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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 199 records · Page 11Linked to original sources
PubMed1993

Potential of measurements of unsaturated vitamin B12-binding capacity in serial colonoscopic biopsy specimens for global and regional assessments of disease severity in inflammatory bowel disease.

We investigated whether measurements of unsaturated vitamin B12-binding capacity (UBBC), in homogenates of serial colonoscopic biopsy specimens, could be used as objective measures of disease severity in ulcerative colitis (UC) and Crohn's disease (CD). On a regional basis UBBC activity correlated with and showed good agreement with endoscopic and histologic activity scores (r = 0.8 and 0.6, respectively, for UC, and r = 0.7 and 0.7, respectively, for CD). For global assessment aggregate UBBC, endoscopic and histologic scores were compared with standard clinical activity scores. In UC, correlations with the van Hees index were r = 0.7, 0.8, and 0.7, respectively, and UBBC assays accurately reflected both regional and global disease activity. In CD, correlations with the CDAI were -0.1, 0.7, and 0.6, respectively. Thus, aggregate UBBC scores failed to reflect disease activity in CD, in which focal deep ulcers may produce high symptom scores but in which adjacent specimens may show no acute inflammation.

Biomarkers↗
PubMed1993

Sarcoidosis.

Explore the source record for details and available documents.

Adult↗
PubMed1993

Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli.

Administration of low doses endotoxin or tumor necrosis factor (TNF) in human experimental models for sepsis results in transient activation of both coagulation and fibrinolysis and subsequent inhibition of the fibrinolytic system by plasminogen activator inhibitor type 1 (PAI-1). We have investigated in a baboon model for sepsis, whether administration of a lethal or sublethal dose of living E. coli could induce similar activation patterns. Levels of thrombin-antithrombin III (TAT) complexes increased significantly to zeniths of 425 and 33 times the baseline values at t+360 in the lethal and sublethal group, respectively. Activation of fibrinolysis, as reflected by plasmin-alpha 2 antiplasmin (PAP) complexes, in the sublethal group was maximal at t+60 and was increasingly inhibited thereafter in spite of a sustained increase of tissue type plasminogen activator (t-PA) levels. In the lethal group PAP complexes increased to a zenith of 38 times the baseline values at t+240. PAI-1 levels increased to 15 times the baseline values at t+360 in the sublethal group, whereas in the lethal group they increased almost linearly to 20 times the baseline values at t+360. Despite high levels of PAI-1, effective inhibition of the fibrinolysis was not established until at T+240 in the lethal group. The difference in activation patterns of both mediator systems in the sublethal and lethal group of baboons indicate that extensive activation of coagulation contributes to the lethal complications in sepsis.

Animals↗
PubMed1993

Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis.

Disseminated intravascular thrombosis is a frequent complication of endotoxic shock, and modulation of endothelial cell hemostatic properties has been proposed to play a role in its pathogenesis based on studies of endothelial cells in culture. This study examined the in vivo expression of tissue factor (TF) and thrombomodulin (TM) in a baboon model of lethal Escherichia coli sepsis using immunohistochemistry with monospecific antibodies. Expression of E-selectin (E-sel) was also determined as a marker of endothelial cell activation. Correlation of immunoreactivity with procoagulant activity in lipopolysaccharide-stimulated cultured human endothelial cells showed that immunohistochemistry was sufficiently sensitive to detect as little as 5% of the maximum in vitro endothelial cell TF response. Vascular endothelium of control animals expressed TM but had no detectable TF or E-sel. Following E. coli infusion, widespread E-sel expression and microvascular fibrin deposition was evident within 6 hours. However, expression of TF by endothelial cells became detectable only in the splenic microvasculature, where endothelial specificity of TF expression was confirmed by dual immunofluorescence of TF with von Willebrand's factor and with TM. In the spleen, there was a dissociation of expression of TF and E-sel, with marginal zone vessels being TF-positive and E-sel-negative, whereas sinusoidal endothelium was E-sel-positive but TF-negative. TM expression was unchanged from controls. Additionally, expression of TF by lung alveolar epithelial cells, splenic macrophages, and epithelial cells of the renal glomeruli was observed to be enhanced in septic animals. This study documents endothelial cell expression of TF in vivo in a relevant pathological setting. At the same time, compared with endothelial cells in culture, there is in vivo both significantly greater control of TF expression than expected, given the strong positive stimuli present in lethal E. coli septic shock and an unpredicted heterogeneity of activation responses.

Animals↗
PubMed1993

Postnatal changes in the expression and distribution of pulmonary cytochrome P450 monooxygenases during Clara cell differentiation in rabbits.

