The effect of estrogen and tamoxifen on hepatocyte proliferation in Vivo and in Vitro

We have previously shown that changes in estrogen‐hepatocyte interaction occur during liver regeneration. Following 70% hepatectomy, estrogen levels in the blood were elevated, the number of estrogen receptors in the liver was increased and there was an active translocation of estrogen receptors from the cytosol to the nucleus. The injection of tamoxifen, an estrogen antagonist, inhibits hepatocyte proliferation following partial hepatectomy. The administration of 1 μg tamoxifen per gm body weight at zero time or 6 hr after the operation resulted in a significant inhibition both of DNA synthesis and of the number of cells in mitosis. Injections of tamoxifen 12 hr or later after the operation had no effect. Concomitant injections of equimolar amounts of estrogen abolished the inhibition by tamoxifen. The effects of estrogen and tamoxifen were also tested on hepatocytes in primary culture. Estrogens in the presence of 5% normal rat serum stimulated hepatocyte DNA synthesis as determined by [3H]thymidine incorporation and the labeling index, whereas epidermal growth factor‐induced DNA synthesis in the absence of normal rat serum was strongly inhibited. Tamoxifen, in contrast, inhibited DNA synthesis of hepatocytes in the presence of 5% normal rat serum and reversed the stimulatory effect of estrogen in the same system. Attempts to elucidate the mechanism of tamoxifen inhibition in vitro indicated that one effect of tamoxifen is to prevent the amiloride‐sensitive Na+ influx necessary to initiate hepatocyte proliferation. Copyright © 1989 American Association for the Study of Liver Disease

Serogrouping and sulphonamide sensitivity of Neisseria meningitidis isolates from the south-western Cape

CITATION: Donald, P.R. et al. 1989. Serogrouping and sulphonamide sensitivity of Neisseria meningitidis isolates from the south-western Cape. S Afr Med J, 76:453.The original publication is available at http://www.samj.org.zaNeisseria meningitidis infections were first reported from the south-western Cape Province in 1883. Since then, against a backdrop of a relatively low incidence with winter exacerbation, epidemic periods have occurred at 10 - IS-year intervals. During the 1978 - 1979 epidemic more than 95% of isolates at Tygerberg Hospital were of serogroup B and only 5% were resistant to sulphonamides. Seventy-seven per cent of patients notified as suffering from meningococcal infections were under 4 years of age.3 In this report we briefly describe the pattern of serogrouping and sulphonamide resistance of N. meningitidis for the period 1980 - 1987.Publisher’s versio

Comparing proportional compositions of geospatial technology-related programs at three universities

Today, graduates seek employment in a global marketplace, regardless of the country in which they studied. Comparing academic programs helps students, academics and employers to make informed decisions about study options, program offerings and the employment of recent graduates. In this study, we juxtapose geospatial technologyrelated programs at three universities located in Europe, Africa and America. Initially, the authors contributed information about these programs through a questionnaire comprising several open-ended questions about the origins and development of the respective programs. Subsequently, the proportional thematic compositions of programs at the three universities were compared. As expected, this study was not without challenges. From the outset, we struggled with agreeing on terminology and semantics. Results of the study indicate that there is not a one-size-fits-all strategy for establishing, shaping and sustaining such programs. Program composition is guided by many factors, including staff expertise, university politics, legislation, attractiveness to students,  technological developments, demands in the job market and requirements set by a professional body. Some of these factors are strongly influenced by the local (university) environment (e.g. staff expertise), others are of national relevance (e.g. legislation and a national professional body), while some apply globally (e.g. technological developments). The study illustrated how a comparison of proportional program composition can reveal significant differences and similarities that are not obvious when only content is compared. The compositional differences naturally result in graduates with different knowledge and skills that allow different career paths and meet different needs of the job market

Evaluation of a diagnostic algorithm for smear-negative pulmonary tuberculosis in HIV-infected adults

Objective: To evaluate the diagnostic accuracy of and reduction in diagnostic delay attributable to a clinical algorithm used for the diagnosis of smear-negative pulmonarytuberculosi& (SNPTB) in HfV-infected adults.Design. An algorithm was designed to facilitate clinicoradiological diagnosis of pulmonary TB (PTB) in HIV-infected smear-negative adult patients. A folder review was performed on the first 58 cases referred for empirical TB treatment using this algorithm.Setting. Nolungile HIV Clinic, Site Khayelitsha.Subjects. Subjects included 58 HIV-infected adult patients with suspected PTB consecutively referred to the local TB clinic for outpatient TB treatment using this algorithm between 12 February 2004 and 30 April 2005.Outcome measures. Outcome measures were response of C-reactive protein, haemoglobin, weight and symptoms to TB treatment, and TB culture result. Diagnostic delay On days) was calculated.Results. Thirty-two of the 58 patients (55%) had positive TB cultures (definite TB). Initiation of TB treatment occurred on average 19.5 days before the positive culture report. A further 21 patients (36%) demonstrated clinical improvement on empirical treatment (probable/possible TB). Two did not improve and subsequently died without a definitive diagnosis. Three patients defaulted treatment.Conclusions.SNPTB is more common in HIV-infected patients and leads to diagnostic delay. This algorithm allowed for earlier initiation of TB treatment in HIV-infected patients presenting with symptoms of PTB and negative smears or nonproductive cough in a high TB incidence setting

