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Biomedical subjects

H Patel

Publications and source records attributed to H Patel.

At least 163 records · Page 9Linked to original sources
PubMed1995

Effects of K+, pH and glutamate on 45Ca kinetics in hippocampal brain slices.

Altered calcium homeostasis is likely to play a pathogenetic role in cerebral ischemia. In order to further understand which factors associated with ischemia contribute to disturbances of calcium metabolism, the influence of 3 isolated insults, 8 mM K+, pH 6.1 and 1 mM glutamate, on total tissue calcium were studied by analysis of steady-state kinetics of 45Ca in 500 microns hippocampal brain slices. 45Ca kinetics were analyzed with 2 bi-exponential models by non-linear least-squares analysis. Tissue wet weight/protein was measured simultaneously. Each experimental condition produced a unique tissue response. Raising K+ had no effect on tissue water but increased the rate of uptake of Ca2+ into the larger, rapidly equilibrating tissue Ca2+ space. Acidosis reduced tissue water and the amount of Ca2+ in the slowly equilibrating compartment due to enhanced efflux from that space. Glutamate increased tissue water in a time-dependent manner and increased the influx and amount of Ca2+ in the slowly equilibrating space. Combined insults revealed minimal interaction between K+ and acidosis or glutamate, but glutamate with acidosis worsened tissue injury. We discuss the relationship of this technique to other methods for studying tissue calcium and the significance of the observations regarding ischemia.

Animals↗
PubMed1995

Clinical correlation of periodic lateralized epileptiform discharges in children.

Fifteen children with periodic lateralized epileptiform discharges are reported and clinical and radiologic features and outcome are presented. Both structural cerebral lesions and metabolic factors were associated with periodic lateralized epileptiform discharges. Although all patients had seizures, 8 had status epilepticus. Seven patients survived and 8 patients died. Six of the 7 survivors had residual seizures. Periodic lateralized epileptiform discharges in children are associated with acute encephalopathies and there is a high incidence of subsequent epilepsy.

Adolescent↗
PubMed1995

Spontaneous extracranial carotid artery dissection in children.

Dissection of cerebral arteries as a cause of stroke is rarely recognized in children. Two patients with stroke due to extracranial carotid artery dissection are reported. A 7-year-old girl with a 2-week history of right arm chorea had a left basal ganglia infarct and is receiving haloperidol for persistent chorea. The second patient, a 15-year-old boy, developed aphasia and right hemiparesis a day before admission during a football game without obvious trauma. He had a large left middle cerebral artery infarct and died of cerebral edema and herniation. We believe that strokes due to arterial dissection are more common than currently recognized, partly because of a lack of history of trauma, and suggest that cerebral artery dissection be considered as an etiology of childhood strokes. Greater awareness of arterial dissection as a cause of stroke and availability of noninvasive techniques like magnetic resonance angiography should result in a more accurate diagnosis and improved prognosis in these patients.

Adolescent↗
PubMed1995

Special considerations in the endourologic management of stones in continent urinary reservoirs.

To various degrees, all continent pouch designs are subject to stones, which often are infected. We report on the endourologic management of large stone burdens in three types of continent reservoirs. Stone in a UCLA and a Kock pouch were managed endoscopically, and stones in an augmented pouch with a Mitrofanoff valve were managed percutaneously. Recommendations are made with regard to the optimal endourologic management of significant stone burdens in each of the common continent urinary reservoirs.

Adult↗
PubMed1995

Variability of intrinsic positive end-expiratory pressure in patients receiving mechanical ventilation.

