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Biomedical subjects

A Fine

Publications and source records attributed to A Fine.

At least 19 recordsLinked to original sources
PubMed1992

Tyrosine hydroxylase-immunoreactive neurons in the nucleus basalis of the common marmoset (Callithrix jacchus).

In the course of characterizing the distribution of putative catecholaminergic neurons in the brain of the common marmoset, we encountered a population of such cells in the basal forebrain. Tyrosine hydroxylase-immunoreactive neurons are abundant within the nucleus basalis magnocellularis throughout its entire rostrocaudal extent, but not in other cholinergic basal forebrain nuclei. Most tyrosine hydroxylase-immunoreactive cells are large and multipolar. Double staining with antibodies to choline acetyltransferase or nerve growth factor receptor confirmed that these tyrosine hydroxylase-immunoreactive neurons are cholinergic, and compose at least 40% of the nucleus basalis cholinergic cells. The presence of a catecholamine-synthesizing enzyme in the neurons that provide the major cholinergic input to the neocortex may have important consequences for cortical function, and may be relevant to the vulnerability of the nucleus basalis in certain neurodegenerative disorders.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Effect of 5-HT receptor and adrenoceptor antagonists on micturition in conscious cats.

Micturition was induced in awake cats by infusing saline into the bladder at a physiological filling rate. Methysergide, a serotonergic antagonist given intrathecally, decreased the volume at which micturition occurred. Phentolamine, a non-specific alpha-adrenoceptor antagonist, also decreased volume threshold. Prazosin, an alpha 1-adrenoceptor antagonist, was without effect on micturition. These results imply that 5-HT receptors and alpha 2-adrenoceptors may be inhibitory to micturition at a spinal level.

Adrenergic alpha-Antagonists↗
PubMed1992

Discordant regulation of human type I collagen genes by prostaglandin E2.

We examined the expression of type I collagen genes in prostaglandin E2 (PGE2)-treated human lung fibroblast cultures. Addition of PGE2 to fibroblast cultures inhibited alpha 1(I) mRNA levels by approx. 25% after 6 h and 60% after 24 h. Further studies showed that dibutyryl cAMP did not inhibit alpha 1(I) mRNA levels and that cycloheximide blocked the inhibitory effect of PGE2. In contrast, PGE2 treatment with or without cycloheximide did not affect alpha 2(I) mRNA levels. Moreover, in vitro translation of RNA derived from untreated and PGE2-treated cells yielded similar amounts of alpha 2(I) collagen peptides. Taken together, these results suggest that PGE2 induces a protein which inhibits alpha 1(I) transcription through distinct regulatory elements not under the control of cAMP and provide further evidence that the type I collagen genes can be discordantly regulated.

Blotting, Northern↗
PubMed1992

Restoration of learning ability in fornix-transected monkeys after fetal basal forebrain but not fetal hippocampal tissue transplantation.

Monkeys with bilateral transection of the fornix were severely but selectively impaired on learning and retention of visuospatial conditional discriminations, visual conditional discriminations and non-conditional spatial-response tasks. Bilateral transplantation of cholinergic-rich fetal basal forebrain tissue into the hippocampus abolished significant learning impairments on all those tasks impaired by fornix lesions when tested three to nine months after transplantation whereas bilateral transplants of non-cholinergic fetal hippocampal tissue into hippocampus showed no such beneficial effect. Acetylcholinesterase staining was severely depleted throughout the dentate gyrus and hippocampus in fornix-transected monkeys compared with animals with control corpus callosum ablations. Staining was largely restored to normal in the host hippocampus and dentate gyrus in monkeys with cholinergic transplants, whereas acetylcholinesterase staining was abnormal in those with non-cholinergic grafts. These experiments suggest that where a "higher order" cognitive function, in this case the acquisition of specific types of information into long-term memory, is disturbed by a neuropharmacologically simple lesion, cognitive function can be restored by transplantation of neurons containing appropriate neurotransmitters.

Analysis of Variance↗
PubMed1992

Modest reduction of serum albumin in continuous ambulatory peritoneal dialysis patients is common and of no apparent clinical consequence.

It is commonly assumed that a reduction in serum albumin is a reliable sign of nutritional inadequacy affecting prognosis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied prospectively 19 patients starting CAPD and monitored them for a minimum of 15 months. Serum albumin, changes in dry weight, morbid events, and, where possible, protein catabolic rates (PCR) and urea nitrogen appearance (UNA) were determined. A modest reduction in serum albumin (25 to 33 g/L [2.5 to 3.3 g/dL]) was found in the majority of patients 3 months after starting CAPD, which persisted for 12 months. Most of these patients gained weight and were not hospitalized in that period. PCR and UNA values showed adequate nutrition. Two patients developed serious medical problems leading to clinical malnutrition and serum albumin rapidly falling below 20 g/L. A modest reduction in serum albumin (25 to 33 g/L) is common in healthy CAPD patients and, if stable, does not indicate a poor prognosis or nutritional inadequacy.

Female↗
PubMed1992

Persistence of individual dendritic spines in living brain slices.

