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M C Williams

Publications and source records attributed to M C Williams.

At least 55 records · Page 3Linked to original sources
PubMed1996

T1 alpha protein is developmentally regulated and expressed by alveolar type I cells, choroid plexus, and ciliary epithelia of adult rats.

T1 alpha is the first marker gene known to be expressed in the adult lung solely by the alveolar type I epithelial cell. Previous studies showed that T1 alpha transcripts are abundant in early rat embryos where they are found in the nervous system and in the foregut and certain of its derivatives including the primitive lung. By mid- to late gestation T1 alpha messenger RNA (mRNA) expression is lost from neural tissues but appears to increase in the lung throughout fetal life. To determine whether the T1 alpha transcripts are translated into protein, especially in early embryos which sometimes express transcripts that are translationally silent, we performed immunohistochemistry on embryos and fetal tissues and analyzed certain tissues by western blotting using a monoclonal antibody against T1 alpha protein. T1 alpha protein is present at all sites that have previously been shown to express the mRNA and at similar developmental stages. As estimated from western blots, T1 alpha protein abundance peaks at about fetal day 16 in the brain and decreases thereafter to a relative level in the adult that is lower than that of the neural tube of the day 13 embryo. Relative protein abundance in the lung is very low, although detectable, on embryonic day 13 but increases slowly until fetal day 20 when there is a dramatic increase. At the time of birth, restriction to the type I cell is not complete and therefore must occur during postnatal lung development. Immunostaining reveals additional sites of expression in fetal and adult rats that had not been clearly visualized in previous in situ hybridization studies. T1 alpha is present in mesonephric tubules and apparently in primitive germ cells but is not detectable in specific cells in the adult kidney, ovary, or testis. However, cells of the choroid plexus of the central nervous system and the ciliary epithelium of the eye express T1 alpha in both fetuses and adults. The well-known functions of these epithelia are to elaborate cerebrospinal fluid and aqueous humor respectively by processes of active ion transport and water fluxes, probably through the aquaporin 1 (channel-forming integral membrane protein [CHIP] 28). We speculate therefore that T1 alpha protein may modulate or participate in these types of cellular functions in the lung.

Age Factors↗
PubMed1996

Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns.

Explants of embryonic lung are often used to characterize lung growth, bronchial tree pattern, and cell differentiation. Most investigators culture lungs for 3-7 days in defined media lacking, e.g., added growth factors or hormones. If growth and differentiation are comparable to that in vivo, these cultures show considerable promise for identifying developmental regulatory molecules and target genes, and for elucidating molecular responses. We used in situ hybridization and RT-PCR to compare times and sites of expression of mRNAs of six epithelial genes in cultured and uncultured fetal rat lungs. These genes, expressed in distal lung of adult rats, are surfactant proteins (SP) A, B, and C; LAR, a receptor-type tyrosine phosphatase; Clara cell secretory protein (CC10, CCSP); and T1alpha. SP-A, SF-B, LAR, and CC10 are expressed by both Clara and Type II cells in adult animals. SP-C and T1alpha are unique markers for Type II and Type I cells, respectively. SP-C, LAR, and T1alpha are expressed before the lung is explanted (Day 13.5); SP-A, -B, and CC10 mRNAs are first detected later. The onset of expression is similar in vivo and in vitro. Although the patterns of expression differ for each mRNA, their sites of expression in culture match those in vivo relative to the bronchial tree. The explanted embryonic lung appears to be an excellent experimental model.

Animals↗
PubMed1996

The role of attention in Wisconsin Card Sorting Test performance.

The present study sought to test the hypothesis that the second factor (consisting of Failure-to-Maintain-Set and other scores) found in two recent factor analyses of the Wisconsin Card Sorting Test reflects attentional function. The effect of color overlays (an experimental manipulation known to influence neural systems linked to attention) was examined in 17 normal control and 14 attention-disordered children (ages 8 to 12). Group and Color main effects were found for Factor 1 (which consists largely of measures of perseveration) and a Color main effect was observed for Factor 2. The Color effect for Factor 2 supported the contention that this factor reflects attentional processes. A hypothesis concerning the relationship between problem solving and attention on the WCST is offered and a means for testing it is discussed.

