Biomedical subjects

S J Chapman

Publications and source records attributed to S J Chapman.

At least 19 recordsLinked to original sources

PubMed2006

A mathematical model for simultaneous spatio-temporal dynamics of calcium and inositol 1,4,5-trisphosphate in Madin-Darby canine kidney epithelial cells.

The landmark paper by Hirose et al. (Hirose, K., Kadowaki, S., Tanabe, M., Takeshima, H., Iino, M., Science 284:1527-1530, 1999) presented experimental investigations to show that not only can calcium upregulate IP(3), but that it can also have an inhibitory effect on IP(3). In this paper, we present a preliminary model, which is consistent with these experiments. This model includes positive and negative feedback between calcium and IP(3) and is able to reproduce more precisely the data presented in Hirose et al. (Hirose, K., Kadowaki, S., Tanabe, M., Takeshima, H., Iino, M., Science 284:1527-1530, 1999). In the second part of the paper, the intracellular and intercellular calcium movement in Madin-Darby canine kidney epithelial cells is investigated. With the aid of the model we are able to identify the aspects of IP(3) and calcium signalling, which should be studied further experimentally before refining the model.

Adenosine Triphosphate↗

PubMed2006

Asymptotics of large bound states of localized structures.

We analyze stationary fronts connecting uniform and periodic states emerging from a pattern-forming instability. The size of the resulting periodic domains cannot be predicted with weakly nonlinear methods. We show that what determine this size are exponentially small (but exponentially growing in space) terms. These can only be computed by going beyond all orders of the usual multiple-scale expansion. We apply the method to the Swift-Hohenberg equation and derive analytically a snaking bifurcation curve. At each fold of this bifurcation curve, a new pair of peaks is added to the periodic domain, which can thus be seen as a bound state of localized structures. Such scenarios have been reported with optical localized structures in nonlinear cavities and localized buckling.

Journal Article↗

PubMed2003

Interaction of two modulational instabilities in a semiconductor resonator.

The interaction of two neighboring modulational instabilities in a coherently driven semiconductor cavity is investigated. First, an asymptotic reduction of the general equations is performed in the limit of a nearly vertical input-output characteristic. Next, a normal form is derived in the limit where the two instabilities are close to one other. An infinity of branches of periodic solutions are found to emerge from the unstable portion of the homogeneous branch. These branches have a nontrivial envelope in the bifurcation diagram that can either smoothly join the two instability points or form an isolated branch of solutions.

Journal Article↗

PubMed1999

Benefits of maternal corticosteroid therapy in infants weighing </=1000 grams at birth after preterm rupture of the amnion.

OBJECTIVE: The aim of the study was to determine the effects of antenatal maternal corticosteroid treatment on selected neonatal outcomes in infants weighing </=1000 g at birth after preterm rupture of membranes. STUDY DESIGN: In a 1-year (1992-1993) prospective observational study, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 766 infants who did not have a major fetal anomaly and who had a birth weight </=1000 g (378 were born after preterm rupture of membranes). Only fetuses deemed potentially viable by the obstetrician were included in our analysis. Selected neonatal outcomes were compared between mothers who did and did not receive antenatal corticosteroids. Logistic regression variables included birth weight, sex, race, amnionitis, tocolytic therapies, mode of delivery, and surfactant use. RESULTS: Two hundred fourteen of the 378 infants whose mothers had preterm rupture of membranes were deemed potentially viable; 62 of these mothers received antenatal steroids and 152 did not. Groups were similar with respect to gestational age, birth weight, race, amnionitis, and delivery mode. Women who received antenatal steroids were more likely to have received tocolysis (P <.001). Univariate and regression analyses controlling for multiple confounders confirmed no neonatal benefits of maternal corticosteroid use. CONCLUSIONS: Corticosteroid treatment in women with preterm rupture of membranes was of no apparent benefit to neonates weighing </=1000 g.

Adrenal Cortex Hormones↗

PubMed1999

Production and distribution of endoglucanase, cellobiohydrolase, and beta-glucosidase components of the cellulolytic system of Volvariella volvacea, the edible straw mushroom.

