High-intensity interval training has positive effects on performance in ice hockey players.

In spite of the well-known benefits that have been shown, few studies have looked at the practical applications of high-intensity interval training (HIIT) on athletic performance. This study investigated the effects of a HIIT program compared to traditional continuous endurance exercise training. 24 hockey players were randomly assigned to either a continuous or high-intensity interval group during a 4-week training program. The interval group (IG) was involved in a periodized HIIT program. The continuous group (CG) performed moderate intensity cycling for 45-60 min at an intensity that was 65% of their calculated heart rate reserve. Body composition, muscle thickness, anaerobic power, and on-ice measures were assessed pre- and post-training. Muscle thickness was significantly greater in IG (p=0.01) when compared to CG. The IG had greater values for both ∆ peak power (p<0.003) and ∆ mean power (p<0.02). Additionally, IG demonstrated a faster ∆ sprint (p<0.02) and a trend (p=0.08) for faster ∆ endurance test time to completion for IG. These results indicate that hockey players may utilize short-term HIIT to elicit positive effects in muscle thickness, power and on-ice performance.

An animal model of varicella virus infection.

Varicella-zoster virus (VZV) causes chickenpox in children; establishes latency in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster. VZV produces disease only in humans. Although attempts to produce disease and study VZV latency in experimentally infected animals have resulted in virus in trigeminal or dorsal root ganglia, no clinical signs of infection or reactivation developed. In contrast, simian varicella virus (SVV) produces a naturally occurring exanthematous disease in non-human primates that mimics human varicella. Experimental inoculation of non-human primates causes similar, if not identical, clinical and pathological changes observed in monkeys naturally infected with SVV. Like VZV, SVV becomes latent in ganglia and reactivates, often with entire body rash. SVV and VZV encode antigenically related polypeptides. Both virus genomes have been sequenced and shown to be colinear, sharing up to 75% DNA homology. During latency, an SVV homolog of one of the five VZV genes transcribed in latently infected human ganglia has been detected in monkey ganglia. Preliminary studies in which monkeys were inoculated intratracheally with SVV revealed the presence of viral DNA and RNA in multiple tissues, including blood mononuclear cells, months after experimental infection. These findings differed from the expected restricted localization of the virus DNA to ganglia only and the expected limited viral gene expression, and probably reflect the high virus load delivered intratracheally compared to natural SVV infection in monkeys. Nevertheless, clinical, pathological, and molecular similarities between SVV and VZV indicate that SVV infection in non-human primates has considerable potential as an animal model for human varicella.

Relationship between desensitization and sequestration of muscarinic cholinergic receptors in two neuronal cell lines.

Agonist-induced sequestration and desensitization of muscarinic receptors was studied in two cell lines that each express differentially-coupled receptors. The NG108-15 glioma x neuroblastoma hybrid cells have muscarinic receptors coupled only to the inhibition of adenylate cyclase, whereas SK-N-SH human neuroblastoma cells have muscarinic receptors coupled only to the turnover of phosphoinositide. In both NG108-15 and in SK-N-SH cells, muscarinic agonists caused a rapid, temperature-dependent, loss of binding sites for [3H] N-methylscopolamine. In contrast, the density of binding sites for [3H] quinuclidinyl benzilate remained almost unchanged after treatment with carbachol. Since carbachol also caused a redistribution of muscarinic receptors from the plasma membrane to a lighter membrane fraction, the loss of binding sites for [3H] N-methyl-scopolamine was interpreted as being due to sequestration of receptors. In addition to agonist-induced sequestration, muscarinic agonists also caused desensitization of the receptor-mediated response in NG108-15 cells. In SK-N-SH cells, however, no such desensitization of the receptor-mediated response was found, despite the agonist-induced sequestration of receptors. These findings demonstrate that agonist-induced sequestration of receptors does not always lead to desensitization of receptors.

Treatment of clinical experimental allergic encephalomyelitis in the rat with monoclonal antibodies.

An anti-CD4 monoclonal antibody of the IgG2a subclass, OX35, and an anti-I-A monoclonal antibody (IgG1) were used in vivo to treat experimental allergic encephalomyelitis in the Lewis rat. The anti-CD4 antibody was as effective in shortening the duration of the disease as the previously reported use of W3/25 (Brostoff and Mason, J. Neuroimmunol., 10 (1984) 331-340). It did not appear necessary for the antibody treatment to remove the CD4+ cells from the circulation in order to show an effect on the clinical course of the disease. The anti-I-A antibody did not have any noticeable effect in this disease model.