Journal Article↗
PubMed1995

Two closely related receptor-type tyrosine phosphatases are differentially expressed during rat lung development.

Transmembrane protein tyrosine phosphatases (PTPases) comprise a newly identified class of receptor-like molecules. In most cases their ligands and the substrates they dephosphorylate are not known. In order to begin to explore the functions of the PTPases in cell physiology and in mammalian development, we examined the expression patterns of two closely related receptor-type tyrosine phosphatase genes, namely LAR and PTP delta, in fetal rat lung and in selected adult rat tissues. In the lung, in situ hybridization and immunohistochemistry show that the LAR mRNA and protein are expressed exclusively in the epithelium. In the early embryonic or fetal lung (day 13 to 18) LAR is expressed by all of the epithelial cells of the forming bronchial tree. This widespread pattern of expression is lost later in fetal life (day 21) as the lung matures and acquires the morphologic and biochemical features of the adult organ. LAR gene expression is then confined to two epithelial progenitor cells of the distal airways, namely the bronchiolar Clara cell and the alveolar type II cell. The LAR gene products were also found abundantly expressed in epithelial progenitor cells of adult esophagus, skin, and small intestine, all of which are continuously renewing epithelia. The rat PTP delta gene, on the other hand, is specifically expressed in the mesenchyme of the developing lung. The level of the PTP delta mRNA decreases as the lung matures. These results suggest that the two closely related receptor-type tyrosine phosphatases are differentially expressed in a tissue-specific fashion. They are expressed mostly in proliferating cells or in cells which have potential to proliferate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives.

We report here the identification and characterization of a novel gene, T1 alpha, expressed in high abundance in adult rat lung, fetal lung, and early fetal brain. T1 alpha was identified by a monoclonal antibody previously shown to be specific for an antigen expressed by alveolar epithelial type I cells. The cDNA for T1 alpha is 1.85 kb and identifies a single mRNA species of the same size on Northern blots of adult rat lung. The longest open reading frame of the cDNA is 498 bases which would encode a protein of approximately 18 kDa. The protein has a putative membrane spanning domain near the C-terminus but lacks consensus sequences for N-glycosylation. Northern blots and RT-PCR show high expression of T1 alpha in adult lung, with marginally detectable expression in adult brain, intestine, and kidney. RT-PCR analysis shows expression of T1 alpha in freshly isolated type I cells (50-60% purity) but not in highly purified type II cells or other lung cells. We believe therefore that T1 alpha is primarily if not uniquely expressed in alveolar type I cells in the adult rat. Polyclonal antisera against a 16-amino-acid peptide identified in the deduced sequence reacts with the apical membranes of adult type I cells in lung tissue sections but does not label other cell types. The above antiserum as well as the original monoclonal antibody recognize a single approximately 18-kDa protein derived from bacterial expression of a construct containing the T1 alpha open reading frame. By RT-PCR T1 alpha is detected in rat lung from Day 13.5 onward, but is detected by in situ hybridization earlier in lung, brain and neural derivatives, and foregut. Expression is down-regulated in all but lung tissues as development proceeds.

Amino Acid Sequence↗
PubMed1995

Pre-induction cervical ripening: a randomized comparison of two methods.

OBJECTIVES: To compare two methods of pre-induction cervical ripening in a randomized clinical trial. METHODS: A single intracervical prostaglandin E2 (PGE2) gel application was compared with a single insertion of hygroscopic dilators in 441 women at term with unfavorable cervical scores. Induction success was defined as entry into active labor within 6 hours of oxytocin infusion. RESULTS: There was no statistical difference in pre- or post-ripening cervical scores. In the group receiving hygroscopic dilators, only 28% entered the active phase of labor within 6 hours of oxytocin infusion compared with 45% (P < .001) in the PGE2 group. Thus, in this study, a change in cervical score did not directly predict induction success. There was a higher rate of postpartum endometritis (24 versus 14%; P = .007) and suspected neonatal infection (10 versus 5%; P = .03) in the dilator group. CONCLUSIONS: Pre-induction ripening by hygroscopic dilators and intracervical PGE2 was equivalent as measured by changes in the cervical score. The change in cervical score, however, was not predictive of successful induction, and PGE2 was more frequently associated with induction success. Hygroscopic dilators were associated with a higher incidence of postpartum maternal and neonatal infection because of a longer duration of labor. Hospital charges for intracervical PGE2 gel totaled $522 compared with $91 for the insertion of three dilators.

