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Biomedical subjects

M C Williams

Publications and source records attributed to M C Williams.

At least 91 records · Page 5Linked to original sources

The effect of magnesium sulfate infusion on systemic and renal prostacyclin production.

Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4.

Adult↗

Optimizing radiation worker protection: the practical application of risk analysis.

This paper presents the concepts of equivalent risk and risk minimization in optimizing radiation worker protection. When prescribing worker protection requirements and identifying work restrictions, all significant contributions to worker risk should be considered, not just the risk associated with radiation dose. This approach requires a practical application of risk analysis that allows comparison of a variety of risks. Examples of the types of worker risks that must be evaluated are given, and the author proposes that the scientific community develops a methodology for risk comparison that can be implemented via an expert system to facilitate risk analysis and decision making.

Humans↗

Interferon-gamma and synthesis of surfactant components by cultured human fetal lung.

We examined the effects of interferon-gamma (IFN-gamma) on development of the surfactant system in alveolar epithelial cells of fetal lung. Explants of second-trimester human fetal lung were cultured for 1 to 6 days in serum-free medium containing recombinant human IFN-gamma (0.03 to 30 ng/ml) and/or dexamethasone (10 or 100 nM). Treatment for 3 days with IFN-gamma alone, dexamethasone alone, and IFN plus dexamethasone increased the content of surfactant protein A (SP-A, 28 to 36 kD) by approximately 3-, 2.5-, and 10-fold, respectively. The biphasic response pattern of SP-A to dexamethasone (stimulation initially and inhibition with continued culture) was not altered by the presence of IFN-gamma. IFN-gamma also stimulated accumulation of SP-A mRNA (2.7-fold at 24 h) but did not affect the levels of mRNAs for surfactant protein B (18 kD) and surfactant protein C (5 kD). To assess the effect of IFN-gamma on synthesis of surfactant lipids, we determined the content of phosphatidylcholine, the rate of labeled choline incorporation into phosphatidylcholine, saturation of newly synthesized phosphatidylcholine, and the activity of fatty acid synthetase, a glucocorticoid-inducible enzyme. Treatment of explants for 5 days with IFN-gamma had no effect on these parameters. Studies by light and electron microscopy revealed little difference between control and IFN-treated explants with regard to cell viability and epithelial cell differentiation. We conclude that IFN-gamma has a selective stimulatory effect on SP-A among surfactant components.(ABSTRACT TRUNCATED AT 250 WORDS)

Choline↗

Expression of cell-specific markers for alveolar epithelium in fetal rat lung.

In adults, the alveolar epithelium is composed of types I and II cells which differ structurally and functionally although they appear to belong to the same cell lineage. Using cell-specific markers (type I cells, monoclonal antibody; type II cells, Maclura pomifera lectin [MPA]), we have determined when and in what pattern their binding sites occur during development of the fetal rat lung. Rather than first appearing on days 19 to 20, when morphogenesis of type I cells occurs and lamellar bodies provide positive identification of type II cells, the markers appeared on day 15 (for type I cell marker) and day 16 (for type II cell marker). The type I cell marker was widespread by day 17 and was sufficiently abundant to be detected on a Western blot. MPA binding appeared more gradually and was often found on isolated cells. On serial sections of day 20 lung, the markers appeared to be localized to the same cells. The early appearance of cell-specific markers suggests an early onset of the developmental program that leads to full differentiation of types I and II cells. Co-expression of both cell-specific markers suggest that fetal cell lineage may differ from the scheme proposed by others that type II cells serve as type I cell precursors during development.

Animals↗

The pathology of experimental Lasiospermum bipinnatum (Thunb.) Druce (Asteraceae) poisoning in sheep. I. Hepatic lesions.

