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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 217 records · Page 12Linked to original sources
PubMed1993

Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression.

The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.

Animals↗
PubMed1992

Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women.

Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.

Adult↗
PubMed1992

Detection of hepatitis C virus infection among cadaver organ donors: evidence for low transmission of disease.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA among cadaver organ donors and to correlate these results with donor liver histologic abnormalities and evidence for transmission of disease through organ transplantation. DESIGN: Retrospective testing of stored serum samples from cadaver organ donors for anti-HCV and HCV RNA. SETTING: Transplantation service of the University of Miami/Jackson Memorial Medical Center and other cooperative medical centers furnishing follow-up data. SUBJECTS: Of 1096 cadaver organ donors harvested between 1 January 1979 and 28 February 1991, 484 had stored serum samples available for analysis. Recipients of organs from recombinant immunoblot assay (RIBA)-positive donors for whom adequate follow-up was available were also included in the analysis. MEASUREMENTS: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Confirmatory testing was done using a second-generation RIBA. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Liver biopsies were obtained from the organ donor and interpreted blindly by a pathologist unaware of the clinical data. Liver chemistry profiles and serum sample analysis for HCV RNA were done for transplant recipients. RESULTS: From the 484 cadaver organ donors, 89 samples (18%; 95% Cl, 15% to 21%) were reactive by ELISA. Of these, 33 (6.8%; Cl, 4.6% to 9%) were RIBA seropositive. Hepatitis C viral RNA sequences were detected in 50% of the RIBA-positive serum samples tested. Liver tissue was available from 24 of the 33 RIBA-positive donors and showed chronic active hepatitis in 16, chronic persistent hepatitis in 2, and no abnormality in 6. Among the 46 recipients of a kidney from a RIBA-positive donor, 13 (28%; Cl, 15% to 41%) developed post-transplant liver disease, of which only 4 cases were highly suggestive of viral transmission from the donor. Little morbidity and no mortality could be attributed to liver disease in this cohort of recipients. CONCLUSIONS: These data suggest that HCV transmission by organ transplantation is low and that the consequences of infection are small. If the medical condition of the potential recipient is so serious that other options no longer exist, the use of an organ from an anti-HCV-seropositive donor should be considered.

Adult↗
PubMed1992

Differential effects of platelet-derived growth factors on fetal hippocampal and cortical grafts: evidence from intraocular transplantation in rats.

Effects of platelet-derived growth factor-AA (PDGF-AA) and platelet-derived growth factor-BB (PDGF-BB) on developing parietal cortex (E16) and hippocampal (E18-E19) grafts were studied using the in vivo method of intraocular transplantation. Survival and growth of grafts in the anterior eye chamber of adult host rats under the influence of regular treatments with 0.5 ng (in a 100 ng/ml concentration) PDGF-AA or PDGF-BB was followed and compared to those receiving vehicle solution alone (0.5 mg HSA/ml Hanks). Both PDGF-AA and PDGF-BB increased the volume of transplanted cortical grafts. PDGF-BB also exerted trophic effects on grafted hippocampal tissue whereas PDGF-AA seemed to inhibit hippocampal growth. Histological and immunohistochemical studies revealed an increase in the density of astroglial elements in PDGF-AA- and PDGF-BB-treated cortical grafts whereas the PDGF-AA- and PDGF-BB-treated hippocampal grafts maintained a cytoarchitecture closely resembling that of control grafts. These findings support in vitro experiments showing that developing glial cells are stimulated by PDGFs and we further propose regional differences of action of PDGFs in the developing central nervous system.

Animals↗
PubMed1992

Alpha-adrenoceptor function before and after chemical sympathectomy in human and feline detrusor muscles.

