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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 289 records · Page 16Linked to original sources

Expression of the beta-nerve growth factor gene in hippocampal neurons.

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.

Animals↗

Ultrastructure of spinal cord grafts with and without cografts of locus coeruleus in oculo.

The ultrastructure of spinal cord and spinal cord-locus coeruleus double grafts transplanted to the anterior chamber of the eye of adult rats was studied. The present results show that single spinal cord grafts express several morphologically organotypical characteristics of normal spinal cord at the ultrastructural level. Thus, the parenchyma was divided into a cell-rich layer corresponding to the normal gray matter and an axonal layer with a large amount of myelinated fibers and immature oligodendrocytes. In the cellular layer, a variety of cell types of different sizes were observed. The neurons had different patterns of cytoplasmic organelles, including Nissl bodies, Golgi apparatus, mitochondria, and polysomes. The Nissl substance was variable and some neurons appeared to be immature. Although the spinal cord grafts are in a state of relative gliosis, surrounded by a glial barrier, cografted fetal locus coeruleus catecholamine neurons are able to innervate the spinal cord grafts and form anatomically relevant synapses with the spinal cord neuronal elements as revealed by TH-immunoelectron microscopy. In conclusion, several organotypical features of normal spinal cord are found. Examples also were found, however, of a disturbed and delayed development that have to be considered when evaluating the functional potential of grafted cells.

Animals↗

Thyrotropin releasing hormone augments growth of spinal cord transplants in oculo.

The effects of thyrotropin releasing hormone (TRH) on spinal cord growth were evaluated using the in oculo transplant model. The growth of fetal spinal cord allografts, placed into the anterior eye chamber of Sprague-Dawley rats, was markedly augmented by acute exposure of the graft and host animal to TRH at the time of transplantation. No significant growth augmentation was seen after equimolar administration of a mixture of the amino acids that comprise the TRH molecule. It is concluded that acutely administered TRH, at the time of grafting, elicits a significant stimulation of the growth of spinal cord tissue. Our data strengthen the rationale for continued clinical trials of this peptide in spinal cord injury.

Amino Acids↗

Expression of eight neuropeptides in intraocular spinal cord grafts: organotypical and disturbed patterns as evidenced by immunohistochemistry.

The present study examines the distribution of several neuropeptides, as revealed by immunohistochemistry in the isolated cord. Fetal rat spinal cord was grafted to the anterior chamber of the adult Sprague-Dawley albino rats. After intraocular maturation for 2-3 months, the amount and distribution of somatostatin, neuropeptide Y, substance P, enkephalin, vasoactive intestinal peptide, peptide histidine-isoleucine, calcitonin gene-related peptide and cholecystokinin immunoreactive terminals and cell bodies were analysed using indirect fluorescence immunohistochemistry. The visualization of immunoreactive cell bodies in the grafts was enhanced using a novel intraocular colchicine treatment. In the graft a rich network of somatostatin-positive terminals was found with a high density in well-demarcated areas reminiscent of substantia gelatinosa of the dorsal horn of normal spinal cord. A large number of small- to medium-sized somatostatin neurons was found throughout the grafts without colchicine treatment. This is in contrast to normal spinal cord, where positive neurons were difficult to visualize without colchicine and were mainly confined to the dorsal horn. Neuropeptide Y had a distribution in the grafts similar to that of somatostatin and neuropeptide Y cells were found throughout the grafts without colchicine treatment. In normal spinal cord, neuropeptide Y-positive fibers were found mainly in substantia gelatinosa with a sparse network in the ventral horn. Enkephalin-positive fibers were found throughout the grafts. The distribution of fibers resembled that of somatostatin and neuropeptide Y with distinct zones of high fiber density in well-demarcated areas, whereas the density of nerve fibers in the rest of the graft neuropil was moderate to low. The distribution of substance P was similar to that of enkephalin. After colchicine treatment, both enkephalin- and substance P-positive cell bodies were visualized. In the intact spinal cord both peptides were seen in the entire gray matter with the highest concentrations in the superficial laminae of the dorsal horn. Antisera against calcitonin gene related-peptide, revealed a sparse terminal network and many large cells, which might represent motoneurons. A sparse network of varicose cholecystokinin-immunoreactive fibers was found evenly distributed in the grafts. In normal spinal cord a dense cholecystokinin-positive network of primary sensory afferent origin was found in the dorsal horn. In the grafts cholecystokinin cell bodies were seen after colchicine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intracerebral xenografts of human mesencephalic tissue into athymic rats: immunochemical and in vivo electrochemical studies.

