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Biomedical subjects

M Redmond

Publications and source records attributed to M Redmond.

12 recordsLinked to original sources

Effects of chronic treatment with typical and atypical antipsychotic drugs on the rat striatum.

Human MRI studies have demonstrated that treatment with typical antipsychotics may increase the volume of the caudate nucleus while clozapine treatment is associated with either no change or a reversal of the previous volume increase. In this study four groups of seven rats were treated for 8 months with either the typical antipsychotic haloperidol, the atypical antipsychotic clozapine, the D2/D3 receptor antagonist raclopride, or vehicle (plain drinking water). Striatal sections were prepared using D1-like and D2-like receptor ligand autoradiography. Images (4-6 sections per rat, per ligand) were digitized and the area of the striatum was measured on each section. Rats treated with haloperidol did not have a larger mean striatum area than the control group on either D1- or D2-like ligand autoradiograms. Using the D2-like ligand autoradiograms, the clozapine treated animals had a smaller mean striatum area than the control group. Mean left striatum area was larger than mean right striatum area in each treatment group and in the control group. In contrast to the MRI findings reported in schizophrenia, the area of the striatum was not increased in rats treated with typical antipsychotic agents, but the clozapine-associated area reduction may parallel the clinical studies.

Animals↗

Immunomodulatory effects of oat beta-glucan administered intragastrically or parenterally on mice infected with Eimeria vermiformis.

The immunostimulatory effect of intragastrically or parenterally administered beta-(1-->3; 1-->4) glucan, extracted from oats (ObetaG), on disease resistance to Eimeria vermiformis was studied in C57BL/6 mice. Multiple administrations of ObetaG by intragastric or subcutaneous routes reduced fecal oocyst shedding compared to the non-treated control group. The administration of ObetaG by subcutaneous route resulted in higher levels of total serum immunoglobulins and antigen (sporozoite and merozoite)-specific immunoglobulins as compared with the non-treated group. To evaluate the effect of a single subcutaneous dose, groups of mice were treated with ObetaG 2 days before E. vermiformis infection, at the time of infection and at 2 or 6 days after infection. From day 11 post-infection the oocyst discharge was significantly diminished (P<0.05-0.01) in the ObetaG-treated groups, except in those treated 6 days after infection, as compared to the non-treated control group. The proliferative responses to E. vermiformis sporozoite antigen of lymphocytes isolated from the spleen were significantly increased (P<0.05) when ObetaG was administered 2 days before or at the time of E. vermiformis infection. Lymphocyte proliferative responses to merozoite antigen were not influenced by treatment. In conclusion, ObetaG appeared to up-regulate immune mechanisms and provide enhanced resistance against eimerian coccidiosis in mice.

Adjuvants, Immunologic↗

Barrett's esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy.

OBJECTIVE: The authors review the results and outcomes of esophagectomy (prophylactic esophagectomy) for patients with Barrett's esophagus and high-grade epithelial dysplasia (HGD). SUMMARY BACKGROUND DATA: The role of prophylactic esophagectomy for Barrett's esophagus with HGD is controversial, with some authors recommending surgery and others favoring endoscopic surveillance until biopsy diagnosis of carcinoma is made. METHODS: Between 1982 and 1994, 30 consecutive patients with HGD underwent esophagectomy and had the pre- and postoperative pathology reviewed at our institution. The medical records were reviewed to determine patient characteristics, preoperative endoscopic data, surgical approach, operative morbidity and mortality, length of hospitalization, and treatment outcome. Patients were divided into two groups based on whether invasive adenocarcinoma was found in the resection specimen (group 1) or not (group 2). RESULTS: The duration of reflux symptoms was 22 +/- 14 years for group 1 and 9 +/- 11 years for group 2 (p = 0.05). There was one operative death (3.3%) and six complications (20%). In 13 patients (43%, group 1), invasive adenocarcinoma was found in the resected esophagus. The American Joint Committee on Cancer stage for these patients was stage I (8 patients), stage II (2 patients), and stage III (3 patients). One stage I patient died of adenocarcinoma (72 months) in an incompletely excised HGD segment. Other stage I and II patients are alive without adenocarcinoma with an 18-and 63-month mean follow-up, respectively. Outcome for stage III patients was one operative death, one noncancer death (6 months), and one patient with metastatic adenocarcinoma (26 months). For group 2 (57%), there were no adenocarcinoma deaths (40 months). CONCLUSIONS: High-grade epithelial dysplasia is an indication for esophagectomy because of the prevalence of occult adenocarcinoma (43%). Esophagectomy can be performed safely, and survival in patients with completely resected Barrett's esophagus and early-stage adenocarcinoma is excellent.

