The influence of mouse genotype on the changes in brain cyclic nucleotide levels induced by acute alcohol administration.

Two mouse strains (C57BL/6By and BALB/cByJ) were found to differ widely in their sleep-time response to ethanol (3 g/kg), but showed no difference in their hypothermic response to the same ethanol dose. Comparison of brain cyclic nucleotide levels in the two strains revealed a strain difference in the brain cyclic AMP response to ethanol but no strain difference in the magnitude of the brain cyclic GMP change. Alcohol produced a significant drop in cerebellar cyclic GMP in both strains, and a decrease in cerebellar cyclic AMP in C57BL/6By mice. The cyclic AMP/cyclic GMP ratio increased following alcohol in the cerebellum of BALB/cByJ mice but not C57BL/6By mice. The results are discussed in terms of possible relationships between alcohol-induced changes in neurochemistry and behavior.     

Growth of mouse embryos in bicarbonate media buffered by carbon dioxide,hepes, or phosphate

The purpose of this study was to determine if mouse embryos could be grown successfully in a culture medium devoid of the carbon dioxide phase (CO₂). Mouse embryos fertilized in vivo were collected and cultured in Hepes medium with and without bicarbonate (HCO₃ ^–) and a phosphate medium with and without HCO₃ ^–. In these experiments no CO₂ gas phase was used. Further embryos were cultured in Whittingham's modified Tyrode's (T6) medium with a CO₂ gas phase and served as controls. The degree of embryonic development was noted. Surviving blastocysts were transferred to the uteri of pseudopregnant mice and delivery at term was allowed to occur. There was no significant difference in the degree of embryonic development in those embryos cultured in T6 or Hepes medium (+HCO₃ ^–) or in the number of live offspring obtained when these blastocysts were placed within the mouse uterus. Although embryonic development apparently proceeded successfully in the phosphate (+HCO₃ ^–) medium, none of these blastocysts survived when transferred to mouse uteri. No embryonic growth occurred in either the Hepes or phosphate media which were devoid of HCO₃ ^–. It appears that a Hepes medium containing HCO₃ ^–, which uses no CO₂ gas phase, is as effective as T6 medium, which uses a gas phase, in supporting in vitro mouse embryonic growth.     

Effect of the menstrual cycle on the auditory brainstem response

The present study sought to determine if the gender difference in auditory brainstem (ABR) latency and peak amplitude varies systematically across the menstrual cycle. Behavioral thresholds and auditory-evoked brainstem responses to alternating click stimuli were obtained from 17 normal hearing young adults (10 female, 7 male). Absolute behavioral thresholds and ABR measurements were compared every other day over a complete menstrual cycle. Results show consistent gender differences in ABR latency, peak amplitude, and behavioral threshold of the ABR stimuli, but these differences do not vary across the menstrual cycle.     

Transplacental stimulation of fetal lung maturation: effect of triiodothyronine in the female and male rabbit fetus

We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.     

Are dysfunctional beliefs about illness unique to hypochondriasis?

Objective: There is evidence that individuals high in hypochondriasis overestimate the likelihood of ambiguous symptoms being indicative of serious illness. However, it is not known whether this tendency is unique to hypochondriasis or whether it can be attributed to high negative affectivity or other anxiety symptoms often found to be comorbid with hypochondriasis. Method: College students (N=133) completed measures of hypochondriasis, depression, anxiety, worry, avoidance and estimated the likelihood of various symptoms indicating catastrophic and minor illnesses. Results: Even after entering the other self-report variables, hypochondriasis was the only variable to predict estimates of the likelihood of serious illness. Conversely, being female, high levels of negative affect, agoraphobic avoidance when accompanied by others and higher estimates about the likelihood of symptoms leading to catastrophic illnesses best predicted hypochondriasis scores. Conclusion: Dysfunctional beliefs about illness appear to be unique to hypochondriasis and to uniquely contribute to the prediction of hypochondriasis.     

Inhibition of a thrombin anion-binding exosite-2 mutant by the glycosaminoglycan-dependent serpins protein C inhibitor and heparin cofactor II

Antithrombin (ATIII), heparin cofactor II (HCII) and protein C inhibitor (PCI; also named plasminogen activator inhibitor-3) are serine protease inhibitors (serpins) whose thrombin inhibition activity is accelerated in the presence of glycosaminoglycans. We compared the inhibition properties of PCI and HCII to ATIII using R93A/R97A/R101A thrombin, an anion-binding exosite-2 (exosite-2) mutant that has greatly reduced heparin-binding properties. Heparin-enhanced PCI inhibition of R93A/R97A/R101A thrombin was only approximately 2-fold compared to 40-fold enhancement with wild-type recombinant thrombin. Thrombomodulin (TM) (with or without the chondroitin sulfate moiety) accelerated PCI inhibition of both wild-type and R93A/R97A/R101A thrombins. HCII achieved the same maximum activity in the presence of heparin with both wild-type and R93A/R97A/R101A thrombins; however, the optimum heparin concentration was 20 times greater than the reaction with wild-type thrombin, indicative of a decrease in heparin affinity. Dermatan sulfate (DSO4)-catalyzed HCII thrombin inhibition was unchanged in R93A/R97A/R101A thrombin compared to wild-type recombinant thrombin. These results suggest that PCI is similar to ATIII and depends upon ternary complex formation with heparin and these specific thrombin exosite-2 residues to accelerate thrombin inhibition. In contrast, HCII does not require Arg(93), Arg(97) and Arg(101) of thrombin exosite-2 and further supports the hypothesis that HCII uses an allosteric process following glycosaminoglycan binding to inhibit thrombin.     

Does schizophrenia result from developmental or degenerative processes?

The debate as to whether schizophrenia is a neurodevelopmental or a neurodegenerative disorder has its roots in the latter part of the 19th century when authorities such as Clouston (1891) posited that at least some insanities were "developmental" in origin. These views were soon eclipsed by Kraepelin's (1896) concept of dementia praecox as a degenerative disease, and the latter view carried not only the day but also much of the 20th century. Then, in the 1980s several research groups again began to speculate that schizophrenia might have a significant developmental component (Feinberg, 1982-1983; Schulsinger et al., 1984; Murray et al., 1985; Murray and Lewis, 1987; Weinberger et al., 1987). What became known as the "neurodevelopmental hypothesis" received support from neuropathological studies implicating anomalies in early brain development such as aberrant migration of neurons. Unfortunately, these studies proved difficult, if not impossible, to replicate (Harrison, 1999). The pendulum, therefore, began to swing again, and in the latter part of the 1990s came renewed claims that the clinical progression of the illness was accompanied by continued cerebral ventricular enlargement and reduction in the volumes of certain brain structures. Nevertheless, since few doubt that there is a developmental component to schizophrenia, the question which we will address in this paper is whether schizophrenia is a) simply the final consequence of a cascade of increasing developmental deviance (Bramon et al., 2001), or b) whether there is an additional brain degeneration following onset of psychosis which is superimposed on the developmental impairment (Lieberman, 1999).