Isolated bladder segments from man and cat were treated with 6-hydroxydopamine (6-OHDA) in vitro. Chemical sympathectomy was evaluated with fluorescence microscopy and found to be very similar to the effect of 6-OHDA administered in vivo to cats. Isometric smooth muscle contractile responses were induced by field stimulation (FS). The amplitude of the responses increased after denervation. The effects of alpha-adrenoceptor agonists and antagonists on the FS-induced contractile responses were compared before and after treatment with 6-OHDA. The reduction in the contractile responses after the addition of noradrenaline to the feline bladder strips was more pronounced after treatment. Phentolamine induced an increase in contractile responses before treatment, an effect not seen afterwards in human bladder strips but which persisted in feline bladder strips. Selective alpha-adrenoceptor agonists did not alter the contractile responses in denervated strips. It is suggested that the function of the alpha-adrenoceptors in the detrusor is to inhibit neuronally mediated contractile responses of smooth muscle.

Adrenergic alpha-Agonists↗
PubMed1992

Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report).

Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Aged↗
PubMed1992

Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease.

Two patients with advanced Parkinson's disease were followed for 6 months before, and 18 months after, receiving stereotaxic grafts of fetal mesencephalic tissue from aborted human fetuses. Parameters studied included a series of standardized tests of movement, response to levodopa, electrophysiological recording of the motor readiness potential, and positron emission tomography (PET) with ligands based upon levodopa and upon the dopamine reuptake inhibitor nomifensine. The patients each received stereotaxic implantation of ventral mesencephalic tissue containing midbrain dopamine neurons from aborted human fetuses of 8 to 10 weeks gestational age into the caudate and putamen of one hemisphere. Throughout their 18-month course, the patients were treated with cyclosporine, azathioprine, and glucocorticoids to minimize the risk of graft rejection. There were no significant complications from the procedure, but there was also no major change in their assessment of impairment on the Hoehn and Yahr scale. However, significant changes were observed in clinical, electrophysiological, and PET measures. Changes in these parameters, apparent at 6 months postoperatively, were described in detail in a previous report. The purpose of this present report is to provide follow-up data from the subsequent year with an emphasis on longitudinal evaluation methodology. Standardized clinical testing showed a small but long-term improvement in the first of the two patients. Following the operation, she was able to walk in "off" periods, which she had not been able to do preoperatively. This improvement was accompanied by increased walking speed and reduction in the time necessary to perform a series of pronation and supination movements using both hands. Although these improvements have continued throughout the postoperative period, they have not alleviated her basic neurological impairment. The second patient showed similar improvement during the first 6 months; she then reverted to her preoperative status at the end of the 18-month follow-up period. The electrophysiological recordings were consistent with the clinical findings. Both patients had significant changes in the motor readiness (bereitschafts) potential amplitude, which was greatest 5 to 7 months postoperation. The amplitude of the potential declined subsequently for both patients, but remained significantly elevated over the preoperative baseline for patient 1. The analysis of the PET scans was somewhat compromised by technical problems in the preoperative scans. However, they are also consistent with the clinical data. In comparisons of the operated and the unoperated sides, fluoro-dopa showed increased uptake in the caudate nucleus of patient 1 at 6 months and at 13 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Tissue Transplantation↗
PubMed1992

Effects of DM-9384, a pyrrolidone derivative, on ischemia-induced changes in the central monoamine systems.

Alterations in brain tissue levels of monoamines and monoamine metabolites were studied in gerbils 60 min after cerebral ischemia induced by 10 min carotid ligation after pretreatment with the antiischemic drug DM-9384 (1, 3, 10, 30 mg/kg, PO). The DA levels decreased in striatum after the ischemia, while cortical and hippocampal DA levels increased. The DOPAC levels increased in cortex, but were essentially unaffected in other regions. The HVA levels increased in all forebrain regions studied. NA levels decreased in hippocampus and superior colliculus, while a general increase in MHPG levels was seen. Decreases in 5-HT levels were seen in all forebrain regions except cortex. The 10 mg/kg and 30 mg/kg doses of DM-9384 counteracted the decrease in striatal 5-HT and hypothalamic MHPG/NA ratio, respectively. Thus pretreatment with DM-9384 exerted minor protective effects on the alterations induced in monoamine systems by transient forebrain ischemia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Stage dependent development of intraocular cochlear grafts.