Treatment of clinical experimental allergic encephalomyelitis in the rat using fragments and combinations of monoclonal antibodies.

We reported previously that two different anti-CD4 monoclonal antibodies (W3/25, MRC OX35) were effective in treating experimental allergic encephalomyelitis in the Lewis rat whereas anti-I-A antibody was ineffective. Further studies with other monoclonal antibodies and fragments have now been performed. Anti-I-E antibody was ineffective in shortening the disease duration even when used in combination with anti-I-A antibody. Anti-CD2 (T11) antibody was marginally effective, shortening the duration of disease by only one day on the average. Combination of anti-CD4 antibody with anti-CD2 antibody did not improve the recovery time over the use of anti-CD4 antibody alone. On the other hand, the F (ab')2 fragment of the anti-CD4 antibody was as effective in the treatment of disease as the intact antibody molecule, indicating that it was sufficient to block the CD4 molecules on the cell surface of the EAE effector cells in order to affect the disease course.

Functional assays for protein C activity and protein C inhibitor activity in plasma.

An assay system for protein C (PC) activity and PC-inhibitor in plasma was developed. The assay was based on: (1) binding of PC to wells of a microtiter plate coated with a murine monoclonal anti-PC antibody (C3) that did not interfere with the activity or activation of PC; (2) activation of immobilized PC with Protac C; (3) incubation with or without a source of activated PC inhibitor; and (4) measurement of amidolytic activity using the substrate S-2366. The activity assay was specific for PC and sensitive to less than 1 microliter of plasma or 4 ng PC. Inhibition of activated PC by plasma followed pseudo first order kinetics. Heparin caused a dose dependent increase in the inhibition rate with half maximal stimulation at approximately 3 U/ml and maximal stimulation at heparin concentrations greater than or equal to 10 U/ml. This assay is suitable not only for determination of functional plasma levels of PC and PC inhibitor activities but also for kinetic studies of inhibition of activated PC in complex systems, such as plasma. Studies showed that urokinase interfered with the inhibition of APC by plasma inhibitor(s).

Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans.

We present evidence for elevated levels of heat shock protein 16 (HSP16) in an intrinsically thermotolerant, long-lived strain of Caenorhabditis elegans during and after heat stress. Mutation of the age-1 gene, encoding a phosphatidylinositol 3-kinase catalytic subunit, results in both extended life span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphrodites. We subjected age-synchronous cohorts of worms to lethal and nonlethal thermal stress and observed the accumulation of a small (16-18 kd) heat-shock-specific polypeptide detected by an antibody raised against C. elegans HSP16. Strains carrying the mutation hx546 consistently accumulated HSP16 to higher levels than a wild-type strain. Significantly, overaccumulation of HSP16 in the age-1(hx546) strain following heat was observed throughout the adult life span. A chimeric transgene containing the Escherichia coli beta-galactosidase gene fused to a C. elegans HSP16-41 transcriptional promoter was introduced into wild-type and age-1(hx546) backgrounds. Heat-inducible expression of the transgene was elevated in the age-1(hx546) strain compared with the wild-type strain under a wide variety of heat shock and recovery conditions. These observations are consistent with a model in which Age mutations exhibit thermotolerance and extended life span as a result of elevated levels of molecular chaperones.

Purification of three arginine esterases from the venom of the Western Diamondback rattlesnake (Crotalus atrox).

Three acidic arginine esterases have been isolated from the venom of the Western Diamondback rattlesnake (Crotalus atrox). These components demonstrated marked differences in ionic characteristics, as noted by KCl gradient elution from a DEAE-Sephadex A-50 column. Molecular weights, as determined from gel permeation chromatography, were estimated at 25,100 (fraction D), 24,000 (B); and 22,900 (F) for the three separate enzymes. The two larger enzymes (B and D) exhibited similar activities toward the synthetic substrates alpha-N-benzoyl-L-arginine ethyl ester and alpha-N-benzoyl-DL-arginine-p-nitroanilide. Hydrolysis rates were similar to commercial trypsin preparations. Fraction F exhibited a markedly lower activity as an arginine esterase and negligible activity as an arginine amidase. Arginine esterase activity was evident for all three enzymes in the presence of ethylenediamine tetra-acetic acid.

