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Biomedical subjects

M C Williams

Publications and source records attributed to M C Williams.

At least 181 records · Page 10Linked to original sources

Permeability of muscle capillaries to microperoxidase.

In this study we attempted to identify a morphologic counterpart of the small pore of muscle capillaries. The existence of such a pore has been postulated by physiologists to explain the permeability of muscle capillaries to small macromolecules. We injected mice intravenously with microperoxidase (MP) and fixed specimens of diaphragm at intervals of 0-250 s after the injection to localize the tracer by electron microscopy. The small size of MP (1,900 mol wt and 20 A molecular diameter [MD]) ensures its ready passage through the small pore since the latter is thought to be either a cylindrical channel 90 A in diameter or a slit 55 A wide. MP appears in the pericapillary interstitium within 30 s of initiation of its intravenous injection. The patterns of localization of MP observed within clefts between adjacent capillary endothelial cells indicate that some endothelial junctions are permeable to this tracer. Although small vesicles transfer MP across the endothelium, we do not believe that the vesicles transfer substantial amounts of MP into the pericapillary interstitium. We did not obtain evidence that MP crosses the endothelium of capillaries through channels formed either by a single vesicle or by a series of linked vesicles opening simultaneously at both surfaces of the endothelial cell. From our observations we conclude that some endothelial junctions of capillaries are permeable to MP, and that these permeable junctions are a plausible morphologic counterpart of the small pore.

Animals↗

Retroperitoneal liposarcoma metastatic to scalp.

Metastasis of liposarcoma to the scalp occurred in a 50-year-old-man. Review of the literature disclosed no documented reports. Although cutaneous metastases from internal malignancies are of relative infrequent occurrence, such metastases may be limited to the scalp and a diagnosis can be established by a biopsy.

Humans↗

Serologic survey of dengue and other arboviruses in Curaçao and Aruba, 1973.

Sera obtained principally from children on the Caribbean islands of Aruba and Curaçao were tested for antibodies to various arboviruses. The test indicated that dengue 2 was endemic on Curaçao but not on Aruba, perhaps because of more effective vector control measures on Aruba. Neutralization tests performed with a samll number of sera suggest that dengue infections may have afforded some level of protection against yellow fever to a portion of the Curacao population.

Adult↗

An outbreak of "kikuyu poisoning" in Western Transvaal.

An outbreak of mortality in cattle grazing kikuyu (Pennisetum clandestinum) pastures on a farm in the western Transvaal is described. These pastures had been heavily infested with army worm (Spodoptera exempta) two weeks preceding the onset of deaths. The main symptoms were excessive salivation, paresis of the tongue and pharynx, localized fine muscular tremors, ruminal tympany and stasis and congested or cyanotic mucous membranes. Significant clinical pathological findings were leukocytosis, elevated blood sugar levels and lowered serum magnesium and sodium levels. Autopsy findings of interest were patchy or diffuse hyperaemia of the rumen and abomasum and small haemorrhages in especially the lymph nodes, heart and tracheal mucosa. The most important histopathological finding was superficial or deep necrosis of the ruminal epithelium with marked neutrophile infiltration. All forms of treatment, including intravenous administration of magnesium sulphate, were of no avail. The condition closely resembles so-called "Kikuyu poisoning" in New Zealand.

Animals↗

Oxidative metabolism and de-ethynylation of 17alpha-ethynylestradiol by baboon liver microsomes.

Incubations of tritiated 17alpha-ethynylestradiol (EE2) with liver explants of baboon and mouse showed the primate species to be more efficient in the removal of the ethynyl group. Liver microsomes from sexually immature male and female baboons were then incubated with tritiated EE2 and estradiol (E2). Each hormone bound irreversibly to the microsomal pellet. Addition of glutathione reduced the irreversible or covalent association. Incubations with E2 demonstrated significant conversion to estrone (E1). The EE2 experiments demonstrated a conversion to estrone only in the presence of an NADPH-generating system, and the addition of SKF-525A reduced the conversion of EE2 to E1. The cleavage reaction appears to be an oxidative event.

Animals↗

Conversion of lamellar body membranes into tubular myelin in alveoli of fetal rat lungs.

