Hemophilia gene therapy knowledge and perceptions: Results of an international survey.

Background: Hemophilia gene therapy is a rapidly evolving therapeutic approach in which a number of programs are approaching clinical development completion.

Objective: The aim of this study was to evaluate knowledge and perceptions of a variety of health care practitioners and scientists about gene therapy for hemophilia.

Methods: This survey study was conducted February 1 to 18, 2019.

Survey of ionospheric Pc3-5 ULF wave signatures in SuperDARN high time resolution data.

Ionospheric signatures of ultra-low frequency (ULF) wave in the Pc3-5 band (1.7-40.0 mHz) were surveyed using ~6 s resolution data from Super Dual Auroral Radar Network (SuperDARN) radars in the northern hemisphere from 2010 to 2016.

Charged dust phenomena in the near-Earth space environment.

Dusty (or complex) plasmas in the Earth's middle and upper atmosphere ultimately result in exotic phenomena that are currently forefront research issues in the space science community. This paper presents some of the basic criteria and fundamental physical processes associated with the creation, evolution and dynamics of dusty plasmas in the near-Earth space environment. Recent remote sensing techniques to probe naturally created dusty plasma regions are also discussed.

Multiscale coherent structures and broadband waves due to parallel inhomogeneous flows.

Linear theory analysis and particle-in-cell simulations show that a spatial transverse gradient in the ion drift parallel to the magnetic field, dV(di)/dx>Omega(i). Nonlinearly, these waves lead to multiscale spatially coherent structures, substantial cross-field transport, ion energization, and phase-space diffusion. Large spikes are formed in the parallel electric field time series.

The national learning disabilities postsecondary data bank: an overview.

A survey was developed to assess support services, procedures, policies, the proportion of students with learning disabilities (LD), and the factors that affect differences in proportion in a nationally representative sample of postsecondary institutions (PSIs). The factors investigated included general characteristics about the PSI, such as size of the student body and type of PSI. The specific characteristics investigated in regard to LD were admissions procedures, year of initiation of LD support services, type and location of support services, eligibility criteria for services and accommodations, the number of students with LD, and demographic and diagnostic information available.

Tumor necrosis factor alpha alters the cytotoxic effect of hydrogen peroxide in cultured hepatocytes.

We examined whether tumor necrosis factor-alpha (TNF) affects the cytotoxic capacity of reactive oxygen species on rat hepatocytes in culture. Both TNF and reactive oxygen species are involved in many inflammatory events including hepatic ischemia/reperfusion injury and endotoxic shock. Synchronous treatment of hepatocytes with both TNF and H2O2 demonstrated that TNF (2000 ng/ml) enhanced the cytotoxic effect of H2O2 (500 microM).

Adults with learning disabilities: occupational and social status after college.

Forty-nine adults with learning disabilities who had attended a large public university between 1980 and 1992 were interviewed about their current employment and social status. Most of the respondents had adjusted well to the demands and complexities of adulthood. More than 80% of the participants not still in college at the time of the interview were employed, mostly in white collar jobs.

Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver.

A bidirectional communication exists between the nervous system and the immune system. Evidence has accumulated suggesting that cytokines-immune peptides influence sympathetic neuronal survival and that cytokines can promote the secretion of catecholamines. Using an isolated perfused rat liver (IPRL) preparation, we have shown that the liver is an important source of circulating cytokines in response to lipopolysaccharide (LPS) and that corticosterone dose dependently influenced LPS-induced production of tumor necrosis factor (TNF) and interleukin-6 (IL-6).

Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver.

Using an isolated perfused rat liver (IPRL) preparation, we assessed whether corticosterone may contribute to the rise in tumor necrosis factor (TNF) and interleukin-6 (IL-6) in rats after injection with lipopolysaccharide (LPS) or exposure to psychological stress. Intravenous infusion of LPS into the IPRL led to dose-dependent increases in TNF and IL-6 concentrations in the effluent. Anisomycin, a protein synthesis inhibitor, completely blocked the rise in TNF and IL-6 concentration in the IPRL effluent, supporting the hypothesis that the synthesis (or release) of these cytokines was dependent on protein synthesis.

Hepatic ischemia/reperfusion injury: importance of oxidant/tumor necrosis factor interactions.

Previous studies have demonstrated a role for both tumor necrosis factor (TNF) and reactive oxygen intermediates (ROI) in hepatic ischemia/reperfusion (I/R) injury. Biologically active TNF was present in liver homogenates in ischemic and nonischemic lobes after 2 h of ischemia but without reperfusion. Using an in situ liver perfusion model, we measured ROI, TNF, and hepatic enzymes in the effluent after 2 h of ischemia.

Tumor necrosis factor, interleukin 6, and the acute phase response following hepatic ischemia/reperfusion.

We report here the production of systemic levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) and associated changes in serum macroglobulin to albumin ratios in a nonlethal rat model of partial hepatic ischemia/reperfusion (I/R). Plasma IL-6 was detectable and elevated at 1 hr of reperfusion as compared to sham-operated controls (I/R rats = 12,100 +/- 3860 pg/ml; sham rats = 5260 +/- 842 pg/ml; IL-6 values = means +/- SEM) and reached maximal levels at 6 hr of reperfusion (I/R rats = 47,400 +/- 25,700 pg/ml; sham rats = 3370 +/- 394 pg/ml), in contrast to maximal TNF levels at 30 min of reperfusion (I/R rats = 72 +/- 15 pg/ml; sham rats = 2 +/- 2 pg/ml; TNF values = means +/- SEM). Pretreatment with neutralizing TNF antisera prior to ischemia resulted in a reduction of IL-6 at 1 hr of reperfusion (anti-TNF = 3870 +/- 2550 pg/ml; control serum = 7650 +/- 1670 pg/ml), but was without effect on IL-6 levels at subsequent time points over the 24 hr of reperfusion.

