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Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 415 records · Page 23Linked to original sources
PubMed1995

Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors.

Thyroid hormone (T3) plays a causative role in amphibian metamorphosis. This regulation is thought to be mediated by heterodimers of T3 receptors (TRs) and retinoid X receptors (RXRs). We report here that Xenopus TRs can indeed form strong heterodimers with Xenopus RXRs on the T3 response element (TRE) present in Xenopus TR beta genes. Using a T3-responsive in vivo transcription system established by introducing TRs and RXRs into Xenopus oocytes, we demonstrated that TR-RXR heterodimers repressed TR beta gene promoter in the absence of T3 and activated the promoter in the presence of the hormone. Furthermore, by analyzing the expression of TR and RXR genes, we showed that TR and RXR genes were coordinately regulated in different tissues during metamorphosis. Thus high levels of their mRNAs are present in the limb during early stages of limb development when morphogenesis occurs and in the tail toward the end of metamorphosis when it is being resorbed. Such correlations coupled with our TRE-binding and in vivo transcriptional activation experiments provide strong evidence that TRs and RXRs function together to mediate the effects of T3 during metamorphosis. These results further suggest a possible molecular basis for the temporal regulation of tissue-specific metamorphosis.

Animals↗
PubMed1995

In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs.

BACKGROUND: The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. METHODS AND RESULTS: To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0-mm expanded polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary-to-systemic blood flow ratio of 2.2 +/- 1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8 +/- 11.7 versus 16.2 +/- 2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P < .05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra-acinar arteries. CONCLUSIONS: In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with cogenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.

Animals↗
PubMed1995

Sequence and arrangement of genes encoding sigma factors in Clostridium acetobutylicum ATCC 824.

The nucleotide sequence of a 2.7-kb region of Clostridium acetobutylicum ATCC 824 DNA containing three open reading frames was determined. They encoded homologs of three proteins of Bacillus subtilis, and the gene arrangement in both organisms was identical. The first gene, orfA, was 801-bp long; the 31-kDa (266 aa) product it encoded exhibited homology with the putative sigma E-processing enzyme. The second gene, sigE, was 708-bp long encoding a 27-kDa (235 aa) product; the third gene, sigG, was 774-bp long encoding a 30-kDa (257 aa) product. These two proteins showed high homology with sigma E and sigma G, two sporulation-specific sigma factors.

Amino Acid Sequence↗
PubMed1995

HIV-1-specific cytotoxic T lymphocyte responses in the first year of life.

HIV-1-specific CTL responses were prospectively evaluated in infants born to HIV-1-seropositive women to assess the capability of the young infant to generate HIV-1-specific CTL and to examine the potential role of HIV-1-specific CTL in the pathogenesis of vertical infection. Our results indicate that some young infants, and even the fetus, seem to be capable of generating virus-specific CTL responses. The detection of HIV-1-specific CTL responses varied among infants, however, with respect to timing, HIV-1 gene product recognition, and the magnitude of detectable responses; HIV-1-specific CTL responses were uncommonly detected in the first few months of life. The less consistent detection of HIV-specific CTL in early infancy contrasts with reports of the detection of HIV-1-specific CTL soon after primary infection in adults. HIV-1-specific CTL were not detected in any uninfected infants born to HIV-1-seropositive women. This description of HIV-1-specific CTL in infants may have important implications for understanding the pathogenesis of vertical HIV-1 infection and for the development of a vaccine to interrupt vertical infection.

Age Factors↗
PubMed1995

Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis.