Administration, Intravaginal↗
PubMed1995

The effect of sample preparation and storage on maternal triple-marker screening.

OBJECTIVE: To evaluate the effect of different sample collection, storage, and preparation techniques on serum alpha-fetoprotein (AFP), beta-hCG, and unconjugated estriol (E3) concentrations. METHODS: A solution containing known concentrations of AFP, hCG, and unconjugated E3 was diluted in blood samples obtained from seven healthy male volunteers. Serum from each blood sample was removed immediately, and either assayed or frozen at -70C. Portions of the remaining blood were handled as follows: centrifuged and refrigerated, centrifuged and left at room temperature, not centrifuged and refrigerated, or not centrifuged and left at room temperature. Serum was removed from these samples for triple-marker analysis at 24, 48, 96, and 168 hours after the initial sample collection. RESULTS: Immediate freezing of serum and subsequent thawing resulted in a significant increase in beta-hCG and unconjugated E3 levels, but no change in AFP levels. There was a significant effect over time on AFP, hCG, and unconjugated E3 concentrations. The change in AFP levels was influenced by centrifugation status, whereas all three analytes were influenced by refrigeration status. CONCLUSION: Different sample collection, storage, and preparation techniques may affect maternal triple-marker screening.

Chorionic Gonadotropin↗
PubMed1995

The effects of spatial filtering and contrast reduction on visual search times in good and poor readers.

Recent experiments with reading disabled children have shown that image blurring (produced with frosted acetate overlays) results in an immediate benefit in search performance, eye movement pattern and reading comprehension. This suggests that the contrast and spatial frequency content of visual stimuli are important factors for these children. In the present experiment, spatial frequency filtering and contrast reduction were employed to determine whether either of these factors contributes to the beneficial effects observed. Letter arrays were spatially filtered to produce low pass (< 3.5 c/deg) and high pass (> 7.0 c/deg) images. In addition, a low contrast control image was generated to match the low contrast of the high pass image. Children classified as good reader controls (CON), specific reading disabled (SRD), attention deficit disordered (ADD) or comorbid SRD/ADD (COM) were asked to perform a visual search task with each type of image. With high contrast, unfiltered arrays, the search times for the CON and ADD groups were much shorter than those of the SRD and COM groups. While both high pass and low pass filter conditions improved the search speed for the COM group, improvement for the SRD group was only obtained with low contrast stimuli. These results support the notion that the beneficial results of image blurring with SRDs derives from the contrast reduction produced by such manipulations.

Child↗
PubMed1995

Retinoic acid induces changes in the pattern of airway branching and alters epithelial cell differentiation in the developing lung in vitro.

Retinoids have been shown to influence pattern formation during development and regeneration in numerous systems such as limbs, vertebrae, and neural tube although there is little information about the effects of retinoids on pattern formation in visceral organs. We investigated the effects of exogenous retinoic acid on the in vitro pattern of airway branching and on lung epithelial cell differentiation. Histology, [3H]thymidine autoradiographies and reverse transcriptase/polymerase chain reaction (RT/PCR) amplification were used to assess the effects of retinoids and the expression of lung epithelial markers of differentiation. We found that retinoic acid interferes, in a dose-dependent fashion, with the expression of epithelial genes that are found in distal segments of the fetal lung (surfactant-associated proteins SP-A, SP-B, and SP-C). At high concentrations, retinoic acid (RA) dramatically altered the developmental pattern of the lung, favoring growth of structures that resemble proximal airways and concomitantly suppressing distal epithelial buds. We hypothesize that this in vitro "proximalizing" effect on the developing lung may be related to alterations in the expression of pattern-related genes.

Animals↗
PubMed1995

Expression of insulin-like growth factor receptors 1 and 2 in the developing lung and their relation to epithelial cell differentiation.