OBJECTIVE: Since variations in breathing pattern may affect the level of intrinsic positive end-expiratory pressure (PEEP), breath-to-breath variation of intrinsic PEEP was assessed. DESIGN: Descriptive and prospective study. SETTING: Medical intensive care unit of a university teaching hospital. PATIENTS: Thirty-four patients requiring mechanical ventilation for a period of time due to respiratory failure. MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was determined using simultaneous recordings of the esophageal pressure and airflow. The breath-to-breath intrinsic PEEP, respiratory rate, tidal volume, inspiratory time, and fractional inspiratory time were measured. Intrinsic PEEP was noted in 33 of 34 patients. For all patients, the mean intrinsic PEEP was 3.59 cm H2O. The group mean standard deviation (SD) of the intrinsic PEEP over 35 breaths was 2.68 cm H2O. In 17 chronic obstructive pulmonary disease patients, the mean intrinsic PEEP was 4.69 cm H2O and the group mean SD of the intrinsic PEEP was 3.19 cm H2O. In the subgroup of patients with significant intrinsic PEEP, the mean intrinsic PEEP was 6.69 cm H2O and the group mean SD was 4.29 cm H2O. The group mean coefficient of variation of intrinsic PEEP for all 34 patients was 123%. Among the 15 patients with clinically significant intrinsic PEEP, the coefficient of variation was smaller (74%). We did not find significant correlation between the coefficients of variation of breathing pattern parameters and the coefficients of variation of intrinsic PEEP. CONCLUSIONS: We conclude that the occurrence rate of intrinsic PEEP in mechanically ventilated patients is high. The degree of variability in intrinsic PEEP on a breath-to-breath basis is also high. It may be difficult to find a specific level of intrinsic PEEP. Addition of external positive end-expiratory pressure without considering the breath-to-breath variability may lead to overdistention of the lung.

Adult↗
PubMed1994

Three-dimensional structure of the platelet integrin recognition segment of the fibrinogen gamma chain obtained by carrier protein-driven crystallization.

We have developed a method for crystallizing small functional protein segments so that their three-dimensional structure can be determined by x-ray diffraction analysis. This method consists of linking a small protein segment of unknown tertiary structure to either the amino or carboxyl terminus of a larger carrier protein of known tertiary structure. Crystallization of the small segment is then driven by crystallization of the carrier protein. Using this approach, we have obtained crystals of the human fibrinogen gamma-chain carboxyl-terminal segment linked to the carboxyl terminus of chicken egg white lysozyme. The three-dimensional structure of the carboxyl-terminal segment of the fibrinogen gamma chain was determined by x-ray diffraction analysis at a resolution of 2.4 A. This segment encompasses the recognition site for the integrin alpha IIb beta 3 receptor on activated platelets and for the clumping receptor on pathogenic staphylococci and also bears donor and acceptor sites for factor XIIIa-catalyzed crosslinking of fibrin. Therefore, the structural information derived from our analysis will provide a rational basis for the design of inhibitors of these important functions of fibrinogen. Moreover, carrier protein-driven crystallization will facilitate the determination of the three-dimensional structure of functional segments of other proteins that are, like fibrinogen, difficult to crystallize in toto.

Amino Acid Sequence↗
PubMed1994

(Trifluoromethyl)lumazine derivatives as 19F NMR probes for lumazine protein.

Lumazine protein acts as an electronic excited state transducer in bioluminescence of Photobacterium species. The protein binds 6,7-dimethyl-8-(D-ribityl)lumazine (1) which serves as the fluorophore. This compound also serves as a biosynthetic precursor of riboflavin and is the substrate of the enzyme riboflavin synthase. This enzyme and lumazine protein show considerable sequence homology. The interaction of lumazine apoprotein with several trifluoromethyl analogs of 6,7-dimethyl-8-ribityllumazine was investigated by 19F NMR spectroscopy. Upon binding to the protein, the 19F NMR resonances of the ligand shift to lower field with broadened line widths to around 30 Hz. By comparison, all ligands studied show more complex NMR spectra when bound to riboflavin synthase. Only one position 7 epimer (designated epimer A) of 6,7-bis(trifluoromethyl)-7-hydroxy-8-(D-ribityl)lumazine binds to lumazine apoprotein and riboflavin synthase. The apoprotein can also bind lumazine derivatives with a quarternary C-7. It is suggested that the binding site of lumazine protein corresponds to the donor binding site of riboflavin synthase.

Fluorine Compounds↗
PubMed1994

Cross-linking of surface IgM stimulates the Ras/Raf-1/MEK/MAPK cascade in human B lymphocytes.

The mechanism by which mitogen-activated protein kinase (MAPK) is activated in human B cells following cross-linking of the antigen receptor was investigated. Following anti-IgM antibody and phorbol 12-myristate 13-acetate (PMA) stimulation, we demonstrate the activation of Ras, Raf-1, and MAPK/ERK kinase (MEK), all of which are thought to participate in an important signaling cascade that leads to MAPK activation. We detected the kinase activities of Raf-1 and MEK toward purified recombinant substrates for each in this pathway (MEK for Raf-1 and MAPK for MEK). Following stimulation with either anti-IgM or PMA, Ras activation was observed, and the ability of Raf-1 to phosphorylate recombinant kinase-inactive MEK was increased by approximately 10-fold. Similarly, MEK activity toward kinase-active or -inactive recombinant MAPK also increased upon anti-IgM or PMA treatment. Furthermore, the activation of both MAPK and p90rsk was demonstrated under identical conditions in the B cells. We conclude that activation of B lymphocytes through the antigen receptor stimulates distinct members of the Ras/Raf-1/MEK cascade and this mechanism is likely to be responsible for MAPK and p90rsk activation in these cells.

