Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.     

Pulmonary vascular disease and operative indications in complete atrioventricular canal defect in early infancy

Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention.     

Review of the maximum efficiency of transmission lines

The problem of maximum efficiency of power transmission lines, solved earlier by the author, is reviewed, clarified, and completed through a detailed analysis of the mathematical properties and physical characteristics involved. The results are presented in a form useful to teachers, students, and practicing engineers in electrical power     

Competitive inhibition by procaine of carbachol-induced stimulus-secretion coupling in rat pancreatic acini

1. Procaine (0.03-10 mM) inhibited carbachol (CCh)-induced amylase release from rat isolated pancreatic acini in a competitive manner. Kinetic analysis of the relation between CCh concentrations and the amount of amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinity constant (pA2) value of 5.00 +/- 0.08. 2. Receptor binding assay confirmed that procaine (0.01-10 mM) competitively inhibited [N-methyl-3H]-scopolamine chloride ([3H]-NMS) binding to its receptor with binding affinity (pKi) of 4.63 +/- 0.10. 3. Procaine transformed CCh-evoked [Ca2+]i dynamics: the initial rise in [Ca2+]i followed by a gradual decay during continuous stimulation with 3 microM CCh was transformed by 0.3 mM procaine to the oscillatory [Ca2+]i dynamics, which resembled the response to 0.3 microM CCh in the absence of procaine. The initial phase of [Ca2+]i oscillation corresponded to the initial phase of CCh-induced amylase release in isolated perfused acini. 4. Procaine (0.3-3 mM) did not inhibit the secretory response to cholecystokinin octapeptide (CCK-8) in isolated incubated acini. A higher concentration of procaine (10 mM) caused weak but significant inhibition of the response to only limited concentrations of CCK-8, 30 and 100 pM. Procaine lower than 10 mM was ineffective on [125I]-BH-CCK-8 binding, although procaine (10 mM) caused weak but significant inhibition of the binding.     

A rapid dot-blot method for species identification of bloodstains

A very simple and rapid test for species identification is reported. Extracts of bloodstains were applied to a synthetic porous membrane and dried. The membrane was then quenched with glycine buffered saline containing BSA and Tween 20. A suspension of colloidal gold particles (GP) coated with rabbit antiserum to human IgG was poured onto, gently whirled and aspirated through the membrane. Spots from the human and monkey bloodstains became red, whereas those from other species of animals remained unstained. This test was completed within 3 to 4 min, and the antibody-coated GP reagent was prepared within 20 min using a very small quantity of antiserum. Cellulose acetate membranes of 0.45 microns or more in pore size were appropriate to this test.     

Ultrastructural studies of the ileum neobladder

Of 101 women, 15-50 years of age, presenting with vaginal discharge, 34 had bacterial vaginosis and were randomly assigned to a seven-day course of oral treatment with either erythromycin (0.5 g b.i.d.) or metronidazole (0.4 g b.i.d.) in a single-blind, cross-over study. Treatment failure (> or = three clinical signs of bacterial vaginosis) occurred in 13 (81%) of 16 patients given erythromycin, as compared with three (17%) of 18 women treated with metronidazole (p < 0.001). Persistence of Gardnerella vaginalis, Mobiluncus species and/or Mycoplasma hominis was found in 14 of 16 patients treated with erythromycin, and in four of 16 patients treated with metronidazole. Treatment with metronidazole was successful (< or = two clinical signs of bacterial vaginosis) in eight of 10 cases of erythromycin treatment failure. Neither of two cases of metronidazole treatment failure was cured with erythromycin. At three-month follow-up of 31 women, persistence or recurrence of bacterial vaginosis was diagnosed in 11 cases (36%).     

Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.     

Design and characteristics of InGaAs/InP composite-channel HFET's

A design for composite-channel structures consisting of an InGaAs channel and an InP subchannel for use as heterostructure field-effect transistors is presented for the first time. This novel channel structure takes advantage of both the high drift velocity and low impact ionization of InP at high electric fields as well as the high electron mobility of InGaAs at low electric fields. It is shown that the doping density of the InP subchannel is the key parameter to realize the advantages of the composite channel. A very high transconductance of 1.29 S/mm and a current gain cutoff frequency of 68.7 GHz are achieved with 0.6 and 0.7 /spl mu/m gates, respectively. The average velocity of electrons in the composite channel is 2.9/spl times/10/sup 7/ cm/s. The devices have no kink phenomena in their I-V characteristics possibly due to low impact ionization in the InP subchannel.<>     

Transfer of rps19 to the nucleus involves the gain of an RNP-binding motif which may functionally replace RPS13 in Arabidopsis mitochondria

The discovery of disrupted rps19 genes in Arabidopsis mitochondria prompted speculation about the transfer to the nuclear compartment. We here describe the functional gene transfer of rps19 into the nucleus of Arabidopsis. Molecular cloning and sequence analysis of rps19 show that the nuclear gene encodes a long N-terminal extension. Import studies of the precursor protein indicate that only a small part of this extension is cleaved off during import. The larger part of the extension, which shows high similarity to conserved RNA-binding domains of the RNP-CS type, became part of the S19 protein. In the Escherichia coli ribosome S19 forms an RNA-binding complex as heterodimer with S13. By using immuno-analysis and import studies we show that a eubacterial-like S13 protein is absent from Arabidopsis mitochondria, and is not substituted by either a chloroplastic or a cytosolic homologue of this ribosomal protein. We therefore propose that either a highly diverged or missing RPS13 has been functionally replaced by an RNP domain that most likely derived from a glycine-rich RNA-binding protein. These results represent the first case of a functional replacement of a ribosomal protein by a common RNA-binding domain and offer a new view on the flexibility of biological systems in using well-adapted functional domains for different jobs.