Biomedical subjects
Publications and source records attributed to S Simpson.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The present study compared performance in basketball as measured by a variety of performance measures to 15 men and 13 women players' moods as measured by the Profile of Mood States. The results suggested that the basketball players' performance was disrupted by a negative mood.
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.
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.
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.
A series of plasmid vectors, pRSET A, B, and C, have been developed for high-level protein expression in prokaryotes and have been characterized. Based upon the T7 RNA polymerase-driven pET system, the pRSET vectors encode recombinant proteins as fusions with a multifunctional leader peptide containing a hexahistidyl sequence for purification on Ni(2+)-affinity resins, a tyrosine residue for radioiodination, and an enterokinase proteolytic cleavage site for leader peptide removal. Monoclonal antibodies (MAbs) to two epitopes on the leader peptide, which also contains amino acids 1-12 of the T7 gene 10 major capsid protein, were developed and provide for universal immunological detection of pRSET-expressed fusion proteins. Subcloning of protein-encoding DNA is facilitated by an 11-site polylinker which is offset for all three ribosomal reading frames, and an f1(+) origin of DNA replication permits single-stranded DNA synthesis for site-directed mutagenesis protocols. Representative fusion proteins overexpressed in Escherichia coli were successfully purified under both denaturing and nondenaturing conditions by single-step Ni2+ affinity chromatography. Purification was independent of recombinant protein solubility in sonicated or freeze-thawed E. coli lysates. Isolation of MAbs for selective recognition of either of two leader peptide epitopes was demonstrated by immunoprecipitation, but this selectivity was less evident under conditions for Western blotting. In combining the utility of T7 RNA polymerase-directed expression with several recent advances in protein purification and detection, the pRSET vectors will serve as a powerful resource for a variety of studies in protein biochemistry.
Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.
To determine if the transition to extrauterine life is facilitated by skin-to-skin contact, six relatively low risk preterm infants experienced six continuous hours of skin-to-skin contact on their mothers' chests beginning within 30 minutes of birth. Heart and respiratory rates and oxygen saturation remained within normal limits and all infant temperatures rose rapidly to thermoneutral range. Two infants developed grunting respirations by the time skin-to-skin contact began, but the grunting disappeared with warm, humidified oxygen and continuous skin-to-skin contact. All infants were fully breastfeeding and ready for discharge by 24-48 hours postbirth. Early skin-to-skin contact was safe and seemed beneficial for these relatively low risk preterm infants.
To examine whether the tumor suppressor gene p53 influences epidermal differentiation, primary cultures of human foreskin keratinocytes and six human papillomavirus (HPV)-positive cell lines were infected with recombinant retroviruses encoding wild-type p53. Overexpression of p53 in organotypic cultures of normal keratinocytes decreased their growth rate and induced premature cell flattening and involucrin expression, a marker of squamous differentiation. However, overexpression of p53 inhibited or delayed production of other epidermal proteins, keratin 10, profilaggrin, and keratinocyte transglutaminase. Furthermore, levels of endogenous cellular p53 dramatically decreased during epidermal differentiation, suggesting that down-regulation of p53 permits complete expression of specific epidermal proteins. Three HPV-immortalized keratinocyte cell lines and three HPV-positive cervical carcinoma-derived cell lines expressed significantly less (< 3-fold) p53 protein than normal keratinocytes. Up-regulation of wild-type p53 (> 5-fold) by retrovirus infection did not significantly inhibit growth or restore normal epithelial differentiation in any line. Thus, overexpression of wild-type p53 can either induce or inhibit expression of specific epidermal proteins in normal keratinocytes but does not reverse immortality or aberrant differentiation of HPV-immortalized or carcinoma-derived cell lines.