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Biomedical subjects

S Simpson

Publications and source records attributed to S Simpson.

At least 73 records · Page 4Linked to original sources

Effects of nerve growth factor on splenic norepinephrine and pineal N-acetyl-transferase in neonate rats exposed to alcohol in utero: neuroimmune correlates.

Prenatal alcohol exposure (FAE) has been associated with multiple anomalies, including a selective developmental delay of sympathetic innervation in lymphoid organs. Sympathetic neurons require nerve growth factor (NGF) for their development and maintenance, and recent evidence has suggested that alcohol impairs the synthesis and/or biological activity of NGF in selected central and peripheral neurons. Thus, the present study examined the hypothesis that NGF administration to FAE rats during early postnatal development would reverse some of the peripheral sympathetic deficits. Neonate rats, FAE and the corresponding control cohorts, received daily treatments of NGF or cytochrome C (0.3 mg/kg; s.c.) for various time intervals, and were killed 24 hr or 10 days after the last treatment. The measured parameters included norepinephrine (NE) concentrations in the spleen and heart, which receive nor-adrenergic innervation from the coeliac ganglion and the superior cervical ganglion (SCG), respectively. In addition, we measured the activity of pineal N-acetyltransferase (NAT), the rate-limiting enzyme of melatonin biosynthesis, which depends on sympathetic innervation from the SCG. The data show that chronic, but not acute, NGF treatments reversed the FAE-related deficits in splenic NE concentrations as well as in pineal NAT activity in a time- and age-dependent manner. Sympathetic neurons play an important role in immune modulation. Thus, the altered splenic NE levels and pineal NAT activity may play a role in immune deficits associated with exposure to alcohol in utero.

Animals↗

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia.

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

Adult↗

Weight loss alters organ concentrations and contents of lead and some essential divalent metals in rats previously exposed to lead.

The loss of adipose tissue during energy restriction may be accompanied by a loss of lean body mass, including bone mass. Because most of the body lead burden is in the skeleton, we studied the effects of weight loss on the concentrations of lead in bone, blood and several organs in rats with prior but not current lead exposure. Concentrations of the essential divalent metals calcium, copper, iron, magnesium and zinc were also determined for comparison with lead. Lead-exposed rats (n = 25) were randomly assigned to one of three treatment groups: weight maintenance (WM), moderate weight loss (MWL) or substantial weight loss (SWL). For the two last-named groups, food intake was restricted for 4 wk to 70 and 40% of that of the WM group. Lead concentrations did not differ significantly (ANOVA, P > 0.05) among the three groups for blood, brain and bone. Significantly higher liver lead concentrations were observed in the SWL rats than in the WM and MWL groups. In general, organ concentrations of calcium, copper, magnesium and zinc were either lower or did not differ in the groups losing weight compared with the WM group. In contrast, organ Iron concentrations of the SWL group were higher than those of the other groups except in brain where there were no significant differences. The total liver content of lead was highest in the SWL group, but the lead content of other organs did not differ among the treatment groups. The contents of calcium, copper, magnesium and zinc generally were lower in the MWL and SWL groups than in the WM group in the liver and some of the other organs. The results demonstrate that weight loss can increase the quantity and concentration of lead in the liver, even in the absence of continued lead exposure. The data also demonstrate considerable differences among organ divalent metals in response to weight loss.

Analysis of Variance↗

Correlations between mood scores and volleyball performance.

Scores on the Profile of Mood States Inventory of 15 volleyball players at a small southwestern university were compared by means of regression analysis to the players' final season statistics. The analysis showed that Vigor as measured was related to several volleyball statistics.

Achievement↗

Transforming growth factor beta 1 supports autonomous growth of human papillomavirus-immortalized cervical keratinocytes under conditions promoting squamous differentiation.

Transforming growth factor beta (TGF-beta) inhibits proliferation of keratinocytes cultured from normal anogenital epithelia; however, human papillomavirus (HPV)-immortalized cell lines often exhibit increased resistance. Present results demonstrate that TGF-beta 1 (1-10 pM) stimulates growth of multiple HPV-immortalized cell lines when cultures are maintained under conditions promoting squamous differentiation (MCDB153-LB medium with 1.0 mM calcium and without epidermal growth factor and bovine pituitary extract). Growth stimulation by TGF-beta 1 was not due to altered expression of type I or II receptors, but was increased after extended passage of cells in culture. Differentiation of immortal keratinocytes resulted in induction of RNAs encoding two markers of squamous differentiation, involucrin and keratin 1, and decreased expression of RNAs for the epidermal growth factor (EGF) receptor and two ligands, amphiregulin and TGF-alpha. Growth stimulation by TGF-beta 1 occurred indirectly via establishment of an autocrine loop. TGF-beta 1 increased expression of RNAs encoding the EGF-R and amphiregulin, and also increased numbers of cell-surface EGF-Rs without altering their affinity. In contrast, TGF-beta 1 inhibited autonomous growth and transcription of amphiregulin RNA in normal keratinocytes. Growth stimulation by TGF-beta 1 could be blocked by a monoclonal antibody that competes for binding to the EGF-R or by a mixture of monoclonal antibodies that neutralize amphiregulin activity, confirming the importance of this autocrine pathway. Thus, partial abrogation of the growth inhibitory response to TGF-beta 1 sensitizes HPV-immortalized keratinocytes to a growth stimulatory signal mediated by an EGF-R-dependent pathway involving autocrine stimulation by amphiregulin.

