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Biomedical subjects

A Fine

Publications and source records attributed to A Fine.

At least 145 records · Page 8Linked to original sources
PubMed1991

Cholinergic neural transplants into hippocampus restore learning ability in monkeys with fornix transections.

Monkeys with bilateral transections of the fornix were severely but selectively impaired at learning visuospatial conditional tasks presented in a Wisconsin General Test Apparatus. Bilateral transplantation of cholinergic-rich embryonic basal forebrain tissue into the hippocampus led to complete recovery from this specific learning impairment across a range of task difficulties. Administration of the direct cholinergic agonist pilocarpine to ungrafted animals immediately before testing also reduced this impairment, suggesting that the graft-associated recovery was mediated by acetylcholine release. Transection of the fornix produced a marked loss of acetylcholinesterase (AChE) staining confined to hippocampus and entorhinal cortex relative to controls. In all transplanted animals densely AChE-staining cellular masses were seen bilaterally in temporal lobe structures, with fibre outgrowth into surrounding host tissue.

Acetylcholinesterase↗
PubMed1991

Remnant kidney metabolism in the dog.

A marked increase in oxygen uptake (Qo2) per nephron has been described in the remnant kidney of the rat. However, it is not known which substrates support renal metabolism in remnant kidney nor is it known whether similar changes in Qo2 occur in other species. Remnant kidney in the dog was induced by ligation of 60 to 75% of the renal arterial branches on one side followed 1 to 2 wk later by contralateral nephrectomy. At 3 months marked hypertrophy of the remnant kidney was found and the glomerular filtration rate was 18 +/- 1.8 mL/min compared with 31 +/- 2 in a normal kidney (P less than 0.01). Qo2 was 689 +/- 60 mumol/min/100 mL glomerular filtration rate in the remnant kidney compared with 564 +/- 42 mumol/min/100 mL glomerular filtration rate in the normal kidney (P less than 0.01). Total renal ammoniagenesis per nephron increased to values found in chronic metabolic acidosis although serum (K+) and (HCO3-) were no different than in the normal dog. The oxidation of glutamine and lactate by remnant kidneys accounted for over 80% of Qo2, similar to that of normal kidneys. It is concluded that hypermetabolism per nephron occurs in the remnant kidney of the dog and that glutamine and lactate are the major energy substrates in remnant kidney. Furthermore, factors other than serum (K+) and (HCO3-) augment ammoniagenesis in this model. However, when these results are expressed per whole kidney or per gram of tissue, hypermetabolism does not occur in these remnant kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1991

Direct purchase contracts carry risks, benefits.

To better control their purchasing of healthcare services, some employers are seeking direct managed care contracts with healthcare facilities. Along with evaluating potential markets introduced by a proposed contract, a provider should develop a pricing strategy, a monitoring system, and a process for internal audit before entering into a direct purchase contract. With the proper checks in place, direct purchase contracts can be mutually beneficial to providers and purchasers.

Contract Services↗
PubMed1990

Phorbol ester-induced inhibition of collagen accumulation by human lung fibroblasts.

The effect of phorbol 12-myristate 13-acetate (PMA) on collagen accumulation by human embryonic lung fibroblasts was determined. PMA (10 nM) dramatically inhibited collagen formation in cultures that were unstimulated or stimulated with transforming growth factor-beta (TGF-beta). Collagen accumulation was decreased by 50% in unstimulated cultures and by 80% in TGF-beta-treated cultures. This inhibition was associated with a marked decrease in steady-state levels for alpha 1(I) collagen mRNA and decreases in alpha 1(I) gene transcription as determined by nuclear run-off assays. The PMA-mediated decrease in alpha 1(I) collagen mRNA was not affected by the addition of cycloheximide or indomethacin. Prolonged treatment with PMA (100 nM) resulted in down-regulation of protein kinase C (PKC) activity to less than 3% of untreated cultures. When PKC activity was down-regulated, treatment with PMA did not block TGF-beta-stimulated collagen formation, and prostaglandin E2-induced inhibition of protein formation was still evident. These results suggests that PKC activity modulates the level of transcription of collagen genes and collagen accumulation in lung fibroblast cultures.

Cell Line↗
PubMed1990

Is glutamate a co-transmitter in cortical cholinergic terminals? Effects of nucleus basalis lesion and of presynaptic muscarinic agents.

To obtain additional evidence in support of the co-transmitter role of glutamate in cortical cholinergic terminals proposed by Docherty et al., the right nucleus basalis in rats was lesioned with ibotenic acid; resulting changes in cortical acetylcholinesterase (AChE) staining, glutamate content, and the release of [3H]acetylcholine ([ 3H]ACh) and glutamate from cortical slices from the two sides were compared. While there was a profound reduction on the lesioned side in cortical AChE activity and in the size of the releasable pool of [3H]ACh, neither the content nor the evoked release of glutamate was reduced significantly on the lesioned side. Furthermore, while oxotremorine strongly depressed the evoked release of [3H]ACh, it had no effect on the evoked release of endogenous glutamate measured simultaneously. These results do not support the co-transmitter role of glutamate in cortical cholinergic terminals, although they cannot statistically exclude that a small fraction of glutamate has a co-transmitter role, as proposed by Docherty et al.

Acetylcholine↗
PubMed1990

Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions.

