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Biomedical subjects

J Norton

Publications and source records attributed to J Norton.

At least 109 records · Page 6Linked to original sources

Supersensitivity to melatonin suppression by light in young people at high risk for affective disorder. A preliminary report.

Affective illness aggregates in families and appears to be heritable. Bipolar affective patients have been found to be supersensitive to the suppressive effect of light on the nocturnal secretion of melatonin, both in ill and well states. We tested young people aged 15 to 25 years with one manic-depressive parent (n = 18), major affective disorder on both sides of the family (n = 7), and age-matched controls (n = 20). The subjects in the high-risk groups were more likely to show supersensitivity in melatonin response to light at night than controls. Follow-up studies are necessary to assess the predictive value of this response.

Adolescent↗

A simplified low iodine diet in I-131 scanning and therapy of thyroid cancer.

A simplified, low iodine diet was developed for outpatient use prior to I-131 scanning and therapy in thyroid cancer. Iodine intake of five subjects on the diet was approximately 50 micrograms a day and this level was maintained for four weeks. The diet required only minimal instruction to be followed reliably. This level of iodine intake may increase radioiodine uptake in thyroid carcinomas.

Adult↗

T cell cytotoxicity to Epstein-Barr virus infected B cells: comparison of patients with rheumatoid arthritis and their HLA identical siblings.

Specific T cell cytotoxicity to Epstein-Barr virus (EBV) infected B cells is reported to be abnormal in rheumatoid arthritis (RA). The regression phenomenon was used to determine whether the immunoregulatory defect in RA is restricted to T cells, B cells, or HLA type. Peripheral blood T and B cells from patients with RA and their HLA identical healthy siblings were mixed in varying ratios with and without EBV, and thymidine incorporation was measured on days 7, 14, and 21. The results suggest that the T cell abnormality is related to disease activity and that an inherent defect exists in the rheumatoid B cell which is independent of disease activity.

Aged↗

Antihypertensive and angiotensin converting enzyme inhibitory activities of a novel dihydrobenzofuran analogue.

1. The biochemical and pharmacological profiles of the novel, orally active angiotensin converting enzyme (ACE) inhibitor, N-[N-[[4-(2, 3-dihydro-2-benzofuranyl)-1-(ethoxycarbonyl)]butyl]-(s)-alanyl]- (s)-proline (BRL 36378), have been compared with those of enalapril and captopril. 2. In the conscious sodium deficient spontaneously hypertensive rat, BRL 36378 and enalapril (0.3-10 mg/kg orally) produced comparable falls in blood pressure; at 3 mg/kg orally, captopril was less active than BRL 36378 and enalapril. 3. In the anaesthetised spontaneously hypertensive rat, enalapril was slightly more potent than BRL 36378 as an inhibitor of angiotensin I (AI) pressor responses whilst BRL 36378 was about twice as potent as captopril in this test (i.v. route used). BRL 36378 and enalapril were equipotent as potentiators of bradykinin depressor responses. 4. In the anaesthetised Wistar rat, the maximum inhibition of AI pressor responses by 0.1 microgram/kg i.v. BRL 36378 and captopril was achieved sooner than after the same dose of enalapril. The inhibitory effect of captopril subsided completely by 40-50 min but the maximum effects of BRL 36378 and enalapril persisted for at least 60 min. 5. In the conscious renal hypertensive cat, captopril was slightly more potent than BRL 36378 or enalapril as a blood pressure lowering agent, over 1-10 mg/kg orally. BRL 36378 was more potent than enalapril as an inhibitor of AI induced pressor responses in this model. Captopril possessed similar inhibitory activity to BRL 36378 although minor differences in time course were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Genotypes and immunophenotypes of Hodgkin's disease-derived cell lines.

This report describes the geno- and immunophenotypic analysis of the Hodgkin's disease-derived cell lines HDLM-2, KM-H2, and L-428. The lines were all positive for the antigens CD15 (Leu-M1), CD30 (Ki-1), Hefi-1 (antigen detected by a monoclonal antibody produced against L-428), HLA class I and II, and activation/proliferation markers. The cells from all 3 cell lines lacked almost all cell lineage-associated/specific markers: HDLM-2 was only CD2+, KM-H2 was only CD9+ and CD21+, and L-428 was negative for all the specific markers tested. Genomic analysis of HDLM-2 cells revealed monoclonal rearrangements of T cell receptor beta and gamma loci and germ line configuration of immunoglobulin genes. Immunoglobulin heavy chain genes were rearranged in KM-H2 and L-428. These data suggest a possible lymphoid origin for HDLM-2, KM-H2, and L-428. Although the data presented do not provide formal proof of a lymphoid nature of Hodgkin and Reed-Sternberg cells and do not unequivocally exclude a derivation from other hematopoietic cells, extrapolation of the results from the in vitro cultures to the in vivo situation suggests a lymphoid (T or B cell) origin of these cells.