Previous studies have indicated that both cytodifferentiation of Clara cells and the onset of pulmonary cytochrome P450 activity are postnatal events. However, the relationship between these two events during lung development remains poorly understood. To determine how these events interrelate, we examined rabbit Clara cells during postnatal differentiation, with the following goals in mind: 1) to identify the patterns of intracellular expression of cytochrome P450 monooxygenase isozymes 2B and 4B and cytochrome P450 reductase, 2) to describe the biogenesis of the organelles with which these isozymes are associated, namely smooth and rough endoplasmic reticulum, and 3) to compare the patterns of expression with cytochrome P450 activity in the whole lung over the same period. Lungs of rabbits ranging in age from 24 days gestational age (DGA) to 25 weeks postnatally were studied. Ultrastructural morphometry showed that smooth endoplasmic reticulum averaged < 5% of the Clara cell volume in late gestational (24-30 DGA) and neonatal rabbits [0-7 days postnatally (DPN)], grew to 20-30% of the cell volume in 14-21-DPN animals, and approximated adult levels (> 40%) in 28-DPN rabbits. In contrast, rough endoplasmic reticulum decreased from > 10% of the cell volume at 27 DGA to < 5% in adults. All postnatal animals showed considerable heterogeneity in the abundance of smooth endoplasmic reticulum among individual cells. Immunohistochemistry revealed that cytochrome P450 reductase appeared in Clara cells earlier (28 DGA) than did either isozyme 2B or 4B (1 DPN). Each antigen was detected first in the apical borders of the cells, then throughout the cytoplasm in a few cells by 7 DPN, and finally in adult abundance by 28 DPN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed that cytochrome P450 protein concentrations increased postnatally. Cytochrome P450 heme protein was not detected spectrophotometrically in the lungs of animals younger than 3 DPN but increased to approximately 70% of adult levels by 28 DPN. Likewise, cytochrome P450 activity (measured as ethoxy- and pentoxyresorufin O-dealkylation) was not detected in animals younger than 2 DPN but increased to approximately 75% of adult levels by 28 DPN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Customised antenatal growth charts.

Charts for fetal growth do not take physiological variables into account. We have therefore designed a computer-generated antenatal chart that can be easily "customised" for each individual pregnancy, taking the mother's characteristics and birthweights from previous pregnancies into consideration. The adjusted birthweight range expected at 40 weeks' gestation is combined with a standard, longitudinal ultrasound-derived curve for intrauterine weight gain. Review at the Queen's Medical Centre, Nottingham, UK, of 4179 pregnancies with ultrasound-confirmed dates showed that, in addition to gestation and sex, maternal weight at first antenatal-clinic visit, height, ethnic group, and parity were significant determinants of birthweight in our population. Correction factors were calculated for each of these variables and entered into a computer program to adjust the normal birthweight centile limits. With adjusted centiles we found that 28% of babies conventionally designated small for gestational age (less than 10th centile) and 22% of those designated large (greater than 90th centile) were in fact within normal limits for the pregnancy. Conversely, 24% and 26% of babies identified as small or large, respectively, with adjusted centiles were "missed" by conventional unadjusted centile assessment. Adjustment for physiological variables will make assessment of fetal growth more precise and reduce unnecessary investigations, interventions, and parental anxiety.

Birth Weight↗
PubMed1992

Removing meconium from infant tracheae. What works best?

OBJECTIVE: At least nine mechanical devices are available for suctioning the tracheae of meconium-stained newborns. To our knowledge, the efficacy of these devices, as well as various suction pressures and patterns, has not been previously compared. We performed this investigation to assess these variables. DESIGN: Fourteen suction techniques (combinations of device, suction pressure, and suction intermittency) were evaluated sequentially in the trachea of each of 14 in vitro newborn piglets (1 to 4 days old); the order was randomized using a Latin square design. We chose three devices to compare: a meconium aspirator (Neotech Products Inc, Chatsworth, Calif), a hand pump (Res-Q-Vac, Repromed Systems Inc, New York, NY), and a 10F suction catheter (Superior Healthcare Group Inc, Cumberland, RI). Both the meconium aspirator and the hand pump were used with a 3.0-mm endotracheal tube. INTERVENTION: We instilled 0.8 mL of a homogeneous mixture of human meconium and saline (44 g of meconium per 100 mL of saline) in the trachea before applying each suction technique. The meconium aspirator and the suction catheter were each evaluated at three different vacuum pressures, -40, -80, and -150 mm Hg, using both continuous and interrupted suction. The hand pump was evaluated with one and two activations (one activation generates -100 cm H2O, according to the manufacturer). MEASUREMENTS AND RESULTS: The percentage of instilled meconium recovered was consistently greatest (P less than .001) with the meconium aspirator (mean, 88.9% at -150 mm Hg, 84.9% at -80 mm Hg, and 73.5% at -40 mm Hg), intermediate with the catheter (mean, 81.0% at -150 mm Hg, 73.2% at -80 mm Hg, and 67.5% at -40 mm Hg), and least for the hand pump (mean, 67.9% with one activation and 72.6% with two activations). Recovery was better with continuous suction (P = .02) and increasing pressure (P less than .001). CONCLUSIONS: Among the techniques compared, the meconium aspirator at -150 mm Hg, using continuous suction, performed best in this model. It is unknown, however, to what extent the tracheal mucosa may be affected by this degree of negative pressure.