The intraocular grafting technique was employed to test whether the peripheral hearing organ, the cochlea, is capable of survival and an organized development in total isolation from the temporal bone. Rat cochleae obtained from gestation day 16, postnatal day 1 and 7 were chosen for transplantation into the anterior chamber of the eye of adult Sprague-Dawley rats. The grafts were maintained in the anterior chamber for 6, 10, or 15 weeks survival time. The salient features of this study is that 1) cochlear structures survive and, 2) the cochlear structures develop beyond their pre-grafted stage as determined from light and electron micrographs. In the present study, the grafts obtained at gestation day 16 (GD 16) and postnatal day 1 gave a much higher rate of survival and development than the postnatal day 7 grafts. In addition, grafts maintained for either 6 or 10 weeks had a better survival rate than those grafts left for 15 weeks. It is estimated from light and electron micrographs that the gestation day 16 otocysts that were maintained for 10 weeks, developed to the equivalent of a postnatal day 10 cochlea. The grafts obtained from postnatal day one rats developed to the equivalent of approximately 14 days after birth. Interestingly, in the absence of synaptic contact, the inner and outer hair cells were capable of survival, differentiation and maturation. It remains to be determined if the spiral ganglion cells require additional neurotrophic factors for survival in the anterior chamber of the eye.

Animals↗
PubMed1992

Postnatal lead exposure affects motor skills and exploratory behavior in rats.

The present study was undertaken to investigate the behavioral effects of postnatal lead exposure. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally daily for 20 days. Control rats received 1 mg/kg sodium acetate, or 8 mg/kg sodium acetate in oversized litters. The high dose lead acetate group and the high dose, oversized sodium acetate group showed impaired weight and length increment during the end of the treatment. Rats treated with the higher dose of lead showed delayed eye opening. The time required to turn in a negative geotaxis test was transiently longer in rats treated with the higher dose of lead. A tendency of reduced forepaw grasping ability was seen in lead-treated rats during the end of the lead exposure. Ambulation and rearing in an open field were lower for the rats treated with the higher dose of lead acetate during certain periods of development. Impaired performance in a balancing rod test was also seen in the rats treated with the higher dose of lead at the adult stage, while no difference was seen in ambulation or gnawing activity during tail pinch-induced stress. Thus, lead intoxication in rats during the early postnatal period, with doses that approximate those in children, induced transient as well as persistent dysfunctions in exploratory behavior and motor skills. These observed actions of lead may be related to impaired maturation of sensitive brain regions which develop postnatally.

Animals↗
PubMed1992

Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are molecules which regulate the development and maintenance of specific functions in different populations of peripheral and central neurons, amongst them sensory neurons of neural crest and placode origin. Under physiological conditions NGF is synthesized by peripheral target tissues, whereas BDNF synthesis is highest in the CNS. This situation changes dramatically after lesion of peripheral nerves. As previously shown, there is a marked rapid increase in NGF mRNA in the nonneuronal cells of the damaged nerve. The prolonged elevation of NGF mRNA levels is related to the immigration of activated macrophages, interleukin-1 being the most essential mediator of this effect. Here we show that transsection of the rat sciatic nerve also leads to a very marked increase in BDNF mRNA, the final levels being even ten times higher than those of NGF mRNA. However, the time-course and spatial pattern of BDNF mRNA expression are distinctly different. There is a continuous slow increase of BDNF mRNA starting after day 3 post-lesion and reaching maximal levels 3-4 wk later. These distinct differences suggest different mechanisms of regulation of NGF and BDNF synthesis in non-neuronal cells of the nerve. This was substantiated by the demonstration of differential regulation of these mRNAs in organ culture of rat sciatic nerve and Schwann cell culture. Furthermore, using bioassays and specific antibodies we showed that cultured Schwann cells are a rich source of BDNF- and ciliary neurotrophic factor (CNTF)-like neurotrophic activity in addition to NGF. Antisera raised against a BDNF-peptide demonstrated BDNF-immunoreactivity in pure cultured Schwann cells, but not in fibroblasts derived from sciatic nerve.

Animals↗
PubMed1992

High and low affinity NGF receptor mRNAs in human foetal spinal cord and ganglia.