Antigens, Differentiation, T-Lymphocyte↗

Functional innervation of the striatum by ventral mesencephalic grafts in mice with inherited nigrostriatal dopamine deficiency.

Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non-grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system.

Animals↗

Nerve cell atrophy and loss in the inferior olivary complex of "Purkinje cell degeneration" mutant mice.

The genetically determined loss of cerebellar Purkinje cells (PCs) in "Purkinje cell degeneration" (pcd) mutant mice deprives inferior olivary (IO) neurons of their major postsynaptic target. The degeneration of PCs starts on postnatal day (P) 17 and loss of these neurons is virtually complete by P45. We examined the inferior olivary complex (IOC) of normal and pcd mutant mice by quantitative light microscopy to determine whether the degeneration of PCs is associated with atrophy and loss of their presynaptic neurons in the IOC. The number of IO neurons in 17-day-old mutants did not differ significantly from controls (P greater than .1). IO neurons in 23-day-old mutants were 23% (95% confidence limits: 12-34%) fewer than in age-matched controls, and in 300-day-old mutants they were 48% (95% confidence limits: 37-58%) fewer than in their controls (P less than .001 in both cases). The decline of the number of IO neurons in pcd mice between days 17 and 300 was 49% (P less than .0001; 95% confidence limits: 38-57%). The medial accessory olive (MAO) appeared less affected than the principal (PO) and the dorsal accessory olive (DAO). The mean neuronal diameter in control mice was 11.6 micron at 23 days and 10.8 micron at 300 days of age. The respective values in pcd mutants were 11.5 micron and 8.7 micron. Diameters in old mutants were significantly smaller than those in both age-matched controls and young mutants (P less than .001). These findings suggest that in the mature olivocerebellar system the stability of IO neurons depends on the state of their postsynaptic PCs.

Animals↗

The effects of adherent cells on measurement of the hyper-responsiveness of rheumatoid B lymphocytes to Epstein-Barr virus.

Rheumatoid peripheral blood mononuclear cells show an increased responsiveness to superinfection with Epstein-Barr virus (EBV). We have investigated the role of adherent cells in this hyperresponsiveness using two different methods of adherent cell depletion. Depletion of adherent cells from both rheumatoid and normal mononuclear cells, using either dextran bead columns or plastic petri dishes, produced inconsistent changes in the response of autologous non-adherent cells to EBV. The addition of supernatants of cultured rheumatoid adherent cells also produced an inconsistent change in response although normal adherent cell supernatants increased the responsiveness of autologous non-adherent cells to EBV. The inconsistencies observed are discussed with respect to adherent cell subpopulations present in rheumatoid and normal peripheral blood mononuclear cell preparations when using recognized methods of adherent cell depletion.

Arthritis, Rheumatoid↗

Anterograde transsynaptic degeneration in the deep cerebellar nuclei of Purkinje cell degeneration (pcd) mutant mice.

The genetically-determined loss of Purkinje cells (PCs) in 'Purkinje cell degeneration' (pcd) mutant mice results in the loss of presynaptic afferents to the deep cerebellar nuclei (DCN). This deafferentation takes place between postnatal day (P)17 and P45, i.e. after the maturation of cerebellar circuitry. We examined the DCN of normal and pcd mutant mice by quantitative light microscopic methods to determine whether neuronal atrophy or loss in the DCN take place during and after the loss of their input from the PCs. Neuronal diameters in control mice were 16.4 +/- 0.72 microns (mean +/- S.D.) at P23 and 15.6 +/- 0.64 microns at P300. The respective values in pcd mutant mice were 15.7 +/- 0.58 microns and 13.5 +/- 0.24 microns. Diameters in 300-day-old mutants were significantly smaller than those in both age-matched controls and 23-day-old mutants (P less than 0.001). Neuronal populations in the DCN of control mice were 10,167 +/- 949 at P23 and 10,429 +/- 728 at P300. The respective values in mutants were 9,436 +/- 1,366 and 7,424 +/- 1,324. There was a significant difference of 29% [95% confidence limits: 9-45%] between 300-day-old mutants and age-matched controls (P less than 0.01), and a significant loss of 21% [95% confidence limits: 4-36%] in 300-day-old mutants with respect to 23-day-old mutants (P less than 0.05). The total volume of the DCN was 22% less in 300-day-old mutants in relation to 23-day-old mutants (P less than 0.05). These findings support the idea that the stability of DCN neurons in the mature cerebellum depends in part on the synaptic input from PCs.

