of the left ventricle (n = 5). Autoradiographic analysis showed a transmural association with cells resulting in an ischemic-to-nonischemic ratio of 3.5 +/- 0.4 (n = 4) for animals with similar residence times. CONCLUSION: The results from both models suggest that BMS-181321 provides a noninvasive marker of regional ischemia in the heart and that this compound may have clinical utility for detection of coronary artery disease.

Animals↗
PubMed1995

Effect of graded hypoxia on retention of technetium-99m-nitroheterocycle in perfused rat heart.

UNLABELLED: The purpose of this investigation was to determine the effects of graded hypoxia on the retention of a 99mTc-labeled nitroimidazole. METHODS: Rat hearts were perfused retrogradely with Krebs-Henseleit buffer at 37 degrees C and paced at 5 Hz. After a 20-min stabilization period, coronary flow was maintained at 8 ml/min/g wet wt and the hearts were perfused with media equilibrated with gas mixtures containing 5% CO2 and various levels of O2, from 544 to 29 Torr. Technetium-99m-O(PnAO-1-(2-nitroimidazole)), BMS-181321, was infused for 20 min into a side port of the aortic cannula. Perfusion continued for an additional 40 min to allow for compound clearance. RESULTS: Each decrease of perfusate PO2 brought about an increase in the retention of BMS-181321, resulting in a good correlation between its retention and perfusate PO2 (r = 0.97). Myocardial oxygen consumption was independent of oxygen delivery when the perfusate oxygen pressure was greater than 350 Torr. Below this value, oxygen consumption declined markedly as influent PO2 was decreased. By contrast, the tissue lactate/pyruvate ratio and lactate efflux rose with each decrease of influent PO2. A good correlation was obtained between retention of the nitroheterocycle and the cytosolic lactate/pyruvate ratio (r = 0.98). When glucose was omitted from the perfusate (PO2 = 27 Torr), retention of the nitroheterocycle was increased by about 25% as compared to hearts perfused in the presence of this substrate. CONCLUSION: These results indicate that myocardial retention of BMS-181321 is coupled to the level of tissue oxygenation and that hypoxic retention may be affected by substrate input.

Animals↗
PubMed1995

Hypoxia induces HSP 70 gene expression in human hepatoma (HEP G2) cells.

Populations of cells within solid tumours are exposed to low oxygen concentrations. The mechanism by which tumour cells tolerate such hypoxia is unknown but it may parallel responses to other types of cellular stress. We investigated the effect of oxygen on steady state levels of inducible heat shock protein 70 mRNA in cultured human hepatoma cells. Northern blot analysis demonstrated that hypoxia increased HSP 70 mRNA levels within 3 hours, with a transient 12-fold increase at 6 hours compared with normoxia. We also showed that heat shock induced a 20-fold increase in HSP 70 mRNA. This data suggests that HSPs may be important in tumour progression by protecting cells from hypoxic stress.

Blotting, Northern↗
PubMed1994

Analysis of the phasing of four spectrin-like repeats in alpha-actinin.

Selected fragments of the central rod of chicken gizzard alpha-actinin were expressed as fusion proteins in Escherichia coli, with the aim of determining the positions in the sequence of the four successive spectrin-like repeats that make up this domain. The criteria for an independently folding unit were resistance to proteolysis and the high alpha helicity characteristic of the native protein. Sequences containing repeats 1-4, 2-4, 3-4 and 4 all generated stable fragments on digestion with trypsin and/or thermolysin and N-terminal sequencing gave the most probable starting position of each repeat. The sequences of all four inferred repeats and the sequences of the entire rod, were separately expressed and were shown to assume a stable, protease-resistant fold in solution. The repeat boundaries established in this way differed from those originally deduced from sequence alignments; the N-terminal boundaries of the repeats were 14-24 residues nearer the C-terminus than predicted. The ability to express individual repeats should facilitate identification of the binding sites for the cytoplasmic domains of beta 1 integrins and intercellular cell adhesion molecule-1 which have been localised to the rod domain of alpha-actinin.

Actinin↗
PubMed1994

Evidence that the recently discovered high-energy nucleotide derivative, oligo(phosphoglyceroyl-ATP) forms the end chains of purinogen, a complex polymeric major storage form of adenine nucleotide and phosphate in heart.

