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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 289 records · Page 16Linked to original sources
PubMed1996

Effect of melittin on electrophysiological parameters in the frog cornea epithelium.

The effect of melittin on electrophysiological parameters of the bullfrog cornea was studied using an in vitro preparation. Epithelial cells of corneas were impaled with microelectrodes. Experiments were done under short-circuit current (Isc) conditions. Melittin was added in concentrations of 10(-5)M to the stromal or 10(-6)M to the tear solution. The effects of melittin were as follows: (i) stromal side, a decrease in Isc; an increase in the apical membrane fractional resistance, fRo; no change in the transepithelial conductance, gt; and a depolarization of the intracellular potential, Vo; (ii) tear side, an initial (first 10 min) increase and then a decrease in Isc; a decrease in fRo; an initial (first 10 min) increase with subsequent small decrease in gt; and a depolarization of Vo. Changes in tear Na+, but not in tear K+, with melittin present in tear solution, induced changes in some electrical parameters. The effects on the tear side may be explained by opening of nonspecific channels in the apical membrane with some specificity for Na+ channel. The subsequent effects on the tear and the effects on the stromal side may be explained by an inhibition of the primary transport system, that is, of the Na+/K+ -ATPase pump located in the basolateral membrane. In these experiments, there was no evidence of opening of channels in the basolateral membrane.

Animals↗
PubMed1996

Effect of acetazolamide and melittin on polarization of the frog gastric mucosa proton pump.

We have shown that polarization of an electrogenic H+/K+ ATPase pump located in the secretory (luminal) membrane of the frog gastric mucosa is the major factor contributing to the change in open circuit potential difference (OCPD) induced by voltage clamping. This transmucosal polarization was markedly reduced by H2 blockers famotidine and cimetidine, and by the H+/K+-ATPase inhibitors omeprazole and SCH 28080. SCN-, a nonspecific H+ secretion inhibitor, did not affect the polarization. In the present experiments, the effects of two other inhibitors of H+ secretion were examined, namely, acetazolamide (AA), a carbonic anhydrase inhibitor, and melittin (MEL), an inhibitor of the H+/K+-ATPase enzyme. When AA 10(-3) M or MEL 10(-5) M was added to the nutrient solution, H+ secretion was completely inhibited. While MEL markedly reduced the polarization induced by voltage clamp, AA did not affect the polarization. These data support the concept that MEL directly affects the electrogenic H+/K+-ATPase pump while the inhibition of H+ secretion by AA is by an indirect mechanism. The data further support the electrogenicity of the H+/K+-ATPase.

Acetazolamide↗
PubMed1996

Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.

BACKGROUND: Acute renal failure is a frequent complication following orthotopic hepatic transplantation. A reduction in the synthesis of intrarenal vasodilator prostaglandins has been proposed as having an important role in the pathogenesis of renal insufficiency associated with hepatic dysfunction, as well as in the nephrotoxicity associated with cyclosporine and FK506 immunosuppressive therapy. Therefore, administration of vasodilator prostaglandins may improve renal function following hepatic transplantation. This study was designed to determine the effect of continuous intravenous alprostadil (prostaglandin E1) on postoperative renal function in hepatic transplant patients. STUDY DESIGN: In a randomized, double-blind, placebo-controlled trial, 21 patients who had undergone orthotopic hepatic transplantation and had a measured postoperative glomerular filtration rate (GFR) of less that 50 mL/minute received intravenous alprostadil at 0.6 microgram/kg/hour or placebo for five days. Glomerular filtration rate and effective renal plasma flow (ERPF) were measured by a single-injection clearance method using a radionuclide agent in 53 patients within 12 hours after admission to our surgical intensive care unit. Usual postoperative care was not modified. Radionuclide GFR and ERPF measurements were repeated on postoperative day 3. Serum creatinine was measured preoperatively and postoperatively on day 3 and on day 5. A 24-hour serum creatinine clearance was measured on days 1, 5, and 14. Urine output was recorded hourly during the infusion period. RESULTS: Ten patients received alprostadil, and 11 patients received placebo. There was a significant increase in GFR and ERPF in both groups on post-operative day 3 as compared with baseline values. There was no difference in GFR and ERPF between the two groups on day 3 (48 +/- 18 and 246 +/- 68 mL/minute in the alprostadil group compared with 53 +/- 17 and 270 +/- 131 mL/minute in the placebo group). Serum creatinine levels increased on day 3 in both groups but returned to baseline by day 5. CONCLUSIONS: These results indicate that a reversible decrease in GFR is common on hepatic transplant patients during the postoperative period. Administration of a continuous intravenous infusion of alprostadil in the immediate postoperative period had no effect on renal function when compared with placebo.

