Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.

Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

Investigating the Neurological Correlates of Workplace Deviance Using a Rodent Model of Extinction.

Employee deviance and time theft is an expensive and pervasive workplace problem. Research indicates that a primary reason employees engage in deviant behaviour is the perception of injustice often associated with psychological contract breach (i.e., broken promises). This study used a rodent model to mimic said experience of broken promises and then examined the subsequent neurophysiological changes that lead to the display of deviant behaviours. Specifically, we generated a psychological contract using a 3 choice serial reaction task, then broke the promise, and finally examined deviant behaviours and neurological correlates. After the broken promise, rats had elevated levels of corticosterone and testosterone, engaged in riskier behaviour, and were more aggressive. The most prominent changes in gene expression were associated with serotonin and stress, and were found in the nucleus accumbens. This study highlights the value of pre-clinical models in the investigation of the theoretical tenants of industrial and organizational psychology.

Bovine viral diarrhea virus is inactivated when whole milk from persistently infected cows is heated to prepare semen extender.

Bovine viral diarrhea virus (BVDV) can be present in cryopreserved bovine semen and be transmitted through artificial insemination. Because BVDV can be shed in milk, the virus might also be introduced as a contaminant of milk-based semen extenders. Thus, the purpose of this study was to evaluate the epidemiologic risk of using heated, BVDV-contaminated milk to prepare semen extender. Milk was obtained from cows free of and persistently infected (PI) with BVDV. Six replicates of milk samples were processed by heating (85-92.2 degrees C, 10min). Samples of milk collected before and after heating were assayed for BVDV. Additionally, milk was injected intravenously into eight BVDV seronegative calves to monitor for seroconversion and viral infection. Virus was not detected in any milk samples from negative animals. Virus was consistently isolated from unheated milk samples from PI cows by passage of somatic cells, ultracentrifugation, and animal inoculation. Virus was usually detected in these samples by RT-nPCR (reverse transcription nested polymerase chain reaction). In heated milk samples from PI cows, no infectious BVDV was detected using any technique, but viral RNA was detected using RT-nPCR in four of six replicates. Bovine viral diarrhea virus in milk from PI cows was inactivated by heating. Therefore, properly heated milk used in semen extenders will not result in transmission of infectious BVDV. Although RT-nPCR detected the presence of viral RNA in milk samples after heating, the virus was not infectious as demonstrated by lack of replication despite using multiple sensitive techniques.

Altered responsiveness to 5-HT at the crayfish neuromuscular junction due to chronic p-CPA and m-CPP treatment.

Serotonin (5-HT) levels in the hemolymph of crustaceans has been implied to alter aggressiveness which influences social interactions. The activation of IP3 as a second messenger cascade within crayfish motor neurons in response to application of 5-HT, suggests that the 5-HT receptor subtypes on the motor neurons are analogous to the vertebrate 5-HT2A receptors. Based on evidence in other systems, it would be expected that chronically sustained 5-HT levels in aggressive individuals would result in a compensatory negative feed-back regulation and/or that target tissues would diminish their sensitivity to high levels of circulating, free 5-HT. We addressed the issue of up- and down-regulation in the sensitivity of the responsiveness to exogenously applied 5-HT at the NMJs of crayfish in which the animals have altered endogenous 5-HT levels. Injections of the 5-HT1 and 5-HT2 vertebrate receptor agonist, 1-(3-Chlorophenyl) piperazine dihydrochloride (m-CPP), for 1 week resulted in a decreased responsiveness to application of 5-HT. The compound p-chlorophenylalanine (p-CPA) blocks the enzymatic synthesis of 5-HT and following 7 days of p-CPA injections, a super-sensitivity to exogenous application of 5-HT for both tonic and phasic neuromuscular junctions (NMJs) was observed. However, acute applications of p-CPA and m-CPP, followed by extensive saline washing, did not reveal any altered receptivity to 5-HT application.

[Chronic inflammation of the colon: a diagnostic problem]. / Przewlekle odczyny zapalne jelita grubego--problem diagnostyczny.

Chronic inflammation of the colon and rectum with associated diarrhea has become more difficult to diagnose recently. Many etiological factors and different therapeutic outlines need to be carefully discussed and summarized. Based on most recent literature, authors present current data on etiology and specific (case-depended) diagnostic procedures in colitis and proctocolitis.