Previous work in our laboratory has shown that free adenine nucleotides in heart, liver and kidney exchange rapidly with a major acid-insoluble species which we have characterised as oligo[3-phospho-glyceroyl-gamma- triphospho(5')adenosine(3')], abbreviated to (PG-ATP)n. This has been found in liver and in heart to be complexed to a specific 3'-phosphodiesterase which releases PG-ATP monomers and is located in mitochondrial inter-membrane space. In [14C]adenosine-perfused hearts, (PG-ATP)n has been shown to reach specific radioactivity equilibrium with free ATP within 30 min. Attempts to estimate the quantities of nucleotide in (PG-ATP)n and free nucleotides in response to a variety of stimuli using previously labelled hearts showed by contrast that the free and sequestered nucleotide pools were not at equilibrium. Re-examination of the rapidly labelled acid-insoluble species led to the recognition of radioactive inhomogeneity and of three additional nucleotide components. Perfusion of hearts with phosphate-free medium increased the proportion of 14C incorporated into the sequestered from by 70% and caused the net transfer of 0.9 mumol.g-1 of purine from free adenine nucleotides to the sequestered form. The findings point to the existence of a more complex polymer whose rapidly exchanging end chains we had previously isolated and characterised as (PG-ATP)n; we suggest the name purinogen for this polymer and show that it can contain between 25% and 55% of the tissue nucleotide pool in rat heart.

Adenine Nucleotides↗
PubMed1994

Micellar electrokinetic chromatography with electroosmotic step gradient elution.

The peak capacity, defined as the maximum number of resolvable peaks, is dependent on the range of the migration-time window in micellar electrokinetic chromatography (MEKC). By applying various radial electric potential gradients across the capillary wall, the direct control of the zeta potential and the electroosmotic flow in MEKC results in a significant increase in the migration-time window and a great enhancement of the separation resolution. The enhancement in the separation resolution is obtained at a large expense in analysis time. To optimize both the separation efficiency and the resolution in MEKC, the dynamic control of electroosmosis and the migration-time window during the separations is demonstrated with the use of neutral and charged phenylthiohydantoin-amino acids (PTH-amino acids) as a model system. A simple mathematic model which is capable of predicting migration times of analytes in electroosmotic step gradient elution MEKC is presented.

Amino Acids↗
PubMed1994

Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy.

A number of growth factors have been implicated in the development and perpetuation of preretinal fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). The aim of this study was to determine the potential role of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in PDR development. Immunostaining for EGF, TGF-alpha, and EGF-R was compared between normal retina, PDR retina, and PDR preretinal membranes. Weak staining for EGF and EGF-R was observed throughout the neural retina from non-diabetic eyes while weak to moderate staining for TGF-alpha was observed in the ganglion cell layer and the inner and outer nuclear layers. In contrast, intense staining for EGF and TGF-alpha and moderate staining for EGF-R were observed throughout the PDR retina. Immunoreactivity for EGF, TGF-alpha, and EGF-R was seen in the majority of the 11 excised membranes studied and, though variable, was generally greater than that observed in normal retinas. These results suggest an autocrine/paracrine role for EGF, TGF-alpha, and EGF-R in PDR.

Diabetic Retinopathy↗
PubMed1994

Oxygen regulation of TGF-beta 1 mRNA in human hepatoma (Hep G2) cells.

Solid tumours comprise populations of cells whose behaviour is thought to be influenced by growth factors and the local oxygen environment. We investigated the effect of oxygen on steady state levels of transforming growth factor-beta 1 mRNA in cultured human hepatoma cells. Northern blot analysis demonstrated that hypoxia mediated an early and sustained induction of TGF-beta 1 mRNA above that seen at higher oxygen tensions. The data suggests that modulation of TGF-beta 1 expression by the local oxygen environment may be important in tumour development and progression.

Blotting, Northern↗
PubMed1994

Antibodies to Toxoplasma gondii in eluates from filter paper blood specimens.

Blood and serum samples were tested directly for antibodies to Toxoplasma gondii, or as eluates from filter paper using the dye test, IgM enzyme-linked immunosorbent assay (ELISA) and IgM immunosorbent agglutination assay (ISAGA). The specificity and reproducibility of all three assays based on filter paper eluate was satisfactory. The sensitivity of testing eluates was 10 IU by the dye test and 53 EIU by IgM ELISA. IgM ISAGA findings, using eluate or sera, were comparable. Seroprevalence studies of congenital toxoplasmosis can be based on IgM measurement by ISAGA using eluates of filter paper stored infants' blood. Dye test and IgM ISAGA testing of eluate can be used to reduce the frequency of venepuncture when investigating infants for suspected congenital toxoplasmosis.

Animals↗