DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53 is transactivation competent and G2/M when it is transactivation defective.

Cisplatin treatment of Epstein-Barr virus-immortalized human B lymphoblastoid cell lines (LCLs) results in p53-mediated apoptosis which occurs largely in a population of cells at the G1/S boundary of the cell cycle. Cell cycle progression appears to be required for this apoptosis because arresting cells earlier in G1 inhibited apoptosis despite the accumulation of p53. Overexpression of wild-type p53 also induces apoptosis in an LCL.

Pancreatic islet insulin secretion is increased after resistance exercise in rats.

The purpose of this study was to determine whether 4 days of resistance exercise facilitated insulin secretory adaptations at the level of the pancreatic islets. Eighteen male 400-g Sprague-Dawley rats were randomly assigned to two groups. All animals were operantly conditioned to engage in a resistance exercise protocol that required full extension of the hindlimbs.

Epstein-Barr virus EBNA-LP and transcription regulation properties of pRB, p107 and p53 in transfection assays.

The EBNA-LP protein (also known as EBNA-5) of Epstein-Barr virus (EBV) has been reported previously to colocalize in the nuclei of cells with the pRb protein and to bind in vitro to pRb and to the p53 protein, suggesting a role for EBNA-LP in modulation of the function of these proteins. Here we test in transfection assays whether EBNA-LP expression has any functional consequence for repression of E2F-1 activity by pRb or p107 or for activation of transcription by the p53 protein. No significant effect could be found, although the assay systems were sensitive to the established effects of simian virus 40 large T antigen and human papillo-mavirus type 16 E6 protein.

Host cell requirements for efficient infection of quiescent primary B lymphocytes by Epstein-Barr virus.

Quiescent primary B lymphocytes are efficiently immortalized by Epstein-Barr virus (EBV). This process requires both the delivery and expression of the viral genome and results in activation of the cell division cycle. Infection of B lymphocytes depends on a direct interaction between the viral glycoprotein gp340/220 and CD21, the C3dg complement receptor.

Sleep apnea in end-stage renal disease patients on hemodialysis and continuous ambulatory peritoneal dialysis.

Fifteen unselected end-stage renal disease patients (nine hemodialysis [HD] and six continuous ambulatory peritoneal dialysis [CAPD]) were randomly selected from four Sydney metropolitan dialysis centers for sleep assessment by full polysomnography. Four of six CAPD patients and eight of nine HD patients were found to have clinically significant obstructive sleep apnea. An additional 21 unselected patients (10 CAPD and 11 HD patients) were assessed using overnight home monitoring of nasal airflow and arterial oxygen saturation.

Repeatability of measurements on human, rabbit, and bull sperm by computer-assisted sperm analysis when comparing individual fields and means of 12 fields.

Objective: To compare repeatability of measurements of human, rabbit, and bull sperm on two Hamilton Thorne Integrated Visual Optical System (IVOS) units, software version 10.

Design: Semen samples from seven normal human subjects, six rabbits, and eight bulls were obtained at regular intervals. The samples were diluted, two chambers were filled, and 12 fields were recorded, using high resolution recorders.

Exercise training-induced changes in anterior pituitary gonadotrope of the female rat.

Chronic exercise training may alter the hypothalamic-pituitary-ovarian axis by affecting gonadotropin secretion and structural indexes of the anterior pituitary gonadotropes. Young female Harlan Sprague-Dawley rats were randomly assigned to either a 12-wk intensive treadmill-running program (n = 16) or to a sedentary untrained group [untrained-proestrus (UTP), n = 16]. After training for 3 mo, animals were killed on proestrous morning, and individual pituitary glands were enzymatically dispersed into single-cell suspensions.

The expression of variant CD44 in nasopharyngeal carcinoma is unrelated to expression of LMP-1.