A number of theories on the cellular basis of learning and memory propose that long-term changes in synaptic strength are encoded by changes in the properties of dendritic spines. Such theories imply that individual spines retain their identity over time. Using a new technique for fluorescent labelling of synaptic structures together with confocal microscopy, we have found that the appearance of individual spines on viable cells remains unchanged over observations periods of up to 5 hours. Even in slices exposed to kainic acid at concentrations that abolished synaptic transmission, groups of spines remained identifiable on cells clearly damaged by the toxin. The robust persistence of individual spines demonstrated here establishes an essential prerequisite for their potential role as mnemonic elements.

Animals↗
PubMed1992

Renal acid-base physiology in marine teleost, the long-horned sculpin (Myoxocephalus octodecimspinosus).

We have sought to define urinary acid-base excretion in the marine teleost using the long-horned sculpin, Myoxocephalus octodecimspinosus. Urine flow (1.7 ml.h-1.kg-1) is relatively high, and glomerular filtration rate is very low (2.9 ml.h-1.kg-1). The urine-to-plasma ratio of inulin is 2. Renal clearance of p-aminohippurate is very high (108 ml.h-1.kg-1); phosphate and divalent cations are also secreted. In this framework we found urinary pH to average 6.6, but infusion of acid or alkali elicited a pH range of 6.1-7.8. Untreated fish may also have alkaline urine; so it is not surprising that precipitates of calcium or magnesium phosphate are sometimes found in bladder. These are of fine sandy quality and never cause blockage. Infusion of buffer (imidazole) increased the concentration of titratable acid 11-fold and output 2.5-fold. Carbonic anhydrase inhibitors had no effect on any urinary component, and histochemical studies revealed that cytoplasm and membranes did not yield the specific cobalt stain for the enzyme. An alkaline load (NaHCO3) is rapidly dissipated by gill excretion, mediated in part by carbonic anhydrase. An acid load (HCl) is rapidly dissipated by gill excretion, not dependent on carbonic anhydrase, and some renal excretion. Comparison and contrast of the low rates of HCO3- reabsorption in the marine teleost (and elasmobranch) with those of mammals suggest strongly that renal carbonic anhydrase evolved in connection with these high reabsorptive rates beginning in freshwater fish and continuing through amphibia and birds.

Acid-Base Equilibrium↗
PubMed1991

Transforming-growth-factor-beta activation elements in the distal promoter regions of the rat alpha 1 type I collagen gene.

We have located a cis-acting element (alpha 1-TAE) within the promoter sequences of the rat collagen alpha 1(I) gene (COL1A1) 1600 bases upstream of the transcription start site which mediates transcriptional activation by transforming growth factor beta (TGF-beta). The functional significance of this region was established by (1) deletion analysis of the alpha 1(I) promoter cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and (2) by co-transfection of promoter constructs with double-stranded oligonucleotides. DNA-mobility-shift assays with radiolabelled alpha 1-TAE demonstrated increased nuclear binding activity after TGF-beta stimulation. Oligonucleotides encoding the alpha 1-TAE, additional upstream regions within the alpha 1(I) promoter, as well as consensus nuclear-factor-1 (NF-1) sequences, competed with the alpha 1-TAE sequence. The two collagen type I genes are stimulated by TGF-beta through different regions of their promoters.

Animals↗
PubMed1991

Dopaminergic grafts in the striatum reduce D1 but not D2 receptor-mediated rotation in 6-OHDA-lesioned rats.

Rats received fetal dopaminergic neuronal grafts in the striatum and/or substantia nigra ipsilateral to a 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). Dopaminergic grafts in the striatum substantially and significantly reduced turning elicited by the selective D1 agonist SKF 38393, but did not reduce turning elicited by the selective D2 agonist LY 171555. Thus, reduced turning in such grafted animals in response to non-selective dopaminergic agonists may be the result of diminished D1 supersensitivity. Fetal dopaminergic grafts in the ipsilateral substantia nigra (SN) did not augment the decreases in turning produced by concomitant ipsilateral dopaminergic grafts in the striatum in response to SKF 38393. LY 171555, D-amphetamine or L-DOPA. Dopaminergic grafts in the SN increased, while dopaminergic grafts in the striatum or in striatum and SN decreased, the facilitatory effect of D-amphetamine on rotation elicited by subsequent injection of dopamine agonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Mouse trisomy 16 neurons, a model of human trisomy 21 (Down syndrome), can be maintained by intracerebral transplantation.

The trisomy 16 mouse is considered to be a model of human trisomy 21 (Down syndrome) due to genetic homology between parts of human chromosome 21 and mouse chromosome 16. Additionally, and because older Down syndrome individuals develop neuropathology indistinguishable from that of Alzheimer's disease, trisomy 16 tissue may provide a model of some pathological processes occurring in Alzheimer's disease. However, trisomy 16 fetuses die in utero or shortly after birth, preventing exploitation of this model. We therefore sought to examine trisomy 16 brain tissue over an extended period of time. We report that neural transplantation to normal hosts allows the maintenance of cortical and hippocampal neurons for at least 8 months, thus providing a model in which to examine pathological processes related to Down syndrome, and perhaps to Alzheimer's disease.

Animals↗
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↗
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↗