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Biomedical subjects

K R Isaacs

Publications and source records attributed to K R Isaacs.

29 records · Page 2Linked to original sources
PubMed1994

A simplified technique for histologic analysis of central nervous system tissues using glycol-methacrylate plastic coupled with pre-embedding immunocytochemistry.

Paraffin and some plastic embedding techniques will destroy many antigens routinely detected by immunocytochemistry performed on frozen tissue sections. However, morphologic quality is compromised to varying extents in frozen tissue, even with the use of cryoprotection. We report a simple glycol-methacrylate (GMA) embedding technique using vibratome-sectioned mouse brain reacted for tyrosine hydroxylase (TH) immunoreactivity before plastic embedding. In this study we used a short (4 h) simple, GMA embedding procedure which subsequently provided 1.5-5.0 microns sections yielding morphologic details superior to frozen or paraffin sections. Prior to embedding we used a peroxidase-antiperoxidase (PAP) reaction with the 3,3'diaminobenzidine tetrahydrochloride (DAB) chromogen visualizing TH. Several different counterstains were used, demonstrating the versatility of this embedding procedure.

3,3'-Diaminobenzidine↗
PubMed1993

A method for quantification of astrocytic processes reveals laminar differences in the dentate gyrus but not in CA1 of the hippocampal formation.

The distribution of astrocytic processes in the dentate gyrus molecular layer and CA1 subregion of the hippocampal formation was examined in 8-microns frozen sections from adult male rats. The stereological cycloid intersection method (Baddeley et al., 1986) was used to estimate surface density of glial fibrillary acidic protein-immunoreactive astrocytic processes. A distinct lamination pattern was delineated in the dentate gyrus which corresponds to the afferent input to this region. No such pattern was detectable in s. radiatum of CA1. By using this relatively new stereological method which utilizes a sensitive sampling scheme, it was possible to increase the reliability in reporting the distribution of fine processes while at the same time greatly reducing the amount of time necessary to estimate the amount of astrocytic processes in a given region.

Animals↗
PubMed1993

Myeloid leukaemia and osteosarcoma in CBA/H mice given 224Ra.

Four groups of 400 12-week-old CBA/H mice were injected i.p. with 69, 139, 280 and 550 Bqg-1 224Ra. A further group of 400 mice were injected i.p. with diluting solution only. The mice were then allowed unrestricted access to food and water until they died or were killed. 53 cases of myeloid leukaemia and 22 cases of osteosarcoma were confirmed in the 2000 mice injected, and for both tumour types direct relationships were shown to exist between the amount of 224Ra administered and the incidence of tumours. It is concluded that mouse is at a greater risk from myeloid leukaemia than from osteosarcoma in the region of administered 224Ra below that which causes a maximum yield of osteosarcoma. These results are discussed in the light of the present acceptance of osteosarcoma as the major risk to man from bone-seeking alpha-particle emitters.

Animals↗
PubMed1992

Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning.

This study compared the morphology of cerebellar cortex in adult female rats exposed for 1 month to repetitive exercise, motor learning, or an inactive condition. In the exercise conditions, rats that were run on a treadmill or housed with access to a running wheel had a shorter diffusion distance from blood vessels in the molecular layer of the paramedian lobule when compared to rats housed individually or rats that participated in a motor skill learning task. Rats taught complex motor skills substantially increased the volume of the molecular layer per Purkinje neuron and increased blood vessel number sufficiently to maintain the diffusion distance. These results dissociate angiogenesis associated with increased neuropil volume (as seen in the motor learning group) from angiogenesis associated with increased metabolic demands (as seen in the exercise groups). While the volume fraction of mitochondria did not differ among groups, the mitochondrial volume fraction per Purkinje cell was significantly increased in the motor skill rats. This appears to parallel the previously reported increase in synapses and associated neuropil volume change.

Animals↗
PubMed1992

Development of the paramedian lobule of the cerebellum in wild-type and tottering mice.

The mutant mouse tottering, (tg/tg), and the compound heterozygote mouse (tg/tg1a) exhibit three neurological disorders: ataxia, petit mal-like absence seizures and myoclonic intermittent movement disorders which are independent of the absence seizures. The tottering mouse carries an autosomal recessive single gene mutation on chromosome 8, and behavioral symptoms are first observed in the 3rd to 4th week of age. Using an additional genetic marker, Oligosyndactyly (Os), it is possible to distinguish tg/tg and tg/tg1a mice from wild-type mice at birth; nonaffected heterozygous littermates carry the Os mutation while tottering and compound heterozygous mice do not carry the Os gene. Similar to neurons found elsewhere in the brain, cerebellar Purkinje cells in both the wild-type and mutant mice were found to decrease in diameter with maturation. Forebrain weight, hindbrain weight, Purkinje cell dimensions and the thickness of the molecular layer in the paramedian lobule of the cerebellum in mutant mice were found to be reduced in mutants after, but not prior to the onset of behavioral symptoms.