Animals↗

Molecular cytogenetics of human papillomavirus-negative cervical carcinoma cell lines.

Cervical cancer is a malignancy closely associated with human papillomavirus (HPV). However, some cervical carcinomas occur in the absence of the virus. Two HPV-negative cervical carcinoma cell lines, C-33A and HT-3, were examined by G-banding and fluorescence in situ hybridization (FISH) using several whole chromosome and satellite probes. Combined conventional banding and FISH analysis significantly enhanced identification of complex and cryptic chromosome rearrangements. Common to both cell lines were translocations of chromosome 1, involving a specific site on the short arm and partial or complete loss of the short arm of chromosome 9, as well as loss of chromosome 13. The C-33A line had a relatively simple chromosomal constitution, with chromosome 1 being involved in translocations with chromosomes 9, 18, and 21. Karyotype reconstruction of G-banded and painted chromosomes indicate a net loss of DNA as a result of unbalanced translocations, which occurred only at site 9p24 and loss of one copy of chromosomes 13 and 14. In contrast, HT-3 cells had complex rearrangements and deletions of chromosomes 1p, 3p, 9p, 10q/p, 11p/q, and 17p, all regions with known tumor suppressor genes. The deletions observed in these HPV-negative cervical carcinomas will be important in delineating regions of tumor suppressor genes.

Carcinoma↗

Information in primary health care.

The results of two recently completed studies, one in the Trent Region and the other in the Anglia and Oxford Region, of the information-related behaviour of general medical practitioners (GPs) and of information activities within the general practices illustrating the information seeking behaviour of GPs, their generation of information, and communication within, to and from the practice. GPs stated that there is a need for more information to enable practices to function within the changing NHS environment. The increasing emphasis on evidence-based medicine also creates the need for appropriate information sources. The Trent study resulted in guidelines for best information practice, especially the need for each practice to have an information strategy. The Anglia and Oxford Study examined the role which the library and information services could play in supporting primary health care.

Communication↗

Selection of peripheral and intestinal T lymphocytes lacking CD3 zeta.

The CD3 zeta chain of the TCR plays a pivotal role in the activation of T cell responses toward foreign antigen and in the selection of the T cell repertoire. T lymphocytes from mice deficient in CD3 zeta (CD3 zeta/eta-/- mice) express very few cell surface TCR-CD3 complexes, and these animals have poorly developed thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a substantial number of single-positive CD4+ and CD8+ T lymphocytes are found in peripheral lymphoid organs of CD3 zeta/eta-/- animals. Using double-mutant mice, generated by breeding CD3 zeta/eta-/- mice with others deficient in the expression of either class I or class II MHC molecules, we demonstrate here that positive selection of peripheral CD4+ and CD8+ T lymphocytes can occur in the absence of CD3 zeta/eta molecules. Analysis of the intestinal intra-epithelial lymphocytes from CD3 zeta/eta-/- mice revealed a novel T cell population expressing high levels of an alternative TCR alpha beta, due to the replacement of CD3 zeta by Fc epsilon RI gamma. Developmentally, these cells also depend on class I MHC expression. In contrast, TCR gamma delta/Fc epsilon RI gamma+ T cells develop independently of MHC class I or class II molecules. These experiments demonstrate that the unique subset of intestinal TCR alpha beta/Fc epsilon RI gamma+ lymphocytes is developmentally dependent on MHC expression. The restricted expression of TCR alpha beta/Fc epsilon RI gamma+ cells in the intestinal mucosa (rather than the thymus or lymph nodes) supports the hypothesis that selection of these T cells occurs extrathymically.

Animals↗

Preliminary results from a psychoeducational program to rehabilitate chronic patients.

Twenty-two chronic psychiatric patients enrolled in a psychoeducational rehabilitation program were assessed before and after the program to determine whether participation decreased severity of psychopathology and improved community functioning and quality of life. The program consisted of five 14-week modules that provided training in five skill areas: medication and symptom self-management, coping with anxiety and depression, social skills, living skills, and leisure skills. Most patients experienced significantly reduced psychopathology and negative symptoms and improved quality of life and community functioning. The program appears helpful to clients, and a controlled trial to further evaluate its effects is underway.

Activities of Daily Living↗

Neuropsychiatry and SPECT of an acute obsessive-compulsive syndrome patient.

