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Biomedical subjects

M C Williams

Publications and source records attributed to M C Williams.

At least 37 records · Page 2Linked to original sources
PubMed1999

Raised salivary endotoxin concentration as a predictor of infection in pediatric leukemia patients.

OBJECTIVE: The aim of this study was to evaluate whether salivary endotoxin could be used as a predictor of infection in pediatric patients (n = 12). STUDY DESIGN: Oropharyngeal carriage of aerobic gram-negative bacilli was monitored and salivary endotoxin concentration determined. Age-matched and gender-matched healthy children were used as controls. RESULTS: The range of salivary endotoxin concentrations in the healthy pediatric population was similar to the range previously reported for healthy adults (0-20 ng/mL; 0-240 EU/mL). CONCLUSION: It was found that salivary endotoxin was not an accurate predictor of sepsis and did not correlate with oropharyngeal carriage of aerobic gram-negative bacilli.

Adolescent↗
PubMed1998

Persistent pulmonary hypertension of the neonate and asymmetric growth restriction.

OBJECTIVE: To evaluate the possible associations between persistent pulmonary hypertension of the neonate, need for extra-corporeal membranous oxygenation, small for gestational age (SGA), and low ponderal index for gestational age in infants with persistent pulmonary hypertension of the neonate and in matched controls. METHODS: Eighty-six infants with persistent pulmonary hypertension of the neonate delivered from 1991 to 1994 at our hospital were matched with 430 contemporaneous control singleton neonates. Birth weight and ponderal indices (100 x weight/length3) less than the tenth percentile for gestational age and gender were defined as SGA and low ponderal index, respectively. We assessed associations between these markers, the presence of persistent pulmonary hypertension of the neonate, and the need for extracorporeal membranous oxygenation. RESULTS: Low ponderal index was associated with persistent pulmonary hypertension of the neonate (odds ratio [OR] 5.4), whereas SGA was not. Low ponderal index (OR 4.0) was an independent correlate of persistent pulmonary hypertension of the neonate after adjustment with logistic regression for 5-minute Apgar scores less than 7, umbilical arterial pH less than 7.10, and presence of meconium. Low ponderal index was associated with need for extracorporeal membranous oxygenation in neonates with persistent pulmonary hypertension (P < .001). CONCLUSION: Fetal developmental events may significantly affect neonatal pulmonary status. Diminished neonatal nutritional status, as measured by low ponderal index for gestational age, is associated with increased risk of persistent pulmonary hypertension of the neonate and severity of the disease process.

Case-Control Studies↗
PubMed1998

Low weight/length ratio to assess risk of cerebral palsy and perinatal mortality in twins.

The etiology of increased rates of cerebral palsy (CP) in twins is unclear, but likely is associated with growth retardation, which occurs more often in twins. Asymmetric growth restriction, a form of growth retardation, has been found associated with increased rates of perinatal morbidity in infants with normal centile birthweights, and occurs more often in twins. Data from 55,457 infants were evaluated. Associations between twinning, CP, and neonatal mortality were evaluated. Influences of confounding factors, such as prematurity, perinatal depression, and asymmetric growth were assessed. Although twinning was a significant univariate correlate of both CP and neonatal mortality, low weight/length ratio (a marker of asymmetric growth) was a better correlate of both outcomes, and twinning was not significantly associated with either outcome after logistic adjustment for factors such as prematurity, perinatal depression, and low weight/length ratio. Low weight/length ratio occurred more often in twins of advancing gestational age, supporting a hypothesis of competition for nutritional resources as the cause for increased rates of low weight/length ratio in twins as compared with singletons. Asymmetric growth restriction is an important correlate of neonatal morbidity in twins, and should be considered when these factors are assessed in infants from multiple gestations.

Birth Weight↗
PubMed1998

Modulation of t1alpha expression with alveolar epithelial cell phenotype in vitro.