The edible straw mushroom, Volvariella volvacea, produces a multicomponent enzyme system consisting of endo-1,4-beta-glucanase, cellobiohydrolase, and beta-glucosidase for the conversion of cellulose to glucose. The highest levels of endoglucanase and cellobiohydrolase were recorded in cultures containing microcrystalline cellulose (Avicel) or filter paper, while lower but detectable levels of activity were also produced on carboxymethyl cellulose, cotton wool, xylitol, or salicin. Biochemical analyses of different culture fractions in cultures exhibiting peak enzyme production revealed that most of the endoglucase was present either in the culture filtrate (45.8% of the total) or associated with the insoluble pellet fraction remaining after centrifugation of homogenized mycelia (32.6%). Cellobiohydrolase exhibited a similar distribution pattern, with 58.9% of the total enzyme present in culture filtrates and 31.0% associated with the pellet fraction. Conversely, most beta-glucosidase activity (63.9% of the total) was present in extracts of fungal mycelia whereas only 9.4% was detected in culture filtrates. The endoglucanase and beta-glucosidase distribution patterns were confirmed by confocal laser scanning microscopy combined with immunolabelling. Endoglucanase was shown to be largely cell wall associated or located extracellularly, with the highest concentrations being present in a region 1 to 2 microm wide immediately adjacent to the outer surface of (and possibly including) the hyphal wall and extending 60 to 70 microm from the hyphal tip. Immunofluorescence patterns indicated little if any intracellular endoglucanase. Most beta-glucosidase was located intracellularly in the apical area extending 60 to 70 microm below the hyphal tip, although enzyme was also evident in the extracellular region extending approximately 15 microm all around the hyphal tip and trailing back along the length of the hypha. The regions of the hypha located some distance from the apical region appeared to be devoid of intracellular beta-glucosidase, and the enzyme appears to be associated almost exclusively with, or located on the outside surface of, the hyphal wall.

Journal Article↗

PubMed1998

Varicella in pregnancy.

Varicella-zoster virus may cause serious infection, particularly pneumonia, in adult women. Women of child-bearing age should be questioned about immunity to varicella preconceptually, and offered serological testing, and VARIVAX vaccine if indicated. All pregnant patients should be questioned about immunity to varicella during their first prenatal appointment. Susceptible patients should be counseled to avoid contact with individuals who have chickenpox. If exposure occurs, VZIG should be administered within 96 hours in an attempt to prevent maternal infection. Varicella embryopathy may occur as a result of maternal infection particularly in the first half of pregnancy with an incidence of 1% to 2%. Varicella of the newborn is a life-threatening illness that may occur when a newborn is delivered within 5 days of the onset of maternal illness or after postdelivery exposure to varicella. Susceptible neonates should receive VZIG. Acyclovir is active against the varicella-zoster virus, and treatment is indicated in seriously ill adults and neonates.

Adult↗

PubMed1997

Randomized trial of single-dose versus multiple-dose cefotetan for the postpartum treatment of intrapartum chorioamnionitis.

OBJECTIVE: Our purpose was to determine whether a single postpartum dose of a cephalosporin would effectively treat women with intrapartum chorioamnionitis and decrease the length of hospitalization. STUDY DESIGN: After vaginal delivery consenting women who had received antibiotics for chorioamnionitis were assigned to postpartum treatment with either a single 2 gm intravenous dose of cefotetan or to cefotetan 2 gm given intravenously every 12 hours for a minimum of 48 hours. Chorioamnionitis was defined as an intrapartum temperature of > or = 100.4 degrees F and maternal or fetal tachycardia, maternal leukocytosis, or uterine tenderness. Patients were discharged when they had received their assigned dosage of cefotetan, were afebrile (temperature < 100.4 degrees F) and > or = 24 hours from delivery. RESULTS: We studied 109 women (55 single dose, 54 multiple dose) with chorioamnionitis. The two groups were similar with regard to demographic and intrapartum characteristics. The median (range) interval from delivery to discharge was 24 hours lower in the single-dose group (33 [16 to 190] vs 57 [36 to 190] hours, p = 0.0001). The incidence of failed therapy was similar (single dose: 6/55, 11%, vs multiple dose: 2/54, 3.7%, p = 0.27). CONCLUSIONS: A single postpartum dose of cefotetan appears to be effective treatment for intrapartum chorioamnionitis after a vaginal delivery and decreases the length of hospital stay.

Cefotetan↗

PubMed1997

One- versus two-layer closure of a low transverse cesarean: the next pregnancy.

OBJECTIVE: To determine whether a low transverse cesarean closure method in one or two layers affects subsequent pregnancy outcome. METHODS: In a prospective trial reported previously, 906 women were assigned randomly to either one- or two-layer uterine closure. One hundred sixty-four women had a subsequent pregnancy and delivery (18 weeks' gestation or longer) at our institution. Maternal and neonatal outcomes were ascertained by medical chart review and compared between the one- and two-layer closure groups. RESULTS: Of the 164 subsequent deliveries, 83 had previous closure in one layer, whereas 81 had involved a two-layer closure. The demographic characteristics of these two groups were similar. Nineteen women (12%) underwent elective repeat cesareans without labor, and the remaining 145 experienced labor. Length of labor, mode of delivery, duration of hospital stay, gestation at delivery, and the incidences of uterine scar dehiscence, chorioamnionitis, postpartum metritis, hemorrhage, transfusion, and abnormal placentation did not differ significantly between the groups. Selected neonatal outcomes, including Apgar scores, cord pH, birth weight, and perinatal death, were similar between groups as well. CONCLUSIONS: These findings suggest that the type of low transverse cesarean closure does not significantly affect the outcome of the next pregnancy.

