Nancy K. R. Smith

Studies on the Metabolism of Meprobamate

Summary Urinary excretion ratios of meprobamate and its major metabolic product, hydroxymeprobamate, were determined in a number of laboratory animal species following administration of meprobamate by several routes. No major differences were apparent. Humans receiving relatively small doses of this drug excreted a higher proportion of unchanged meprobamate, especially after a single administration of the drug. Chronic administration of meprobamate to humans appeared to stimulate its metabolism.

CALCIUM AMELIORATION OF CADMIUM-INDUCED CYTOTOXICITY IN CULTURED RAT HEPATOCYTES

SummaryParenchymal hepatocytes from neonatal rats were isolated, cultured about 24 h, exposed to cadmium with or without calcium, and processed for scanning electron microscopy. To assess the severity of cadmium-induced changes, exposed hepatocytes were categorized based upon the extent of morphological damage. Differences in surface blebbing, alterations in microvilli, variations in the degree of swelling, and changes in cell shape were used to categorize the severity of cell damage. A double-blind morphometric analysis (a geometricostatistical processing of two-dimensional data for the collection of three-dimensional information) of cellular changes was conducted for each exposure time and for each concentration of cadmium in the presence or absence of calcium. Significant decreases occurred in the percent relative volume of normal, flattened cells present in cultures exposed for 30 min to 50 or 100 μM cadmium in the absence of calcium. In contrast, the percent relative volume of severely damaged spherical cells was significantly increased after exposure to solutions containing 50 or 100 μM cadmium and lacking calcium. Percent relative volume of intermediate cells (which were slightly swollen and showed changes in microvillar number) was significantly increased following a 30 min exposure to all cadmium concentrations in the absence of calcium. The examination of hepatocytes exposed for 60 min showed that the degree of cadmium-induced cytotoxicity was more severe in the absence of calcium than was the case for the hepatocyte cultures exposed for 30 min: approximately 30% more spherical cells and 30% fewer flattened cells were present if cultures were exposed in the absence of calcium for 60 min compared to those exposed for 30 min. The degree of blebbing was significantly greater at all cadmium concentrations in the absence of calcium. The presence of calcium, therefore, reduced cadmium-induced cytotoxicity in primary cultures of rat hepatocytes subjected to morphometric analysis after scanning electron microscopy.

Adherence of Group B Streptococci and Human Erythrocytes to Influenza A Virus-Infected MDCK Cells

Summary Scanning electron microscopy was used to compare the adherence of group B streptococci (types Ia, Ic, and II) and human erythrocytes to canine kidney cell monolayers inoculated 24-48 hr earlier with influenza A/NWS/33 virus. Streptococci and erythrocytes adhered to the kidney cell surface membranes and filamentous projections of some but not all the cells in virus-inoculated monolayers, while they did not adhere to control monolayers. Streptococcal adherence was blocked when the virus-infected cells were first exposed to erythrocytes. Likewise, hemadsorption was blocked when the virus-infected cells were first exposed to streptococci. In mixed bacterial adherence-hemadsorption tests bacteria adhered only to hemadsorption-positive virus-infected cells. Adherence of streptococci types Ia and Ic and erythrocytes was inhibited when the streptococci and erythrocytes were pretreated with receptor destroying enzyme. However, enzyme treatment of type II streptococci did not affect their ability to adhere to virus-infected cells.

A review of sources of spurious silicon peaks in electron microprobe X-ray spectra of biological specimens.

Abstract The presence of Si peaks in X-ray spectra of biological specimens can lead to misinter-pretation of data if one is unaware of potential sourees of artifactual Si. Silicontcontamination may be acquired from oils or greases during the course of specimen preparation or from the vacuum system of the electron microscope. In energy dispersive X-ray detection, the level of the Si peak cannot be reduced below that of the internal fluorescence peak obtained from the dead layer of the detector.