T1alpha is a recently identified gene expressed in the adult rat lung by alveolar type I (AT1) epithelial cells but not by alveolar type II (AT2) epithelial cells. We evaluated the effects of modulating alveolar epithelial cell (AEC) phenotype in vitro on T1alpha expression using either soluble factors or changes in cell shape to influence phenotype. For studies on the effects of soluble factors on T1alpha expression, rat AT2 cells were grown on polycarbonate filters in serum-free medium (MDSF) or in MDSF supplemented with either bovine serum (BS, 10%), rat serum (RS, 5%), or keratinocyte growth factor (KGF, 10 ng/ml) from either day 0 or day 4 through day 8 in culture. For studies on the effects of cell shape on T1alpha expression, AT2 cells were plated on thick collagen gels in MDSF supplemented with BS. Gels were detached on either day 1 (DG1) or day 4 (DG4) or were left attached until day 8. RNA and protein were harvested at intervals between days 1 and 8 in culture, and T1alpha expression was quantified by Northern and Western blotting, respectively. Expression of T1alpha progressively increases in AEC grown in MDSF +/- BS between day 1 and day 8 in culture, consistent with transition toward an AT1 cell phenotype. Exposure to RS or KGF from day 0 prevents the increase in T1alpha expression on day 8, whereas addition of either factor from day 4 through day 8 reverses the increase. AEC cultured on attached gels express high levels of T1alpha on days 4 and 8. T1alpha expression is markedly inhibited in both DG1 and DG4 cultures, consistent with both inhibition and reversal of the transition toward the AT1 cell phenotype. These results demonstrate that both soluble factors and alterations in cell shape modulate T1alpha expression in parallel with AEC phenotype and provide further support for the concept that transdifferentiation between AT2 and AT1 cell phenotypes is at least partially reversible.

Animals↗
PubMed1997

TGT3, thyroid transcription factor I, and Sp1 elements regulate transcriptional activity of the 1.3-kilobase pair promoter of T1alpha, a lung alveolar type I cell gene.

Alveolar type I epithelial cells form the major surface for gas exchange in the lung. To explore how type I cells differ in gene expression from their progenitor alveolar type II cells, we analyzed transcriptional regulation of T1alpha, a gene expressed by adult type I but not type II cells. In vivo developmental patterns of T1alpha expression in lung and brain suggest active gene regulation. We cloned and sequenced 1.25 kilobase pairs of the T1alpha promoter that can drive reporter expression in lung epithelial cell lines. Deletion analyses identified regions important for lung cell expression. The base pair (bp) -100 to -170 fragment conferred differential regulation in lung epithelial cells compared with fibroblasts. Sequence alignment of this fragment with type II-specific surfactant protein B and C promoters shows similar consensus elements arranged in a different order. Gel retardation studies with alveolar epithelial cell line nuclear extracts, thyroid transcription factor I (TTF-1) homeodomain, hepatic nuclear factor (HNF)-3beta, or Sp1 proteins, and supershift assays were used to characterize TTF-1, HNF-3 (TGT3), and Sp1/Sp3 binding sites. The TGT3 site binds factors with binding properties similar to HNF-3/Fkh (hepatic nuclear factor-3/forkhead) proteins but different from HNF-3alpha or HNF-3beta. Co-transfection with a TTF-1 expression vector moderately transactivated the -170 bp-reporter construct. Mutational analysis of these three binding sites showed reduced transcriptional activity of the -170 bp promoter. Therefore, several regulatory sequences involved in type II cell gene regulation are also present in the T1alpha promoter, suggesting that genes of the peripheral lung epithelium may be regulated by similar factors.

Adult↗
PubMed1997

Nitrogen dioxide exposure activates gamma-glutamyl transferase gene expression in rat lung.

Exposure to nitrogen dioxide (NO2) has been shown to activate glutathione metabolism in lung and lung lavage. Since GGT is a key enzyme in glutathione metabolism and we have previously characterized GGT expression in distal lung epithelium and in lung surfactant, we examined the NO2 exposed lung for induction of gamma-glutamyl transferase (GGT) mRNA, protein, and enzyme activity. We found that the GGT gene product is induced in lung by NO2. The GGT mRNA level in lung increases 2-fold within 6 hr and 3-fold after 24 hr of exposure to this oxidant gas, and this 3-fold elevation persists even after 14 days of exposure. The pattern of GGT mRNA expression switches from the single GGT mRNA III transcript in the normal lung to the dual expression of GGT mRNA I and mRNA III. Enzyme activity in whole lung increases 1.6- to 2.5-fold while extracellular surfactant-associated GGT activity accumulates 5.5-fold and GGT protein accumulates in lung surfactant. Induction of GGT mRNA and protein is evident in cells of the bronchioles by in situ hybridization and immunolocalization, respectively. In contrast, alveolar type 2 cells lack an in situ hybridization signal and exhibit a reduction in the intensity of immunostaining with prolonged exposure. Our studies show that NO2 induces GGT mRNA expression, including GGT mRNA1, in lung and GGT protein and enzyme activity in lung and lung lavage in response to the oxidative stress of NO2 inhalation.

