The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B.

The Us3 kinase is part of the antiapoptotic arsenal that salvages herpes simplex virus (HSV)-1-infected cells from damage caused by different stimuli. We demonstrate that Us3 protects HSV-1-infected cells from lysis by MHC class I-restricted CD8T cells without affecting antigen presentation. Expression of Us3 was associated with inhibition of caspase activation and reduced cleavage of the proapoptotic protein Bid.

Technological changes in the management of prostate cancer result in increased healthcare costs--a retrospective study in a defined Swedish population.

Objective: In two previous studies we calculated direct costs for men with prostate cancer who died in 1984-85 and 1992-93, respectively. We have now performed a third cost analysis to enable a longitudinal cost comparison. The aim was to calculate direct costs for the management of prostate cancer, describe the economic consequences of technological changes over time and estimate total direct costs for prostate cancer in Sweden.

Intracellular pathways involved in upregulation of vascular endothelin type B receptors in cerebral arteries of the rat.

Background And Purpose: Previous studies have shown that contractile endothelin type B (ETB) receptors are upregulated in cerebral arteries after experimental focal cerebral ischemia. The aim of this study was to examine the upregulation of contractile ETB receptors in cerebral arteries after organ culture and to elucidate the intracellular pathways involved.

Methods: Rat middle cerebral arteries (MCAs) were incubated with or without inhibitors.

Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene.

Reconstitution of telomerase activity by ectopic expression of telomerase reverse transcriptase (hTERT) results in an immortal phenotype in various types of normal human cells, including fibroblasts. Despite lack of transformation characteristics, it is unclear whether hTERT-immortalized cells are physiologically and biochemically the same as their normal counterparts. Here, we compared the gene expression profiles of normal and hTERT-immortalized fibroblasts by using a cDNA microarray containing 20,736 cDNA clones and identified 172 dysregulated genes or expressed sequence tags (ESTs).

Does the functional reach test reflect stability limits in elderly people?

Objective: To explore how the Functional Reach test correlates with the displacement of the centre of pressure and whether the test is a measure of the stability limits in healthy elderly people. Also to explore the performance parameters during the Functional Reach test.

Design: Method comparison study.

The Mad and Myc basic domains are functionally equivalent.

The Myc/Max/Mad family of transcription factors plays a fundamental role in the regulation of cell proliferation, oncogenic transformation, and cell differentiation. However, it remains unclear whether different heterodimers, such as Myc/Max and Mad/Max, recognize the same or different target genes in vivo. We show by chromatin immunoprecipitation that Myc target genes are also recognized by Mad1 in differentiated HL60 cells.

A nonphosphorylated 14-3-3 binding motif on exoenzyme S that is functional in vivo.

14-3-3 proteins play an important role in a multitude of signalling pathways. The interactions between 14-3-3 and other signalling proteins, such as Raf and KSR (kinase suppressor of Ras), occur in a phospho-specific manner. Recently, a phosphorylation-independent interaction has been reported to occur between 14-3-3 and several proteins, for example 5-phosphatase, p75NTR-associated cell death executor (NADE) and the bacterial toxin Exoenzyme S (ExoS), an ADP-ribosyltransferase from Pseudomonas aeruginosa.

Molecular effects of proinsulin C-peptide.

The proinsulin C-peptide has been held to be merely a by-product in insulin biosynthesis, but recent reports show that it elicits both molecular and physiological effects, suggesting that it is a hormonally active peptide. Specific binding of C-peptide to the plasma membranes of intact cells and to detergent-solubilised cells has been shown, indicating the existence of a cell surface receptor for C-peptide. C-peptide elicits a number of cellular responses, including Ca(2+) influx, activation of mitogen-activated protein (MAP) kinases, of Na(+),K(+)-ATPase, and of endothelial NO synthase.

Exoenzyme S shows selective ADP-ribosylation and GTPase-activating protein (GAP) activities towards small GTPases in vivo.

Intracellular targeting of the Pseudomonas aeruginosa toxins exoenzyme S (ExoS) and exoenzyme T (ExoT) initially results in disruption of the actin microfilament structure of eukaryotic cells. ExoS and ExoT are bifunctional cytotoxins, with N-terminal GTPase-activating protein (GAP) and C-terminal ADP-ribosyltransferase activities. We show that ExoS can modify multiple GTPases of the Ras superfamily in vivo.

Range of motion training in brace vs. plaster immobilization after anterior cruciate ligament reconstruction: a prospective randomized comparison with a 2-year follow-up.

