Renal nerve responses to somatic nerve activation in stroke-prone spontaneously hypertensive rats

Antidepressant-induced adverse sexual effects are becoming more frequently reported by patients who require pharmacotherapy. A MED-LINE search was conducted to generate articles reporting such events. We report here on the sexual side effects associated with tricyclics, monoamine oxidase inhibitors including moclobemide, selective serotonin reuptake inhibitors, bupropion, and on the newer antidepressants venlafaxine and nefazadone. We conclude that adverse sexual effects are an increasingly important side effect of antidepressant medications, and patients must be routinely asked about their occurrence.     

Relationship between expression of epidermal growth factor and simian virus 40 T antigen in a line of transgenic mice

The pattern of expression of the simian virus 40 (SV40) T antigen gene and resultant dysplasia were re-examined in a line of transgenic mice in which the T antigen gene was under the control of the SV40 early promoter. We found that T antigen expression in the kidney, and resulting dysplastic lesions, occurred exclusively in the distal convoluted tubules and the ascending limbs of Henle. Epidermal growth factor (EGF) expression in the kidney of normal mice was similarly immunolocalized. The correlation between high EGF immunoreactivity in normal mouse tissues and T antigen expression in the transgenic counterpart was also seen in the choroid plexus epithelium and in the submandibular glands of male mice. T antigen was not found in the submandibular gland of transgenic females. Similarly, EGF was only rarely detected in the normal female submandibular gland. In contrast to the correlation between T antigen expression in the transgenic mice and EGF expression in the corresponding tissues of the normal mice, within the dysplastic lesions of the transgenic mice EGF expression was severely diminished. Adenocarcinomas of the male submandibular gland from another line of transgenic mice that expresses the Int-1 transgene, showed similarly reduced levels of immunostaining for EGF. Thus, reduced expression of EGF might be a general feature of dysplasia and tumorigenesis in those tissues that normally express EGF.     

Detection of alcoholism in schizophrenia using the MAST

1. alpha-toxin of Staphylococcus aureus readily permeabilized rat uterine smooth muscle after incubation for a short time. 2. The permeabilized muscle responded to Ca2+ dose-dependently and repeatedly in the same manner. 3. The threshold concentration of Ca2+ for contraction was 0.1-0.3 microM and the maximal contraction was achieved with 1 or 3 microM Ca2+. 4. GTP gamma S or GTP augmented the contractile response to Ca2+. 5. GDP beta S or GDP suppressed the contraction. 6. The role of GTP-binding protein in sensitization of Ca(2+)-induced contractile response of smooth muscle is discussed.     

Identification of nonproliferating but viable hypoxic tumor cells in vivo

We have used the combination of pimonidazole labeling of hypoxic cells, bromodeoxyuridine labeling of proliferating cells, and cell sorting based on Hoechst 33342 perfusion to directly study hypoxia and proliferation in human tumor xenografts and transplantable murine tumors in vivo. Hypoxia was largely confined to cells in regions with the least perfusion, although in tumors exhibiting transient blood flow, hypoxic cells were not as highly localized. Similarly, proliferation and hypoxia were mutually exclusive except in areas of a tumor subjected to transient changes in perfusion. By determining the clonogenic potential, pimonidazole labeling intensity, and radiosensitivity of sorted tumor cell subpopulations, we have provided direct evidence that pimonidazole identifies hypoxic tumor cells of therapeutic relevance in vivo. Given that pimonidazole exhibits few diffusion or delivery problems and no apparent cytotoxicity, it appears to be a versatile and useful label for hypoxic cells in solid tumors.     

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.     

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.     

Uptake characteristics of loracarbef and cephalexin in the Caco-2 cell culture model: effects of the proton gradient and possible presence of a distinctive second component

The mechanisms of apical (AP) uptake of cephalexin (CEPH) and loracarbef (LOR) in the absence or presence of an (extemally imposed) proton gradient were determined using well-stirred diffusion chambers that minimize the effects of the unstirred water layer. The results indicated that, compared to AP uptake in the presence of an imposed proton gradient, AP uptake in the absence of an imposed proton gradient had higher K(m) values and lower Jmax values. Furthermore, when inhibition studies were performed in the absence of a proton gradient, only natural peptides were effective, whereas the peptide analogs (e.g., enalapril) were not. In addition to the effects of concentration and competitive inhibitors, the results also indicated that (1) the AP uptake of both drugs was decreased more than 60% by FCCP, regardless of whether the proton gradient was present or absent; (2) effects of protein kinase C promoter were dependent upon the presence of a proton gradient; and (3) AP uptake in the presence of an imposed proton gradient was not affected by feeding restriction, whereas AP uptake in the absence of an imposed proton gradient was. These results showed for the first time that two substrates with similar AP uptake characteristics in the presence of an imposed proton gradient may not share those characteristics in the absence of an imposed proton gradient. Taken together, these results suggest that the AP uptake component that functions in the absence of an imposed proton gradient is distinctly different from the one that functions in the presence of an imposed proton gradient. Data generated from the present study and those in the literature lend support to the hypothesis that this distinctive component represents the second binding site on the AP peptide transporter. However, an alternative hypothesis that there are two AP peptide transporters remains to be disapproved.     

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.