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Biomedical subjects

J C Gilbert

Publications and source records attributed to J C Gilbert.

At least 19 recordsLinked to original sources
PubMed1992

Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirubinemia.

The minimal hepatic mass necessary to reverse the metabolic defect of unconjugated hyperbilirubinemia in the rat model of Crigler-Najjar type I deficiency was determined using heterotopic (auxiliary) partial liver transplantation (HLT) and orthotopic liver transplantation (OLT). In HLT, the donor graft consisted of the right upper and/or right lower hepatic lobe(s) depending on the final mass of liver tissue desired for transplantation. The mass of the donor graft ranged from 12% to 23% of the whole organ (n = 12). The serum unconjugated bilirubin levels decreased quickly after HLT from a preoperative value of 8.98 +/- 0.34 mg/dL to 0.63 +/- 0.11 mg/dL in 24 hours, which was similar to OLT in which the levels decreased from a preoperative value of 8.20 +/- 0.44 mg/dL to 0.24 +/- 0.07 mg/dL in 24 hours. Conjugated bilirubin was excreted from the graft liver shortly after OLT and also from both the host and graft livers after HLT. This study demonstrates that using as little as 12% of the whole liver mass in HLT reduces serum bilirubin significantly in 24 hours in a fashion similar to whole-organ OLT. The clinical application of alternative therapies to whole-organ OLT such as HLT or hepatocyte transplantation may provide sufficient replacement therapy in metabolic disease.

Animals↗
PubMed1992

Hypoxia in human gliomas: demonstration by PET with fluorine-18-fluoromisonidazole.

Positron emission tomography (PET) with the hypoxic-cell tracer [18F]fluoromisonidazole presents a possible means of noninvasively demonstrating tumor hypoxia. PET studies using this tracer were performed in three patients with malignant glioma, and in all patients the tumor was clearly seen at 5 min postinjection and initial tumor activity exceeded cortical activity. In one patient, there was no tumor retention of [18F] fluoromisonidazole and tumor activity fell while cortical activity increased, with the two tissues reaching equality at 40-50 min. The tumor-to-plasma ratio was 0.71 at 3 hr. The other two patients showed variable tumor retention of [18F]fluoromisonidazole, with tumor-to-plasma ratios of 1.10 and 1.49 at 2 and 3 hr. These results demonstrate the feasibility of using [18F]fluoromisonidazole PET to detect hypoxia in human gliomas in vivo. Clinical trials are needed to determine whether a relationship exists between [18F]fluoromisonidazole uptake and tumor radiation response.

Adult↗
PubMed1991

Inositol trisphosphate promotes Na-Ca exchange current by releasing calcium from sarcoplasmic reticulum in cardiac myocytes.

An early inward tail current evoked by membrane depolarization (from -80 to -40 mV) sufficient to activate sodium but not calcium current was studied in single voltage-clamped ventricular myocytes isolated from guinea pig hearts. Like forward-mode Na-Ca exchange, this early inward tail current required [Na+]o and [Ca2+]i and is thought to follow earlier reverse-mode Na-Ca exchange that triggers Ca2+ release from sarcoplasmic reticulum. The dependence of the early inward tail current on [Ca2+]i was supported by the ability of small (+10 mV) and large (+80 mV) voltage jumps from -40 mV to decrease and increase, respectively, the size of early inward tail currents evoked by subsequent voltage steps from -80 to -40 mV. As expected, tetrodotoxin selectively inhibited the early inward tail current but not the late inward tail current that followed voltage jumps to +40 mV test potentials. Although tetrodotoxin also blocked the fast Na+ current, replacement of extracellular Na+ by Li+ sustained the fast Na+ current. However, Li+, which does not support Na-Ca exchange, reversibly suppressed both the early and late inward tail currents. Inhibitors (ryanodine and caffeine) and promoters (intracellularly dialyzed inositol 1,4,5-trisphosphate) of sarcoplasmic reticulum Ca2+ release decreased and increased, respectively, the magnitude of the early inward tail current. The results substantiate the hypothesis that Ca2+ release from the sarcoplasmic reticulum participates in early Na-Ca exchange current and demonstrate that inositol 1,4,5-trisphosphate, by releasing Ca2+ from the sarcoplasmic reticulum, can promote Na-Ca exchange across the plasma membrane.

