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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 415 records · Page 23Linked to original sources
PubMed1981

Effect of dopamine agonists and antagonists on the electrical activity of substantia nigra neurons transplanted into the lateral ventricle of the rat.

Pieces of fetal rat mesencephalon containing the substantia nigra were transplanted into the lateral ventricle of rats pretreated with 6-OHDA injections into the ipsilateral substantia nigra. Extracellular recordings from these grafts revealed spontaneously active neurons with action potential waveforms and firing rates similar to those found in substantia nigra zona compacta in situ. Furthermore, local application of dopamine agonists inhibited, while dopamine antagonists increased zona compacta activity, both in situ and of cells from nigral grafts. We conclude that substantia nigra grafts contain spontaneously active neurons similar to those of zona compacta in situ, and that some of the mechanisms regulating nigral neuronal activity in situ are also present in this preparation.

Action Potentials↗
PubMed1981

Effect of colestipol and clofibrate, singly and in combination, on plasma lipid and lipoproteins in type IIb hyperlipoproteinemia.

The effect of colestipol, clofibrate and a combination of these two drugs on plasma lipid and lipoprotein levels was evaluated in 14 adult male patients with Type IIb hyperlipoproteinemia. A crossover design with each patient receiving all three treatments was utilized. Twenty g of colestipol per day reduced total and LDL cholesterol by 39.1 and 51.5 mg/dl, respectively (p less than 0.001). There was an associated rise in total triglycerides of 63.5 mg/dl (p less than 0.01) with no significant change in HDL cholesterol. Clofibrate, 2.0 g per day, did not significantly lower either total (-7.9 mg/dl) or LDL cholesterol (+8.7 mg/dl). There was marked interpatient variability in terms of the LDL cholesterol response to clofibrate, but the majority of patients demonstrated an increase. HDL cholesterol levels increased by 6.7 mg/dl (p less than 0.01) and total triglycerides were reduced by 94.6 mg/dl (p less than 0.001). Utilizing the same dosages of both drugs, the combination of colestipol and clofibrate were less effective in lowering total and LDL cholesterol than colestipol therapy alone, and increases in HDL cholesterol and decreases in triglycerides similar to those obtained with clofibrate were observed.

Adult↗
PubMed1981

Long-term study of vascularized free-draining intraperitoneal pancreatic segmental allografts in beagle dogs.

The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors. Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated lymphocytotoxicity (CML) assays revealed increases in CML before graft rejection in low MLC reactors, and decreases in both CML and MLC responses before graft rejection in high MLC reactors. FDPS graft survival was indefinite (>6 mo) in group II dogs, despite low-grade MLC reactivity (2:4 dogs) and CML responses (4:4 dogs). Biopsies of FDPS grafts at 6 mo in normoglycemic dogs showed disappearance of exocrine tissue and coalescence of islets in both groups I and II, but with less fibrosis in group I (immunosuppressed). These results indicate that (a) pancreatic islets in vascularized grafts (FDPS) may survive indefinitely in the presence of a good tissue match best predicted by MLC testing, (b) tissue specific histocompatibility factors appear to be common enough between kidney and pancreas to allow for long-term survival of both organs transplanted from the same donor, at least in appropriate recipients (group II), and (c) immunosuppression is associated with less fibrosis in FDPS allografts.

Animals↗
PubMed1981

Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring.

We attempted to modulate several determinants of the host immunologic profile to improve kidney transplant survival: (1) genotype matching of the cadaver donor with the recipient, (2) assessment in recipients of living related donors (LRD) for predisposition to generate suppressor cells in mixed lymphocyte culture (MLC), (3) pretransplant splenectomy and transfusions, and (4) posttransplant immunologic monitoring. Between January, 1979, and July, 1980, 48 primary renal transplants were performed and followed up between 6 and 24 months. Pretransplant splenectomy was performed, and transfusions were administered in 38 of 48 and 48 of 48 patients, respectively. Donors and recipients of 10 of 11 cadaveric transplants were genotyped and selected for one HLA haplotype identity. All 10 proved to also be one DR antigen matches. There were no cadaveric kidney losses, but one surgical antibody to T cell subtest were used to modulate rejection therapy. The LRD group (n = 37) included 13 HLA-identical, seven haploidentical low MLC reactors, and 17 haploidentical high MLC reactors. Three deaths occurred (diabetes and myocardial infarction, stroke, and pancreatitis). A three-component coculture assay was used in the LRD group before transplantation to determine the capacity to generate specific and nonspecific MLC suppressor cells. Suppressor cells were seen in 17 patients given standard immunosuppression postoperatively without rejection episodes. However, in 20 patients incapable of generating suppressor cells, seven biopsy-proved rejection episodes occurred. There were no kidney losses, with 44 of 48 surviving recipients demonstrating normal renal function.