Poisoning with the plant Lasiospermum bipinnatum was studied in 9 lambs. Intraruminal doses, varying from 1-12 g/kg/day of dried plant, were administered to 8 animals and 1 was fed 2.5 g/kg/day of the material mixed with maize meal for 13 days. Periodic serum analyses were done to monitor liver function. Lambs given 6-12 g/kg/day died or were killed in extremis. Clinical signs included progressive anorexia and depression in all these lambs and icterus in 2 animals. Lambs given 1-4 g/kg/day were sacrificed after about 2 weeks. Clinical signs in these animals were minimal or absent. Hepatosis was found in all the lambs, the severity of which correlated with levels of plant administered. Centrilobular necrosis and haemorrhage occurred in 2 of the 4 lambs given high doses; single cell necrosis of hepatocytes was observed with intermediate doses, and diffuse degeneration, which was more severe peripherally, was seen at various doses. In 1 lamb, degeneration was most severe midzonally. Bile ductule epithelial proliferation was observed in 7 of the 9 poisoned animals. Marked hypertrophy of hepatocellular smooth endoplasmic reticulum was seen in 3 lambs given low doses. The hepatic lesions were compared with those reported for poisoning by other hepatotoxic plants belonging to the family Asteraceae and found to be indistinguishable.

Animals↗

The pathology of experimental Lasiospermum bipinnatum (Thunb.) Druce (Asteraceae) poisoning in sheep. II. Pulmonary and miscellaneous lesions.

Poisoning with the plant Lasiospermum bipinnatum was studied in 9 lambs at various dose levels. Dyspnoea and tachypnoea, which were dose-related, were observed in 4 of the lambs. Gross and microscopic pulmonary lesions were found in all the lambs receiving plant material originating from one source but not in those given plant from another locality. The severity of the lesions appeared to be dose-dependent. Macroscopic lesions included pulmonary and mediastinal emphysema, congestion and oedema. Microscopically Clara cell hypertrophy and hyperplasia, and interstitial pneumonia were the most outstanding findings. It is speculated that the pulmonary lesions were induced by a furanosesquiterpene or tryptophan or a combination of both of these toxins in the dosed plant material. Miscellaneous and inconsistent lesions observed in the experimental animals included widespread haemorrhage (1 lamb), transudations into the body cavities and adrenocortical hyperplasia.

Animals↗

Perceptual consequences of a temporal processing deficit in reading disabled children.

Recent research suggests that some children who are reading disabled exhibit sensory deficits associated with poor temporal processing. The performance of disabled readers on various perceptual tasks is consistent with a temporal processing deficit hypothesis. Visual masking paradigms were utilized to obtain direct measures of the temporal aspects of processing in normal and disabled readers, and showed that the visual processing of disabled readers is characterized by a longer integration time and a slower processing rate for both simple and word-like stimuli. Image blurring, which reduces the contrast of high spatial frequencies, reestablished normal temporal processing of words in disabled readers.

Child↗

Impaired plasma cholesteryl ester transfer with accumulation of larger high density lipoproteins in some families of baboons (Papio sp.).

Baboons from some families have a higher concentration of plasma high density lipoproteins (HDL) on a chow diet and accumulate large HDL (HDL1) when challenged with a high cholesterol and high saturated fat (HCHF) diet. HDL1 from high HDL1 animals contained more (1.5-fold) cholesteryl ester than HDL (HDL2 + HDL3) from high or low HDL1 animals. HDL from high HDL1 baboons had lower triglyceride content than that from low HDL1 baboons. HDL3 or HDL labeled with [3H]cholesteryl linoleate was incubated with entire lipoprotein fraction (d less than 1.21 g/ml) or very low density lipoprotein + low density lipoprotein (VLDL + LDL) (d less than 1.045 g/ml) and with lipoprotein-deficient serum (LPDS), and the radioactive cholesteryl ester and mass floating at d 1.045 g/ml (VLDL + LDL) after the incubation was measured. The transfer of cholesteryl esters from either HDL or HDL3, prepared from plasma of high HDL1 animals fed chow or the HCHF diet, was slower than the transfer from either HDL or HDL3 of low HDL1 animals, regardless of the source of transfer activity or the ratio of LDL:HDL-protein used in the assay. Addition of HDL from high HDL1 baboons into an assay mixture of plasma components from low HDL1 baboons decreased the transfer of cholesteryl ester radioactivity and mass from HDL to VLDL and LDL. In addition to HDL, a fraction of intermediate density lipoprotein (IDL) and denser HDL were also effective in inhibiting the transfer. These observations suggest that accumulation of HDL1 in high HDL1 baboons fed an HCHF diet is associated with a slower transfer of cholesteryl esters from HDL to LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lead poisoning in a dog.

