PubMed HealthSearch

Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 37 records · Page 2Linked to original sources

Hypoxia-ischemia stimulates hippocampal glutamate efflux in perinatal rat brain: an in vivo microdialysis study.

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on hippocampal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right hippocampus of postnatal d 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and animals were exposed to 8% oxygen for 2 h (n = 6, histologically verified). Ten 20-min dialysis fractions were collected from each animal: three sequential 20-min baseline samples, six samples during hypoxia, and a recovery sample in room air. Eight amino acids were detected in dialysates with a HPLC assay. There was marked intra- and interanimal variation in glutamate efflux; mean glutamate efflux increased from 17 pmol/min in baseline samples to 51 in the 2nd h of hypoxia (p = 0.002, Kruskal Wallis test). There was a concurrent decline in glutamine efflux (310 to 207 pmol/min, p = 0.0005). Alanine efflux doubled during hypoxia (p = 0.015). There were no changes in efflux of the other five amino acids analyzed. In this experimental model of perinatal stroke, during the acute evolution of hypoxic-ischemic brain injury, transient large increases in glutamate efflux and corresponding declines in glutamine efflux were detected. These data support the hypothesis that synaptic concentrations of the endogenous excitatory amino acid glutamate increase during the evolution of hippocampal ischemic injury.

Amino Acids

Hypoglycemia alters striatal amino acid efflux in perinatal rats: an in vivo microdialysis study.

In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin-induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in each animal a 30-minute baseline sample was obtained. Then insulin (0.6 mu/kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level less than 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre-column derivatization with o-phthaldialdehyde, dialysate samples were assayed by high-pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 +/- 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 +/- 5% of baseline, p = 0.002, ANOVA), and taurine efflux increased (up to 310 +/- 120% of baseline; p less than 0.06, ANOVA). In contrast with 9- to 12-fold increases in aspartate efflux reported in adult striatum, aspartate efflux increased only slightly (to 174 +/- 69% of baseline; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Nosocomial bacteremias in measles.

The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions. In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57). Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant. All the isolates from the general patients were fully susceptible to antibiotics. The duration of hospitalization was more than doubled in both groups of affected patients. The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients. Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients.

Adolescent

An antiserum to the extracellular domain of the Alzheimer amyloid precursor recognizes 70 and 88 kDa brain proteins.

An antiserum raised to the extracellular domain (residues 556-566) of the Alzheimer amyloid precursor protein recognized 70 and 88 kDa proteins in Western blots of rat, Alzheimer, Down's syndrome and control human brain separated by SDS-PAGE. The 70 kDa protein band was resolved into 5 spots by two-dimensional electrophoresis. The findings provide further evidence that a 70 kDa protein is a metabolite of the amyloid precursor protein and reveal an 88 kDa protein which was reduced in 3 out of 6 brains with Alzheimer pathology.

Alzheimer Disease

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia.

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.

Adolescent

Cholinergic enzymes in the spinal cord in Alzheimer-type dementia.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease.

Acetylcholinesterase

Studies concerning the effect of external irradiation on localization of radiolabeled monoclonal antibody B72.3 to human colon carcinoma xenografts.

Recent studies in animal models involving antibody tumor targeting of hepatoma and melanoma and clinical trials involving hepatoma patients have suggested that preirradiation of tumors may enhance antibody tumor targeting. These reports led us to study the effect of external irradiation on monoclonal antibody (MAb) targeting of human carcinomas; as a model system, we used MAb B72.3 and the LS-174T human colon carcinoma xenograft in athymic mice. LS-174T tumors exposed to 300 cGy grew to approximately 93% the size of non-irradiated tumors, while those exposed to 600, 900, or 2,000 cGy were approximately 41% the size of control tumors. Splitting the 900 cGy into three 300-cGy fractions yielded a two-fold lower tumor volume compared with a single 900-cGy fraction. Histochemical evaluation of the carcinomas revealed a decrease in the number of mitoses per high power field consistent with early effects of radiation exposure. Using the avidin-biotin complex immunoperoxidase technique, carcinomas were assayed for expression of the tumor associated glycoprotein (TAG)-72, the high-molecular-weight mucin detected by MAb B72.3. No discernable variation was observed in the staining intensity among tumors in both the control and radiation treated group; that is, differences among tumors within each group were compatible with the known heterogeneous expression of TAG-72. Exposure of carcinomas to 300 or 900 cGy in a single fraction or 900 cGy split in three 300-cGy fractions did not yield a consistent or substantial enhanced localization of radiolabeled MAb B72.3 IgG or F(ab')2 to tumors. A 1.5-fold augmentation of MAb binding to tumors was observed in preirradiated mice; however, these results were not statistically significant. Inherent differences in tumors such as cell type of origin, size, spatial configuration, extent of vascularization and volume of interstitial space may contribute to variability of the effect of preirradiation of tumors on antibody binding. Our results suggest that consistent augmentation of radiolabeled antibody localization to tumors is not a universal phenomenon.