Deciliation in the Puerperal Fallopian Tube

Tubal segments obtained from patients at cesarean section and at intervals during the first 5 postpartum days were examined to evaluate puerperal changes in the tubal epithelium. The specimens of tubal epithelium were examined under the scanning and transmission electron microscopes. Ciliated cells were most densely distributed on the fimbria and in the ampulla, and were relatively sparsely distributed in the isthmus. Progressive diminution of numbers of ciliated cells and deciliated of individual cells were noted in specimens obtained during the puerperium. Nonciliated cells were in the resting stage at term pregnancy. Secretory activity returned during the puerperium.

Electron probe X-ray microanalysis of arsenic inclusions in fish

Adult green sunfish were exposed to aqueous solutions of arsenic as sodium arsenate and sacrificed at regular intervals for morphological and analytical procedures including scanning transmission electron microscopy (STEM), electron probe X-ray microanalysis (XRMA), high voltage electron microscopy (HVEM), and conventional transmission electron microscopy (CTEM). The CTEM and HVEM data indicated that the inclusion is not associated with the nucleous and that it is composed of bead-like subunits arranged linearly to form a structure which twists and coils throughout the nucleus. The use of specimen preparation procedures eliminating osmium tetroxide post-fixation, as well asen bloc and post-stains, allowed visualization of the inclusion despite reduction in contrast compared to specimens prepared by standard methods. Therefore, prior to STEM and XRMA analyses, it was assumed that this unusual morphological entity represented an arsenic deposit which initiated some cytotoxic reaction and subsequent preferential staining in the standard osmium-fixed, stained specimens. The XRMA and STEM data verify the presence of arsenic within the arsenic inclusion; in addition, the ratio of the arsenic K photopeak to the sulfur photopeak was 6 to 1—perhaps indicative of a direct association between arsenic and sulfur-rich protein molecules. The possibility was also considered of arsenate substitution for phosphate on deoxyribonucleic acid.

Comparison of two techniques of suturing in microsurgical anastomosis of the rabbit oviduct.

Microsurgical reconstruction of the rabbit oviduct was undertaken utilizing either through-and-through sutures including the mucosa, or sutures penetrating the serosa and myosalpinx but not the mucosa. Patency and pregnancy rates did not seem to vary with the suturing technique. However, scanning electron microscopic observation revealed abnormal mucosal fold patterns at 3 weeks after surgery. Fibrinous exudates over the surface of the intraluminal sutures increased with time until the entire surface was thickly veiled by 9 weeks. The observation also revealed regeneration of epithelial cells along the suture. These cells included many abnormal forms such as giant cells and misshapen cells. The majority of these were nonciliated. In theory, the intraluminal suture could form a nidus for epithelial hyperplasia which might cause future tubal obstruction. However, the patency and pregnancy rates obtained with through-and-through suturing were similar to those obtained when the endosalpinx was excluded, both in this study and in previous studies from these laboratories.

Changes in the concentration of ions during senescence of the human erythrocyte.

Flash frozen samples of normal human blood were cryosectioned and cryodried for electron probe x‐ray microanalysis of the concentration of ions and elements in individual erythrocytes (RBCs). The data (expressed in mM/kg dry weight) demonstrated a systematic pattern of variation between the concentration of ions and elements in the RBCs. Specifically as K+ and Cl decreased in concentration, Ca2+ and sulfur increased in concentration. Phosphorous, Na+ and Mg2+ did not demonstrate a significant pattern of change. These findings are related to the dehydration and to the volume decrease that accompanies senescence of the RBC.

Dark exposure inhibits the mitotic activity of thyroid follicular cells in male mice with intact pineal.

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Hemosiderin Granules: Cytotoxic Response to Arsenic Exposure in Channel Catfish

Adult channel catfish were exposed to 0 or 15 ppm arsenic as sodium arsenate in synthetic lake water for approximately six months. After sacrifice, livers were removed and examined by conventional transmission electron microscopy, optical microscopy, scanning electron microscopy, and electron probe X-ray microanalysis. Cytoplasmic structures in the nuclei were found to contain highly concentrated deposits of iron. Thirty percent of these structures were also found to contain arsenic at a level above the minimum detectable level for the conditions of the study. The size, shape and relative position of the cytoplasmic structures were the same as the hemosiderin granules observed by conventional transmission electron microscopy. (JMT)