A case of lead poisoning caused by ingestion of a lead roof-washer is described in a one-year-old, spayed Fox Terrier bitch, presented with nervous signs, and basophilic stippling of red blood cells. Blood concentrations of lead were in the low toxic range. Radiography of the abdomen revealed radio-dense objects in the stomach, which on gastrotomy included a lead roof-washer. Prior to removal of the foreign bodies, the dog showed remarkable improvement on non-specific symptomatic treatment alone, and recovered well after surgery, only to die unexpectedly several hours later. Concentrations of lead in the liver and kidneys were extremely high, and histology revealed typical intracellular inclusions and organ degeneration. In the light of these findings, it is suggested that all cases of suspected or confirmed lead poisoning be given specific chelation therapy.

Animals↗

The fetal board.

The fetal board is a multidisciplinary approach to complex perinatal clinical problems. It has a model in the tumor board, which has been used in many institutions to plan and coordinate care for patients with a malignancy. The pregnancy with a known or suspected abnormal fetus represents a clinical setting in which consultants from several disciplines have a potential role in the ultimate outcome. Therefore, a fetal board provides prospective opportunities for clinical diagnosis, counseling, and comprehensive care of the maternal patient and her fetus before, during, and after delivery. The fetal board's purpose is to incorporate the expertise of various specialties and subspecialties to provide optimum care for the abnormal fetus. The board also provides educational opportunities to all involved in patient care, including perinatologists, obstetricians, neonatologists, pediatricians, nursing staff, social service providers, and other health professionals.

Congenital Abnormalities↗

Monoclonal antibodies specific to apical surfaces of rat alveolar type I cells bind to surfaces of cultured, but not freshly isolated, type II cells.

The alveolar surface of the lung is lined by two classes of epithelial cells, type I and type II cells. Type I cells cover more than 97% of the alveolar surface. Although this cell type is felt to be essential for normal gas exchange, neither unique identifying characteristics nor functions have been described for the type I cell. We have produced monoclonal antibodies to (a) component(s) of molecular weight 40,000 and 42,000 of the apical surface of rat alveolar type I cells. The antibodies are specific to the lung in Western blots of organ homogenates. In immunocytochemical studies of frozen lung at the level of both light and electron microscopy, the monoclonal antibodies appear to react specifically with the apical plasma membrane of type I cells. Airway, vascular, interstitial cells, type II cells and macrophages are not immunoreactive. Western blots of isolated type I cells (approx. 70% pure) also demonstrate immunoreactivity at molecular weights of 40,000 and 42,000. When the lung is injured, type I cells may be damaged and sloughed from the alveolar surface. Alveolar repair occurs when the second type of alveolar cell, the type II cell, divides. Cell progeny may retain type II cell morphology or may differentiate into type I cells. Western blots of freshly isolated type II cells (approx. 85% pure) do not display immunoreactivity with our monoclonal antibodies. However, type II cells maintained in culture acquire immunoreactivity to monoclonal antibodies, demonstrating that type II cells in vitro have the capacity to develop a characteristic associated with type I cells in situ. The availability of markers for a specific membrane component of type I cells should facilitate the study of many questions on alveolar functions, development and response to injury.

Animals↗

Temporal order judgements in good and poor readers.