Adolescent↗
PubMed1980

Nerve growth factors in the rat iris.

Nerve growth factor (NGF) activity was not detected by bioassay in irides killed immediately after excision but NGF appeared within 24 h in living irides placed in culture or grafted to a host eye. Furthermore, sensory and, although less effective, sympathetic denervation of irides in situ led within 10 days to the appearance of NGF activity. In addition, freezing and thawing released a parasympathetic neuronotrophic factor activity from irides.

Animals↗
PubMed1980

Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioral, biochemical, and histochemical studies.

Motor deficits produced in rats by unilateral substantia nigra lesions have been found to be reduced by grafts of fetal rat substantia nigra to the dopamine denervated caudate nucleus. In the present study these grafts were examined behaviorally, histochemically, and biochemically over six to 10-month periods. The grafts were found to survive in a healthy condition and contain catecholaminergic cells and fibers after eight to ten months. Concentrations of dopamine in adjoining parts of the caudate nucleus were increased when examined six months after grafting. Apomorphine induced rotation was reduced by the grafts, and these reductions persisted for at least six months. Although signs of aging were observed in the brains of the host animals when sacrificed eight to ten months after grafting, the grafts remained healthy and showed no signs of aging or deterioration. It is concluded that substantia nigra grafts can become permanent, functional constituents of the brains of host animals with prior substantia nigra lesions.

Animals↗
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: I. Histochemical evidence from intraocular double grafts.

The developing hippocampal anlage of rats was homologously grafted to the anterior chamber of the eye of adult recipients. After intraocular maturation of the hippocampal graft and removal of the sympathetic innervation of the eye by ipsilateral superior cervical ganglionectomy, four types of monoamine neurons were transplanted to the eye chamber: Peripheral sympathetic neurons, central adrenergic neurons of locus coeruleus, central dopaminergic neurons of substantia nigra, and central 5-hydroxytryptamine neurons of the lower raphe nuclei. All four classes of monoamine neurons were able to reinnervate the hippocampal graft, but the fiber ingrowth differed markedly. Although peripheral sympathetic neurons produced a pattern of adrenergic innervation in the hippocampal graft which resembled innervation of the hippocampus by the locus coeruleus in the brain, locus coeruleus neurons themselves produced an extremely dense plexus of fibers within the graft. This hyperinnervation remained intact for up to 9 months, the longest period of time studied. The locus coeruleus graft itself received fibers from the hippocampus graft, as demonstrated by the retrograde transport of horseradish peroxidase. We conclude that the hippocampal graft exerts a much stronger growth stimulation on the locus coeruleus neurons than on the peripheral sympathetic neurons. The difference between innervation patterns suggest that both presynaptic and postsynaptic influences determine fiber ingrowth in the central nervous system.

Adrenergic Fibers↗
PubMed1980

Conditions for adrenergic hyperinnervation in hippocampus: II. Electrophysiological evidence from intraocular double grafts.

Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.

Adrenergic Fibers↗
PubMed1980

Effect of probucol on plasma lipids and lipoproteins in type IIb hyperlipoproteinemia.

Probucol was administered for 4 months in 20 adult males with Type IIb HLP in a total daily dose of 1.0 g per day. All patients had achieved a stable weight and diet response prior to entering the study. Plasma lipid and lipoprotein determinations were done at monthly intervals. Probucol produced mean reductions to TPC of -38.8 mg/dl (P < 0.0001), in LDL of -26.7 mg/dl (P < 0.001) and HDL of -8.1 mg/dl (P < 0.0001) for the entire treatment period. The mean LDL/HDL ratio increased from 5.43 to 6.08 (P < 0.02). There was no significant change in TG levels. During the study a progressive decrease in mean HDL levels from 38.9 to 29.2 mg/dl was noted. A progressive increase in the LDL/HDL ratio from 5.43 to 6.35 was also observed. These findings suggest that probucol should be used cautiously in patients with Type IIb HLP, because an inverse relationship between HDL levels and IHD incidence has been demonstrated in epidemiologic studies.

