Familial hypokalemic periodic paralysis. Clinical, diagnostic and therapeutic aspects

A model of induced lactation was modified to examine the effects of bovine prolactin (bPRL) and bovine placental lactogen (bPL) on mammary growth and differentiation. Thirty-two peripubertal, non-pregnant Holstein heifers were given daily s.c. injections of oestradiol (0.05 mg/kg) and progesterone (0.25 mg/kg) for 7 days to initiate mammary growth. Treatment with bromocriptine (40 mg/3 days) reduced serum PRL concentrations to approximately 25% of pretreatment levels, for the duration of the study. On the day following the last steroid injection, groups of eight heifers were given twice daily s.c. injections of either saline (negative control), recombinant bPRL (rbPRL; 80 mg/day) or recombinant bPL (rbPL; 80 and 160 mg/day) for 7 days. At the end of this period (day 15), growth and differentiation of the mammary glands were assessed. Treatment with rbPL increased total mammary DNA above control value by 50 and 60% for the 80 and 160 mg/day doses respectively. However, total DNA was not different for the control and rbPRL-treated groups. The blood serum concentration of alpha-lactalbumin was measured daily throughout the study and used as an index of mammary differentiation. Both rbPRL and rbPL stimulated mammary differentiation (i.e. induction of milk synthesis), although rbPRL appeared to be more potent than rbPL. These results indicate that rbPL is lactogenic in vivo and strongly suggest that bPL is a mammary mitogen.     

Interleukin-5 expressed by a recombinant virus vector enhances specific mucosal IgA responses in vivo

Several in vitro studies have shown that murine interleukin-5 (mIL-5) enhances IgA production by activated mucosal B cells. To date, however, there is no evidence that this factor significantly up-regulates mucosal IgA responses in vivo. Here, we show that expression of the gene for mIL-5 in a recombinant vaccinia virus vector markedly increases IgA responses to co-expressed heterologous antigen in the lungs of mice given intranasal inocula of the virus. The elevated local IgA responses to vectors expressing mIL-5 peaked at a fourfold higher level than those elicited by control virus at 14 days after infection and were sustained for at least 4 weeks. Increased IgA responses were abrogated in mice treated with monoclonal antibody against mIL-5 and were not detected in systemic lymphoid tissue. No enhancement of specific IgG levels was found either locally or systemically. Our results indicate that mIL-5 selectively enhances the development of mucosal IgA responses in vivo and suggest that expression of this factor in mucosal vaccine vectors may stimulate local immune reactivity.     

Are different parts of the extended amygdala involved in fear versus anxiety?

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding brain systems that are important for anxiety, it is equally clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Studies in patients with posttraumatic stress syndrome indicate these individuals seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones, touch) activates the central nucleus of the amygdala, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear. Somewhat less explicit information, such as that produced by exposure to a threating environment for several minutes or by intraventricular administration of the peptide corticotropin-releasing hormone may activate a brain area closely related to the amygdala, called the bed nucleus of the stria terminalis, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear or anxiety. Because the nature of this information may be less specific than that produced by an explicit cue, and of much longer duration, activation of the bed nucleus of the stria terminalis may be more akin to anxiety than to fear.     

Alagille syndrome: family studies

Alagille syndrome (AGS) is one of the major forms of chronic liver disease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity of interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically investigated parents in 14 families with an affected child. Clinical examination was supplemented by liver function tests, echocardiography, radiographic examination of the spine and forearm, ophthalmological assessment, and chromosome analysis. Six parents had typical anomalies in two or more systems pointing to the presence of autosomal dominant inheritance. Systematic screening of parents for the features defined in this study should improve the accuracy of genetic counselling.     

Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

Transient hot-electron effect and its impact on circuit reliability

Transient hot-electron effect and its impact on circuit reliability are investigated. The rate of device decay is monitored as a function of the gate pulse transient period. Simulation results reveal that excess charges during a fast turn off time may cause an increase in the maximum substrate current. This, along with our experimental data, identifies that transient excess carrier may cause the enhancement of device degradation under certain stress conditions. The enhancement factor of the degradation is a function of the gate pulse transient time. Correlation between the analysis based upon AC/DC measurement and calculations based upon transient simulation are shown in the paper. Better agreement with experimental data is obtained by using the transient analysis and on chip test/stress structures. The correlation between AC and DC stress data is also shown based on the impact ionization model. A hot-electron design guideline is proposed based on the circuit reliability analysis. This guideline can help improve the circuit reliability without adversely effecting the circuit performance.