The cellular localization of mRNAs encoding the low affinity NGF receptor (here referred to as LANR) and the putative high affinity receptor for NGF, trk, have been studied in the human foetal spinal and sympathetic ganglia, and spinal cord, using in situ hybridization. The receptor mRNAs were highly expressed in the spinal and sympathetic ganglia, with most but not all neurons expressing both LANR and trk mRNA. Spinal nerve rootlets distal to the spinal ganglia expressed LANR but not trk mRNA, confirming the presence of the low affinity receptor in developing Schwann cells. In the spinal cord, LANR mRNA was found throughout the medial and lateral motor columns while, trk mRNA was detected in scattered cells in the dorsal aspect of developing grey matter.

Fetus↗
PubMed1992

Reported home health agency referrals by internists and family physicians.

OBJECTIVE: To evaluate the frequency of home health agency referrals (HHRs) by internists and family physicians. DESIGN: Telephone survey of a randomly selected, nationally representative, stratified physician sample. PARTICIPANTS AND SETTING: One thousand one hundred sixty-one interviews with 576 family physicians and 585 internists selected from the American Medical Association Physician Masterfile. MAIN RESULTS: Most respondents (88%) reported making HHRs (mean for those making HHRs = 43/year). Physicians with > or = 48 annual HHRs (n = 315) reported a mean of 2.6 hours/week in home care telephone management and 2.1 hours/week on related paperwork. Rural internists and family physicians (n = 230) reported less availability of several types of non-physician home health services than non-rural respondents (n = 931), yet rural physicians were more likely to refer patients to home health agencies. Using multivariate linear regression, the reported frequency of HHRs was significantly related to rural practice location, number of home-bound patients, proportion of geriatric patients, number of house calls, graduation from a U.S. or Canadian medical school, physician knowledge of community resources, and physician experience either as a medical director, a member of the board of directors, or a consultant for a home health agency. CONCLUSIONS: Internists and family physicians who work at least 10 hours per week in ambulatory care report making approximately three home health agency referrals per month and spending substantial amounts of time coordinating home health agency care. Despite reporting less availability of many home health agency services, rural physicians report greater involvement than non-rural physicians in the delivery of home care.

Attitude of Health Personnel↗
PubMed1992

A national survey of the home visiting practice and attitudes of family physicians and internists.

BACKGROUND: Over the past decade, while physician home visiting has continued to decline, the home care industry has been experiencing dramatic growth. In response, several major physician organizations have been encouraging increased physician education and involvement in home care and urging related health policy changes. This study provides the first in-depth, nationally representative descriptive data on the current home visiting practice and related attitudes of physicians. METHODS: Data were gathered through a structured 15-minute telephone survey, consisting of 141 items covering physician's general practice, personal home visiting practice, interaction with other home care providers, and attitudes regarding home care issues. Subjects were a nationally representative, randomly selected sample of 2200 family practice physicians (FPs) and internal medicine physicians (IMs) currently in active practice with at least 10 hours per week of professional time spent in ambulatory care. RESULTS: Sixty-five percent of eligible participants completed the survey. Of all physicians surveyed, 65% of FPs and 44% of IMs reported that they may make house calls (P less than .001). Mean number of visits per year was 21.2 (median, 10) for FPs, and it was 15.7 (median, 6) for IMs. Physicians in rural practice were more likely to make home visits (P less than .001). Physician attitudes related to home care reflect a strong dissatisfaction with reimbursement, but positive opinions about the use of other home care professionals and the importance of home visits for selected patients. Logistic regression analysis comparing home-visiting physicians with non-visiting physicians allowed for prediction of the correct classification 73% of the time, and it revealed six variables that were significant predictors of home visiting. The strongest of these predictors were the physician's positive attitude regarding the importance of home visits for selected patients and his or her perception of having time available for home visits. Other significant variables predictive of home visiting were family practice specialty, rural location of practice, greater numbers of referrals to home care agencies, and, interestingly, dissatisfaction with reimbursement. CONCLUSIONS: Although the great majority (over 75%) of FPs and IMs still regard the physician home visit as important for the care of selected patients, only about half report making one or more home visits within a 12-month period. Family physicians generally report a greater involvement in home care than do IMs. Physician reimbursement for home visits is perceived to be inadequate, and almost half (45%) indicate that they would do more home visits if reimbursement were increased. Most physicians (over 80%) have the opinion that home care agencies should be used more.