Insulin-like growth factors (IGFs) and their receptors have been implicated as regulators of cell differentiation and cell proliferation in a number of systems and have been shown to play an important role in embryonic development. In this study we examined expression of mRNA for IGF-I and IGF-II, IGF binding protein 2 (IGFBP-2), and IGF receptors 1 (IGFR-1) and 2 (IGFR-2) during fetal lung development and in early postnatal and adult lungs by the polymerase chain reaction (PCR). IGF-I mRNA was found in embryonic and postnatal lungs at all ages as was IGFBP-2, whereas IGF-II mRNA was present only in prenatal lungs. IGFR-1 was present in all but the adult lungs. Lung epithelial cells expressed IGFR-1 at 14 days' gestation but not at 18 days' gestation as measured by PCR and in situ hybridization. Alveolar epithelial cells re-expressed IGFR-1 mRNA in the early postnatal period but not in the adult lung. IGFR-2 was expressed by PCR and in situ hybridization in 14-day embryonic epithelium, was not present at 18 days or at birth, but was re-expressed at high levels in the early postnatal alveolar wall. Immunocytochemical localization of IGFR-2 confirmed its absence in the late fetal and newborn lung. It reappeared in alveoli, exclusively in type 1 cells, in early postnatal and adult lungs. These studies demonstrate the stage- and cell-specific appearance of IGF receptors in the developing and postnatal lung. They also establish IGFR-2 as a marker of the mature alveolar type 1 cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Vacuum-assisted delivery.

The literature seems to allow certain general conclusions regarding the choice of instrument for assisted vaginal delivery. Both forceps and vacuum extraction offer certain advantages and drawbacks. Forceps are more difficult to apply, more prone to potentially significant facial injuries, require generally better maternal analgesia, and are associated with increased maternal soft tissue trauma. Vacuum extractors in general are easier to apply, are more likely to result in scalp trauma, and may be associated with increased rates of intracranial trauma. It seems likely that factors particular to each patient may play a significant role in the genesis of delivery associated with maternal and neonatal morbidity. Because of the ease of application, vacuum extractors may be used potentially in circumstances in which forceps assistance would not be attempted, allowing an operator of average experience to perform rotational deliveries. The use of vacuum extraction does appear to decrease the incidence of cesarean section in delivery populations. Given the apparent association between difficult assisted deliveries and increased neonatal morbidity, it is incumbent on the operator to attempt delivery only when vaginal delivery seems to be a safe option. Furthermore, the operator in such circumstances must be willing to reassess the attempt if initial attempts are not met with success. The minimal rates of significant intracranial injury associated with vacuum extraction in randomized studies of the method demonstrate the relative safety of the vacuum extraction when used judiciously. The ultimate choice of the route of delivery and method of assisted delivery should reflect a consideration of the fetal station, presentation, and maternal and fetal circumstances. It is hoped that further investigations in this area may clarify some of the issues discussed in this article.

Birth Injuries↗
PubMed1994

A hydrodynamic interpretation of crisis in sickle cell anemia.

The occurrence of crisis events in patients with sickle cell disease is associated with an increase in blood plasma viscosity, the hydrodynamic consequences of which are examined here. A mathematical model of the flow of sickle cells in capillaries predicts that for moderate increases in plasma viscosity, a regime of multivalued solutions for blood velocities is encountered, and the likely physical response is a precipitous drop to the lowest velocity solution. This behavior results from the coupling of the hydrodynamics with sickle erythrocyte rheology and oxygen transport to the surrounding tissue; no such catastrophe is predicted for normal erythrocytes. The type of velocity changes predicted by the model strongly suggest that plasma viscosity changes may play an important role in initiating or exacerbating crisis.

Anemia, Sickle Cell↗
PubMed1994

Maximizing morphologic data from lung biopsies from normal and asthmatic humans.

Obtaining lung biopsies from human patients is important because information gained from studies of the lung cells, tissue, and molecules is useful for both diagnosis and research. Because of their value these specimens should be handled carefully and analyzed with the best procedures available. Two morphologic techniques, immunocytochemistry and in situ hybridization, are particularly useful because they are sensitive and yield highly specific information. When combined with analysis of mRNAs by the reverse transcription-polymerase chain reaction, biochemical and morphologic data can be obtained from these small specimens. Multidisciplinary approaches such as these are proving to be very promising approaches to understanding asthma.