Towards a Robuster Interpretive Parsing

The input data to grammar learning algorithms often consist of overt forms that do not contain full structural descriptions. This lack of information may contribute to the failure of learning. Past work on Optimality Theory introduced Robust Interpretive Parsing (RIP) as a partial solution to this problem. We generalize RIP and suggest replacing the winner candidate with a weighted mean violation of the potential winner candidates. A Boltzmann distribution is introduced on the winner set, and the distribution’s parameter $T$ is gradually decreased. Finally, we show that GRIP, the Generalized Robust Interpretive Parsing Algorithm significantly improves the learning success rate in a model with standard constraints for metrical stress assignment

Progressive MS Alliance Industry Forum: maximizing collective impact to enable drug development

The Progressive MS Alliance Industry Forum describes a new approach to address barriers to developing treatments for progressive multiple sclerosis (MS). This innovative model promises to facilitate robust collaboration between industry, academia, and patient organizations and accelerate research towards the overarching goal of developing safe and effective treatments for progressive MS

Epidemiology of post-neonatal bacterial meningitis in Cape Town children

CITATION: Hussey, G. 1997. Epidemiology of post-neonatal bacterial meningitis in Cape Town children. South African Medical Journal, 87(1):51-56.The original publication is available at http://www.samj.org.zaBacterial meningitis is a major cause of childhood morbidity and mortality in South Africa. However, comprehensive regional or national epidemiological data, essential for rational public health interventions, are lacking. The purpose of this 1-year prospective study, from 1 August 1991 to 31 July 1992, was to define the magnitude of the problem of childhood bacterial meningitis in Cape Town. The study group consisted of all children, aged > 1 month to < 74 years, who presented with proven bacterial meningitis at all the hospitals in the Cape Town metropolitan area. During the year 201 cases were identified: 101 (50.2%) were due to Neisseria meningitidis, 74 (36.8%) were due to Haemophilus influenzae and 26 (12.9%) were due to Streptococcus pneumoniae. The overall incidence rate (95% confidence interval) for children less than 14 years, 5 years and 1 year was 34 (30 - 40), 76 (65 - 88) and 257 (213 - 309) per 100 000 children, respectively. The rate was highest in black infants, 416 (316 - 545)/100 000. This was 2 times greater than the rate in coloured infants and about 4.5 times greater than the rate in white infants. The median age of all the children was 10 months. The ages of children with haemophilus and pneumococcal meningitis were similar, 9 and 7.5 months respectively (P = 0.43), while children with meningococcal meningitis were significantly cider (22 months) than the others (P < 0.01). The overall case fatality rate was 5%, and 12.9% of survivors had significant neurological sequelae (disability) on discharge.Publisher’s versio

Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS

Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature.

BACKGROUND: Electrophysiological data suggest that cardiac KATP channels consist of Kir6.2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart. RESULTS: Immunohistochemistry of cardiac cryosections demonstrate Kir6.1 protein to be expressed in ventricular myocytes, as well as in the smooth muscle and endothelial cells of coronary resistance vessels. Endothelial capillaries also stained positive for Kir6.1 protein. Kir6.2 protein expression was found predominantly in ventricular myocytes and also in endothelial cells, but not in smooth muscle cells. SUR1 subunits are strongly expressed at the sarcolemmal surface of ventricular myocytes (but not in the coronary vasculature), whereas SUR2 protein was found to be localized predominantly in cardiac myocytes and coronary vessels (mostly in smaller vessels). Immunocytochemistry of isolated ventricular myocytes shows co-localization of Kir6.2 and SUR2 proteins in a striated sarcomeric pattern, suggesting t-tubular expression of these proteins. Both Kir6.1 and SUR1 subunits were found to express strongly at the sarcolemma. The role(s) of these subunits in cardiomyocytes remain to be defined and may require a reassessment of the molecular nature of ventricular KATP channels. CONCLUSIONS: Collectively, our data demonstrate unique cellular and subcellular KATP channel subunit expression patterns in the heart. These results suggest distinct roles for KATP channel subunits in diverse cardiac structures