Adenocarcinoma↗

Responses of systemic and pulmonary veins to the presence of an intravascular stent in a swine model.

The outcome of stent implantation for children with pulmonary venous obstruction has been characterized by late reocclusion associated with a marked vessel neointimal proliferation. The purpose of this study was to compare the responses of the systemic vein and pulmonary vein to the presence of an intravascular stent, using a Yorkshire swine (N = 10) model. Under cardiopulmonary bypass, a single Palmaz stent was placed in the inferior vena cava (IVC) and right lower pulmonary vein (PV) with sacrifice at 4.9-6.1 months. Angiography and hemodynamic data were determined at 1 and 3 months post-stent implant and prior to euthanasia. All stents were found to be patent, with no difference in degree of thrombosis or neointimal formation. No statistical difference was found in the initial and final stent diameter for both inferior vena cava and pulmonary vein stents (PV initial 6.8 +/- 0.9; final 7.1 +/- 0.6) (IVC initial 10.4 +/- 1.2; final 10.4 +/- 1.2). Electron microscopy demonstrated smooth endothelialization of both pulmonary and systemic venous stent devices. No thrombosis was found on gross morphology. The data indicate that there is no intrinsic difference in the response of the pulmonary vein to the presence of a stent device. The clinical experience of restenosis following stent implantation for pulmonary vein stenosis appears to be more related to variables of final stent diameter combined with the marked intrinsic abnormal vessel architecture, as seen with this condition.

Angiography↗

Recognition of rotavirus antigens by mouse L3T4-positive T helper cells.

A lymphocyte proliferation assay was used to examine the helper T cell response to rotavirus in mice following parenteral immunization with the UK strain of bovine rotavirus. Mixed populations of lymphocytes prepared from spleen or peripheral lymph nodes were tested for proliferation in the presence of UK strain rotaviruses, prepared as cell culture lysates, ultracentrifuged (pelleted) lysates, sucrose-purified virus and caesium chloride-purified virus. Live rotavirus induced non-specific stimulation of lymphocytes, which was not observed in response to inactivated virus. Putative helper T cells of the L3T4+ phenotype were prepared as an enriched population from UK strain-immunized mice or grown in vitro as a polyclonal T cell line. The response of L3T4(+)-enriched cells from mice immunized with inactivated virus was dependent on antigen-presenting cells (APCs). Cells obtained following immunization with live virus did not require further addition of APCs. The response of the L3T4+ T cell line was wholly dependent on APCs. UK strain-specific L3T4+ cells responded to whole UK rotavirus and to isolated VP6 of both UK and C486 rotavirus strains. The results indicate that virus-specific L3T4+ T cells are induced following rotavirus immunization and can respond to epitopes on VP6. UK strain-primed L3T4+ cells also responded to an avian rotavirus strain, Ch2, which shares only minimal serological cross-reactivity with the UK strain. T cell recognition of rotavirus may thus be broadly cross-reactive.

Animals↗

EEG and prognosis of neurologic recovery of dogs under profound hypothermic circulatory arrest.

Deep hypothermia (18-20 degrees C) (DH) during prolonged circulatory arrest and cardiopulmonary bypass is used to repair complex intracardiac lesions and vascular neurosurgical lesions. DH diminishes the risk of ischemic damage and multiorgan failure after circulatory arrest. Profound hypothermia (PH) to 6-7 degrees C has recently been reported to improve the neurological outcome of dogs after 2 h of circulatory arrest. There are no reports of the possible utility of EEG activity to predict the neurological outcome. As a part of a controlled study of cardiopulmonary bypass and 2 h of circulatory arrest we compared EEG recovery to the neurological outcome in 2 groups of dogs: 4 under DH and 4 under PH. All of the dogs under PH had a good outcome: mean neurodeficit score was 6.25/500 in PH and 139.25/500 in DH dogs (P < 0.03); mean histopathological score was 19.25/100 for DH and 47.75/100 in PH dogs (P < 0.03). EEG activity 2 h after reperfusion and starting of rewarming correlated with eventual neurological outcome. EEG variables associated with good outcome were: main final frequency and degree of rhythmicity of the activity. We conclude that PH exerted a protective effect for animals undergoing 2 h of circulatory arrest. EEG was a useful tool for predicting neurological outcome under the studied conditions.

Animals↗

A molecular-genetic analysis of cytotoxic T lymphocyte function.