The purpose of this prospective and randomized study was to compare rehabilitation with early range of motion (ROM) training vs immobilization following anterior cruciate ligament (ACL) reconstruction. Fifty patients, undergoing an ACL reconstruction with a bone-patellar tendon-bone graft, were postoperatively allocated randomly to either a plaster cast or a brace for 5 weeks. The brace group had ROM exercises from postoperative day 7.

Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells.

This study addresses the interactions between the adaptor protein Shb and components involved in T cell signalling, including SLP-76, Gads, Vav and ZAP70. We show that both SLP-76 and ZAP70 co-immunoprecipitate with Shb in Jurkat T cells and that Shb and Vav co-immunoprecipitate when cotransfected in COS cells. We also demonstrate, utilizing fusion protein constructs, that SLP-76, Gads and Vav associate independently of each other to different domains or regions, of Shb.

The histone deacetylase inhibitor trichostatin A derepresses the telomerase reverse transcriptase (hTERT) gene in human cells.

Activation of telomerase, essential for cellular immortalization and transformation, requires the induction of its catalytic component, telomerase reverse transcriptase (hTERT). However, biochemical and genetic mechanisms for the control of hTERT expression remain undefined. In the present study, we demonstrate that the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) induces hyperacetylation of histones at the hTERT proximal promoter, directly transactivates the hTERT gene in normal human telomerase-negative cells, and upregulates hTERT expression in telomerase-positive tumor cells.

Adult schizotypal personality characteristics and prenatal influenza in a Finnish birth cohort.

Recent evidence suggests that schizophrenia may result from a disruption of normal brain development during a critical, prenatal risk period in the 6th month of gestation. The phenotypic diagnostic manifestation of a basic genetic-neurodevelopmental disorder may consist of characteristics approximated by the DSM-IV diagnosis of "schizotypal personality disorder" (SPD). We identified male conscripts in Finland who, as fetuses, were exposed to the 1969 Hong Kong Influenza epidemic, along with a group of controls born during a relatively low year (1971) for infectious epidemics.

Depressive symptoms in middle-aged women are more strongly associated with physical health and social support than with socioeconomic factors.

The association of socioeconomic factors, health-related factors, and social support with depressive symptoms has been extensively studied. However, most epidemiological studies have focused on a few factors such as marital status, social class, and employment. In this study of middle-aged women we analyzed both univariate and multivariate associations of socioeconomic factors, perceived physical health factors, and social support with self-rated depressive symptoms measured with the Beck Depression Inventory.

Repression of in vivo growth of Myc/Ras transformed tumor cells by Mad1.

The Myc/Max/Mad network of transcriptional regulatory proteins plays an essential role in cell proliferation, growth, apoptosis, and differentiation. Whereas Myc proteins affect cell cycle progression positively, Mad proteins are negative regulators of cell proliferation. It has been shown in several in vitro systems that Mad proteins antagonize c-Myc functions.

Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.

Background: In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors.

Methods: We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice.

c-myc Suppression in Burkitt's lymphoma cells.

The purpose of the study was to elucidate how DNA tetraplex (also referred to as G-quadruplex)-forming oligonucleotides mediate suppression of the human c-myc gene at the level of transcription initiation. A 22-base-long oligonucleotide, which is rich in guanines and folds into an intrastrand DNA tetraplex under physiological conditions, was administered to a Burkitt's lymphoma cell line overexpressing a (8:14) translocated c-myc allele. Administration of the oligonucleotide at nanomolar concentrations to the surrounding medium resulted in efficient cellular uptake, and was accompanied by a substantial concentration- and conformation-dependent decrease in growth rate.

Differential expression of class I HDACs: roles of cell density and cell cycle.

Enzymes which affect histone acetylation status have been shown to play an important role in determining transcriptional activity in chromatin through conformational modification of its structure. Since the timely presence of such enzymes may be of critical importance, our experiments were designed to determine whether the level of expression of HDAC1 is cell cycle dependent and/or affected by a high cell density. Our results show that in mouse fibroblasts the expression of mHDAC1 is neither affected by cell cycle phases nor by cell density.

Postural control after anterior cruciate ligament reconstruction and functional rehabilitation.

Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months (range, 27 to 44) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects. Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance, double-legged stance, or both, with the eyes open and closed. Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open.

C-peptide binding to human cell membranes: importance of Glu27.

In addition to its established role in proinsulin folding, C-peptide has a function in regulation of cellular activity. The 31-residue peptide influences renal, vascular, and metabolic functions in patients with insulin-dependent diabetes mellitus. Binding to cells has been demonstrated for C-peptide, which can be displaced by its C-terminal pentapeptide.