Animals↗

Multiple chromosome abnormalities in a drug resistant TdT positive B-cell leukemia.

A 17-year old caucasian male presented with B-cell acute leukemia which proved aggressive and refractory to treatment. Cytogenic investigation showed a single clone with a complex karyotype 49,XY,del(2)(p13),+4,del(4)(p11),-6,+i(6)(p),+7,+8, t(8;14), (q24;q32),del(17)(p11). This includes the Burkitt's translocation and a deletion at the site of the immunoglobulin kappa light chain gene. Clonal evolution included tetraploidy, duplication of the derived chromosomes and, terminally, trisomy 1q. Immunological investigation revealed a monoclonal population of B-cell blasts, expressing the kappa light chain, and with an extremely rare combination of SIg and TdT positivity. Immunoglobulin gene rearrangement confirmed monoclonalility. Tetraploidy of the clone and del(17)(p11) have been previously described only in a cell line or at end stage disease in B-ALL. It is suggested that the chromosomal abnormalities present at diagnosis were directly related to the refractory nature of this leukemia.

Acute Disease↗

The family's adaptation to childhood leukemia.

This baseline study obtained data measuring the specific effects of the stress of childhood leukemia on family life and on the lives of individual family members. Mothers, fathers, siblings, and patients were included in the data collection. Specific variables measured were marital adjustment, anxiety level, dynamics of family interaction, and the school behavior of patients and siblings. The data were collected at designated intervals over a one year period beginning at the time of diagnosis. In addition, the data were utilized to speculate on those families that appeared to be at risk for the development of long-term psychosocial problems secondary to, or aggravated by the illness. Results indicated that patterns of coping for families, as well as for individual family members, were relatively constant over time. Families with predominantly stable relationships and adequate support within the family unit were able to maintain their usual quality of life over an extended period of time despite the onset of acute stress. However, families with pre-existing problems prior to diagnosis for the most part experienced increased deterioration in family life and had difficulty coping. Results of the Spielberger State-Trait Anxiety Scale, the Locke-Wallace Marital Adjustment Test, the Moos Family Environment Scale, the MMPI, and school data supporting these conclusions are given.

Adaptation, Psychological↗

Determinants of survival 10 to 14 years after coronary bypass: analysis of preoperative variables in 1,448 patients.

To determine which preoperative variables were most predictive of long-term survival after coronary bypass surgery, the status of 1,448 consecutive patients was determined 10 to 14 years after operation. All patients were operated on at least 10 years ago and follow-up at 10 years was 93.8% complete. The overall 14-year survival probabilities were: for one-vessel disease, 73.3%; for two-vessel disease, 45.9%; for three-vessel disease, 34.2%; and for left main coronary artery disease, 41.9%. Patients with good left ventricular function had an overall survival rate of 53.3%, and patients with poor ventricular function had a survival rate of 31.9%. Preoperative variables predictive of greater risk of total mortality were: digoxin usage, multivessel disease, poor quality of left ventricular function, age at operation, electrocardiographic evidence of myocardial infarction, previous stroke, diabetes, heart failure, diuretic usage, cigarette smoking, and residual ungrafted coronary artery disease. The major determinants of long-term survival were variables associated with preoperative left ventricular function. Diabetes was the only important metabolic risk factor identified. This study suggests that unfavorable preoperative conventional risk factors should not be considered a contraindication to operation in patients with adequate coronary anatomy and left ventricular function.

Coronary Artery Bypass↗

The effect of nutritional support on outcome from severe head injury.