Animals↗
PubMed1989

Repair of pectus excavatum using a substernal metal strut within a Marlex envelope.

In a retrospective review, 82 children aged 3 to 16 years who had repair of pectus excavatum from 1963 to 1987 were divided into three groups according to type of repair: those without a metal substernal strut, those with a metal substernal strut, and those with a metal substernal strut within a Marlex envelope. In group 1 (n = 50) there were five recurrences; in group 2 (n = 18) and group 3 (n = 14) there were no recurrences. There was migration of the substernal strut in eight patients in group 2 (44%) and three patients in group 3 (21%). There were minor wound infections in groups 1 and 2 only. There were no deaths. Results of this study suggest that the use of a substernal strut significantly reduced recurrence and that the addition of a Marlex envelope around the strut reduced migration of the strut with no associated complications.

Adolescent↗
PubMed1988

Reduced affinity of peripheral benzodiazepine binding sites in elderly insomniac patients.

Peripheral-type benzodiazepine binding sites on intact platelets from untreated chronic insomniac patients and those chronically treated with benzodiazepine hypnotics were investigated to evaluate their putative involvement in sleep pathology and the influence of treatment. There were 34 elderly subjects in the study, 14 controls (80.7 years) and 20 insomniac patients, of whom 7 were untreated (61.1 years) and 13 were treated (84.4 years). There was an equivalent number of peripheral-type benzodiazepine 3H-PK 11195 binding sites on platelets from untreated (7.61 pmol/mg protein) and treated insomniacs (6.39 pmol/mg protein) and on platelets from the controls (6.21 pmol/mg protein). However, there was a twofold reduction in the affinity of these sites in untreated (Kd = 8.02 nM) and treated (Kd = 7.40 nM) insomniacs compared to controls (3.79 nM). This difference raises the possibility that peripheral-type benzodiazepine sites are involved in abnormal sleep.

Adult↗
PubMed1987

Binding sites for a peripheral type benzodiazepine antagonist ([3H]PK 11195) in human iris.

Peripheral-type benzodiazepine binding sites have been characterized on sections of 8 normal human iris/ciliary-body preparations. Saturability was determined at 25 degrees C with [3H] PK 11195 (1 nM) a specific ligand of peripheral type sites. The studies revealed a single class of binding sites for PK 11195 with a nanomolar range affinity (KD = 1.45 nM) and a maximal capacity (Bmax) of 35.5 fmol/mg protein. The displacement potency order of the benzodiazepines tested suggest that these sites belong to the peripheral type: PK 11211 (IC50 = 12 nM) greater than Ro 5-4864 (IC50 = 770 nM) greater than clonazepam (IC50 = 20,000 nM). The present data demonstrate that high affinity binding sites for peripheral type benzodiazepines are present in human iris/ciliary-body. This tissue is therefore a suitable tool for evaluation of the putative functional role of these binding sites.

Aged↗
PubMed1987

Quantitative autoradiographic determination of binding sites for a peripheral benzodiazepine ligand ([3H]PK 11195) in human iris.

Specific binding sites of peripheral-type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color-coded prints and densitometric quantification of autoradiograms were performed on slides (20 micron) labelled with [3H]PK 11195 (1 nM) at 25 degrees C. Nonspecific binding was determined with PK 11211 (5 microM) or Ro 5-4864 (5 microM). Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris, and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively, were: 42.7 +/- 0.2, 30.1 +/- 0.5, and 37.4 +/- 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle. The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.

Aged↗
PubMed1986

Ultrasound monitored hepatic cryosurgery: longevity study on an animal model.

Ultrasound imaging has been proposed to monitor the amount of frozen tissue during hepatic cryosurgery of primary and metastatic tumors. In this follow-up study, a cryolesion was produced in an adult pig under ultrasound monitoring. The animal was allowed to recuperate for 3 days before being sacrificed. Pathologic and histologic evaluation showed extremely close correlation with the ultrasound image. The necrotic region was clearly observable in the sonogram after 3 days. Ultrasonography can accurately represent the extent of the cryolesion both during as well as following cryosurgery.

Animals↗
PubMed1986

Stimulation of p-nitrophenylphosphatase activity of mung bean shoot extracts. Preliminary observations as a possible screening test for anticonvulsant drugs.