BACKGROUND: A 71-year-old man with no previous psychiatric history presented with an acute onset of obsessive-compulsive disorder (OCD) symptoms associated with a right inferior parietal infarct. There were no abnormal neurological signs. There were no noteworthy abnormalities on neuropsychological testing. METHOD: Whereas a computerised tomography scan showed only a right inferior parietal infarct, a single photon emission computerised tomography (SPECT) scan revealed that in addition to the infarct there was decreased regional cerebral blood flow in the right basal ganglia and temporal areas. There was higher activity in the right orbitofrontal area than in the left. RESULTS: The patient improved with standard drug therapy and psychotherapy. CONCLUSIONS: SPECT is effective in the diagnosis of neuropsychiatric disorders such as OCD, and the pathological changes in brain metabolism detected by SPECT may be reversed by both drug therapy and psychotherapy.

Aged↗

Information in general medical practice: a qualitative approach.

The aims of the study reported here were to describe the information-related behavior of general medical practitioners, to study information communication in general practices, and to establish guidelines for good practice. General practitioners (GPs) were interviewed, and information and communication audits also involving other staff at the practices were undertaken. The main reasons why GPs needed information were for patient care, managing the practice, legal and ethical matters, and teaching trainee GPs. Most practices had problems with internal and external communication and the storage and retrieval of information. The main conclusion is that practices need to have an information strategy that considers human, manual, and computer aspects of information handling.

Appointments and Schedules↗

Hantavirus pulmonary syndrome: clinical, diagnostic, and virologic aspects.

Hantavirus pulmonary syndrome is an acute pneumonitis with a high mortality rate that is caused by a newly recognized hantavirus. Four Corners virus (also known as Muerto Canyon virus and Sin Nombre virus) is enzootic among deer mice (Peromyscus maniculatus). Incidental transmission to humans can result in a disease characterized by rapidly progressive respiratory insufficiency, diffuse noncardiogenic pulmonary edema, vascular volume contraction with hemoconcentration, lactic acidosis, depressed cardiac output, and cardiac dysrhythmias preterminally. The onset of pulmonary edema is preceded by a prodrome of fever and severe myalgias. Characteristic laboratory abnormalities include thrombocytopenia, leukocytosis with prevalent immature myeloid cells, and the presence of immunoblastic lymphocytes in the peripheral blood. Agent-specific diagnosis is based on the detection of Four Corners virus-specific antibodies in serum by Western blot assays and the detection of Four Corners virus RNA in peripheral blood mononuclear cells by the reverse transcriptase-polymerase chain reaction. Effective treatment depends on the rapid institution of intensive care support.

Adolescent↗

Scores on profile of mood states of college football players from nonscholarship and scholarship programs.

Scores on the Profile of Mood States of football players from three small football programs (ns = 85, 71, and 91) were compared. Scores of athletes from the two nonscholarship programs did not conform to the "iceberg profile," differing mainly on Anger. These same players differed significantly from the scholarship athletes at a major college on all mood states. Mean total mood scores fell between those for major college scholarship athletes and high school athletes. Means for players associated with the small scholarship program more closely resembled means of major college athletes on both the individual mood states and the total mood score. The results supported the hypothesis that nonscholarship collegiate athletes differ in significant ways from those receiving scholarships.

Adult↗

JCAHO standards: options and opportunities.

The 1994 Joint Commission on Accreditation of Healthcare Organizations (JCAHO) standards focus on the hospital as a system. Chapters of the manual are configured around major patient care functions and organizational structures. JCAHO envisions that if these functions are performing well, quality outcomes will result. The standards are written in a generic fashion, which gives hospitals maximum opportunity to develop programs of standards compliance within the resources and capabilities of their organization. Nurse managers have an opportunity to facilitate creative methods to meet standards' compliance.

Guidelines as Topic↗

Unit-based shared governance can work!

The Nurse Executive Council at a 540-bed community teaching health center planned and implemented Shared Governance in a 10-bed Medical Intensive Care Unit (MICU). Paid time was provided for nurses to take part in one of four councils. After a pilot year resulting in satisfaction with job autonomy and input into decision-making, staff reaffirmed their commitment to shared governance as a permanent "way of life" in the MICU. During the second year, patient care assistants and unit clerks were integrated into the Councils and staff began serving as consultants to other units and institutions.

Decision Making, Organizational↗

A Burkitt lymphoma cell line with integrated Epstein-Barr virus at a stable chromosome modification site.

Fluorescence in situ hybridization (FISH), Southern, and slot blotting were used to detect Epstein-Barr virus (EBV) DNA and RNA sequences in a Burkitt's lymphoma (BL) cell line derived from a North American patient (NAB-2). FISH analysis after hybridization with a BamHI "V" region of EBV showed that NAB-2 cells have EBV genome integrated at a single site on the short arm of chromosome 2(p13). Single hybridization signals were detected at homologous sites on both chromatoids and nuclei. Furthermore, hybridization of intact nuclei without formamide denaturation and heat allowed the detection of single specific viral RNA transcripts visible as "tracks" or "traces." Southern blot analysis confirmed the integration of EBV genome into the host DNA. Quantification of slot blot hybridization revealed that NAB-2 cells have on average one copy of EBV per cell. Virus insertion into chromosomal DNA caused a stable modification site expressed as a distinctive achromatic region adjacent to the band 2p13. The chromatid lesion at the site of EBV integration involving a recombinogenic and fragile site may have contributed to the development of the NAB-2 BL.

Blotting, Southern↗