OBJECTIVE: To define the safety of major hepatectomy for hepatocellular carcinoma (HCC) associated with cirrhosis and the selection criteria for surgery in terms of hospital mortality. DESIGN: Major hepatectomy for HCC in the presence of cirrhosis is considered to be contraindicated by many surgeons because the reported mortality rate is high (26% to 50%). Previous workers recommended that only selected patients with Child's A status or indocyanine green (ICG) retention at 15 minutes of less than 10% undergo major hepatectomy. A survey was made, therefore, of our patients with HCC and cirrhosis undergoing major hepatectomy between 1989 and 1994. SETTING: A tertiary referral center. PATIENTS: The preoperative, intraoperative, and postoperative data of 54 patients with cirrhosis who had major hepatectomy were compared with those of 25 patients with underlying chronic active hepatitis and 22 patients with normal livers undergoing major hepatectomy for HCC. The data had been prospectively collected. INTERVENTION: Major hepatectomy, defined as resection of two or more liver segments by Goldsmith and Woodburn nomenclature, was performed on all the patients. MAIN OUTCOME MEASURE: Hospital mortality, which was defined as death within the same hospital admission for the hepatectomy. RESULTS: Preoperative liver function in patients with cirrhosis was worse than in those with normal livers. The intraoperative blood loss was also higher (P = .01), but for patients with cirrhosis, chronic active hepatitis, and normal livers, the hospital mortality rates (13%, 16%, and 14%, respectively) were similar. The hospital mortality rate for patients with cirrhosis in the last 2 years of the study was only 5%. Patients with cirrhosis could tolerate up to 10 L of blood loss and survive the major hepatectomy. By discriminant analysis, an ICG retention of 14% at 15 minutes was the cutoff level that could maximally separate the patients with cirrhosis with and without mortality. CONCLUSION: Major hepatectomy for HCC in the presence of cirrhosis is associated with a mortality rate that is not different from the rate for patients with normal livers. An ICG retention of 14% at 15 minutes would serve as a better selection criterion than the 10% previously used.

Adult↗
PubMed1995

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions.

Mesenchymal cells are required for the induction of epithelial development during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epithelial cells, suggesting that it may play a role in mediating these interactions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGFR) transcripts during organogenesis and limb formation in mouse embryos (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clones were isolated. There was extensive identity between the deduced mouse KGF protein sequence and that of its human and rat cognates, indicating that this gene has been highly conserved during mammalian evolution. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointestinal, and urogenital systems, whose development is dependent upon mesenchymal-epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR, KGF and KGFR mRNA was also expressed in certain other tissues such as perichondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesenchymal-epithelial interactions. KGF expression was also detected in tissues isolated from human embryos, suggesting similar functions for KGF in human development. Taken together, our results suggest that KGF plays an important role in mediating mesenchymal-epithelial interactions during organogenesis, but may also have other developmental functions in tissues not governed by such interactions.

Adult↗
PubMed1995

Free radical-induced endothelial membrane dysfunction at the site of blood-brain barrier: relationship between lipid peroxidation, Na,K-ATPase activity, and 51Cr release.

Na,K-ATPase activity, membrane lipid peroxidation (TBARM), and membrane 'leakiness' for small molecules were examined in rat cerebromicrovascular endothelial cells (RCEC) following exposure to hydrogen peroxide and xanthine/xanthine oxidase. Whereas short-term (15-30 min) exposure to either oxidant decreased ouabain-sensitive 86Rb uptake and increased TBARM in a concentration-dependent fashion, significant release of 51Cr (30-40%) from cells was observed only after one hour exposure to the oxidants. By comparison, much longer exposure times (i.e., 4 hours) were needed to induce significant lactate dehydrogenase release from oxidant-treated cells. The oxidant-evoked decrease in Na,K-ATPase activity and increases in TBARM and RCEC 'permeability' were abolished in the presence of the steroid antioxidants U-74500A and U-74389G (5-20 microM). Reduced glutathione (4 mM) partially attenuated oxidant-induced changes, whereas ascorbic acid (2 mM) and the disulfide bond-protecting agent, dithiothreitol (1 mM), were ineffective. These results suggest that the oxidant-induced loss of Na,K-ATPase activity in RCEC results primarily from changes in membrane lipids, and implicate both the inhibition of Na,K-ATPase and membrane lipid peroxidation in the mechanism responsible for the delayed free radical-induced increase in RCEC membrane 'permeability'.

Animals↗
PubMed1995

Chronic venous insufficiency in a Chinese population: an anatomic and functional study by continuous-wave Doppler and photoplethysmography.

A total of 1583 limbs in 878 patients who presented with symptoms of chronic venous insufficiency of the lower limbs were examined in the vascular laboratory. The anatomic distribution of valvular insufficiency was determined by continuous-wave Doppler ultrasound and functional severity was determined by the venous refilling time (VRT) using photoplethysmography. Severity of reflux was assessed using a four-class grading scale (classes 0 to 3) based on clinical and VRT criteria. A mixed incompetence of the valves in the superficial system and the perforators was encountered in the majority of patients (44% in class 0 and 85% in class 3). Deep vein incompetence was less common and usually consisted of isolated proximal incompetence of the common femoral vein (up to 32% in class 3) or was of a mixed type (21% in class 3). Isolated distal deep vein incompetence was uncommon. Proximal femoral vein incompetence and superficial system incompetence at the saphenofemoral junction were associated with severe reflux. There was significant improvement in the VRT in patients with more severe reflux (class 2 or 3) after application of an ankle tourniquet. Symptoms of moderate to severe chronic venous insufficiency and ankle ulceration may be a result of long-standing superficial system incompetence rather than deep venous disease and may thus be amendable to simple saphenofemoral ligation and interruption of perforators.