Administration, Inhalation↗
PubMed1997

The value of the cervical score in predicting successful outcome of labor induction.

OBJECTIVE: To compare cervical dilation and the Bishop score as correlates of successful labor induction and vaginal delivery and to determine whether the prognosis of post-ripening cervical characteristics varies with the method of ripening used. METHODS: Four hundred forty-three women with Bishop scores less than 9 who required induction of labor were assigned randomly to cervical ripening with prostaglandin E2 gel or hygroscopic dilation. The Bishop score and its component characteristics were evaluated as univariate correlates of successful induction of labor and vaginal delivery and then were assessed using logistic regression to adjust for other maternal and fetal factors. The differences in the association between method of ripening and successful labor induction were evaluated relative to pre-ripening and post-ripening cervical examination characteristics. RESULTS: Cervical dilation was a better correlate of successful labor induction and vaginal delivery than was the Bishop score, even after exclusion of patients with initial Bishop scores greater than 6 and dilation greater than 3.0. Both ripening methods yielded similar success in labor induction and vaginal delivery, but when categorized by post-ripening cervical examinations, patients undergoing hygroscopic ripening had lower rates of successful labor induction and vaginal delivery. CONCLUSION: Cervical dilation is a better predictor of successful labor induction and vaginal delivery than either the Bishop score or any other Bishop score component characteristic. The likelihood of successful labor induction and vaginal delivery based on post-ripening cervical characteristics varies by the ripening method used.

Cervix Uteri↗
PubMed1997

Simultaneous in situ hybridization and TUNEL to identify cells undergoing apoptosis.

Apoptotic cells in tissue sections can be localized by in situ labelling of partly degraded DNA. In a heterogeneous population of cells, however, the specific identity of cell types undergoing apoptosis often cannot be reliably achieved at the light microscope level because of the marked alterations in cellular morphology that characterize apoptosis. In order to clearly specify cell types undergoing apoptosis, in situ end labelling has been coupled to immunohistochemistry. This method is limited by the availability of antibodies that bind to cell-specific protein markers in tissue sections. In contrast, we describe a method that combines in situ end labellin with in situ hybridization, a technique that specifies cell types based on mRNA expression. Taking advantage of the specific expression of surfactant protein C mRNA in type II alveolar epithelial cells, we demonstrate that this technique has the ability to localize alveolar type II cells undergoing apoptosis in vivo after the intratracheal instillation of an antibody that activates the cell surface Fas protein. The wide availability of cell-specific gene markers suggests that this method can be adapted to define cell types that undergo apoptosis during various physiological and pathological states in vivo.

Animals↗
PubMed1997

Cerebral palsy in infants with asymmetric growth restriction.

The relationship between low ponderal index and cerebral palsy was evaluated. National Collaborative Perinatal Project and University of California Child Health and Development Study data were analyzed. Associations between low ponderal index (ponderal index < 5% for gestational age) were evaluated in the combined population, in term and preterm infants, and in non-SGA infants (with birth weights > 5% for gestational age and gender). Data from 55,571 infants, including 232 cases of cerebral palsy, were evaluated. Low ponderal index was significantly associated with CP in the delivery population (Relative risk 2.2) and in non-SGA infants (RR 1.9). Low ponderal index was a significant independent correlate of cerebral palsy (RR 1.9) in non-SGA infants after using logistic regression to correct for effects of prematurity and gender. Low ponderal index is associated with increased risk of CP, even in non-SGA infants. Assessment of the neonatal ponderal index provides an additional method of documenting prior abnormal fetal growth and development.

Birth Weight↗
PubMed1997

Factorial structure of the Wisconsin Card Sorting Test.