Adult↗
PubMed1991

Temporal and spatial expression of NGF receptor mRNA during postnatal rat brain development analyzed by in situ hybridization.

The expression of nerve growth factor (NGF) receptor mRNA was examined in the rat brain during postnatal development using in situ hybridization. Cells expressing NGF receptor mRNA were detected in the basal forebrain at all ages examined, with a peak in expression at 2 weeks of age. NGF receptor mRNA was further demonstrated to be expressed transiently in several brainstem nuclei. Expression of NGF receptor mRNA was high at postnatal day (P) 1 and 1 week of age in the facial and abducens nuclei, but was undetectable in the facial nucleus by 2 weeks of age. In the abducens nucleus, a few labeled cells were still present at 2 weeks of age, but absent by 3 weeks. In the cerebellum, a strong signal was present at P1 and 1 week of age which clearly diminished by 2 weeks and disappeared by 3 weeks of age. The labeled cells in the cerebellum had the size and morphology of developing Purkinje cells. These data suggest that the population of NGF-responsive cells in the brain is more widespread during development than in the adult, and that the trophic requirements of specific brain regions are altered with maturity.

Animals↗
PubMed1991

Brain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies.

The recent cloning of a second member of the nerve growth factor family, brain-derived neurotrophic factor (BDNF), has prompted investigation into the cells that express this factor's mRNA and protein. In the present study, antibodies raised against unique peptide sequences within the porcine BDNF protein detect BDNF-like immunoreactivity in neurons in rat hippocampal and cortical areas consistent with the distribution of BDNF mRNA as detected with in situ hybridization. Within these neurons, BDNF-like immunoreactivity was observed in the cytoplasm, dendrites, and nuclei. In addition, BDNF immunoreactivity was observed in the cytoplasm of cholinergic neurons that do not express detectable levels of BDNF mRNA. Thus, anti-peptide antibodies can be used to detect this neurotrophic factor protein in cytoplasmic sites of synthesis and in areas of probable action. We propose that one form of the BDNF protein enters the nucleus and may directly influence transcription, while another fraction of the protein is transported out of the synthesizing cell and can be detected, after retrograde axonal transport, in cytoplasmic granules in the perikarya of cholinergic neurons. These basal forebrain cholinergic neurons project to regions enriched in BDNF-synthesizing cells and are known to be responsive to BDNF in vitro. Our data provide information regarding the cellular distribution of BDNF protein in vivo and suggest a dendro-axonic interneuronal transfer of BDNF as well as an additional, intracellular signaling pathway not previously thought to occur in postmitotic neurons in brain.

Animals↗
PubMed1991

Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson's disease. One-year follow-up of first clinical trial.

Experimental studies in rodents show that beta-nerve growth factor can increase the survival, neurite outgrowth, and functional effect of grafts of adrenal chromaffin cells to the basal ganglia. We, therefore, have begun to investigate whether treatment with nerve growth factor might also increase the functional effect of autografts of adrenal medullary tissue in patients with Parkinson's disease. Previous studies have shown that stereotactic implantation of adrenal tissue pieces produces a transient functional improvement that lasts for a few months. This report describes a trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor. The patient is a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia, despite optimized medical management. The left adrenal gland was removed, and the medulla was dissected into 1- to 2-mm3 pieces in a solution containing nerve growth factor purified from mouse submandibular gland. Pieces were implanted in six tracts 3 to 4 mm from a previously placed cannula in the left putamen. Through the cannula, nerve growth factor was infused for 23 days for a total dose of 3.3 mg. Clinical assessment consisted of global ratings for rigidity and/or hypokinesia and for drug-induced hyperkinesia. Measures of gait and fine-motor control were also made. The motor readiness potential and auditory evoked potentials were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