Animals↗
PubMed1990

Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats.

The role of the cerebellar cortex in motor learning was investigated by comparing the paramedian lobule of adult rats given difficult acrobatic training to that of rats that had been given extensive physical exercise or had been inactive. The paramedian lobule is activated during limb movements used in both acrobatic training and physical exercise. Acrobatic animals had greater numbers of synapses per Purkinje cell than animals from the exercise or inactive groups. No significant difference in synapse number or size between the exercised and inactive groups was found. This indicates that motor learning required of the acrobatic animals, and not repetitive use of synapses during physical exercise, generates new synapses in cerebellar cortex. In contrast, exercise animals had a greater density of blood vessels in the molecular layer than did either the acrobatic or inactive animals, suggesting that increased synaptic activity elicited compensatory angiogenesis.

Animals↗
PubMed1989

Coronary vascular lesions in dogs treated with phosphodiesterase III inhibitors.

A treatment-related coronary arteriopathy has been observed in the dog following the oral or intravenous administration of 4 potent phosphodiesterase type III inhibiting inodilators at high multiples of their ED50 for periods from 1 day to 6 months. A fifth compound of a similar pharmacological class exhibited limiting toxicity at low multiples of its ED50 and this compound failed to induce coronary arterial lesions. The earliest treatment-related findings observed were medial hemorrhage and necrosis with focal breaks in the internal elastic lamina. Later changes, observed from day 9 onwards, included intimal thickening consisting of smooth muscle proliferation with a mucoid ground substance, variable and inconsistent inflammatory changes involving one or more arterial tunics and adventitial hemorrhage, fibrosis and neovascularization. The changes were restricted to the coronary arteries including the extramural and intramural branches. The distribution of lesions varied from widespread, multifocal involvement of both coronary arterial systems to focal lesions with no obvious site of predilection. Induction of this lesion may involve changes in coronary flow and pressure as a result of an exaggerated pharmacological response to this class of compound. The susceptibility of other species (rat, cynomolgus monkey, or pig) to this effect has been investigated with no treatment-related arteriopathy being observed.

Aminophylline↗
PubMed1985

Epinephrine facilitation of appetitive learning: attenuation with adrenergic receptor antagonists.

Previous studies using aversive training tasks have reported that retention is enhanced by post-training administration of epinephrine. This study investigated the effects of post-training administration of epinephrine on retention of an appetitive task. The results indicate that epinephrine can enhance retention performance in an appetitive task of both rats and mice. Pretraining injections of propranolol and phenoxybenzamine, alpha- and beta-adrenergic receptor antagonists, attenuate the memory-enhancing effects of epinephrine. These results are consistent with the view that release of peripheral epinephrine may regulate storage of new information and may mediate memory modulation produced by a variety of treatments.

Animals↗
PubMedDate not supplied

Usual vs. successful aging: some notes on experiential factors.

A common analogy to aging is that of a boulder being worn down to rubble by the unremitting onslaught of time. In contrast, Swaab's "use it or lose it" concept is important because it emphasizes some positive consequences of experience. For example, early exposure to complex experience may offer some protection from "wear and tear" degradation through improvements in vascular support, diet, exercise, and coping with stress. Exposure to complex experience in old age can also generate new synapses in the cerebral cortex and cerebellum. This new perspective is not completely positive, however, because it appears that the senescent breakdown of supporting systems may ultimately constrain the positive benefits of experience in old age. Thus the evidence indicates that the use of environmental therapies should encompass the entire life span to produce successful aging.

Aged↗
PubMedDate not supplied

Synapse formation occurs in association with the induction of long-term potentiation in two-year-old rat hippocampus in vitro.

Following induction of long-term potentiation in subfield CA1 of the hippocampal slice from 26-month-old rats, shaft synapse numbers increased by 44% and sessile spine synapses (synapses on stubby, headless spines) by 72%, with the more common mushroom-shaped spine synapses statistically unaltered. These effects are smaller than in prior work with young adults, whereas population spike amplitude changes were comparable to young adults. Reasons for the discrepancy are unclear, but the results confirm continuing capacity for induction of LTP in aged rats and indicate that substantial synaptogenic capacity also persists, but may be impaired, at these ages.

Animals↗