Adult↗

PubMed1997

Pregnancy outcomes following false-positive multiple marker screening tests.

Pregnancy outcomes in women with a false-positive midtrimester multiple marker screening test (MMST) were reviewed. A genetic database was used to identify all women > or = age 30 who had a MMST at 15-20 weeks of gestation, a targeted ultrasound, and amniocentesis, and complete pregnancy outcome data. All patients with an abnormal fetal ultrasound (US) or karyotype were excluded. The incidence of adverse outcomes (defined as fetal death, preterm delivery, or a birth weight less than the 10th percentile for gestational age), in those women with a positive MMST (risk of Down's syndrome > or = 1:190) was compared to the incidence of adverse outcomes in control women with negative MMST. Chi-square analysis and Fisher's exact tests were used for comparisons as appropriate. Complete data was available from 1135 women. Seventy-seven percent were over age 35. Two hundred and forty-six women (22%) had a positive multiple marker test. No significant differences in outcomes were discovered after comparisons to controls: fetal death 1 of 246 (0.4%) versus 12 of 889 (1.3%), p = 0.32; preterm delivery 32 of 246 (13.0%) versus 147 of 889 (16.5%), p = 0.17; birth weight less than the 10th percentile, 9 of 246 (3.7%) versus 30 of 889 (3.4%), p = 0.83. Our data suggest that women > or = age 30 with a false-positive MMST and a normal midtrimester obstetrical sonogram are not at an increased risk for adverse pregnancy outcomes in later gestation.

Adult↗

PubMed1996

Complications of midtrimester pregnancy termination: the effect of prior cesarean delivery.

OBJECTIVE: Our purpose was to determine whether a prior cesarean delivery affects the incidence of complications in women having an indicated midtrimester medical pregnancy termination. STUDY DESIGN: A retrospective review of women who underwent a midtrimester medical termination of pregnancy from January 1980 to July 1995 ascertained obstetric history, uterotonic agent(s), and the occurrence of uterine rupture, blood transfusion, or curettage. The frequencies of maternal complications were compared in women with and without a prior cesarean section. RESULTS: Our study population included 606 women with a mean gestational age of 21.1 +/- 3.1 weeks and a mean maternal age of 26.3 +/- 7 years. Seventy-nine (13%) had undergone a prior cesarean section. There was no significant difference in the need for curettage between women with and without a prior cesarean section. However, there was an increased need for blood transfusions in women with a prior cesarean delivery (11.4% vs 5.3%, odds ratio 2.3, 95% confidence interval 1.1 to 5.0, p = 0.04). The incidence of uterine rupture was significantly higher among women with a prior cesarean (3.8% vs 0.2%, odds ratio 20.8, 95% confidence interval 14.1 to 104, p = 0.008). CONCLUSION: Our data suggest that a prior cesarean section is a risk factor for uterine rupture and blood transfusion in women having a midtrimester pregnancy termination.

Abortion, Induced↗

PubMed1991

Lipids, proteins and corneocyte adhesion.

Three factors were examined for their relative contribution to corneocyte cohesion in normal adult pig ear: (1) extracellular lipids derived from membrane-coating granules (MCG); (2) corneosomes (modified stratum corneum desmosomes); and (3) corneocyte covalently bound lipid envelopes. Cohesion strength of the outer stratum corneum was measured directly by cohesometry, then altered by removing MCG lipids with solvents of varying potency. Cohesion changes were related to degree of lipid removal and ultrastructural alterations. Trypsin was also used to see if proteolysis of corneosomes promoted squame shedding. Potent solvents increased cohesion in relation to the amount of MCG lipid extracted. Tighter cohesion was due to fusion of the outer leaflets from covalently bound lipid envelopes on adjacent corneocytes. However, lipid envelopes are unlikely to mediate normal stratum corneum cohesion since MCG lipids play a significant anti-cohesive role preventing their apposition. Mild solvents partially removed MCG lipids causing a slight decrease in cohesion compared with untreated samples. This suggests a minor cohesive role for MCG lipids, consistent with maintaining their barrier function. We believe that corneosomes are the major determinant of stratum corneum cohesiveness because, in untreated skin, both cohesion and the number of corneosomes increased from the surface towards the granular layer. Furthermore, corneosome digestion with trypsin induced superficial squame shedding.