Fluid-filled lumina of fetal rat lungs contain lamellar bodies (LBs) as well as tubular myelin (TM), both of which are thought to be stores of phospholipid-rich pulmonary surfactant. The alveolar epithelium is believed to secrete LBs, but neither the origin nor the mechanism of TM formation is entirely certain. The main objective of this study was to determine the relationship between secreted LBs and TM and to define membrane phenomena which occur during TM formation. I examined lung tissues of 20-21 day-old fetuses (day 22 = term) using transmission and high voltage transmission electron microscopy and cytochemistry. My findings indicate that secreted LBs, identified by the presence of an acid-phosphatase reactive core, are the precursor of TM. Secreted LBs are highly organized structures which contain structurally specialized areas, one of which is a "mini-lattice" structure similar to TM. During TM formation, fuzzes or 8.0-nm diameter particles appear on transition membranes, although LB membranes appear to lack both structures. Similar particles are present on TM membranes and are generally associated with membrane intersections. My results provide evidence that TM is formed from LBs within the alveolar lumen by mechanisms which may be complex.

Animals↗

Isolation and properties of type II alveolar cells from rat lung.

Type II alveolar cells can be isolated and partially purified from adult rat lung by a series of steps that includes enzymatic digestion of the lung with trypsin and separation of cells on a discontinuous albumin density gradient. The yield of the isolated type II cells depends on the supplier and the housing of the rats used to prepare the cells. With specific pathogen-free rats housed in a laminar flow hood, the yield was 20.3 x 10(6) cells per rat, of which 50 per cent were type II cells. With rats from 2 other suppliers and no special housing, the yields were 8.8 and 8.3 x 10(6) cells per rat, of which 67 and 65 per cent were type II cells. The ultrastructural appearance of the isolated cells was similar to that of cells from intact lung, except for some dilatation of the endoplasmic reticulum and the perinuclear space. Most cells (92 +/- 5 per cent) excluded the vital dye, trypan blue. The cells consumed O2 at the rate of 76 +/- 12 nmole per 10(6) cells per hour and released only 5.7 +/- 2.0 per cent of their lactate dehydrogenase, a cytoplasmic enzyme, into the medium after 1 hour of incubation. The isolated type II cells contained disaturated phosphatidylcholine, a major component of purified surface-active material. The cells, however, had a low glucose utilization compared to their O2 consumption, which may indicate an abnormality in the metabolism of glucose. This population of cells could be further purified to 89 per cent type II cells by unit gravity velocity sedimentation.

Animals↗

Sarcoidosis: analysis of cells obtained by bronchial lavage.

The cellular content of bronchial lavage was studied in 14 patients with sarcoidosis and 20 normal volunteers. There was no alteration in the total number of cells recovered, except for the expected increase in cellularity in smokers. Nonsmoking patients with sarcoidosis had 19.6 per cent lymphocytes, compared to 8.1 per cent lymphocytes in nonsmoking control subjects. The percentage of alveolar macrophages showing spontaneous adherence of one or more bronchial lymphocytes were, respectively, 10.8 and 8.4 in nonsmoking and smoking patients with sarcoidosis, compared to 1.8 and 2.1, respectively, in nonsmoking and smoking control subjects.

Adult↗

Shear-induced hemolysis with commercial and glow discharge silicones.

The hemolytic characteristics of 14 different polydimethyl-siloxane materials were studied, using a rotating disk device to shear whole human blood for 6000 sec. Disk surfaces included commercial Silastic products with and without silica filler, coatings formed from hexa-methyl and tetra-methyl disiloxane monomer vapors by glow discharge, and heparinized silicones. Results are presented in the form of kinetic hemolysis curves (KHC)--plots of plasma hemoglobin vs. time--and analyzed in terms of the slopes of these curves in the 1500-6000 sec region where the KHC is nearly linear. It was found that most silicone products are low-hemolysis materials, comparable to polyethylene (PE) but often about 20% less ehmolytic; one product was superior by about 40%. The only consistent exceptions to this were the glow discharge surfaces from HEXA-methyl disiloxane (15-80% poorer than PE) and heparinized surfaces (70-280% more hemolytic than PE).

Dimethylpolysiloxanes↗

Inhibition of HeLa cell messenger RNA translation by 7-methylguanosine 5'-monophosphate.