Interleukin-6 (IL-6) gene expression and secretion by cytokine-stimulated human retinal pigment epithelial cells.

Retinal and choroidal inflammatory lesions are important causes of visual loss, but the mechanisms regulating intraocular inflammation remain poorly understood. By virtue of its position at the blood-retina barrier, the retinal pigment epithelium (RPE) cells may be critical to the initiation and propagation of ocular inflammation. Previously we showed that cytokine-stimulated RPE cells produce interleukin-8, a well-defined chemotactic factor for neutrophils and lymphocytes.

Interleukin-6 expression in immunologically elicited murine macrophages.

We report the expression of both interleukin-6 (IL6) messenger RNA and biological activity in complete Freund's adjuvant-elicited peritoneal macrophages (CFA-M phi). IL6 mRNA expression peaked between 4 and 8 h of lipopolysaccharide (LPS) stimulation; biological activity was maximal at approximately 18 h of stimulation. LPS-induced IL6 mRNA was inhibited by treatment with cycloheximide (5 micrograms/ml), implicating the participation of a secondary protein mediator in the induction process, or the dependence upon protein synthesis for receptor ligand interactions.

In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell expression, and glucocorticoid effects.

Using a model of sepsis induced by parenteral challenge of mice with bacterial lipopolysaccharide (LPS), the authors analyzed the in vivo expression of interleukin-1 (IL-1) alpha,beta and tumor necrosis factor (TNF). Both TNF and IL-1 alpha,beta were detected in hepatic sinusoidal macrophages (Kupffer cells), immunohistochemically. Kinetic analysis showed a clear sequence of synthesis.

Regulation of monokine gene expression: prostaglandin E2 suppresses tumor necrosis factor but not interleukin-1 alpha or beta-mRNA and cell-associated bioactivity.

Prostaglandin E2 (PGE2)-mediated suppression of macrophage interleukin-1 alpha,beta and tumor necrosis factor-alpha synthesis was examined at the cellular and molecular levels. Treatment of lipopolysaccharide (LPS)-stimulated adjuvant-elicited murine macrophages with 5 x 10(-7) M PGE2 caused a 70% reduction in cell-associated TNF but had no suppressive effect on cell-associated interleukin-1 (IL-1) activity. Consistent with this result, Northern blot and nuclear transcription analyses demonstrated suppression of TNF mRNA but PGE2 had no effect on IL-1 alpha and IL-1 beta mRNA accumulation, as compared to LPS controls.

In situ hybridization analysis of macrophage-derived tumor necrosis factor and interleukin-1 mRNA.

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) play an intimate role in the initiation and maintenance of inflammatory reactions due to their pluripotent activities. In this paper, we describe the use of an in situ hybridization analysis as an effective means to probe for TNF and IL-1 mRNA levels in primary macrophage cultures and macrophage cell lines. A significant increase in lipopolysaccharide (LPS)-induced TNF mRNA accumulation was demonstrated by in situ hybridization using either a 35S-labeled synthetic oligonucleotide (30-mer) complementary to TNF mRNA or a 35S-randomly primed labeled TNF DNA probe.

Human circadian rhythms in temperature, trace metals, and blood variables.

The literature supports the concept that circadian changes in body temperature reflect changes in the thermoregulatory set point. We were interested in studying the relationship between the circadian rhythm in body temperature and 24-h variations in plasma concentrations of iron, zinc, circulating leukocyte counts, and plasma interleukin 1 (IL-1) activity. Eight healthy men were studied for two separate 48-h sessions.

Effect of antipyretic drugs on circadian rhythm in body temperature of rats.

In many species, including the laboratory rat, body temperature varies on a circadian (24 h) basis. There is considerable evidence that the circadian rise in body temperature is attributable to an elevation in thermoregulatory set point. We hypothesized that this rise in set point may be mediated by prostaglandins.

Low-molecular-weight substance in peritoneal exudate is antibacterial at febrile temperature.

Peritoneal exudate was collected from rabbits 18 hr after ip injection of shellfish glycogen. The fluid was centrifuged and the peritoneal exudate supernatant (PES) retained for use in growth studies. The growth of Pasteurella multocida in PES was inhibited at 41 degrees C (febrile temperature for rabbits) as compared with 39 degrees C (afebrile temperature), suggesting the presence of an antibacterial agent active at febrile temperature.

Intestinal absorption in Saudi Arabia: an evaluation of the one hour blood xylose test.

The screening value of the one-hour blood xylose test, corrected for body surface area, was prospectively studied in Saudi Arabian adults and children under investigation for suspected intestinal malabsorption. Sensitivity of discrimination between patients with and without upper small bowel disease was 91%, compared to 85% for the five-hour urine xylose test. Primary small bowel disorder was rare.

Purification and characterization of a glycosyltransferase complex from the culture broth of Streptococcus mutans FA1.

The extracellular glycosyltransferases from Streptococcus mutans FA1 were purified by using the following procedures: ammonium sulfate precipitation, poly-(acrylamide) gel filtration, DEAE-cellulose chromatography, and agarose-gel filtration. The dextransucrase and levansucrase activities were purified 350- and 500-fold, repsectively, and the ratio of the two activities remained almost constant throughout the purification. Both enzymes have a pH optimum of 6.