Adult↗
PubMed1980

Release of [14C]quinacrine from peripheral and central nerves.

Incubations of intestinal mouse smooth muscle sheets including Auerbach's plexus and slices of the spinal cord in buffer containing low concentrations of labelled quinacrine ([14C]QC) result in a high affinity binding of QC to certain nerve fibres. Various means of depolarization, such as veratridine, high potassium and electrical field stimulation, were used to assess quantitatively the release of QC from nerves. Under optimal release conditions, all 3 types of depolarizations induced a clearcut increase in radioactivity of a continuously superfused buffer. When intestinal muscle sheets were incubated in high concentrations of QC (5 . 10(-6)--5 . 10(-5) M) the depolarization-induced release was blocked. Similarly, high concentrations of QC (10(-5) M) blocked release of [3H]noradrenaline from adrenergic nerves. Low QC concentrations did not affect the depolarization induced release of [3H]noradrenaline from adrenergic nerves but caused a moderately increased spontaneous overflow of noradrenaline. The present data, together with previous studies, permit the conclusion that QC in low concentrations can be used to label selectively a population of non-adrenergic nerve fibres. This binding is closely related to the transmitter storage and release mechanisms and can be used to study the activity of such nerves.

Animals↗
PubMed1980

Substance P, VIP, enkephalin and somatostatin immunoreactive neurons in intestinal tissue transplanted to the anterior eye chamber.

Tissue pieces of small and large intestine from pre- and postnatal and adult rats, respectively, were transplanted to the anterior eye chamber of the rat. Immunohistochemical studies revealed high numbers of substance P-, vasoactive intestinal polypeptide (VIP)- and enkephalin-containing nerve fibers, especially in the circular smooth muscle layer and in the myenteric plexus of the intestinal tissue transplants. A small number of somatostatin-containing fibers were observed. The distribution patterns of the various peptide-containing neurons in the grafts resembled those which have been described in the intact gastro-intestinal wall. Substance P, VIP, enkephalin and somato-statin immunoreactive fibers were seen also in the host irides. No obvious differences in peptide innervation in grafts and host irides were observed between normal and sympathectomized animals and animals lesioned in the trigeminal ganglion. These findings suggest that most of the peptide-containing fibers in the intestinal transplants and the host irides originate in the transplanted tissue. Thus, it is shown that peptide neurons can survive in this transplantation model, which may be useful for functional studies of intestinal physiology including peptidergic mechanisms.

Animals↗
PubMed1980

Quinacrine-binding nervous elements in intraocular grafts of intestinal smooth muscle tissue.

Quinacrine (QC) histofluorescence demonstrates a population of nerve fibres in the intestine that are probably non-adrenergic and non-cholinergic. To discover whether these nerves are intrinsic to the intestinal wall smooth muscle layers of distal ileum from foetal mice and foetal and adult rats were homologously transplanted to the anterior chamber of the eye of adult animals. Transplants were well organized although devoid of their normal extrinsic nervous connections. QC-positive beaded nerve terminals were found in the smooth muscle layers of the grafts and QC-positive cell bodies in Auerbach's plexus. Since QC-binding nerves are not normally present in the host iris it was concluded that the gut contains intrinsic QC-binding neurons.

Animals↗
PubMed1980

A system of atypical catecholamine-containing nerve fibres in the rat iris present after total superior cervical ganglionectomy.

A system of hitherto unknown weakly fluorescent fibres was detected in the rat iris by Falck-Hillarp fluorescence histochemistry after superior cervical ganglionectomy. These long smooth winding (SW)-fibres had a scarce and unusual distribution, forming loops and meandering for long distances with limited branching. Pharmacological tests suggest that they store a catecholamine but differ from adrenergic nerves in lacking an efficient uptake mechanism for amines. SW-fibres reached all parts of the iris and gave rise to few scattered extremely faint green fluorescent, limited plexuses of irregularly bulgy fibres. Suggestions as to the cellular origin of the SW-fibres include the ciliary ganglion and the central nervous system.

Animals↗