Intracerebral allografts of fetal neurons have been studied in both rodents and nonhuman primates. Such research has been directed towards problems in developmental neurobiology and in animal models of neurological diseases. Whether intracerebrally transplanted human fetal neurons are capable of forming synapses and releasing neurotransmitters are key questions in any application of this approach to human brain development and dysfunction. We studied these questions by examining the immunocytochemical and in vivo electrochemical properties of xenografts of human mesencephalic dopaminergic neurons placed into athymic "nude" rats. The transplanted neurons survive, continue to express human-specific Thy-1 immunoreactivity, and extend neuronal processes into the host brain where morphologically identifiable synapses form. Potassium-evoked release of monoamines occurs in the vicinity of the graft but is absent in more remote areas of the host neuropil. These results indicate that human fetal tissue fragments can provide a source of viable neuroblasts for transplantation. Further, synapses form between pre- and postsynaptic elements expressing different species-specific cell surface markers; thus, these markers do not play a determining role in synaptogenesis.

Animals↗

Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat.

In situ hybridization using beta-nerve growth factor (NGF) DNA probes was used to demonstrate NGF mRNA in spermatocytes and early spermatids of adult mouse. NGF mRNA-containing cells were also identified in the epithelium of convoluted ducts in mouse corpus epididymidis. Blot-hybridization analysis of RNA prepared from mouse testis and epididymis as well as from rat epididymis confirmed the presence of a 1.3-kilobase (kb) NGF mRNA in these tissues. In the rat testis, however, only a 1.5-kb NGF mRNA was found, corresponding in size to a minor NGF mRNA detected in the rat brain, heart, and epididymis. By using affinity-purified anti-NGF antibodies, NGF-like immunoreactivity was observed in germ cells of rat and mouse testis and in the lumen of epididymis. Extracts of both mouse epididymis and testis stimulated fiber outgrowth in cultured sympathetic ganglia, and the effect was blocked by antibodies to mouse NGF. A two-site enzyme immunoassay showed the presence of 10 and 70 ng of NGF per g of tissue in the mouse testis and epididymis, respectively. Furthermore, RNA blot analysis showed the presence of mRNA for the NGF receptor in mouse testis. These results suggest a nonneurotrophic role for NGF in the male reproductive system, possibly in survival maturation and/or motility of spermatozoa.

Animals↗

Improvement in NYHA functional class 4 congestive heart failure patients with nifedipine: a hemodynamic evaluation.

Twelve patients referred for evaluation of functional class 4 heart failure as classified by the New York Heart Association underwent treatment with nifedipine after other regimens proved unsatisfactory. Seven men and five women with a mean age of 63 years and a mean ejection fraction of 28% underwent hemodynamic evaluation after insertion of a pulmonary artery monitoring catheter. Nifedipine was administered as a 10 mg sublingual dose, followed by 10 mg orally every 8 hours for 24 hours. Seven patients experienced improvement of symptoms of dyspnea (group 1) and continued nifedipine as outpatients for one month. An improvement in function to class 3 (five subjects) and class 2 (two subjects) was observed. The remaining five patients experienced no improvement (group 2) and did not receive nifedipine after 24 hours. Statistical analysis of the hemodynamic variables revealed that the responders (group 1) had a significant decrease in the pulmonary vascular resistance from 250 dynes second cm-5 at baseline to 155 dynes second cm-5 at 15 minutes after sublingual nifedipine (p less than .05 and 135 dynes second cm-5 at 24 hours while on oral nifedipine. Although trends were seen with other variables, none was statistically significant. After one year of extended follow-up, six of seven group 1 subjects (responders) were alive, compared to only one of five group 2 subjects (p less than .05). All five deaths were related to progressive heart failure. Although ejection fraction did not correlate with final outcome, the duration of heart failure was significantly longer in the nonresponders (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of in vitro and in vivo anticanine T lymphocyte and anticanine class II-specific monoclonal antibodies in the beagle.