Unilateral injections of kainic acid into the basal forebrain in a series of rats resulted in an increase in large amplitude slow waves, a correlated burst-suppression pattern of multi-unit activity, and a decrease in acetylcholinesterase staining in the neocortex ipsilateral to the kainic acid injection. Subsequently, a cell suspension, prepared from rat embryonic basal forebrain tissue, was injected adjacent to the recording electrodes ipsilateral to the kainic acid injection. This produced a gradual recovery of low voltage fast activity (LVFA) and a correlated continuous discharge pattern of multi-unit activity in the neocortex ipsilateral to the kainic acid injection. LVFA recovered more slowly at neocortical recording sites that received an injection of a cell suspension of hippocampal primordial cells or no injection at all. Acetylcholinesterase-positive fibers from the basal forebrain tissue invaded host cortex; no comparable outrgrowths were demonstrable in the hippocampal primordium tissue grafts. Restoration of cholinergic electrocortical activation may play an important role in the improvements in behavioral performance produced by basal forebrain grafts in the cortex in animals with basal forebrain lesions.

Acetylcholinesterase↗
PubMed1990

Modulation of experimentally induced epilepsy by intracerebral grafts of fetal GABAergic neurons.

Systemic administration of pilocarpine to rats induces seizures that resemble complex partial epilepsy in humans. Susceptibility to these seizures is increased by lesion of the GABAergic striatonigral projection. Transplantation of fetal GABAergic neurons, but also of control non-GABAergic tissue, to the deafferent substantia nigra can reduce such lesion-increased seizure susceptibility. These observations are consistent with prior evidence that GABAergic basal ganglia outflow plays an important role in controlling the spread of seizures, and raise the possibility that intracerebral grafts may be of use for therapy of medically-unresponsive epilepsies.

Animals↗
PubMed1990

The accumulation of type I collagen mRNAs in human embryonic lung fibroblasts stimulated by transforming growth factor-beta.

We examined the expression of type I collagen mRNAs (alpha 1(I) and alpha 2 (I)) by embryonic lung fibroblasts in cultures treated with transforming growth factor-beta (TGF-beta). TGF-beta caused a concentration dependent increase in the expression of alpha 1(I) mRNA for type I collagen. TGF-beta at low concentration (0.1 ng/ml) slightly increased the level of alpha 1(I) mRNA. Higher concentrations of TGF-beta (1.0 and 5.0 ng/ml) further increased the amount of alpha 1(I) mRNA. The increase in alpha 1(I) mRNA was associated with a marked increase in production of intact type I collagen molecules. TGF-beta did not increase expression of alpha 2(I) mRNA. The alpha 2(I) mRNA levels in human lung fibroblast cultures were not affected by varying the duration of exposure to TGF-beta nor the concentration of TGF-beta. In contrast, TGF-beta increased the amount of both alpha 1(I) and alpha 2(I) mRNA in NIH3T3 cells. These data suggest that the amount of alpha 2(I) mRNA is not rate limiting with respect to type I collagen production during TGF-beta stimulation in human lung fibroblast cultures.

Cells, Cultured↗
PubMed1990

Changes in endogenous creatinine clearance in man on a controlled protein diet: effect of route of administration of a protein load.

Dietary protein has been implicated in the progressive decline in renal function seen in association with chronic renal failure. An acute protein load has been reported to increase creatinine clearance; however this alteration in function is variable. Therefore, the route of administration of a protein load was examined in this study while the dietary protein was controlled. Sequentially, both oral and intravenous protein loads were administered to the same volunteer while initially on a low protein diet (0.75 g/kg/24h) for three weeks followed by three weeks of an ad libitum protein diet (1.31 g/kg/24h). Neither the baseline serum creatinine nor the creatinine clearance were altered by the diet. Only the oral protein load resulted in an increase in the creatinine clearance. This study demonstrated that the route of administration, but not the dietary protein, is a determinant of the response of endogenous creatinine clearance to an acute protein load.

Adult↗
PubMed1990

Remnant model of renal failure in the dog: avoidance of second surgery by chemical nephrectomy.

Experimental chronic renal failure in the dog is usually studied by a two-step surgical procedure. However, it is becoming increasingly difficult, due to animal welfare concerns, to get permission for such procedures in Canada. We describe a method for obviating the need for second surgery by injecting absolute alcohol into a renal artery, which leads to immediate functional nephrectomy.

Animal Welfare↗
PubMed1989

The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts.

We examined the effect of prostaglandin (PG) E2 on transforming growth factor-beta (TGF-beta) and insulin-stimulated collagen formation in lung fibroblast cultures. TGF-beta increased type I collagen production 2-3-fold as determined by the densitometric analysis of autoradiograms from polyacrylamide gels and by measuring the amount of nondialyzable hydroxyproline. This was associated with a 5-6-fold increase in alpha 1(I) mRNA levels. PGE2 at 10(-7) M strongly inhibited type I collagen formation in TGF-beta-stimulated cultures by 60-70%. PGE2 blocked collagen formation in TGF-beta-stimulated cultures by decreasing levels of alpha 1(I) gene expression. PGE2 inhibited alpha 1(I) gene expression in part through inhibition of transcription. In contrast, insulin increased type I collagen production 2-fold and was associated with a 30-40% increase in alpha 1(I) mRNA. Although PGE2 also decreased alpha 1(I) mRNA levels in insulin-treated cultures, PGE2 had no effect on collagen formation. Taken together, these results demonstrate that collagen formation may proceed through two distinct pathways. These two pathways are distinguishable by their sensitivity to PGE2 treatment and their relationship to increases in collagen mRNAs.

Collagen↗