Animals

Union election activity in the hospital industry.

In the past five years, there has been a dramatic decrease in the number of representation elections in the hospital industry. Once a union is in place, however, decertification is less likely to occur than in other industries.

Collective Bargaining

A large multicentre, parallel group, double-blind study comparing tenoxicam and piroxicam in the treatment of osteoarthritis and rheumatoid arthritis.

A total of 1,328 patients with osteoarthritis or rheumatoid arthritis were entered into this double-blind, parallel group study of tenoxicam and piroxicam. The patient populations were well matched. An improvement was seen in pain on moving and at night in both groups and in both indications. Stiffness was also improved by both drugs, being most marked in the rheumatoid arthritis group. The primary efficacy variable was global assessment, and this showed tenoxicam to have slightly greater effect in osteoarthritis and the reverse in rheumatoid arthritis. There were no statistically significant differences in any of these findings. There were no significant differences in tolerance ratings, although the more serious gastrointestinal events occurred in the piroxicam group.

Adult

An antiserum to the C-terminus of the Alzheimer amyloid precursor recognizes a soluble 70 kDa protein.

A rabbit antiserum to the C-terminus of the putative brain amyloid precursor was used to probe Western blots of tissue proteins separated by SDS-PAGE. The antiserum specifically labelled a protein of approx. 70 kDa in the Tris buffer-soluble fraction of brain samples from rat, Alzheimer subjects, cases of young and old Down's syndrome, and age-matched controls. The 70 kDa protein was present in low concentrations in human liver and kidney, and was undetectable in human skeletal muscle. The 70 kDa protein may be a metabolite of the amyloid precursor.

Adult

Cytologic diagnosis of papillary carcinoma of the breast in needle aspirates.

Eleven cases of rare papillary carcinoma of the breast diagnosed by fine-needle aspiration cytology (FNAC) are reported. Five of these were pure papillary carcinomas and six were mixed papillary and ductal, lobular, or mucinous carcinomas. In each case, cytological material was collected by washing the needle and syringe contents into 30% alcohol in saline, and the Gelman cytosieve method was used for the cytological preparations. In this article, the cytological features of these tumors are described, including the presence of single papillae and papillary clusters, tall columnar cells, diathesis of blood with hemosiderin-laden macrophages, naked nuclei, and high cell recovery.

Adenocarcinoma, Mucinous

Fine-needle aspiration cytology of breast: its impact on surgical practice with an emphasis on the diagnosis of breast abnormalities in young women.

Fine-needle aspiration cytology (FNAC) of the breast is a minimally invasive yet maximally diagnostic method, often precluding the need of an open biopsy. In young women, in whom breast cancer is a rare disorder, it is also important that carcinoma is recognized without delay so that an appropriate plan of management can be adopted. In this study, we reviewed our experience in a total of 3,226 needle aspirates of breast with particular emphasis on the diagnosis of carcinoma in women under the age of 30.

Adult

Comparison of monoclonal antibodies for the detection of occult breast carcinoma metastases in bone marrow.

Twenty percent (n = 6) of Stage III or IV breast cancer patients (n = 30) had bone marrow metastases detected in bilateral bone marrow biopsy/aspiration preparations using standard histologic preparations. Each metastasis was also detected by four separate monoclonal antibodies (MAbs) which recognize breast carcinoma associated antigens (DF3, anti-EMA, HMFG-2, and CAM5.2). These MAbs were then utilized to stain other bone marrow preparations (n = 81) to determine their utility for the detection of micrometastatic breast carcinoma. MAbs HMFG-2, anti-EMA, and DF3 were each strongly reactive with bone marrows containing histologically-evident metastatic breast carcinoma (18/18). These anti-epithelial membrane antigen MAbs, however, were also reactive with rare plasma cells and immature cells (as well as cell clusters) in some of the control bone marrow samples tested, including those from normal patients and patients with hematologic disorders. They also reacted with some of the preparations from patients with leukemia and lymphoma, and with uninvolved marrows from patients with non-epithelial malignancies. The anti-keratin MAb CAM5.2, in contrast, reacted with 83% (15/18) breast cancer metastases and failed to stain any cells in the various categories of control marrow preparations. These data suggested that MAb CAM5.2 might be utilized to immunohistochemically differentiate micrometastatic breast carcinoma from immature myeloid or erythroid elements. Each MAb was then reacted with histologically uninvolved marrow preparations from the remaining 24 of 30 breast cancer patients in an attempt to identify occult breast carcinoma metastases. While MAbs HMFG-2, DF3, and anti-EMA demonstrated reactive cells in some of these marrows, this reactivity was similar to that seen with control preparations. MAb CAM5.2, in contrast, was negative with all specimens. These data suggest that MAb CAM5.2 may be a useful immunologic probe for the detection and confirmation of metastatic breast carcinoma in bone marrow, while more caution must be employed in the interpretation of results obtained using MAbs anti-EMA, DF3, and HMFG-2.

Adolescent

Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis.

The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation.

Animals