This study examined the factorial structure of the Wisconsin Card Sorting Test (WCST) in normal university students (N = 135) and a mixed clinical sample (N = 139). Two highly stable orthogonal factors were observed accounting for 70 and 21 per cent of the variance, respectively. Factor I was interpreted as reflecting undifferentiated executive function while Factor II may measure cognitive abilities associated with attentional function. This work can serve as the basis for further examination of the construct validity of the WCST and has implications for its use.

Adult↗
PubMed1997

Ontogeny of gamma-glutamyltransferase in the rat lung.

gamma-Glutamyltransferase (gamma-GT) is a key enzyme in the metabolism of glutathione and glutathione-substituted molecules. The gamma-GT gene is expressed in two epithelial cells of the adult lung, the bronchiolar Clara cell and the alveolar type II cell. Because pulmonary glutathione metabolism may be important in the perinatal period, we studied gamma-GT ontogeny in the developing rat lung. In the late fetal and early postnatal lung, gamma-GT mRNA was below detectable limits on Northern blots. Pulmonary gamma-GT protein and enzyme activity were present at low levels after fetal day 18. gamma-GT protein appeared as a high-molecular-mass band (>95 kDa), with small amounts of enzymatically active gamma-GT heterodimer. Between the 2nd and 3rd postnatal wk, pulmonary gamma-GT mRNA expression increased in association with an increase in gamma-GT protein and enzyme activity that reached adult lung levels. At this time, gamma-GT protein appeared predominantly in the heterodimeric form with small amounts of the >95-kDa protein. Immunocytochemistry revealed that, in the fetal and early postnatal lung, gamma-GT was expressed only in the alveolar type II cell, whereas the Clara cell became the major site of gamma-GT mRNA and protein expression by 2-3 wk and in the adult. Type II cells isolated from the fetal lung express gamma-GT mRNA and synthesize the >95-kDa form of gamma-GT in excess of the heterodimer. These studies demonstrate that the alveolar type II cell is the only cell producing gamma-GT in the newborn lung and that it synthesizes a form of gamma-GT that appears to differ from that produced at a later time point by the Clara cell.

Aging↗
PubMed1997

Fas expression in pulmonary alveolar type II cells.

Fas, a type I membrane receptor protein, transduces a signal culminating in apoptosis after binding to the Fas ligand. Information regarding the expression of Fas in nonlymphoid tissues, although limited, suggests a role for Fas in epithelial progenitor cell populations. In this paper, we provide several lines of evidence indicating that the progenitor cell of the alveolus, the type II cell, displays restricted expression of Fas. We found 1) Fas gene expression in RNA derived from fresh isolates of primary rat type II cells; 2) restriction of Fas expression to a subset of alveolar type II cells by in situ hybridization and immunohistochemistry of the normal mouse lung; 3) induction of apoptosis in a mouse lung type II epithelial cell line (MLE) after activation of Fas; and 4) induction of apoptosis in a subpopulation of type II cells after the intratracheal instillation of an activating anti-Fas antibody in mice. These findings suggest that Fas-dependent apoptosis is involved in regulating turnover of the alveolar epithelium.

Animals↗
PubMed1996

Forensic examination of a mouse allegedly found in a previously sealed can of milk stout.

A mouse carcase, allegedly found in a can of commercial milk stout sealed 3 months previously, was examined. Because of uncertainty as to the time of death of the mouse, a pilot trial, designed to determine whether the mouse had been canned simultaneously with the milk stout, was performed. Twelve mice were killed, and canned in 450 ml beer cans. After periods varying from 1 day to 3 months the cans were opened and the state of decomposition of the mice was recorded. By comparing the state of the submitted mouse with that of the experimental mice it was established, without doubt, that the submitted mouse could not have been in the can at the time the consumer had opened it.

Animals↗
PubMed1996

Retinoic acid alters the expression of pattern-related genes in the developing rat lung.