B-Lymphocytes↗
PubMed1994

Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways.

We investigated the effect of Ba 679 BR, a novel long-acting antimuscarinic agent, on cholinergic neural responses in guinea pig and human airways. Ba 679 BR, atropine, and ipratropium bromide inhibited electrical field stimulation (EFS)-induced contraction with IC50 values of 0.17, 0.74, and 0.58 nM, respectively, in guinea pig trachea. Ba 679 BR had a slower onset and longer duration of action than atropine or ipratropium bromide (the times required to attain 50% of the maximum response were 34.8, 3.8, and 7.6 min, respectively, and the times required for 50% recovery of the response were 540, 31.6, and 81.2 min, respectively). Ba 679 BR, as well as atropine and ipratropium bromide, facilitated evoked [3H]acetylcholine release (an inhibitory effect on prejunctional muscarinic M2 receptors). The facilitation of acetylcholine release by Ba 679 BR was lost 2 h after washout, however, when there was still complete blockade of cholinergic contractile responses evoked by EFS (an effect on airway smooth muscle M3 receptors), confirming binding studies that suggest that Ba 679 BR shows "kinetic receptor subtype selectivity" for M3 over M2 receptors. The high potency, slow onset, and long duration of action of Ba 679 BR were also observed in human bronchi, suggesting that Ba 679 BR may be a useful drug to provide convenient therapy for patients with obstructive airway disease.

Acetylcholine↗
PubMed1994

Ligation of the T cell receptor complex results in activation of the Ras/Raf-1/MEK/MAPK cascade in human T lymphocytes.

Stimulation of T cells with antibodies directed towards the T cell receptor complex results in the activation of mitogen-associated protein kinase (MAPK). Two pathways have been described in other cell types that can lead to MAPK activation. One of these pathways involves the activation of Ras, leading to the activation of Raf-1, and the subsequent activation of MEK (MAPK or ERK kinase). The contribution of this pathway in T cells for anti-CD3 or phorbol myristate acetate (PMA)-mediated MAPK activation was examined. We detected the kinase activities of Raf-1 and MEK towards their substrates (MEK for Raf-1 and MAPK for MEK) in this pathway leading to the activation of MAPK. Stimulation of the T cells with either anti-CD3 antibody or PMA resulted in a rapid activation of both Ras and Raf-1. MEK activity towards kinase-active or -inactive recombinant MAPK also increased upon stimulation. In addition, both MAPK and p90rsk were activated in these cells. We suggest that activation of MAPK and the subsequent activation of ribosomal S6 kinase (p90rsk) occurs by the Ras/Raf-1/MEK cascade in T lymphocytes stimulated by ligation of the T cell receptor complex.

CD3 Complex↗
PubMed1994

Thrombosis of abdominal aortic aneurysms.

The usual complication of abdominal aortic aneurysms is rupture. Although thrombosis of peripheral aneurysms is common, thrombosis of abdominal aortic aneurysms is rare. Sudden thrombosis of abdominal aortic aneurysms constitutes a surgical emergency, with a mortality of 50 percent. The patient often presents with cool and mottled skin, and with severe pain from the umbilicus to the lower extremities. Femoral pulses are rarely present, and neurologic deficits below the level of occlusion are common. We reviewed four recent patients with thrombosed abdominal aortic aneurysms. They presented with a range of symptoms that included impotence, abdominal pain, lower extremity pain, coolness, and weakness. Angiography in three of the patients revealed complete occlusion of the aorta. The fourth patient did not undergo angiography because of hemodynamic instability. Three of the four patients underwent thrombectomy, aneurysmectomy, and bypass grafting. The other patient underwent axillofemoral bypass grafting in lieu of aneurysmectomy because of severe coronary arteriosclerotic heart disease. All patients did well postoperatively. Our limited experience suggests that prompt diagnosis and surgical management of patients with thrombosed aortic aneurysms can lead to a successful outcome.

Acute Disease↗