Animals↗
PubMed1992

Prelabour rupture of the membranes at term and unfavourable cervix; a randomized placebo-controlled trial on early intervention with intravaginal prostaglandin E2 gel.

Fifty nine women with prelabour rupture of membranes, unfavourable cervix and no evidence of infection or fetal distress were randomized formally to receive prostaglandin E2 (3mg) gel or sterile K-Y Jelly intravaginally. Conservative expectant management was followed for the next 24 hours. The subsequent management of the labour followed departmental protocol. The women who received prostaglandin went into labour sooner and were delivered earlier but the duration of labour was not significantly different. There were no significant differences in other clinical outcomes. There was 1 case of uterine rupture in the prostaglandin group. We conclude that early intervention with prostaglandin E2 gel intravaginally confers no advantage compared with conservative management except for earlier confinement in this group of patients.

Administration, Intravaginal↗
PubMed1992

Activation of the contact system in lethal hypotensive bacteremia in a baboon model.

The hypotension in septicemia is believed to be mediated by the combined action of many mediators including cytokines, prostaglandins, and complement components. To evaluate the contribution of the contact/kinin-forming system to hypotension, the authors used an established experimental baboon model of bacteremia in which two concentrations of Escherichia Coli (E. coli) were used to produce lethal and nonlethal hypotension. The lethal group (n = 5) developed irreversible hypotension that significantly correlated with the decline in levels of high molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced reversible hypotension, a less striking decline in HK, and only slight elevation in alpha 2M-kal. No significant changes were found in levels of factor XII, prekallikrein, and factor XI in either group. A significant change in the contact system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system.

Animals↗
PubMed1992

Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis.

Morphologic changes in the pituitary, liver, and pancreas of mice with the metallothionein-human growth hormone--releasing hormone (MT-hGRH) transgene were analyzed by in situ hybridization histochemistry (ISH). There was progression from somatotroph hyperplasia to neoplasia in pituitaries of transgenic mice. Pituitary neoplasms were present between 9 to 12 months of age in some mice. Magnetic resonance imaging (MRI) readily identified enlarged pituitaries in MT-hGRH transgenic mice. Serum mouse GH and hGRH levels were marked elevated in MT-hGRH transgenic mice. In situ hybridization histochemistry showed mRNA for hGRH in liver, pituitary, pancreas, spleen, and in most other tissues examined. Combined ISH and immunohistochemistry in the pituitary gland showed that some of the GH cells also produced hGRH, and ultrastructural immunohistochemical analysis of pituitaries showed that GH and hGRH were localized in the same cell and within the same secretory granules. Liver cells of MT-hGRH transgenic mice showed evidence of hypertrophy, and the pancreatic islets were hyperplastic with significant increases in the islet cell areas. The morphologic changes in the liver were distinctive enough to separate control littermates from MT-hGRH transgenic mice in all cases. The enlarged pancreatic islets had increased numbers of insulin-producing cells. Immunoreactive hGRH and hGRH mRNA were both localized in islet cells, and an intense hybridization signal of hGRH mRNA, but only weak staining for hGRH protein, were detected in the liver of transgenic mice. These results indicate that excessive hGRH production leads to distinct morphologic changes in various organs in MT-hGRH transgenic mice and that there is temporal progression from hyperplasia to adenomatous somatotrophs in pituitaries with chronic stimulation by hGRH that involves paracrine, endocrine, and autocrine mechanisms.

Adenoma↗
PubMed1991

Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development.

A [35S]cRNA probe was used for the visualization of GABAA/benzodiazepine (GABAA/BZ) receptor alpha 1 subunit mRNA in developing reeler mutant mouse cerebellum. A clear hybridization signal was observed throughout the malformed reeler cerebellum from birth. Labeling was associated with Purkinje cell bodies located in three subcortical masses. Additional labeled Purkinje cells were observed within the granule cell layer and at their normal position at the interface between the molecular and granule cell layers. All reeler Purkinje cells had comparable levels of grain density, regardless of their location within the cerebellar cortex. These results indicate that Purkinje cell malpositioning, and the resulting absence of a major complement of afferents throughout development, does not impair the expression of mRNA coding for the alpha 1 subunit of the GABAA/BZ receptor.

Animals↗