Adolescent↗
PubMed1995

The relationship of plasma norepinephrine levels and aortic distensibility in elderly with isolated systolic hypertension.

The present study evaluated the relationship of plasma norepinephrine (NE) and aortic distensibility (AOD) in a group of elderly patients with isolated systolic hypertension. Aortic distensibility was calculated as AOD = 2 x (delta aortic diameter)/diastolic aortic diameter) x (delta aortic pressure). Results indicate that the aortic diameters were significantly increased while the diastolic blood pressure and heart rate were decreased, in response to combined alpha- and beta-receptor blockade (labetalol). However, we found that AOD was not significantly related to plasma NE. We therefore conclude that AOD can be increased in elderly hypertensives by alpha-beta-blockade, as has been found in younger patients, but plasma NE is not a useful marker for AOD in this population.

Aged↗
PubMed1995

Comparison of simulated and in-vivo plasma levels of cilastatin following intravenous in-line drug administration.

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.

Animals↗
PubMed1995

Evidence that the modulation of membrane-associated protein kinase C activity by an endogenous inhibitor plays a role in N1E-115 murine neuroblastoma cell differentiation.

Murine neuroblastoma cells, N1E-115, were induced to differentiate into neuron-like cells by serum deprivation for 18 h. As previous studies have shown that the suppression of protein kinase C (PKC) activity by selective inhibitors or neutralizing antibodies induces neuroblastoma cells to differentiate, we tested the hypothesis that serum deprivation may cause a rapid loss in membrane PKC activity that occurs well before the morphological changes that are characteristic of cell differentiation. A significant reduction in particulate (membrane) PKC activity was indeed observed within 3 h of serum withdrawal when enzyme activity was measured in intact native membranes by the recently described in vitro "direct" assay. This rapid reduction in enzyme activity was confirmed by the decreased phosphorylation of the MARCKS protein, an endogenous PKC-selective substrate, in intact cells. The decrease in membrane PKC activity occurred without any loss in the amount of membrane-associated enzyme, suggesting that some factor(s) resident in neuroblastoma membranes was suppressing PKC activity. Indeed, results indicate the presence of an endogenous inhibitor of PKC tightly associated with neuroblastoma membranes. This inhibitory activity increased in the membranes of cells subjected to serum deprivation, raising the possibility that it was likely responsible for the decline in membrane PKC activity in differentiating N1E-115 cells. Preliminary characterization indicated that the inhibitory activity is a protein and is localized mainly in the membrane fraction. Thus, these results demonstrate directly that endogenous inhibitor can regulate membrane-associated PKC activity in cells and thereby modulate PKC-related neuronal functions.

Animals↗
PubMed1995

Hepatic resection for hepatocellular carcinoma. An audit of 343 patients.

OBJECTIVE: The authors summarize the results of patients who had hepatectomy for hepatocellular carcinoma over a 22-year period. SUMMARY BACKGROUND DATA: Recent reports showed improved perioperative results and long-term prognosis. METHODS: The perioperative outcome of 343 patients was studied according to three different time periods: before 1987 (n = 149); 1987 to 1991 (n = 128); and 1992 to present (n = 66). Survival analysis was made by stratifying patients into two categories--either before or after 1987. The majority of patients had large tumors (78%), cirrhosis (73%), and a major hepatectomy (73%). RESULTS: Besides an increased resectability rate (23%), there was a marked reduction of the recent morbidity (32%; p < 0.001), operative (4.5%; NS) and hospital (6%; p < 0.02) mortality rates. The recent surgical approach was identified as a significant contributory factor to the lowered hospital mortality rate. Patients in the latter part of the study had significantly better survival, with a 1-, 3- and 5-year survival rate of 68%, 45%, and 35%, respectively. Early detection and effective treatment of recurrences contributed to the improved prognosis. CONCLUSIONS: The recent management strategy and technological advances improved the results of surgical treatment for patients with hepatocellular carcinoma.

Adult↗
PubMed1995

Endothelinb receptor agonists produce pulmonary vasodilation in intact newborn lambs with pulmonary hypertension.

