Differences in the stimulation of NO synthesis during heat shock in genetically different rats]

OBJECTIVES: In certain younger patients with congestive heart failure (CHF), Doppler/echocardiography has identified a "restrictive" pattern of early diastolic ventricular filling characterized by very rapid early filling and a steep deceleration slope. We asked whether a similar restrictive pattern can be identified in very old patients with CHF, and if so, what are its clinical correlates and prognostic implications. DESIGN: Retrospective cohort with prospective follow-up. SETTING: Academic long-term care facility. PARTICIPANTS: Thirty-nine residents with clinical CHF (age 89 +/- 5 (SD) years) MEASUREMENTS: Transmitral Doppler flow, clinical characteristics, recurrent CHF episodes, hospitalizations, and mortality were measured. RESULTS: Fifteen (38%) of the subjects had restrictive filling patterns, characterized by a ratio of early to late flow (E/A) > 1.00 and 24 (62%) had nonrestrictive patterns. The restrictive pattern was associated with a longer duration of CHF, more angina, and higher rate of symptomatic recurrences of CHF. CONCLUSION: A restrictive diastolic filling pattern may represent a late stage in the evolution of congestive heart failure when left ventricular filling pressure is markedly increased. The treatment of CHF in older patients may need to account for different patterns of diastolic filling.     

Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis

The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role of T cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC-E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 36-49 and OGDC-E2 peptide 100-113 thereby identifying a common T cell epitope "motif" ExETDK. The peptide 163-176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.     

Beliefs about smoking and diabetes care

PURPOSE: Wrestlers often engage in unhealthy practices to achieve a low body weight for competition. This study examined beliefs, practices, and potential support systems to promote safe weight loss among scholastic wrestlers. METHODS: A written questionnaire was developed and administered to all nine high school wrestling teams in one rural county. Responses were obtained from 197 wrestlers. RESULTS: Most wrestlers reported that "making weight" was very important. Increased activity and decreased food intake were the most frequent weight loss methods. Unsafe methods such as vomiting and use of laxatives were sometimes used, even though many wrestlers recognized these practices were unhealthy and decreased performance. Personal desire to win, coaches, and teammates were reported to be the greatest influences on weight loss efforts. Wrestlers believed that coaches and physicians were the most accurate sources of weight loss information. CONCLUSION: Nutrition counseling which goes beyond simply providing information about the risk of rapid weight loss among adolescent wrestlers is needed. Emphasis on motivating wrestlers to adopt healthy weight management strategies is important. Wrestlers perceive physicians as credible sources of information, and physicians should become more actively involved in educating both coaches and athletes about safe weight management.     

Self-reported hearing problems in daily life throughout adulthood

The authors assessed age differences on self-reported hearing problems on the performance of auditory tasks in the natural environment. The Your Hearing questionnaire was administered to 265 respondents (aged 20-94 years). Both the degree and variability of self-reported hearing problems were found to increase significantly with age, including those associated with listening to speech under conditions of background noise, the perception of normal and distorted speech, and the perception of short segments of speech and the perception of high-pitched sounds. Experienced hearing problems were greater for Ss who judged their hearing as being of poor quality. Findings suggest that self-report measures can provide valuable insights into the impact of age-related hearing disability on daily life that are not provided by more traditional laboratory-based studies.     

Decreased cell-mediated immunity and lack of skeletal problems in broiler chickens consuming diets amended with fusaric acid

Young female broiler chickens fed diets amended with 0, 35, 75, and 150 mg fusaric acid (FA)/kg diet for 3 weeks showed no aberrations in behavior, feed intake, weight gain, or appearance of the visceral organs. Furthermore, there was no correlation between the dietary concentration of FA and incidence of tibial dyschondroplasia and leg-shape deformities. Ash content of dry fat-free tibiae was not influenced by FA; thus, no rickets was present in these chickens. FA enhanced the humoral response to sheep erythrocytes but significantly reduced cell-mediated cutaneous response to phytohemagglutinin-P.     

The role of gentle ventilation in prevention of subglottic stenosis in the newborn

Although stuttering has long been acknowledged as a familial disorder, the nature of a genetic component remains unclear. Most previous data used in genetic studies were obtained primarily from adults who stutter and may be biased in several respects. The purpose of this investigation was to quantify the frequency of stuttering in relatives of preschool-age children who stutter, and who were first seen close to the onset of the disorder. Detailed pedigrees (family trees), including first-, second-, and third-degree relatives, were obtained from parents of 69 children who stuttered. We found, as have previous studies, that more male than female relatives ever stuttered, but that female subjects who stuttered had more female relatives who ever stuttered than did male subjects. In order to identify the genetic model most consistent with the observed patterns of stuttering transmission, we conducted segregation analyses. Results from these analyses suggest that transmission of a single major genetic locus increasing the liability to stuttering best accounts for the transmission of stuttering in families of preschool-age children who stutter.     