Translation of HeLa cell RNA containing poly(A) in a wheat germ cell-free system is markedly but incompletely inhibited by 7-methylguanosine 5'-monophosphate (m7G5'p). We have analyzed the translation products synthesized in the presence of different concentrations of m7G5'p and find that translation of all mRNAs is equally inhibited. To demonstrate the specificity of the inhibitor for RNAs with 5'-terminal m7G5' ppp... we show that specific translation products of satellite tobacco necrosis virus RNA, which does not have this 5' terminus, are synthesized in the presence of m7G5' p. Protein synthesis programmed by endogenous mRNA in a HeLa cell-free system is inhibited after a 10-min lag by m7G5' p. Other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position are not inhibitor. We show that translation of all mRNAs is inhibited to a similar extent by m7G5'p in the HeLa cell-free system, by synthesizing 35S-labeled proteins in the presence of different inhibitory concentrations of this nucleotide and analyzing the translation products by electrophoresis and autoradiography. Translation of encephalomyocarditis virus RNA added to the HeLa cell-free system is not inhibited by m7"g5p; this viral RNA does not have this nucleotide at the 5' terminus. This indicates that m7G5'p specifically inhibits translation of mRNAs with the 5' terminus m7G5'ppp... and suggests that initiation of translation of picornavirus RNA may proceed via a mechanism different from that of cellular mRNAs.

Globins↗

Human urinary and liver conjugates of 17alpha-ethnylestradiol.

Chromatographic profiles of the conjugates of 17alpha-ethynylestradiol (EE2) were obtained from the urine of castrate and normal women given tritium labeled EE2 orally. Five distinct radioactive peaks were observed, with considerable quantitative variation between individuals. Glucosiduronate fractions comprised the dominant excreted radioactivity. In vitro incubation of normal human liver also produced five conjugate types. Simultaneous intravenous/oral (14C/3H) administration of EE2 demonstrated conversion to identical urinary conjugate and free steroid products, with a greater excretion of the intravenous material. Authentic 3-glucuronide of EE2 was synthesized and its position in the chromatographic system relative to the urinary conjugate peaks demonstrated.

Adult↗

Discoidal bilayer structure of nascent high density lipoproteins from perfused rat liver.

Rat livers were perfused for 6 h without added plasma proteins using washed erythrocytes and buffer in a recirculating system. An inhibitor to the enzyme lecithin-cholesterol acyltransferase (5,5'-dithionitrobenzoic acid) was added in some experiments to prevent modification of substrate-lipids contained in secreted lipoproteins. The inhibitor did not detectably alter hepatic ultrastructure or gas exchange, but it inhibited the secreted lecithin-cholesterol acyltransferase by more than 85%. Very low density lipoproteins in perfusate were unaltered but the high density lipoproteins obtained from livers perfused with the inhibitor appeared disk-shaped in negative stain by electron microscopy with a mean edge thickness of 46 +/- 5 A and a mean diameter of 190 +/- 25 A. The high density lipoproteins were composed predominantly of polar lipids and protein with only small amounts of cholesteryl esters and triglycerides. The major apoprotein of these discoidal fractions had the same electrophoretic mobility as the arginine-rich apoprotein, whereas plasma high density lipoproteins contained mainly the A-I approtein. In all these respects the discoidal perfusate high density lipoproteins closely resemble those found in human plasma which is deficient in lecithin-cholesterol acyltransferase. Perfusate high density lipoproteins obtained in the absence of the enzyme inhibitor more closely resembled plasma high density lipoproteins in chemical composition (content of cholesteryl esters and apoproteins) and in electron microscopic appearance. Purified lecithin-cholesterol acyltransferase synthesized cholesteryl esters at a substantially faster rate from substrate lipids of perfusate high density lipoproteins than those from plasma. The discoidal high density lipoproteins were the best substrate for this reaction. Thin sections of plasma high density lipoproteins indicated a spherical particle whereas discoidal high density lipoproteins stained with the characteristic trilaminar image of membranes. These observations suggest that the liver secretes disk-shaped lipid bilayer particles which represent both the nascent form of high density lipoproteins and preferred substrate for lecithin-cholesterol acyltransferase.

Animals↗