Two murine anticanine lymphocyte monoclonal antibodies, designated T83 and B1F6, were assessed for (1) in vitro antiepitope activity to circulating lymphocyte subsets, their functional effects on lymphoproliferative assays and binding specificities to diverse cell suspensions and tissue sections; (2) in vivo effects after administration on cells expressing the target epitopes, lymphoproliferation, and allograft survival; and (3) the host immune response to the injected murine immunoglobulins. The monoclonal antibody T83 (IgG3) appeared to be specific for a T cell subset with an up-regulating function on lymphoproliferation. It caused a profound depletion of cells with the appropriate epitope after intravenous administration but it bound to lymphocyte membrane epitopes on some cells in peripheral blood that did not become depleted and putatively caused other modulating effects on lymphocyte function. The monoclonal antibody B1F6 (IgG2a, previously described) was immunologically specific in vitro for cells expressing class II major histocompatibility complex antigens. In the dog, this also consisted of 50% of T lymphocytes. After intravenous administration, there were functional effects similar to those of T83. A modest prolongation of survival of renal allografts was observed when both mAbs were used as the sole immunosuppressive agent. These studies also demonstrated the occurrence of natural canine antimurine IgG antibodies. Administration of either monoclonal antibody was followed by a rapid increase in the concentration of the antimouse antibody(s). We postulate that the presence of canine natural antimouse IgG markedly influenced the biologic effects of in vivo administered monoclonals.

Animals↗

Organ donation in three major American cities with large Latino and black populations.

It has been suggested that areas with large inner-city Black and Latino populations have worse organ donation rates than those with large suburban and rural White populations. Yet data are sparse. We studied family refusal rates (FRRs) to cadaver organ donation between 1/84 and 5/87 in three United States city-areas (New York, Los Angeles, and Miami) with large Black and distinct Latino populations. Blacks are at least 18% and Latinos at least 25% of the combined general population of the three cities, totaling over three and four million people, respectively. In addition, Blacks and Latinos represent 42% of cadaver transplant recipients, 49% of patients on waiting lists, and 57% of the patients on dialysis in the three cities. Combining the data from the three cities, Black (45%) and Latino (43%) FRRs were similar (P = .78), and each was significantly higher than that in the White population (17%) (P less than 0.0001). The overall refusal rate in NYC (42%) was significantly higher (P less than .0001) than in LA (26%) or Miami (21%), and LA's refusal rate was significantly higher than Miami (P = .03). The refusal rates for the White (31%) and Black (55%) populations in NYC were each significantly higher than their respective populations in LA (14% and 33%) or Miami (11% and 36%) (P less than .05). Although Miami Latinos had a lower FRR (35%) than Latinos in NYC (46%) or LA (45%), the difference was not statistically significant (P = .19 and P = .20, respectively). In the three cities combined, 515 of a possible 1772 medically and legally eligible organ donors were lost during the 40 months studied due to families' refusal of consent. This represents approximately 1000 transplantable kidneys and large numbers of extrarenal organs. Further studies are needed to elucidate the reasons for differences in donation rate among groups and regions in the United States.

Black or African American↗

Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus.

Eleven children with bronchiolitis induced by respiratory syncytial virus received 10,000 to 70,000 U of recombinant interferon alpha-2a per kg of body weight per day. None developed signs of toxicity, and all but one developed an antiviral state following treatment. Interferon alpha-2a appears to be safe for infants with bronchiolitis. Its efficacy for the treatment of this condition remains to be determined.

Antibodies↗