Protecting adolescents from harm. Findings from the National Longitudinal Study on Adolescent Health.

CONTEXT: The main threats to adolescents' health are the risk behaviors they choose. How their social context shapes their behaviors is poorly understood. OBJECTIVE: To identify risk and protective factors at the family, school, and individual levels as they relate to 4 domains of adolescent health and morbidity: emotional health, violence, substance use, and sexuality. DESIGN: Cross-sectional analysis of interview data from the National Longitudinal Study of Adolescent Health. PARTICIPANTS: A total of 12118 adolescents in grades 7 through 12 drawn from an initial national school survey of 90118 adolescents from 80 high schools plus their feeder middle schools. SETTING: The interview was completed in the subject's home. MAIN OUTCOME MEASURES: Eight areas were assessed: emotional distress; suicidal thoughts and behaviors; violence; use of 3 substances (cigarettes, alcohol, marijuana); and 2 types of sexual behaviors (age of sexual debut and pregnancy history). Independent variables included measures of family context, school context, and individual characteristics. RESULTS: Parent-family connectedness and perceived school connectedness were protective against every health risk behavior measure except history of pregnancy. Conversely, ease of access to guns at home was associated with suicidality (grades 9-12: P<.001) and violence (grades 7-8: P<.001; grades 9-12: P<.001). Access to substances in the home was associated with use of cigarettes (P<.001), alcohol (P<.001), and marijuana (P<.001) among all students. Working 20 or more hours a week was associated with emotional distress of high school students (P<.01), cigarette use (P<.001), alcohol use (P<.001), and marijuana use (P<.001). Appearing "older than most" in class was associated with emotional distress and suicidal thoughts and behaviors among high school students (P<.001); it was also associated with substance use and an earlier age of sexual debut among both junior and senior high students. Repeating a grade in school was associated with emotional distress among students in junior high (P<.001) and high school (P<.01) and with tobacco use among junior high students (P<.001). On the other hand, parental expectations regarding school achievement were associated with lower levels of health risk behaviors; parental disapproval of early sexual debut was associated with a later age of onset of intercourse (P<.001). CONCLUSIONS: Family and school contexts as well as individual characteristics are associated with health and risky behaviors in adolescents. The results should assist health and social service providers, educators, and others in taking the first steps to diminish risk factors and enhance protective factors for our young people.

Efficacy of ebrotidine and ranitidine combined with amoxicillin and metronidazole in the eradication of Helicobacter pylori in patients with duodenal ulcer.

This double-blind, randomized, phase III clinical trial was carried out in two parallel groups to assess the efficacy of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) 400 mg and ranitidine 300 mg given in single evening dose, combined with amoxicillin 750 mg and metronidazole 500 mg three times daily for 14 days, in the eradication of Helicobacter pylori in patients with duodenal ulcer. Thirty patients were included, divided into two groups of 15, to whom one of the study therapies was administered based on a randomization code. Clinical and endoscopic controls were performed 4, 6 and 8 weeks after the onset of the treatment. No differences were seen between the two treatment groups with regard to demographic parameters and clinical histories. They were both perfectly homogeneous. There were no differences between the eradication of both therapies in both the antrum and gastric body samples (over 80% eradication), allowing the results to be classified as satisfactory. Moreover, perfect control was achieved through the study of clinical symptoms, which even disappeared in some cases. There were no differences in the healing rate of the duodenal ulcer after four weeks, 86.7% being achieved for both groups.

[Immunologic reactions in the male and female reproductive system]. / Reakcje immunologiczne zachodzace w zenskim i meskim ukladzie rozrodczym.

This review describes presence and significance of antisperm antibodies (ASA) in male and female reproductive compartments. We described their relevance to infertility in humans. A structure and function of cervical mucus as the environment of females defensive reactions against all the invasive factors is outlined. There are also briefly characterized techniques of ASA detection.

Physical progress and residual impairment quantification after functional restoration. Part I: Lumbar mobility.