The amount of time required to make accurate (75% correct) temporal order judgements was measured in groups of 3rd and 4th grade children who were selected on the basis of reading ability. The stimuli, two words (Box and Fox), were tachistoscopically presented to the left and right or above and below a fixation point. Subjects were asked to say which word came first under one condition, or which position contained the stimulus that occurred first under another condition. The stimulus onset asynchrony (SOA) was varied in half octave steps until threshold was determined. The results indicate that good readers required significantly longer SOAs to achieve 75% correct than adults, but significantly shorter SOAs than poor readers. There was not a significant difference in thresholds for the word and position conditions for adults or good readers, but poor readers required significantly more time to achieve criterion for the word condition. The word thresholds were highly correlated (-0.77) with reading level, but the correlation between position threshold and reading level was not significant. The implications of a temporal order deficit are discussed.

Adult↗

Monoclonal antibodies to surfactant proteins SP28-36 label canine type II and nonciliated bronchiolar cells by immunofluorescence.

The major 28,000- to 36,000-dalton proteins of pulmonary surfactant (SP28-36) have been shown by various techniques to be synthetic and secretory products of alveolar type II cells. Surfactant lipids are also secreted by these cells. Immunocytochemical studies of human and rodent lungs have indicated that nonciliated epithelial cells of small bronchioles appear to contain SP28-36 in their synthetic organelles and secretory granules. Because these observations were obtained with polyclonal antibodies against SP28-36, it was possible that bronchiolar cell staining was due to contaminant antibodies not detected by biochemical analyses. To clarify the role of bronchiolar cells in the metabolism of SP28-36, we have prepared 5 monoclonal antibodies against canine SP28-36. Electrophoresis and immunoblots of surfactant showed that each antibody reacted with SP32 and 36, as well as SP28, the nonglycosylated species. This indicates that the antibodies are directed against the protein rather than carbohydrate moieties of SP28-36. Immunoblot analysis of collagenase-treated SP28-36 showed that the antibodies DS-3 and DS-1 were directed against the noncollagen region of the protein. Immunoblot analysis of whole canine lung homogenates showed that a single protein species was recognized by the antibodies. Immunofluorescence studies of cryostat sections of canine lung showed that both type II and nonciliated bronchiolar cells were specifically labeled with each antibody. These and previous data are consistent with and support the idea that bronchiolar cells synthesize and secrete SP28-36.

Animals↗

Divalent cation and hydrogen ion effects on the structure and surface activity of pulmonary surfactant.

The structure and surface activity of the extracellular fraction of pulmonary surfactant known as tubular myelin are Ca2+ dependent. Previous studies have demonstrated surfactant-specific proteins with monomeric molecular weights of 28,000-36,000 (SP28-36) are associated with this fraction. In reassembled lipoprotein mixtures, SP28-36 promotes the Ca2+-induced aggregation and surface activity of surfactant lipids, but the detailed interactions between Ca2+, SP28-36, and surfactant lipids have not been established. In this study, we investigated the effect of various cations on the aggregation of surfactant lipid liposomes in the presence of SP28-36. SP28-36 reduced the threshold ion concentration for liposome aggregation from greater than 10 to 0.5 mM for Ca2+, Ba2+, and Sr2+ but not Mg2+ or Mn2+. The liposome aggregation was reversed by ethylenediaminetetraacetic acid and not associated with leakage of carboxyfluorescein. SP28-36 promoted similar liposome aggregation at pH less than 5 in the absence of divalent cations. Surfactant lipids adsorbed slowly to an air-fluid interface in all ionic conditions unless SP28-36 was present. Both Ca2+ and H+ induced rapid lipid adsorption in the presence of SP28-36. The surface activity of native surfactant had a similar ion dependence. Electron micrographs of native surfactant showed typical tubular myelin structures at pH 7.4 only in the presence of Ca2+. At pH 4.4 in the absence of Ca2+, similar but not identical structures were seen. In the reconstituted system, SP28-36 in the presence of Ca2+ induced the formation of larger multilayered structures including parallel bilayers and small areas of squares and triangles with dimensions similar to structures found in the native material.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