CD44 expression in undifferentiated nasopharyngeal carcinoma has been analyzed by sequencing cDNA clones and by immunohistochemical staining using monoclonal antibodies specific for defined variant exons. Both sequencing and antibody staining revealed expression of CD44 variants containing exon v6, which has been linked to tumor metastasis. Although nasopharyngeal carcinoma typically contains a mixture of epithelial tumor cells and infiltrating lymphocytes, the CD44 v6 variant expression could be assigned to the tumor cells in biopsies and in a mouse xenograft system.

Epstein-Barr virus efficiently immortalizes human B cells without neutralizing the function of p53.

Epstein-Barr virus (EBV) efficiently converts resting human B cells into actively cycling, immortal, lymphoblastoid cell lines (LCLs). Here we show that LCLs expressing the full complement of latent viral genes are very sensitive to DNA-damaging agents such as cisplatin. The response includes a rapid accumulation of the tumour suppressor protein p53 and induction of the cellular genes mdm2 and WAF1/p21.

Oral supplementation with a high-fat, high-energy product improves nutritional status and alters serum lipids in patients with cystic fibrosis.

Objective: To assess the tolerance and acceptability of a nutrition supplement in patients with cystic fibrosis (CF), to monitor changes in dietary intake, and to evaluate nutritional status.

Design: Subjects were their own controls for this 3-month, prospective, open study. Acceptability and tolerance questionnaires and 3-day food records were completed at baseline and monthly intervals.

Epstein-Barr virus immortalizing genes.

Epstein-Barr virus (EBV) is linked to several types of human cancer and immortalizes human B cells very efficiently; at least six viral genes are required for this. The mechanism by which EBV immortalizes cells is particularly interesting because its immortalization genes are not obvious homologues of those of other DNA tumour viruses.

Efficient EBV superinfection of group I Burkitt's lymphoma cells distinguishes requirements for expression of the Cp viral promoter and can activate the EBV productive cycle.

Group I Burkitt's lymphoma cell lines conditionally expressing the CD21 receptor for EBV infection were superinfected with EBV. The incoming EBV entered its normal program of gene expression, producing EBNA-2 and LMP-1 and activating the Cp EBNA promoter, but the endogenous virus in the BL lines was not induced to express EBNA-2 or transcribe RNA from Cp. LMP-1 was, however, expressed from the endogenous genome in response to superinfection.

Expression of cyclin D2 in Epstein-Barr virus-positive Burkitt's lymphoma cell lines is related to methylation status of the gene.

The cyclin D2 gene is not expressed in resting primary B lymphocytes or in group I Burkitt's lymphoma (BL) cell lines that retain the characteristics of authentic BL cells. Expression of cyclin D2 is induced in primary B lymphocytes following infection with Epstein-Barr virus (EBV) or transfection of the EBV genes EBNA-LP and EBNA-2. However, attempts to induce cyclin D2 expression in BL cell lines by the enforced expression of EBV genes were unsuccessful.

Novel hypotheses for the roles of EBNA-1 and BHRF1 in EBV-related cancers.

Epstein-Barr virus has been linked to several types of human cancer including Burkitt's lymphoma and nasopharyngeal carcinoma but the mechanisms by which the virus might contribute to cancer remain obscure. Here we consider the possibility that EBNA-1, which is expressed in both tumours, directly transactivates cell genes. The EBNA-1 protein was tested for transcription transactivation domains and the human genome was screened for high-affinity EBNA-1-binding sites that might mediate transactivation.

Sleep apnea in CAPD.

Sleep disturbances are common complaints of dialysis patients, and sleep studies have suggested that sleep apnea may occur frequently. We performed sleep studies on 18 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Our results indicate that 6 of 18 patients (33%) had a respiratory disturbance index (RDI) greater than 15, which indicates severe sleep apnea.

Beneficial effects of culturing rabbit zygotes to blastocysts in 5% oxygen and 10% carbon dioxide.

Zygotes were collected from superovulated Dutch-belted rabbits 19 h after injection of LH and insemination. Oocytes that appeared to be unfertilized were discarded. The zygotes were distributed equally within each donor female across all culture treatments.

Epstein-Barr virus SM protein.