Quantification of human performance in chronic low back pain (CLBP) patients is essential to initiate effective treatment and guide progress in a disability-oriented functional restoration program, as well as to objectively evaluate impairment and functional limitations at the time of maximum medical improvement. One such important measure of physical ability is range of motion. Patients who suffer from CLBP almost invariably have some disturbance of mobility. The major goals of the present study were to: 1) develop a database of anticipated range of motion levels at different points in time in a representative sample of CLBP patients; 2) within the sample, determine any gender or spinal surgery-induced differences; 3) evaluate change in range of motion produced by participation in a comprehensive functional restoration treatment program; and 4) identify residual impairment of regional range of motion. Four separate groups of CLBP patients were evaluated: Group 1 (n = 92), unoperated men; Group 2 (n = 26), postdiscectomy men; Group 3 (n = 59), unoperated women; and Group 4 (n = 17) postdiscectomy women. Patients in each group were assessed for spinal range of motion measures at three points in time, for sagittal/coronal motion and validity (employing the relationship between pelvic motion and supine leg raising). Results demonstrated dramatic patient improvements in range of motion from initial referral to program completion. The most significant gains were made in pelvic motion, which returned to near normal levels, indicating that the vast majority overcame low effort or movement inhibition produced by pain or fear of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical probes using tumor necrosis factor in treatment of neoplastic diseases]. / Próby kliniczne zastosowania czynnika martwicy nowotworów (tumor necrosis factor alfa-TNF) w leczeniu chorób nowotworowych.

Tumor necrosis factor-TNF is a cytokine that is predominantly produced by the activated macrophages. It was shown that TNF has the antineoplastic activity in vitro or in tumor xenografts on the animals in vivo. Clinical trials phase I and II carried out in many centers assessed toxic effects of TNF administration, as well as its pharmacokinetic and therapeutic effect. The following paper is a survey of the results of clinical trials which could be useful for the assessment of TNF role in oncological immunotherapy.

Walking the new-supervisor tightrope.

Hospitals have traditionally expected technologists to learn supervision on their own. Here's a mini-seminar to help brand-new supervisors maintain that delicate balance.

A self-splicing RNA excises an intron lariat.

We have investigated the in vitro self-splicing of a class II mitochondrial intron. A model pre-mRNA containing intron 5 gamma of the oxi 3 gene of yeast mitochondrial DNA undergoes an efficient intramolecular rearrangement reaction in vitro. This reaction proceeds under conditions distinct from those optimal for self-splicing of class I introns, such as the Tetrahymena nuclear rRNA intron. Intron 5 gamma is excised as a nonlinear RNA indistinguishable from the in vivo excised intron product by gel electrophoresis and primer extension analysis. Studies of the in vitro excised intron product strongly indicate that it is a branched RNA with a circular component joined by a linkage other than a 3'-5' phosphodiester. Two other products, the spliced exons and the broken form of the lariat, were also characterized. These results show that the class II intron products are similar to those of nuclear pre-mRNA splicing.

Exercise reverses photoperiodic anestrus in golden hamsters.

In contrast to the inhibitory effects of endurance exercise on reproductive function in women athletes, voluntary running induces estrous cyclicity in anestrous female hamsters maintained in the nonstimulatory short-day photoperiod. Increased concentrations of circulating prolactin (Prl) seen in these animals are not responsible for the reversal of photoperiodic anestrus as demonstrated by experimental manipulations of prolactin secretion. Voluntary running also facilitates growth hormone (GH) release and somatic growth in hamsters independently of the photoperiod. Thus, it appears that endurance exercise can have facilitatory as well as inhibitory effects on the reproductive function in female mammals.

Small effect of brown adipose tissue and major effect of photoperiod on body weight in hamsters (Mesocricetus auratus).

It has been suggested that brown adipose tissue plays a special role in the control of body weight. This hypothesis was investigated by measuring the body weight of female hamsters over a two month period following removal of interscapular brown adipose tissue. Two groups of animals were used, one maintained on a short day (10:14 light: dark ratio) and the other on a long day (16:8 light: dark ratio) photoperiod. Under both photoperiod conditions hamsters with interscapular brown adipose tissue removed gained somewhat more weight than their corresponding sham operated controls. Photoperiod, however, had a much larger effect on body weight. Hamsters maintained on short days increased their body weight by about 60 percent during the two months of the experiment whereas the hamsters maintained on long days increased their body weight by only about 17 percent. It was concluded that brown adipose tissue plays a small non special role in the control of body weight in the female hamster, but that the light-dark ratio is quantitatively much more important under these experimental conditions.