Comparisons of African American and White women in the parent care role.

Little is known about African American women's experiences providing care to impaired older relatives. This study investigated potential differences in depressive symptomatology, parent care stress and rewards, parent care mastery, and the quality of the parent care relationship between 261 White and 56 African American daughters and daughters-in-law who were providing care for an impaired parent or parent-in-law. Multivariate analysis of variance, controlling for significant background characteristics and interrelationships among caregiving experiences, revealed that African American women reported less stress and more rewards in the parent care role than White women did. Race did not have a significant effect on caregivers' depressive symptomatology, parent care mastery, or the quality of their relationship with the parent. However, this research demonstrates the importance of examining a broad range of caregiving experiences in order to detect both similarities and differences between African American and White caregivers.

Conformance of clinical practice to established recommendations for the diagnosis and treatment of venous thromboembolic disease: Robin revisited.

Over a decade ago, Dr. Robin expressed concern regarding overdiagnosis and overtreatment of pulmonary embolism. Since that time, significant advances have been forthcoming in the diagnosis and treatment of venous thromboembolic disease. Using Continuous Quality Improvement concepts, this study revisits Robin's concerns and assesses the conformance of clinical practice at one institution with established requirements for the diagnosis and treatment of venous thromboembolic disease to identify remaining opportunities to improve care. The study design is a retrospective chart review. Medical records of all patients (N = 63) discharged from a university-affiliated teaching hospital from 7/1/89 to 6/30/90 with a diagnosis of primary venous thromboembolic disease were studied. Requirements for the diagnosis and treatment were established through review of the medical literature. Conformance to these requirements was assessed and described. Descriptive statistics were used. Only 7 of 63 charts (11%) met all requirements for the diagnosis and treatment of venous thromboembolic disease. Fifty-six charts (89%) failed to meet at least one criterion. There was no evidence of overdiagnosis of venous thromboembolic disease in patients with a discharge diagnosis of pulmonary embolism (N = 17). Eight of 62 patients (13%) demonstrated potential overdiagnosis of venous thromboembolic disease involving the lower extremities. Nine of 60 (15%) heparin therapies demonstrated significant nonconformance to recommendations. Fifty-four of 59 (91%) warfarin therapies failed to conform to recommendations. Eighty-three percent of these warfarin errors were considered to be technical. However, 17% were determined to be clinically significant. Of 5 patients treated with a transvenous filter device, 1 failed to meet therapeutic requirements. No patients received thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The capture and use of detailed process information in the Dialogix system for structured web-based interactions.

Information gathering tools, such as questionnaires, surveys, and structured interviews, are ubiquitously used in evaluating patients and systems. Despite their common use, there is a desperate need for better questionnaires in medical research and epidemiology, and an infrastructure that lets them be publicly scrutinized. Unfortunately, there has been no common platform that supports the deployment of arbitrary information gathering tools. Some psychiatric diagnostic interviews and epidemiological trials require sophisticated structured interviews containing complex branching logic, dynamic phrase composition, and multiple languages. The Dialogix system was developed to meet this need and facilitate the rapid definition and web-based deployment of structured human-computer interactions. This paper describes the content and process-related information captured by Dialogix, and how that information has been used in the development and deployment of two large epidemiological studies.

Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3.

Two monoclonal antibodies, designated MRC OX-41 and MRC OX-42, have been shown to label subsets of macrophages. Using immunoperoxidase and immunofluorescence analysis, tissue macrophages were shown to be heterogeneous with respect to binding of MRC OX-41 and MRC OX-42 antibodies. Although both antibodies labelled subsets of macrophages, the antibodies also reacted with granulocytes and dendritic cells. The antigens recognized by these antibodies were identified by metabolic and cell surface labelling followed by immunoprecipitation and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MRC OX-41 recognized a surface protein of 110,000-120,000 MW, while MRC OX-42 immunoprecipitated three polypeptides with molecular weights of 160,000, 103,000 and 95,000. The Fab fragment of MRC OX-42 antibody inhibited complement-mediated rosette formation between sensitized erythrocytes and rat macrophages and granulocytes. Membrane molecules with similar biochemical and functional properties to MRC OX-42 antigen have been identified in mouse and man as the receptors for iC3b, and it is probable that MRC OX-42 antibody recognizes the rat homologue of the receptors in these other species.