Asthma↗
PubMed1993

Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality.

OBJECTIVE: To determine if premature luteinization has an adverse effect on oocyte and, hence, embryo quality. DESIGN: Retrospective evaluation of anonymous ovum donors/oocyte recipients. SETTING: A large oocyte donation program. PATIENTS, PARTICIPANTS: Sixty-eight women undergoing controlled ovarian hyperstimulation (COH) as ovum donors were matched to 68 women with ovarian failure as ovum recipients who had endometrial maturation exogenously controlled by an identical hormone replacement protocol. INTERVENTIONS: Serum was collected for E2 and P in donors and recipients. MAIN OUTCOME MEASURES: The incidence of premature luteinization was determined in donors. Cycle characteristics were compared between donors with and without premature luteinization, with emphasis on oocyte and embryo quality. Implantation rates per embryo and delivery rates per transfer were measured in recipients. RESULTS: Twenty-one (31%) of the donors demonstrated premature luteinization. Serum P was higher on day before hCG, day of hCG, and day after hCG in women demonstrating premature luteinization. However, there were no differences between donor cycles with or without premature luteinization as determined by donor age, ampules of gonadotropins used, day of hCG administration, peak E2, total number of oocytes, and number of mature oocytes retrieved. Ovum recipients were of similar age and had similar E2 exposure (area under the E2 curve) before P administration. Similar fertilization rates, incidence of polyspermia, number of embryos transferred of similar embryo grade, and similar implantation rates and deliveries per transfer were observed in women receiving oocytes from donors with and without premature luteinization, respectively. CONCLUSIONS: Similar oocyte quality, fertilization, and polyspermia rates, embryo quality, implantation, and delivery rates suggest that any negative impact of premature luteinization on pregnancy rates in COH cycles from young women is not due to an adverse effect of PL on oocyte and hence embryo quality, but rather on the endometrial environment.

Chorionic Gonadotropin↗
PubMed1993

[Suspected inherited granulocytopathy in four Holstein Friesian calves].

Five Holstein Friesian calves varying in age from 7 to 9 weeks old, were suspected of suffering from an inherited granulocytopathy known as bovine leucocyte adhesion deficiency (BLAD). Four of them were examined clinically and at necropsy. The most significant clinical findings were fever, depression, weakness, emaciation, diarrhoea, pseudomembranous gingivitis, loose teeth, respiratory infection and occult blood in the faeces. Significant clinicopathological findings were marked leucocytosis, mainly due to a neutrophilia, hypoalbuminemia, hypogammaglobulinemia, increased alpha- and beta-globulins, elevated alkaline phosphatase enzyme activity, hypoglycaemia, and decreased blood urea concentrations. The necropsy revealed emaciated carcasses, granulomatous to necrotising gingivitis, pseudomembranous to necrotising enteritis with perforations, bronchopneumonia, splenic atrophy, and hypoplasia of the thymus. Histopathological examination supported the macroscopic findings.

Animals↗
PubMed1993

The cupruretic effect of two chelators following copper loading in sheep.

The cupruretic effect of 2 copper chelators, d-penicillamine and trientine, was assessed in 12 fistulated South African Mutton Merino rams of approximately 6 mo age following copper loading. Each animal received 20 mg CuSO4.5H(2)0/kg body mass as an 0.5% m/v aqueous solution, intraruminally, daily for 35 d. The animals were randomly assigned to either a d-penicillamine (n = 4) or trientine treatment group (n = 4) or an unmedicated control group (n = 4). A separate group of 3 rams were kept as non-copper-loaded controls. Urinary copper excretion was measured before and during treatment. All the sheep were housed individually or placed intermittently on steel metabolic crates to facilitate urine collection. At the end of the trial the animals were euthanatized and specimens of organs collected for determination of copper concentrations. d-Penicillamine significantly (p < 0.05) increased urinary copper excretion. Trientine failed to increase copper excretion in the urine when compared to the unmedicated and non-copper-loaded control groups.

Animals↗