Two genes that are specifically expressed in T cells with cytolytic activity were isolated from a CTL cDNA library by differential screening. Both appear to encode serine proteases, thus suggesting a cascade mechanism, similar to complement, in activated CTL. Both CTL-specific proteases have a number of unusual structural features that suggest that they will have novel substrate specificities. One of the proteins (CCPI) has been oriented to the granules found in the cytoplasm of CTL. Taken together, these data strongly suggest that these molecules play an important role in target-cell lysis by CTL. Furthermore, we believe that the detailed molecular knowledge being accumulated through these studies may lead to the development of innovative forms of immunotherapy.

Amino Acid Sequence↗

State Data Centers: improving access to census information.

"The U.S. Bureau of the Census created the State Data Center program in 1978 to improve public access to census information. This article discusses the background, structure, and services of that program; the role of libraries in the program; and future directions in State Data Center/library relationships. The appendix lists contact person names, as well as addresses and telephone numbers for State Data Center lead agencies."

Americas↗

Molecular cloning of human ornithine aminotransferase mRNA.

The isolation and characterization of a cDNA clone for the mRNA of human ornithine aminotransferase (OATase; ornithine-oxo-acid aminotransferase; L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13), a nonabundant mitochondrial matrix enzyme that is severely deficient in a hereditary chorioretinal degenerative disease (gyrate atrophy), is described. Human liver, retina, and retinoblastoma (Y79) mRNAs were prepared and tested for the OATase mRNA content by in vitro translation, immunoprecipitation, and NaDodSO4/PAGE. The retinoblastoma cells were found to be expressing this enzyme at a relatively high level. The primary translation product of the OATase mRNA is larger than the pure OATase protein on NaDodSO4/PAGE by approximately equal to 4 kDa, suggesting a precursor protein. lambda gt11 cDNA libraries were prepared from the human mRNAs, and the recombinant clones were immunoscreened as plaques with two different preparations of rabbit anti-human OATase antibodies. A clone (lambda gtRB315) was isolated from the retinoblastoma library that reacts with both of the antibody preparations, and the DNA sequence of its 2.1-kilobase-pair cDNA insert was obtained. An open reading frame consisting of 1371 nucleotides is present in the sequence, and a putative translational initiation methionine codon is identified at position 55. A putative leader sequence consisting of 32 amino acid residues is identified, resulting in a precursor protein of 439 amino acid residues and a molecular mass of 48,534 Da and a mature protein of 407 residues and 45,136 Da. The amino acid sequences of seven tryptic peptides (115 amino acid residues) of the pure human OATase were obtained by microsequencing. When the tryptic peptide and cDNA-derived amino acid sequences were compared, homologies in 111 of 115 residues, including a match of 20 consecutive residues, were observed. An RNA blot hybridization of 32P-labeled OATase cDNA to normal human retina and retinoblastoma mRNAs demonstrated an OATase mRNA species of approximately equal to 2.2 kilobases. The level of OATase mRNA in the normal human retina is approximately equal to 1/100th the level of rhodopsin mRNA and 1/5th to 1/10th the level present in the retinoblastoma cells.

Amino Acid Sequence↗

Pathophysiology of cerebral injury and future management.

Central nervous system dysfunction continues to represent significant morbidity and associated mortality in patients undergoing cardiac surgery. Neurological dysfunction is most exaggerated in patients undergoing hypothermic circulatory arrest (HCA). Although surgical techniques, anesthetic management, and postoperative care have significantly improved over the past two decades, the incidence of stroke and other neurocognitive deficits remains problematic. Understanding the mechanisms of cell death associated with HCA may provide information that is germane to all types of cerebral injury involved in cardiac surgery. Using a closed-chest cardiopulmonary bypass model, dogs underwent 2 hours of circulatory arrest at 18 degrees C followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis and receptor autoradiography for NMDA glutamate receptor subtype expression. Using a selective NMDA (-glutamate) receptor antagonist (MK801), an AMPA-antagonist (NBQX) and a nonspecific neuroprotectant (GM1-ganglioside), the role of glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. Using a similar canine preparation, a microdialysis technique was used to evaluate the role of nitric oxide in neuronal death. Arginine plus oxygen is converted to nitric oxide plus citrulline by the action of nitric oxide synthase. Simultaneous infusion of artificial cerebrospinal fluid containing L-[14C] arginine or L-[14C] arginine and L-NAME (a nitric oxide synthase inhibitor) was performed in contralateral hemispheres. Citrulline recovery in the cerebrospinal fluid, citrulline production in vitro from canine cortical homogenates, and nitric oxide metabolites in the serum were all significantly increased during HCA and reperfusion. These studies demonstrated that neurotoxicity following HCA involves a significant and early induction of neuronal NOS expression and neuronal processes leading to widespread augmented NO production in the brain. Continued research into the pathophysiologic mechanisms involved in cerebral injury will undoubtedly yield a safe and reliable neuroprotectant strategy.

Animals↗