Animals↗

PubMed1991

Sugars protect desmosome and corneosome glycoproteins from proteolysis.

Adhesional glycoproteins of desmosomes possess asparagine-linked, complex oligosaccharide side chains. We investigated the potential of these sugars to protect the core proteins of desmosomes and corneosomes (modified stratum corneum desmosomes) against proteolysis. Isolated pig ear epidermis was exposed sequentially to individual hydrolases, and their effect monitored ultrastructurally. Two major steps were employed: (1) glycosidases, to remove stepwise the sugars in a typical complex oligosaccharide chain; and (2) proteolysis using both endopeptidases and an exopeptidase. Controls were exposed to the same sequence of buffers, but without enzymes. Proteases alone induced no major changes in desmosomes or corneosomes compared with controls. Glycosidases alone, or proteases followed by glycosidases, caused mild fragmentation of the desmosomal interspace, but no widening. However, dramatic changes occurred when glycosidase treatment was followed by proteolysis. The interspace of both desmosomes and corneosomes was extensively digested, and consequently widened, causing loose packing of the epidermis. These findings indicate that sugars are potentially anti-proteolytic in both desmosomes and corneosomes. Sugars may, therefore, be a factor in preventing premature desquamation, by protecting desmosomes and corneosomes against extracellular proteases derived from membrane-coating granules.

Animals↗

PubMed1991

Epidermolysis bullosa simplex (Dowling-Meara type) is a genetic disease characterized by an abnormal keratin-filament network involving keratins K5 and K14.

The distribution and morphology of tonofilament (TF) clumps were examined by light and electron microscopy in skin samples from a total of 17 patients with the Dowling-Meara (DM) form of epidermolysis bullosa simplex (EBS). TF clumps extending from the basal to the upper-spinous epidermal layer were seen in all lesional skin samples and in the majority of peri-lesional and non-lesional skin samples. TF clumps were also noted in adnexal epithelia, including outer hair root sheaths, sweat ducts, and sebaceous glands. Cultured keratinocytes from two patients also demonstrated characteristic TF clumps. All these epithelial cells have in common their expression of the keratin pair K5 and K14. Post-embedding immunogold electron microscopy using antibodies to K5, K14, and K10 showed similar expressed keratins in DM-EBS skin from four patients compared with normal skin, with K5 and K14 predominantly in the basal cell layer and K10 in the suprabasal layers. The clumped TF in DM-EBS samples were labeled strongly with anti-K5 and K14 antibodies in the basal and suprabasal layers. In contrast, the suprabasal clumps were only slightly reactive with anti-K10 antibodies and labeling was usually restricted to the periphery of the clumps. We conclude that DM-EBS is associated with an intrinsic abnormality of the keratin-filament network involving the K5 and K14 pair that is likely to result in impaired resistance of basal epidermal cells to external shearing forces, leading to the characteristic intraepidermal blisters. DM-EBS may become the first genetic skin disease to be recognized as having a specific keratin abnormality.

Adolescent↗

PubMed1991

Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings.

Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV), whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition.

Child↗

PubMed1990

Desmosomes, corneosomes and desquamation. An ultrastructural study of adult pig epidermis.

We recently developed a pig skin model to determine the role of corneosomes (modified desmosomes in the stratum corneum) and extracellular lipids in desquamation. The present study provides control morphometric data on the morphological changes in desmosomes and corneosomes leading to desquamation in adult pig epidermis in vivo. The extracellular space within desmosomes gradually widened from the basal to the granular layer, and decreased slightly in the stratum corneum. Mid-dense line broadening, and increased electron density of the distal light layers, coincided with membrane-coating granule extrusion in the outer granular layer. Corneocyte attachment correlated with corneosome distribution. Compactum packing was relatively tight and corneosomes were numerous. Cohesion was mainly peripheral in the disjunctum, and corneosomes were restricted to corneocyte edges. Adhesion had a tongue-and-groove appearance with corneosomes riveting corneocyte peripheries into a lipped groove on adjoining cells. Cells shed by peeling radially towards the lipped groove, and corneosomes decreased from lower to upper disjunctum. Corneosome breakdown commenced with an electron lucent band forming between the plug and lipid envelope. The plug was then unzipped from the lipid envelope and degraded. Corneosomes did not form squamosomes.

Animals↗

PubMed1990

Abnormal expression of hemidesmosome-like structures by junctional epidermolysis bullosa keratinocytes in vitro.

