Glucocorticoids potentiate kainic acid-induced seizures and wet dog shakes

Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes.     

Sites in the male primate brain at which testosterone acts as an androgen

Quantitative autoradiographic analysis was used to identify regions in the brain of the male primate where androgen binding sites may be involved in the actions of testosterone. Three days after castration, adult male rhesus monkeys received a subcutaneous injection of either dihydrotestosterone propionate (DHTP, 20 mg, n = 6), testosterone propionate (TP, 100 mg, n = 2), or oil vehicle (control males, n = 4). Three hours later, 5 mCi [3H]testosterone was administered as an i.v. bolus. At 60 min, brains were rapidly removed and the left halves were used for autoradiography. In control males, highest percentages of labeled neurons (20-84% using a rigorous Poisson criterion) were observed in the ventromedial, arcuate and premammillary nuclei (n.) of the hypothalamus, medial preoptic n., bed n. of stria terminalis, intercalated mammillary n., lateral septal n. and the medial, cortical and accessory basal n. of the amygdala. Pretreatment with DHTP eliminated labeling in androgen target tissues of the genital tract, and reduced the percentages of labeled neurons to 4-22% of control values in the arcuate, lateral septal, premammillary and intercalated mammillary n., indicating that in these regions testosterone acted predominantly at androgen binding sites. However, in the medial preoptic n., the ventromedial hypothalamic n. and the accessory basal amygdaloid n., DHTP pretreatment resulted in much less blocking which, together with other data, suggested that in these sites, testosterone's actions involved aromatization and interaction with estrogen-binding sites.     

The modern diagnosis of gonorrhea

Modern identification of Neisseria gonorrhoeae may be either accomplished by direct detection of gonococcal antigen, i.e. without microbiological culturing, or, following culturing, by rapid culture confirmation. The direct detection of gonococcal antigen in an enzyme immuno-assay (Gonozyme) shows reduced specifity especially with mixed microbial flora, and decreased sensitivity with small numbers of organisms. Culture confirmation may be achieved by a rapid sugar degradation test (API----quadFERM+), by specific enzyme detection using chromogenic substrates (Gonochek II), or by demonstration of protein I specific for Neisseria gonorrhoeae by means of monoclonal antibodies (Mikrotrak, Phadebact monoclonal GC, Gonogen II). Detection of protein I is highly sensitive and specific in both the tests of immunofluorescence and coagglutination.     

The endoscopic bronchial picture of patients with pulmonary tuberculosis of various age groups

Endoscopic pictures of the bronchi were studied in 509 new cases of pulmonary tuberculosis. Tuberculosis of the bronchi and its aftereffects such as cicatricial lesions were detected in 31.1 per cent of the children and adolescents, 7.9 per cent of the adults at the age of 18 to 29 years, 9.0 per cent of the adults at the age of 30 to 55 years and 14.7 per cent of the adults at the age of 56 to 75 years. Nonspecific endobronchitis was diagnosed in 27.9 per cent of the children and adolescents, 44.9 per cent of the adults at the age of 18 to 29 years, 46.3 per cent at the age of 30 to 55 years and 44.1 per cent at the age of 56 to 75 years. The incidence and nature of tuberculosis of the bronchi and nonspecific endobronchitis were not related to the patients' age.     

Treatment of primary hypogonadism in men by the transdermal administration of testosterone

We tested the efficacy of a thin flexible testosterone-impregnated membrane applied to the scrotum for the long term treatment of male hypogonadism. Ten men with primary hypogonadism were treated for 3 months (2 men) or 13 months (8 men). Serum testosterone concentrations increased in all 10 men, to within the normal range in 8. Serum dihydrotestosterone concentrations increased to supranormal values in all of the men, decreased to the normal range in 6, indicating the biological effectiveness of the testosterone in those subjects. Two men whose serum LH concentrations did not fall to normal had small or distorted scrotal surfaces. Seven of the 8 men whose serum testosterone concentrations became normal said that their hypogonadal symptoms were corrected by this treatment. We conclude that the transdermal administration of testosterone is an effective means of treating the majority of hypogonadal men who have a normal scrotum.     

Effects of sensory and motor functioning on adult intellectual performance

This study examined longitudinal health and intelligence data to determine whether sensory or motor deficits account for some of the age-related intellectual changes that are commonly seen from midlife onward. Although sensory and motor functioning did not account for the age-related decrements in performance on speeded, visual perceptual tasks found for this sample in previous work, we did find that hearing deficits added error variance to performance estimates on two verbal subtests of the Wechsler scales.     

Recovery of memory after severe closed head injury: dissociations in recovery of memory parameters and predictors of outcome

This study examined selective reminding and recognition memory performance of 21 severe closed-head injured patients tested within 6 months of regaining consciousness and then again after at least 1 year. Performances on selective reminding parameters were highly correlated and patients performed significantly worse at both testings than did hospitalized controls matched for age, education, and sex. Patients improved from testing 1 to testing 2 on only four of six memory variables. Average Impairment Rating at testing 1 was a marginally better predictor of memory performance at testing 2 than was length of coma. Results are discussed in terms of (a) utility of selective reminding parameters and predictors of outcome and (b) dissociations in recovery of memory parameters.     

Amphotericin B: a novel class of antiscrapie drugs

Amphotericin B (AmB) has been able to lengthen the incubation period of intracerebrally (ic) scrapie-injected hamsters to 45 d. This article reports a linear relationship between AmB doses and the duration of the incubation periods of ic-treated animals compared with controls, a greater effect of AmB treatment administered 2 w before or the same day of ic scrapie incubation, and the ineffectiveness of mepartricin, an AmB analogue, in prolonging the incubation period of ic scrapie-injected hamsters. The beneficial effect of AmB appears due to a delay in the replication of the scrapie agent in the brain of infected hamsters. Moreover, AmB suppresses scrapie replication in the spleen of treated animals. Three hypotheses may explain these results: (1) AmB alters a hypothetical scrapie receptor, preventing the entry of the agent into central nervous system (CNS) target cells; (2) AmB interferes with mechanisms involved in scrapie replication; (3) AmB prevents the formation and accumulation of a scrapie-specific amyloid protein responsible for the disease. Whatever the mechanism of action, AmB is the only currently available drug to modify experimental CNS scrapie infection, so AmB is proposed as a novel class of antiscrapie drugs.     

Positive genetic selection for gene disruption in mammalian cells by homologous recombination.

Efficient modification of genes in mammalian cells by homologous recombination has not been possible because of the high frequency of nonhomologous recombination. An efficient method for targeted gene disruption has been developed. Cells with substitution of exogenous sequences into a chromosomal locus were enriched, by a factor of 100, using a positive genetic selection that specifically selects for homologous recombination at the targeted site. The selection is based on the conditional expression of a dominant selectable marker by virtue of in-frame gene fusion with the target gene. The dominant selectable marker was derived by modification of the Escherichia coli neo gene so that it retains significant activity in mammalian cells after in-frame fusion with heterologous coding sequences. In the example presented here, homologous recombinants were efficiently recovered from a pool in which the targeted gene was disrupted in 1 per 10,000 cells incorporating exogenous DNA.