The p-nitrophenylphosphatase (pNPPase) activity of mung bean shoot extracts has similar characteristics to that of animal tissue. Mung bean shoot pNPPase activity is maximal between pH 7.8 and 8.2 and at a substrate concentration between 10 and 20 mM and is inhibited by sodium ions. Mung bean shoot pNPPase activity is competitively inhibited by ATP with a Ki value of 2.8 mM. A wide range of anticonvulsant drugs tested all stimulated the pNPPase activity of the mung bean shoot extracts. The nonanticonvulsant drugs tested did not have this effect, with the exception of pemoline, which, although not acknowledged to be an anticonvulsant drug, did show anticonvulsant activity when tested using conventional methods involving animals. In double-blind trials, 12 out of 15 compounds were correctly classified as anticonvulsants or nonanticonvulsants. It is proposed that the pNPPase activity of mung bean shoot extracts may be useful as a preliminary screen for anticonvulsant drugs.

4-Nitrophenylphosphatase↗
PubMed1986

Effects of lithium salts on lipid peroxidation activity of synaptosomes and kidney homogenates.

Lithium carbonate increased the lipid peroxidation while lithium sulphate and lithium chloride had no significant effects on lipid peroxidation activity of rat cerebral cortex synaptosomes and kidney homogenates. However, lithium chloride plus sodium carbonate significantly increased the lipid peroxidation activity of kidney homogenates. It is concluded that accompanying anions of lithium salts might play a major role in the increase of lipid peroxidation of both synaptosomes and kidney homogenates.

Animals↗
PubMed1985

Real time ultrasonic monitoring of hepatic cryosurgery.

Cryosurgery has a number of advantages that make it particularly appealing in the treatment of liver cancer. However, a major problem in the clinical application of hepatic cryosurgery is the lack of a precise means of monitoring the freezing process in situ. Preliminary investigations on simulated tissue have shown that standard ultrasonography is capable of accurately determining the amount of frozen material during a cryosurgical procedure. To extend these results to living tissue, cryosurgery was performed, in vivo, on the livers of four mongrel dogs. An ultrasound imaging device using a new intraoperative ultrasound transducer monitored the entire process in real time. The results indicate that the entire freezing and thawing cycle can be monitored easily using real time ultrasound. During freezing, the solidification interface can be seen to move through the tissue allowing clear imaging of the cryolesion. After complete thawing, the cryolesion became less echogenic than before freezing and was therefore distinguishable under ultrasound. Postsurgical pathologic examination showed excellent correlation between the lesion size and its ultrasonic image.

Animals↗
PubMed1985

Lipid peroxidation as a possible mechanism for the neurotoxic and nephrotoxic effects of a combination of lithium carbonate and haloperidol.

Lithium carbonate as well as haloperidol increased lipid peroxidation in rat cerebral cortex synaptosomes and rat kidney homogenates while sulpiride had no significant effects. A combination of lithium carbonate and haloperidol caused a greater increase in lipid peroxidation than did either lithium carbonate or haloperidol alone. It is concluded that the neurotoxic and nephrotoxic effects of lithium carbonate and haloperidol might be a consequence of increased lipid peroxidation in the cerebral cortex and the kidney, respectively.

Animals↗
PubMed1983

ATPase activities and lipid peroxidation in rat cerebral cortex synaptosomes.

ATPase activities and lipid peroxidation as measured by malonaldehyde formation in rat cerebral cortex synaptosomes depend on the time of incubation of the tissue. ATPase activities decreased but lipid peroxidation activity increased with increasing incubation periods. Effects of catechol- and non-catechol molecules on lipid peroxidation in synaptosomes have been determined. Drugs previously shown to stimulate ATPases inhibited lipid peroxidation. It seems likely that close relationships exist between stimulation of ATPase activities and inhibition of lipid peroxidation.

Adenosine Triphosphatases↗
PubMed1982

The effects of dopamine agonists and antagonists on Na+,K+-ATPase and Mg2+-ATPase activities of synaptosomes.

The effects of dopamine agonists and antagonists on the Na+,K+-ATPase and Mg2+-ATPase activities of rat cerebral cortex synaptosomes have been determined. Dopamine, ADTN, apomorphine and S-584, but not piribedil, stimulated the activities of the enzymes. The stimulatory effect of dopamine was not antagonised by dopamine antagonists and apparently the catechol group is responsible for the enzyme stimulation.

Adenosine Triphosphatases↗