Exogenous retinoids alter pattern formation and differentiation in many developing systems, such as limb, vertebrae, and central nervous system. Many of these effects are mediated by changes in expression of patterning genes such as Hox genes and Sonic hedgehog. We have previously shown that exogenous retinoic acid, administered to the embryonic rat lung in culture alters the structural pattern of the developing lung, suppressing formation of distal lung and favoring growth of proximal tubules. To determine whether these retinoic acid-induced changes in lung development were linked to alterations in pattern-related genes, we characterized the expression of Hoxa-2, Hoxb-6, and Sonic hedgehog mRNAs in vivo and in vitro, with or without 10(-5)M retinoic acid, by in situ hybridization and quantitative polymerase chain reaction. Each of these genes demonstrated unique timing and distribution of expression that was similar in vivo and in control cultured embryonic lungs. Hoxb-6 and Sonic hedgehog mRNAs both decreased during lung development in vivo or in vitro. From the patterns of mRNA expression we propose that Hoxb-6 is involved in distal airway branching while Hoxa-2 is involved in differentiation of proximal mesenchymal derivatives and vasculogenesis in the lung. RA upregulated all three genes, changing their developmental pattern of distribution and preventing the developmental decrease in Sonic hedgehog expression. We propose that RA acts to maintain high levels of expression of these and likely other pattern-related genes in a fashion that is characteristic of the immature lung, promoting continued formation of proximal lung structures and preventing formation of typical distal lung structures of the mature lung.

Animals↗
PubMed1996

On a failure to replicate: methodologically close, but not close enough. A response to hogben et al.

Williams, Brannan and Lartigue (1987) (Clinical Vision Science, 1, 367-371) reported that poor readers took significantly longer to search letter arrays for a target than did good readers. In addition, they reported that blurring the letter arrays leads to faster search times for poor readers and a loss of the significant differences between the groups seen with unblurred displays. In a recent attempt to replicate these findings, Hogben et al. (1996) (Vision Research, 36, 1503-1507) found no differences in search rates between good and poor readers using unblurred arrays, and no differences in search rate between the groups when blurred arrays were used. In the present article, we have compared these two research efforts, and a third paper on the same topic, with regard to methodological factors in an attempt to understand how these two different results could occur. It is our belief that the letter spacing employed in the two studies may account for the difference and should be the focus of future studies of the original effect.

Child↗
PubMed1996

Cerebral palsy, perinatal depression and low ponderal index.

To determine whether asymmetric growth restriction, abnormally lean body morphology, is associated with cerebral palsy (CP) in infants born with perinatal depression, perinatally depressed Collaborative Perinatal Project infants were assessed. Rates of ponderal index less than 5% for gestational age and race (low PI), a marker for asymmetric growth, were compared in infants either neurologically normal or having CP at 7 years of age. Low PI was associated with CP in infants with Apgar scores of 0 to 3 at 10, 15 or 20 minutes in both of these groups, after exclusion of small-for-gestational-age infants, and was a significant individual correlate of cerebral palsy with multiple logistic regression. The attributable risk of cerebral palsy related to low Pl was 12.4%.

Apgar Score↗
PubMed1996

Type I receptor serine-threonine kinase preferentially expressed in pulmonary blood vessels.

Type II and type I receptor serine-threonine kinases (RSTK) are important components of the transmembrane signaling machinery that allow cells to respond to the transforming growth factor-beta (TGF-beta) superfamily of cytokines. We have cloned from rat lung and report here a 3,935-base pair (bp) cDNA encoding a type I RSTK previously identified as R-3 (rat) or ALK-1 (human). Northern blot analysis reveals that the R-3 mRNA is more abundant in lung than in other adult rat tissues. With the use of in situ hybridization, the R-3 transcripts are found exclusively in the pulmonary vessels of all sizes, as well as in aorta, vena cava, and certain blood vessels of kidney, spleen, heart and intestine. In most blood vessels, a higher level of gene expression is found in endothelium than in adjacent smooth muscle. The R-3 transcripts are also found in splenic macrophages, as well as within cells of marginal zone of the splenic lymphoid tissue. In fetal rat lung, the expression of R-3 transcripts differs from the expression patterns of two other type 1 RSTK. The R-3 is expressed in vessels; the activin type IB receptor (R-2) is preferentially expressed in putative developing airways, whereas the TGF-beta type I receptor (R-4) transcripts appear to be ubiquitous. Our data suggest that in vivo R-3 may propagate signaling of TGF-beta in selected cell types. The differential expression of multiple type I receptors within different cell lineages may therefore define cell specific responses to TGF-beta.

Aging↗