Identification of mRNA species that code for extra-embryonic endodermal cytoskeletal proteins in differentiated derivatives of murine embryonal carcinoma cells.

The messenger RNA species that code for two extra-embryonic endodermal cytoskeletal proteins (Endo A and Endo B) have been identified. Endo A and Endo B messenger RNA species are differentially expressed. They are absent, or at basal levels, in undifferentiated embryonal carcinoma cells (F9.22 cell line) and relatively abundant in parietal endoderm (PFHR9 cell line) or in embryonal carcinoma cells that have been induced, by retinoid acid, to differentiate to parietal endoderm. Endo A and Endo B messenger RNA can be detected in F9.22 cells 48 to 72 h after exposure to retinoic acid, which is coincident with the expression of Endo A and Endo B proteins. The size of Endo A and Endo B messenger RNA has been determined by denaturing methyl mercury hydroxide agarose gels to be 2.0 +/- 0.1 and 1.5 +/- 0.2 kilobases, respectively.

Construction and identification of bacterial plasmids containing nucleotide sequence for human leukocyte interferon.

Bacterial plasmids containing human leukocyte interferon sequences were constructed and identified. Identification was confirmed by correspondence of the nucleotide sequence with out amino acid sequence of human leukocyte interferon. The finding of bacterial recombinants containing distinct leukocyte interferon sequences is consistent with our purification of different leukocyte interferon species. We conclude that what has been designated human leukocyte interferon is, indeed, a class of homologous proteins. Preliminary indications suggest that their diversity appears to be represented by individual genomic equivalents. Each of the individual species exhibits characteristic activities. The structural modulation of these biological activities has immense significance for understanding the natural role of the interferons and for refining and developing their ultimate therapeutic potential.

Human leukocyte interferon produced by E. coli is biologically active.

A human leukocyte interferon cDNA was enzymatically synthesized, inserted into the vector pBR322, and cloned in Escherichia coli. The DNA sequence codes for a 23-amino acid signal peptide followed by an interferon polypeptide of 165 amino acids. An expression plasmid was constructed which permits the synthesis in E. coli of 2.5 x 10(8) units of interferon per litre of culture. This LeIF protected squirrel monkeys from lethal encephalomyocarditis virus infection.

A coliphage lambda vector with enhanced biological containment: lambda gtALO.lambda B.

The biological containment of the lambda gt family of cloning vectors has been enhanced by conditionally blocking DNA replication as well as head and tail morphogenesis. The vector, lambda gtALO.lambda B, was constructed by crossing the Oam29, Aama1 and Lam439 mutations into lambda gt.lambda B. The mutation blocking phage DNA replication, Oam29, is suppressed by suII+ or suIII+. The head gene mutation, Aama1, is suppressed by suIII+ but not by suII+ and the tail gene mutation, Lam439, is suppressed by suII+ but not by suIII+. This allows the option of increasing the biological containment by producing heads when a large amount of cloned DNA is being prepared from an individual isolate. A model recombinant, lambda gt Aama1 Lam439 Oam29.KmR' (lambda gtALO.KmR') was constructed and the containment of the vector was evaluated by the series of standardized experiments required for EK2 certification.

Somatic, behavioral, and reproductive disturbances in mice following neonatal administration of sodium L-aspartate.

Sodium L-aspartate (ASP) was administered to neonatal mice according to an increasing dose schedule from Days 2--11 after birth. Adult ASP-treated animals showed large increases in body weight over controls along with stunted body length. The ASP group also showed decreases in locomotor and exploratory behavior. Reproductive dysfunction occurred in both female and male ASP-treated animals. Among treated animals, females had fewer pregnancies and smaller litters while males showed reduced fertility. Evidence of multiple endocrine dysfunction in ASP-treated animals was reflected by decreased pituitary, thyroid, ovaries and tested weights, along with delayed onset of puberty in females. These results demonstrate that sodium L-aspartate produces a syndrome similar to that seen following the administration of monosodium L-glutamate.