Hemidesmosomes are frequently rudimentary in junctional epidermolysis bullosa (JEB), and JEB keratinocytes display abnormal attachment to the substrate in culture. Our aim was to determine whether this abnormality reflects defective hemidesmosome synthesis in vitro. Keratinocytes from five JEB patients were cultured under standard conditions. Control cultures, from four healthy males, three patients with dystrophic EB (DEB), and one patient with the simplex variant (EBS), were also examined. Post-confluent cultures were processed for transmission electron microscopy. Hemidesmosome-like structures were counted in electron micrograph montages. The number of hemidesmosome-like structures in JEB cultures (0.97 +/- 0.57, per 10 microns of basal cell membrane) was approximately 17% of the value for normal controls (5.81 +/- 3.08, P less than 0.02). The values for EBS (3.72) and DEB (3.28 +/- 1.44) were not statistically different from normal controls. In addition hemidesmosome-like structures in JEB cultures were morphologically ill-defined, compared with those from controls. This correlated with the loose apposition between JEB keratinocytes and the substrate, which appeared tight in controls. JEB keratinocytes continue to express in vitro a major phenotypic abnormality which characterizes the disease in vivo. Therefore, this model should prove useful in studies determining the pathogenesis and possible new treatments of JEB.

Adolescent↗

PubMed1989

Membrane-coating granules are acidic organelles which possess proton pumps.

Lysosomes are by definition organelles that maintain an internal acidic pH and contain hydrolytic enzymes. Membrane-coating granules contain a battery of hydrolytic enzymes, in addition to their lamellar discs, and are therefore commonly assumed to be lamellate lysosomes. Although there are data confirming the existence of enzymes in membrane-coating granules, there is no direct evidence to suggest that their internal pH is acidic. As part of a wider program on their role in desquamation, our aim was to determine whether membrane-coating granules are indeed acidic and possess proton pumps. Chloroquine and monensin were selected as the pH markers because both induce swelling of acidic organelles. In four repeat experiments dermatome slices of pig ear skin (2 mm2 x 0.5 mm) were incubated as organ cultures either alone (control) or with 1 mM chloroquine or 25 microM monensin. Ultrastructural observations revealed no swelling in control specimens. In contrast, the inclusion of chloroquine or monensin caused swelling of specific organelles including membrane-coating granules, lysosomes, and trans elements of Golgi stacks, but not mitochondria, rough endoplasmic reticulum, or nuclear envelopes. Swelling of membrane-coating granules and the other organelles was prevented by pretreatment with N,N'-dicyclohexylcarbodiimide, a known inhibitor of lysosomal H+ ATPase activity. These findings suggest that membrane-coating granules actively maintain an acidic interior with the aid of proton pumps. Furthermore, membrane-coating granules are heterogeneous because swelling of the whole population did not commence simultaneously. However, it remains to be determined whether this heterogeneity reflects variations in membrane-coating granule pH, leakiness of their membranes to cations, or the number or activity of their proton pumps.

Animals↗

PubMed1989

A fully differentiating epidermal model with extended viability: development and partial characterization.

A highly differentiated porcine skin organ culture model has been developed for future investigations of membrane-coating granules (MCG) and their role in epidermal differentiation. In contrast to many previous systems, cultures do not undergo necrosis of the upper epidermis or display dermo-epidermal separation, but survive for at least 3 weeks, at which time mitotic cells are still evident. Although rete projections are gradually smoothed out and the viable epidermis thins at a rate of approximately 0.35 cells per day, the stratum corneum gains approximately 1.5 corneocytes per day. Furthermore, at 3 weeks all the major differentiation markers are expressed, including keratohyalin granules, MCG, and an orthokeratotic stratum corneum. The system is inexpensive, simple to establish, and does not require elevated oxygen levels. The main requirements are 1) the use of Dulbecco's minimal essential medium supplemented with 2) hydrocortisone (100 micrograms/ml), 3) growth at an air/liquid interface, and 4) attached connective tissue. The further addition of vitamin C (300 micrograms/ml) and/or bovine serum albumin (2 mg/ml) offered no obvious advantage. Degeneration of organ cultures in standard cell culture media was discovered to be caused by fetal bovine serum (FBS). FBS-induced degeneration was not prevented by adding any of the supplements tested, or the inclusion of 3T3 fibroblasts, even when culturing at an air/liquid interface. Complete submersion rapidly killed specimens, presumably through oxygen starvation. The ability to maintain a fully keratinizing system for several weeks, in a totally chemically defined medium, will prove valuable for research not only into the role(s) of MCG in epidermal biology but also studies of desquamation and epidermal differentiation.

Animals↗