Adult↗
PubMed1996

Mutation spectrum in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia: identification of twelve different mutations in the WASP gene.

Twelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.

Base Sequence↗
PubMed1996

Lung scan detection of SVC clot with collateral flow to liver.

We present a case of visualization of a clot in the superior vena cava with collateral flow to the liver during a lung perfusion scan. A digital venogram performed after injection through the right central venous line confirmed the presence of a clot in the superior vena cava with retrograde flow into the azygous venous system.

Aged↗
PubMed1996

Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration.

PURPOSE: This article presents the rationale and an experimental strategy for the development of new treatment modalities for glaucomatous neuropathy. Accumulating evidence suggests that regardless of the primary trigger of the retinal and optic nerve damage in glaucoma, the disease will continue to progress even when the cause is removed. The resulting damage can be mimicked by the progression of damage secondary to an acute partial crush injury at the optic nerve head. Such secondary damage includes degeneration of the directly injured optic nerve fibers culminating in death of their cell bodies, as well as degeneration of nerve fibers that escaped acute injury but nevertheless deteriorate as a result of their exposure to injury-induced mediators of secondary degeneration released by the directly affected neurons. CONCLUSION: We therefore propose that substances found to be effective in rescuing fibers from secondary degeneration and in increasing the survival rate or prolonging survival of retinal ganglion cells in the partially lesioned optic nerve may be useful for the treatment of glaucoma. The new approach does not replace hypotensive therapy, but addresses the glaucoma-induced damage by promoting nerve protection and neuroregeneration.

Animals↗
PubMed1996

Effects of nutrient HCO3- and Cl- on potential difference responses to nutrient Na+ changes in secreting and inhibited states of frog stomach.

Previously, it was found that a decrease in nutrient (serosal) Na+ decreased the transmucosal potential difference (PD) in the secreting and inhibited states of fundi of stomachs of Rana pipiens. This PD response, designated as anomalous, was explained by two different models, an electrogenic NaCl symport and an electrogenic NaHCO3 symport. To test these hypotheses, experiments were done at pH approximately 7.4 in which the PD response to a change in nutrient Na+ was compared in 25, 5, and 0 mM nutrient HCO3- solutions. In the H+ secreting state, all HCO3- concentrations gave, for a 10-fold decrease in nutrient Na+, about the same PD response (9-12 mV). The PD response was 8.5, 2.9, and 0 mV higher in the inhibited state for 25, 5, and 0 mM HCO3- , respectively. Experiments with decreasing nutrient Cl- decreased the anomalous PD response to Na+ changes, and the response became insignificant at Cl- concentrations of 20 mM or less in the secreting state. The anomalous PD response to a decrease in Na+ concentration was obtained for all Cl- concentrations (0-79 mM), becoming less with decreasing Cl- in the inhibited state. These results support a NaCl symport to explain the PD response in the secreting state and a NaHCO3 symport to explain the enhancement in the inhibited state.

Animals↗
PubMed1995

Effect of current direction and K+ on polarization of the frog gastric mucosa proton pump.