The protein products of the Epstein-Barr virus (EBV) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells. The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein. SM is a phosphoprotein in EBV-infected cells and can be phosphorylated in vitro with casein kinase II (CKII).

Effect of exercise training on the onset of type I diabetes in the BB/Wor rat.

The effects of regular exercise training on the onset and/or severity of hyperglycemia were studied in female diabetes-prone Biobreeding/Worcester (DP BB/Wor) rats. At 38-39 d of age, animals were weight-matched and randomly assigned to exercise-trained (T) and untrained (Unt) groups. The T rats exercised on a rodent treadmill at a moderate workload, 5 successive days with the 6th day being one of rest.

Newborn screening for cystic fibrosis in Wisconsin: first application of population-based molecular genetics testing.

Infants born in Wisconsin are being screened for cystic fibrosis (CF) associated with the F508 mutation. This screening program has been developed during 9 years of research supported by the National Institutes of Health and involves a unique, two-tier system employing measurement of immunoreactive trypsinogen (IRT) initially. When the IRT level is high, DNA is extracted from the neonatal dried blood specimen and analyzed for the F508 mutant allele, following polymerase chain reaction (PCR) amplification; the F508 mutation is present in more than 90% of CF patients and accounts for the common, severe form of the disease.

EBNA-2 and EBNA-LP cooperate to cause G0 to G1 transition during immortalization of resting human B lymphocytes by Epstein-Barr virus.

Epstein-Barr virus (EBV) is unusual among DNA tumour viruses in that the virus particle is able to infect and immortalize resting cells with very high efficiency. Mutation of the viral genome has indicated that at least six viral genes (LMP-1 and EBNAs 1, 2, 3A, 3C and LP) are essential for immortalization. We demonstrate that the activation of a G1 cyclin, cyclin D2, is an early event following infection with EBV and that cyclin D2 activation is dependent on the expression of viral genes.

Viruses and human cancer.

Epstein-Barr virus (EBV), hepatitis B virus (HBV), HTLV-I and some human papillomaviruses (HPVs) appear to contribute to the development of a large proportion of certain human cancers. Although the epidemiological evidence linking infection with these viruses to malignancies is generally convincing, only for the HPVs have experimental systems indicated a clear role for some of the HPV encoded genes in tumour cell growth. In these cases, molecular analysis is revealing the mechanisms by which the virally encoded oncogenes function to perturb the normal regulation of cell growth.

Epstein-Barr virus nuclear antigen EBNA3C/6 expression maintains the level of latent membrane protein 1 in G1-arrested cells.

The Epstein-Barr virus in the Burkitt lymphoma-derived cell line Raji has a deletion in the EBNA3C gene. When Raji cells are allowed to grow to high density and most of the cells become growth arrested in the G1 phase of the cell cycle, the level of detectable latent membrane protein 1 (LMP1) is substantially reduced. After dilution of the cells with fresh growth medium, within 8 h, there is a large increase in LMP1 mRNA, and by 12 h, LMP1 is expressed to a high level (H.

Influence of opioids in hypothalamic nuclei on cold thermogenesis of lean and obese LA/N-cp rats.

An overactive endogenous opioid peptide system (EOP) in the hypothalamus of the obese rats could contribute to a subnormal metabolic response to cold stress. Specific mu, delta, kappa opioid receptor antagonists and naloxone were infused into cannulaes aimed at the paraventricular nucleus (PVN) of awake freely moving obese (LA/N-cp corpulent) and lean littermate rats. Metabolic responses were measured by indirect calorimetry during thermoneutrality (30 degrees C) and at 10 degrees C for 60 minutes each.

Human and rodent muscle Na(+)-K(+)-ATPase in diabetes related to insulin, starvation, and training.

As determined by vanadate-facilitated [3H]ouabain binding to intact samples, semistarvation and untreated streptozotocin- or partial pancreatectomy-induced diabetes reduced rat soleus muscle Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) concentration by 12-21% (P < 0.05). Conversely, insulin treatment of rats with streptozotocin-induced diabetes induced an increase of 18-26% above control (P < 0.