New evidence for the structure of myxinol

1. Preliminary spectroscopic examination of a second component of hagfish bile salts suggested that it might be 3β,7α,26(27)-trihydroxy-5α-cholestane. 2. Impure reduction products of the 3β,26(27)-dihydroxycholestane-7,16-dione previously made from myxinol disulphate appeared also to have the 5α-configuration. 3. Infrared, nuclear-magnetic-resonance and mass-spectrographic as well as optical-rotatory-dispersion measurements on 3β,26(27)-dihydroxycholestane-7,16-dione showed that it was a 5α-compound. 4. Myxinol is thus 3β,7α,16α,26(27)-tetrahydroxy-5α-cholestane; new nuclear-magnetic-resonance measurements on myxinol tetra-acetate at higher resolution confirm this structure.     

Amino acid metabolism in various fractions of rat-brain homogenates with special reference to the effect of ethanol

1. The increase in brain γ-aminobutyrate, glutamate and aspartate and the decrease in brain glutamine that occur when ethanol is administered to rats in vivo could be reproduced by incubating brain homogenates from rats pretreated with ethanol. 2. For the demonstration of the effects of pretreatment with ethanol on the metabolism of γ-aminobutyrate and glutamine, the whole homogenate could be replaced by various supernatant preparations, and even by the soluble protein fraction, which was less active, however. The `postmitochondrial' sediment could likewise mediate the effects of pretreatment with ethanol. 3. When the brain homogenates from control and ethanol-treated rats were allowed to `age' at 2° for more than 7 days, the metabolic difference at incubation could no longer be demonstrated. The capacities of the homogenate from the control rats had changed to resemble those of ethanol-treated rats. 4. Data are given on the effects of the incubation time and of the concentration of homogenate.     

Studies on the biosynthesis of gramicidin S in a cell-free system from Bacillus brevis. Further attempts to elucidate its mechanism of synthesis

1. The pH optima for the incorporation of (14)C-labelled amino acids into gramicidin S by an 11000g cell-free extract from Bacillus brevis have been determined. The pH optima for leucine, proline, phenylalanine, ornithine and valine were 7.5-7.7, 7.5-7.7, 7.7-7.9, 7.7-7.9 and 8.0-8.2 respectively. Hence the greatest difference in pH optima existed between leucine and valine, where it was 0.5pH unit. 2. The 11000g cell-free extract incorporated into gramicidin S only the l-isomers of valine, proline and ornithine. However, both isomers of leucine are utilized and the experiments indicate that a leucine racemase exists in the 11000g cell-free extract. With phenylalanine the l-isomer is utilized much more effectively than the d-isomer. This is noteworthy since it is the d-isomer that occurs in gramicidin S. The experiments indicate that conversion of the l-isomer into the d-form takes place at a stage beyond that of the free amino acid.     

Temperature-related divergence in experimental populations of Drosophila melanogaster. II. Correlation between fitness and body dimensions

From a laboratory stock of Drosophila melanogaster (Oregon), reared for more than 20 years at 18° C, a new population was derived and maintained at 28° C for 8 years. The chromosomal and cytoplasmic contribution to genetic divergence between the two populations was estimated. Six body traits and reproductive fitness were taken into account. The third chromosome is responsible for the adaptive difference for temperature between the two lines. Temperature-selected genes which control body size are located on the second and third chromosomes, although the contribution of each chromosome depends on the environment in which the flies develop. The correlation between the chromosomal and cytoplasmic contributions to different traits and fitness, changes with temperature. At 28° C the correlation between fitness and each body trait is proportional to the response to selection exhibited by each of them, but this is not true at 18° C. Body size has, therefore, an adaptive significance in relation to temperature, which is expressed only in the environment where selection occurs. Cytoplasmic genes affect almost all characters to an extent similar to that of chromosomal genes. Inter-chromosomal and nucleo-cytoplasmic interactions are present and also change with temperature. In general, genes selected in a given environment produce greater phenotypic changes in that environment than in another. The population that experienced both temperatures is fitter in both environments, suggesting that the capacity to adapt to warm temperatures depends on genes other than those which are involved in the adaptation to cold.     

Pattern of simulated snoring is different through mouth and nose

Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring.     

Estimation of regional cutaneous cold sensitivity by analysis of the gasping response.

Regional cutaneous sensitivity to cooling was assessed in males by separately immersing four discrete skin regions in cold water (15 degrees C) during head-out immersion. The response measured was gasping at the onset of immersion; the gasping response appears to be the result of a nonthermoregulatory neurogenic drive from cutaneous cold receptors. Subjects of similar body proportions wore a neoprene "dry" suit modified to allow exposure to the water of either the arms, upper torso, lower torso, or legs, while keeping the unexposed skin regions thermoneutral. Each subject was immersed to the sternal notch in all four conditions of partial exposure plus one condition of whole body exposure. The five cold water conditions were matched by control immersions in lukewarm (34 degrees C) water, and trials were randomized. The magnitude of the gasping response was determined by mouth occlusion pressure (P0.1). For each subject, P0.1 values for the 1st min of immersion were integrated, and control trial values, although minimal, were subtracted from their cold water counterpart to account for any gasping due to the experimental design. Results were averaged and showed that the highest P0.1 values were elicited from whole body exposure, followed in descending order by exposures of the upper torso, legs, lower torso, and arms. Correction of the P0.1 response for differences in exposed surface area (A) and cooling stimulus (delta T) between regions gave a cold sensitivity index [CSI, P0.1/(A.delta T)] for each region and showed that the index for the upper torso was significantly higher than that for the arms or legs; no significant difference was observed between the indexes for the upper and lower torso.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ploidy and morphology in osteosarcoma

In a cytometric DNA study of high-grade osteosarcoma, the relationship between DNA content and morphology was analyzed. The investigation, based on microspectrophotometry of tissue sections and flow cytometry (FCM), included both primary lesions and recurrences. FCM analysis, applied to a consecutive series of 47 primary osteosarcomas, disclosed that 2 were diploid and 45 were nondiploid, 8 of which were tetraploid. Multiple aneuploid peaks were detected in 13 tumors. Among the nondiploid tumors, there was no clear relationship between the peak DNA value(s) and the histologic subtype (osteoblastic, chondroblastic, fibroblastic) or grade (III-IV). The proliferative activity, as reflected by the percentage of S-phase cells, could be determined in 38 of the 47 tumors analyzed by FCM. The percentage was higher for aneuploid than for tetraploid lesions; however, the distribution of S-phase cells was not related to the histologic subtype or the grade of the tumors. To assess the reliability of a single sample for FCM, the DNA content of biopsy and surgical specimens was compared in 20 tumors; there was complete agreement in all cases with respect to the classification of the lesion as diploid, tetraploid or aneuploid. Analysis by FCM or microspectrophotometry of 12 local recurrences and 16 metastases and the corresponding 19 primary tumors showed that an aneuploid characteristic of the primary lesion was retained during progression of the disease. In 12 tumors analyzed by microspectrophotometry in tissue sections, comparison of chondroblastic and osteoblastic/fibroblastic areas within the same lesion consistently disclosed hyperploidy in both areas.(ABSTRACT TRUNCATED AT 250 WORDS)