Transmembrane signaling by the interleukin-2 receptor: progress and conundrums

Activation of the multicomponent interleukin-2 receptor (IL-2R) complex leads to a rapid increase in tyrosine phosphorylation of a number of cellular proteins including the IL-2R beta and IL-2R gamma chains of the IL-2R and the RAF-1 serine threonine kinase. In addition, phosphatidylinositol 3-kinase (PI-3K) protein and activity can be immunoprecipitated with anti-phosphotyrosine and anti-IL-2R beta antibodies from IL-2-activated but not resting T lymphocytes. We have demonstrated that the SH2 (SRC homology 2) domains of the 85 kDa subunit of PI-3K are sufficient to mediate binding of the PI-3K complex to tyrosine phosphorylated, but not non-phosphorylated IL-2R beta, suggesting that tyrosine phosphorylation is an integral component of the activation of PI-3K by the IL-2R. Since none of the members of the IL-2R complex contains an intrinsic tyrosine kinase domain, IL-2-induced tyrosine phosphorylation must be the consequence of activation of intracellular tyrosine kinases. SRC family members including lck, lyn and fyn have been demonstrated to associate with IL-2R beta through binding of the kinase domain to the acidic domain of IL-2R beta. However, we have demonstrated that the serine rich (SD) region of the cytosolic domain of IL-2R beta is also required for association of a tyrosine kinase with the IL-2R complex and that IL-2 can induce proliferation and tyrosine phosphorylation in cell lines which lack the known SRC family kinases expressed by T lymphocytes. Thus members of other kinase families besides SRC may also be involved in mediating IL-2 signal transduction. Biochemical studies and studies of cells expressing mutant IL-2 receptors indicate that IL-2-induced tyrosine kinase activation initiates a complex signaling cascade. The cascade includes SRC family kinase members such as lck, fyn, and lyn, activation of Raf-1 and PI-3K, and ras, and increased expression of the fos, fra-1, and jun protooncogenes. In addition, ligation of the IL-2R leads to rapid increases in myc expression and more delayed increases in the expression of the cdc2 and cdk2 kinases and the cyclins through a tyrosine phosphorylation independent pathway. Whether other biochemical processes initiated by IL-2R ligation, including activation of the MAP2, p70S6 and p90RSK serine threonine kinases, activation of NF-kappa B, and increased expression of Raf-1, Pim-1, bcl-2, IL-2R alpha and IL-2R beta, are consequences of the IL-2-induced tyrosine kinase cascade remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized, controlled trials

OBJECTIVE: Reducing serum cholesterol lowers the risk for ischemic heart disease, but its effects on other vascular diseases are unknown. Published trials were reviewed to determine the effect of cholesterol-lowering interventions on fatal and nonfatal stroke. DESIGN: Meta-analysis of randomized, controlled trials. DATA IDENTIFICATION: A literature search of English-language studies examining the effect of modified diets or medications on cardiovascular end points from 1965 to 1992 using MEDLINE and a review of references of five quantitative overviews of cholesterol reduction and coronary disease. DATA ANALYSIS: Thirteen studies met three eligibility criteria: patients randomized to intervention or control; fatal or nonfatal stroke reported separately; and end points assessed without knowledge of treatment status. Heterogeneity among studies and overall effects of treatment on fatal and nonfatal stroke were estimated using the Mantel-Haenszel-Peto method to combine independent study results. The influence of various study designs and interventions was explored using subgroup comparisons. RESULTS: For fatal stroke, the overall odds ratio associated with cholesterol-lowering interventions in 13 trials was 1.32 (95% Cl, 0.94 to 1.86), and the odds ratio for the 10 single-intervention trials was 1.34 (Cl, 0.91 to 1.96). Among eight trials reporting nonfatal events, the summary odds ratio for nonfatal stroke for treated participants compared with controls was 0.88 (Cl, 0.70 to 1.11), and the odds ratio for total strokes was 0.98 (Cl, 0.80 to 1.19). Among three trials using clofibrate, treatment significantly increased the risk for fatal stroke (odds ratio, 2.64; Cl, 1.42 to 4.92) but not for nonfatal stroke (odds ratio, 0.87; Cl, 0.61 to 1.26). Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the risk for fatal stroke. CONCLUSIONS: Lowering serum cholesterol through modified diets or medications does not reduce stroke mortality or morbidity in middle-aged men. Clofibrate appears to increase the risk for fatal strokes, but the mechanism for this effect is unknown.     

Gallium-67 radiotoxicity in human U937 lymphoma cells

Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use.     

Hydrocephalus in Apert syndrome: a retrospective review

We report six cases of Morgagni hernia diagnosed and operated on in our pediatric surgical unit during a 14-year period. Four children were younger than 1 year and two between 1 and 2 years. Predominance in males was found. Associated congenital pathology was present in 3 children (Down's syndrome, diaphragmatic relaxation, criptorquidia and pyelo-ureteral stenosis). Predominant clinical features were respiratory infections and vomiting. In only one patient clinical onset was with respiratory distress. Plain chest x-ray was the most used diagnostic procedure. In all cases barium enema was performed to confirm the clinical diagnosis. Most frequent surgical approach was a midline supra-umbilical laparotomy. Diaphragmatic defect was left sided in 3 children and right-sided in the other 3. Transverse colon and liver were the most frequent herniated viscera. Postoperative follow-up showed no complications or recidives.