The Combined Intracranial and Orbital Operation for Bilateral Retinoblastoma.
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Biomedical subjects
Publications and source records attributed to R Jaeger.
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Previous work using homogenate binding has shown that the development of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the height of the plastic period, and decreases in adulthood. We have studied the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the development of other binding sites in the visual cortex. After confirming the original finding, we extended it by showing that the sensitivity of MK-801 binding sites to glutamate and glycine decreases when the cat becomes an adult. We then examined the regional specificity of MK-801 binding. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 days to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adulthood was less dramatic in the hippocampus than in the visual cortex and was statistically significant only when binding was measured per milligram protein. Saturation analyses also showed a difference in the two structures. Bmax in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these developmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and muscimol. Like MK-801, kainate binding increased from 7 days to 42 days and decreased from 42 days to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly from 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate binding suggests that their associated receptors may have a role in determining the plastic period of visual cortex.
An ATP-dependent transport system is responsible for the cellular extrusion of cGMP. The objective of the present study was to determine the effect of Mg2+, ATP and other nucleotides (2'-dATP, GTP and ADP), exogenous ATPase modulators (such as metavanadate, ouabain, EGTA, NEM, bafilomycin A1 and oligomycin A) on the cGMP transport. The uptake of [3H]-cGMP (1 microM) at 37 degrees C was studied in inside-out vesicles from human erythrocytes. Magnesium caused a maximal activation between 5 and 10 mM and the optimal ATP concentration was 1.25 mM with K50-values of 0.3-0.5 mM. Among other nucleotides tested, 2'-dATP (K50 of 0.7 mM) was nearly as effective as ATP, whereas cGMP accumulated slowly in the presence of GTP. ADP and metavanadate (P-type ATPase inhibitor) showed to be competitive inhibitors with Ki values of 0.15 mM and 10 microns, respectively. NEM (a sulphydryl agent) reduced the ATP-dependent uptake in a concentration-dependent manner with a Ki value of 10 microM. Ouabain (Na+/K(+)-ATPase inhibitor) had no effect. Bafilomycin A1 (V-type ATPase inhibitor) and oligomycin (F-type ATPase inhibitor) were the most potent inhibitors with Ki values of 0.7 and 1.8 microM, respectively. The present study suggests that the cellular cGMP extrusion is energized by an ATPase with a unique inhibitor profile, which clearly differentiates it from the other major classes of membrane-bound ATPases.
During 1979-1984 we auxotyped 1822 strains of Neisseria gonorrhoeae and recorded the site of isolation and sexual orientation of the patients. Auxotypes were determined by the growth requirements of strains for proline (Pro-), uracil (Ura-), hypoxanthine (Hyx-), citrulline (Cit-), or citrulline replaceable by ornithine (Orn-). Of all isolates from homosexual men, 96% belonged to three auxotypes: nonrequiring (NR), Pro-, or Orn-, and only 1.5% belonged to the Pro-, Cit-, Ura- and Orn-, Ura-, Hyx- auxotypes. Of the isolates from women, 49.9% belonged to these latter two auxotypes. Of the strains isolated from male homosexuals, 19.5% were resistant to 1.0 microgram of erythromycin/ml, whereas only 9.6% of strains from other men and 2.6% of strains from women were resistant to this concentration. We suggest that strains of N. gonorrhoeae infecting homosexual men tend to be less demanding in their nutritional requirements and more resistant to erythromycin than strains infecting heterosexual men and women.
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The ratio between extracellular levels of cGMP and cAMP (cGMPex/cAMPex) has been proposed as diagnostic tool in many forms of malignancies. In vitro and in vivo studies have shown that sex steroids effect extracellular levels of cyclic nucleotides. Cyclic changes of these hormones in premenopausal women may disturb the interpretation of the diagnostic marker. C4-I cells grew in the presence of beta-estradiol and progesterone in a chemically defined medium. Cells were sampled during the logarithmic growth phase. Cyclic nucleotide levels were determined by RIA. Receptor status was evaluated by immunocytochemistry. Progesterone increased the cGMPex/cAMPex at all cell densities tested. This effect resulted from increased cGMP and reduced cAMP extrusion. Estradiol had no clear effect on cGMPex/cAMPex even when inhibition of cAMP extrusion was observed at low cell density. Receptors for steroids were not detectable. Sex steroids interact with cyclic nucleotides in C4-I cells in a non-genomic manner.
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