MRC OX-43: a monoclonal antibody which reacts with all vascular endothelium in the rat except that of brain capillaries.

A mouse monoclonal antibody, MRC OX-43, has been shown to label vascular endothelium in all tissues of the rat except that of brain capillaries. Using immunoperoxidase staining, the antigen was shown to be expressed on the luminal surface of blood vessels. In addition, this antibody recognized a surface antigen on circulating erythrocytes and some macrophage populations, namely all those in the peritoneal cavity and a subset of alveolar macrophages. The antigen recognized by this antibody was identified on macrophages by metabolic and cell surface labelling followed by immunoprecipitation and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and found to be a surface protein of 90,000 MW.

Identification of simian varicella virus homologues of varicella zoster virus genes.

Clinical, pathologic, immunologic and virologic features of simian varicella virus (SVV) infection in primates resemble human varicella-zoster virus (VZV) infection. Further, the SVV and VZV genomes are similar in size and structure, show striking homology in their configuration and DNA sequences, and encode antigenically related polypeptides. Although the entire VZV genome is present during latency in human ganglia, transcription is limited. VZV genes 21, 29, 62 and 63 are transcribed during latency, while genes 4, 10, 40, 51 and 61 are not transcribed. The entire VZV genome has been sequenced, but the SVV genome has not. Thus, to analyze SVV genes transcribed during latency, we have begun to identify SVV homologues of the above VZV genes. We used nick-translated [32p]-labeled-VZV open reading frame (ORF)-specific probes to screen Southern blots containing EcoRI-digested SVV genomic DNA and recombinant clones of SVV EcoRI and BamHI DNA fragments spanning approximately 97% of the virus genome. We showed that SVV homologues of VZV ORFs 4, 10, 29, 40, 51 and 61 mapped to SVV DNA fragments EcoRI I, A, N, BamHI E, EcoRI D and E, respectively. We also confirmed earlier reports that SVV homologues of VZV genes 21 and 63 mapped to SVV EcoRI DNA fragments H and C, respectively. Viral genes on the SVV and VZV genomes seem to be collinear.

Thermotolerance of a long-lived mutant of Caenorhabditis elegans.

Age-synchronous cohorts of Caenorhabditis elegans were grown at 20 degrees C, then stressed at 30 degrees C or 35 degrees C. Intrinsic thermotolerance of wild type and age-1 mutant strains was assessed by measuring either progeny production or survival. In addition to increased life span (Age), mutation of age-1 results in a highly significant increased intrinsic thermotolerance (Itt) as measured by survival at 35 degrees C. Mean survival of Age strains is approximately 45% longer than that of non-Age strains for both sterile and nonsterile worms. Thermotolerance declines across the life span of both Age and non-Age strains, but Itt was observed at almost all ages. Unstressed age-1 animals showed a consistent and significant fertility deficit. Short thermal stresses can cause a dramatic reduction in progeny production for both Age and non-Age genotypes. Mutants of age-1 showed a small but consistent increased thermotolerance as measured by fertility. We propose that the enhanced ability of Age strains to cope with environmental stress may be mechanistically related to their lower age-specific mortality rates.

Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress.

We have discovered that three longevity mutants of the nematode Caenorhabditis elegans also exhibit increased intrinsic thermotolerance (Itt) as young adults. Mutation of the age-1 gene causes not only 65% longer life expectancy but also Itt. The Itt phenotype cosegregates with age-1. Long-lived spe-26 and daf-2 mutants also exhibit Itt. We investigated the relationship between increased thermotolerance and increased life-span by developing conditions for environmental induction of thermotolerance. Such pretreatments at sublethal temperatures induce significant increases in thermotolerance and small but statistically highly significant increases in life expectancy, consistent with a causal connection between these two traits. Thus, when an animal's resistance to stress is increased, by either genetic or environmental manipulation, we also observe an increase in life expectancy. These results suggest that ability to respond to stress limits the life expectancy of C. elegans and might do so in other metazoa as well.