Fifty-one brain-injured patients with peak 24-hour admission Glasgow Coma Scale (GCS) scores of 4 to 10 were prospectively randomly assigned to receive total parenteral (TPN) or enteral (EN) nutrition. Patients were studied from hospital admission to 18 days postinjury. Outcome was assessed by the Glasgow Outcome Scale at 3 months, 6 months, and 1 year postinjury. The TPN group received a significantly higher cumulative mean intake of protein than the EN group (mean +/- standard error of the mean: 1.35 +/- 0.12 vs. 0.91 +/- 0.9 gm/kg/day; p = 0.004). Mean cumulative caloric balance was also significantly higher in the TPN than in the EN group (75.6% +/- 5.13% vs. 59% +/- 4.26%; p = 0.02). Nitrogen balance was significantly more negative in the EN group during the 1st week postinjury (p = 0.002). The incidence of pneumonia, urinary tract infections, septic shock, and infections was not significantly different between groups. Classic nutritional assessment parameters such as anergy screens, total lymphocyte counts, and albumin levels were not significantly different between groups. The 11 patients in the EN group who did not tolerate tube feedings for 1 week postinjury had a significantly higher incidence of septic shock (p = 0.008). The change over time in GCS scores between groups was significantly different, with the TPN group showing a mean four-point increase in GCS score compared with a three-point increase in the EN group (p = 0.02). At 3 months the TPN group had a significantly higher percentage of favorable outcomes (43.5% vs. 17.9%, respectively; p = 0.05). At 6 months, 43.5% of the TPN group had a favorable outcome while 32.1% of the EN group had a favorable outcome (p = 0.29). By 1 year, 47.8% of the TPN group and 32.1% of the EN group had a favorable outcome (p = 0.20). In conclusion, more calories and protein usually can be administered to acute brain injury patients via the TPN route than by EN feedings via nasogastric or nasoduodenal routes. Traditional parameters for nutritional assessment are not useful in studying the efficacy of nutritional support during the first 2 weeks after head injury. Neurological recovery from head injury occurs more rapidly in patients with better early nutritional support.

Craniocerebral Trauma↗

Passage of somatostatin analogue across human and mouse skin.

Recent studies have documented beneficial effects of the somatostatin analogue, SMS 201-995 (hereafter referred to as SMS), when administered subcutaneously to patients with a variety of disorders. Since SMS is a small peptide, we tested the ability of two penetrant enhancers--dimethylsulfoxide and N-decylmethylsulfoxide (C10MS)--to promote transcutaneous passage of SMS. Samples of skin from human cadavers and hairless mice were tested in a static diffusion chamber. Application of SMS in conjunction with 1% C10MS resulted in rapid transdermal passage of SMS. These data were confirmed for hairless mouse skin in experiments with a modified diffusion chamber having continuous flow-through of receptor fluid in the subdermal reservoir. In this system, the cumulative amount of SMS that permeated hairless mouse skin was 20 micrograms/cm2/24 hours. Topical application of SMS with C10MS beneath a patch to mice confirmed in vitro data. Topical application of 10 micrograms of SMS resulted in plasma SMS levels of greater than 8,000 pg/ml within 2 hours. We conclude that SMS will cross both human and mouse skin, with a clinically significant flux, when administered topically with C10MS. The data support the feasibility of in vivo human trials of topical SMS therapy.

Administration, Cutaneous↗

The patient with critical neurological disease.

The known metabolic abnormalities and nutritional requirements of the brain injury, spinal cord injury, and acute stroke patient have been presented. Further investigations are required in all these conditions to identify specific nutritional requirements and metabolic abnormalities. The specific role of nutritional support on outcome, immune function, and body structure requires further study.

Acute Disease↗

Differentiation of adrenal masses by magnetic resonance imaging.

Eighty-one adrenal masses in 68 patients were examined with magnetic resonance imaging (MRI). Masses included nonfunctioning adenomas (17), metastases (25), adrenocortical carcinomas (10), and pheochromocytomas (23). T1-weighted pulse sequences depicted the anatomy with a resolution comparable to that of computed tomography (CT). T2-weighted pulse sequences provided some histologic specificity separating nonfunctioning adenomas with low signal-intensity from metastases with intermediate signal-intensity and pheochromocytomas with high signal-intensity. Pheochromocytomas could always be distinguished from other adrenal masses. In 20% of the cases, metastases with low signal-intensity could not be distinguished from nonfunctioning adenomas.

Adenoma↗