When current was sent from serosa (S) to mucosa (M) across the frog stomach, there was a polarization (POL) of the open circuit potential (OCPD). POL was not affected by NaCl-free solutions, but was decreased by inhibitors of the H+ pump. In present experiments, current was sent to clamp the PD (VC) across the mucosa in steps of 20 mV up to 100 mV below the control OCPD, that is, current was sent from M to S. All experiments were performed in NaCl-free solutions. The POL was expressed as a % of the difference between the VC PD and the control OCPD. In 4 mM K+ control solutions, the POL was 11.8%; with 10(-3) M omeprazole (H+/K+ pump inhibitor), 1.1; with 10(-5) M SCH 28080 (H+/K+ pump inhibitor), 3.6; with 10(-3) M famotidine (H2 blocker), 1.6; and with 10(-2) M SCN-, 25.4 (inhibition of H+ sec, but not of the pump); in 79 mM K+ control solutions, 26.2; with 10(-3) M omeprazole, 4.2; with 10(-5) M SCH 28080, 15.9; with 10(-3) M famotidine, 5.6; and with 10(-2) M SCN-, 29.9. POL was higher in high K+ than in low K+ solutions contrary to what was observed in previous experiments with current sent from S to M. Results are explained on the basis of an electrogenic H+/K(+)-ATPase pump which includes a H+ channel, permeable to K+. With high K+ solutions, K+ is driven through the H+ channel onto the antiporter (ATPase) when current is sent from M to S, resulting in a greater POL of the pump.

Animals↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

The effect of interposition membrane on the outcome of lumbar laminectomy and discectomy.

STUDY DESIGN: This study evaluated clinical and magnetic resonance imaging differences of patients treated surgically for lumbar disc herniation. Clinical follow-up and magnetic resonance imaging evaluation of epidural fibrosis were used to assess patient outcome. OBJECTIVES: The purpose of this study was to evaluate the difference in clinical outcome with either free-fat graft, Gelfoam, or no interposition membrane placed in the laminectomy defect after nerve root decompression. SUMMARY OF BACKGROUND DATA: Epidural fibrosis has been considered a cause of recurrent symptoms after lumbar laminectomy, and numerous materials have been evaluated for prophylaxis of the "laminectomy membrane." These have been mainly histologic and animal studies with no data correlating clinical symptoms and postoperative epidural scar formation. METHODS: One hundred fifty-six patients who were treated surgically for lumbar disc herniation were randomly assigned to one of three groups and followed prospectively for at least 1 year. Thirty-three of these patients were received magnetic resonance imaging evaluations after 6 months by an independent radiologist who graded the amount of epidural scar formation. The patients were assessed at 1 year and given a rating of excellent, good, fair, or poor, and the scar was graded as none, minimal, or moderate. RESULTS: Although 97% of all patients improved, 83% were rated excellent or good. There were no statistical differences between the three groups clinically and radiographically. Patients with workers compensation had a statistically significant lower success rate (P < 0.001). CONCLUSIONS: Clinical outcome after lumbar disc surgery does not correlate with the use or type of interposition membrane used to prevent epidural fibrosis.

Adolescent↗
PubMed1995

Direct involvement of p53 in programmed cell death of oligodendrocytes.

A covalent dimer of interleukin (IL)-2, produced in vitro by the action of a nerve-derived transglutaminase, has been shown previously to be cytotoxic to mature rat brain oligodendrocytes. Here we report that this cytotoxic effect operates via programmed cell death (apoptosis) and that the p53 tumor suppressor gene is involved directly in the process. The apoptotic death of mature rat brain oligodendrocytes in culture following treatment with dimeric IL-2 was demonstrated by chromatin condensation and internucleosomal DNA fragmentation. The peak of apoptosis was observed 16-24 h after treatment, while the commitment to death was already observed after 3-4 h. An involvement of p53 in this process was indicated by the shift in location of constitutively expressed endogenous p53 from the cytoplasm to the nucleus, as early as 15 min after exposure to dimeric IL-2. Moreover, infection with a recombinant retrovirus encoding a C-terminal p53 miniprotein, shown previously to act as a dominant negative inhibitor of endogenous wild-type p53 activity, protected these cells from apoptosis.

Animals↗
PubMed1995

Glial cell types, lineages, and response to injury in rat and fish: implications for regeneration.

Axons of the mammalian central nervous system do not regenerate spontaneously after axonal injury, unlike the central nervous system axons of fish and amphibians and the peripheral nervous system of mammals, which possess a good regenerative ability (Grafstein: The Retina: A Model for Cell Biology Studies, Part II, 1986; Kiernan: Biol Rev 54:155-197, 1979; Murray: J Comp Neurol 168:175-196, 1976; Ramón y Cajal: Degeneration and Regeneration of the Nervous System, 1928; Reier and Webster: J Neurocytol 3:591-618, 1974; Sperry: Physiol Zool 23:351-361, 1948). It was previously believed that intrinsic differences between the central nervous system neurons of mammals and fish account for their differences in regenerative ability. The past decade, however, has seen an accumulation of evidence, indicating that mammalian central nervous system neurons are able to regenerate injured axons, at least to some extent. This was first demonstrated by Aguayo and colleagues (David and Aguayo: Science 214:931-933, 1981; Kierstead et al: Science 246:255-257, 1989), who showed that injured mammalian central nervous system axons can grow for a considerable distance into an autograft of a peripheral nerve. It was also demonstrated that injured rabbit optic axons can regenerate into their own environment (i.e., into the distal part of the injured optic nerve), if the injured nerve is treated so as to make it conducive for growth (Lavie et al: J Comp Neurol 298:293-314, 1990; Eitan et al: Science 264:1764-1768, 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Dibutyryl cAMP reduces nonparenchymal cell damage during cold preservation of rat livers.

Sinusoidal lining cells are the main target for cold preservation injury and are further damaged with reperfusion. Different agents known to increase intracellular cAMP levels have been shown beneficial. This study was designed to assess the possible protective effect of a cAMP analogue on nonparenchymal cells of rat livers, during cold storage and during reperfusion. Parameters reflecting the status of the liver microvasculature were analyzed. The initial effluent collected after preservation reflects release during the cold storage period; therefore we measured interleukin-1 (IL-1) and endothelin-1 (ET-1) levels in these samples in order to detect and quantitate the degree of activation and/or disruption of Kupffer and sinusoidal endothelial lining cells. Rat livers were harvested after in situ flush with Ringer's lactate with or without 2 mM dibutyryl cAMP, excised, and stored in the same solution at 4 degrees C. After 6 hr, livers were perfused with Krebs-Henseleit buffer for 90 min. Physiological parameters were monitored throughout the perfusion. Perfusate samples were collected every 30 min for RIA measurements of IL-1 and ET-1. Treatment resulted in a significant decrease in release of ET-1 and IL-1 during storage. Likewise, livers treated with cAMP had a significantly improved bile output and decreased portal vein resistance during reperfusion. The beneficial effect granted by the analogue during cold storage and reperfusion was evident on parenchymal and nonparenchymal cells. Levels of ET-1 and IL-1 in the caval effluent confirm and quantitate preservation damage.

Animals↗
PubMed1995

High incidence of cystic fibrosis on the Faroe Islands: a molecular and genealogical study.

We have studied the genetics of cystic fibrosis (CF) in The Faroe Islands. Based on the number of affected children born during the period 1954-1993, the incidence of CF at birth is 1:1775, which is more than twice the incidence in the rest of Denmark. We have tested all known CF patients and/or their parents for the presence of delta F508 and found it to be the only CF mutation in this population. Based on testing 881 unrelated control individuals, the carrier frequency was estimated to be 1:24, given a calculated incidence of 1:2300. Genealogical studies enabled us to trace several of the families over seven generations. Haplotype investigations within the families suggest that delta F508 was introduced by two founders, probably from the Celtic population in Brittany, Ireland, Wales or the North West of Scotland.

Cystic Fibrosis↗