The hemodynamic effects of endothelin-1 (ET-1) are mediated by at least two distinct receptors: ETa and ETb receptors. Recently, ETb receptor agonists (4 Ala ET-1 and IRL 1620) were developed. To investigate the role of ETb receptor activation on the pulmonary and systemic circulations, we studied the hemodynamic effects of intrapulmonary arterial injections of these receptor agonists in 10 intact newborn lambs. At rest, 4 Ala ET-1 (290-1,725 ng/kg) changed no hemodynamic variables. IRL 1620 (180-1,095 ng/kg) decreased mean pulmonary arterial pressure (PAP, 16.8% +/- 15.0 and 17.8% +/- 8.5, p < 0.05) and left pulmonary artery blood flow (21.6% +/- 22.1 and 33.4% +/- 27.7, p < 0.05) at the two highest doses only. During U46619-induced pulmonary hypertension, both 4 Ala ET-1 (3.2% +/- 8.0 to 15.9% +/- 6.4, p < 0.05) and IRL 1620 (8.7% +/- 6.3 to 21.9% +/- 4.1, p < 0.05) produced selective dose-dependent decreases in PAP. The decrease in mean PAP induced by 4 Ala ET-1 and IRL 1620 was attenuated by N omega-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis] (16.6% +/- 3.5 vs. 5.9% +/- 2.3 and 16.2% +/- 3.4 vs. 6.6% +/- 2.8, p < 0.05) and by glybenclamide (a blocker of ATP-dependent potassium channels) (18.2% +/- 7.9 vs. 7.5% +/- 8.3 and 14.7% +/- 3.6 vs. 6.3% +/- 3.2, p < 0.05). ETb receptor activation produces selective pulmonary vasodilation during pulmonary hypertension in intact newborn lambs. The vasodilating properties are mediated in part by release of ENDO and by potassium channel activation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Cluster of five children with acute encephalopathy associated with cat-scratch disease in south Florida.

Between August 12 and September 27, 1994, five children in South Florida were hospitalized at a single hospital because of encephalopathy, presenting as status epilepticus, associated with cat-scratch disease (CSD). Diagnoses were confirmed by using an indirect fluorescent antibody test to detect antibody to Bartonella henselae, the causative agent of CSD. These cases represent the first cluster of CSD encephalopathy cases to be recognized in the United States. The patients lived within 7 miles of each other and all reported contact with pet or stray cats before developing regional lymphadenopathy and encephalopathy. All recovered fully. A high proportion of 124 cats from the local area were seropositive (62%) or bacteremic (22%). This study suggests that B. henselae can be associated with geographically focal clusters of CSD encephalitis and should be considered in the evaluation of children with acute encephalopathy.

Animals↗
PubMed1995

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow.

Animals↗
PubMed1995

The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation.

Alprazolam, a benzodiazepine derivative, stimulates specific gamma-aminobutyric acidA receptors and has been found to inhibit CRH activity in the brain. This study examined the effect of alprazolam on serum cortisol and LH pulsatility in six women in the early follicular phase (EFP), six women in the midluteal phase (MLP), and six women with stress-related anovulation (SRA) of normal weight, but with a previous history of anorexia nervosa. Subjects were given alprazolam (2 mg, orally) or an identical placebo capsule at 0900 h, and blood samples were collected through an indwelling venous catheter every 10 min for 8 h in the SRA women and 10 h in EFP and MLP women. Women with SRA were also given clomiphene (100 mg/day) for 5 days before a further 8-h blood sampling session. As expected, there was a diurnal decline in serum levels of cortisol, which was significantly less in women with SRA (55 +/- 4%) than those in both EFP (76 +/- 4%) and MLP women (75 +/- 3%; P < 0.005). The food-related rise of cortisol that follows lunch in normal women was absent in women with SRA. Alprazolam accentuated the decline in serum cortisol, and in all three groups, the mean serum cortisol level after alprazolam treatment was significantly less (P < 0.05) than that after placebo. In SRA women, alprazolam restored visible LH pulses in all women and increased the mean LH pulse frequency (P < 0.02) and pulse amplitude (P < 0.05). This was associated with an increase in mean serum LH from 1.3 +/- 0.3 to 3.0 +/- 0.06 IU/L (P < 0.02). In EFP women, alprazolam reduced the frequency of LH pulsatility from a mean of 5.8 +/- 0.7 to 3.2 +/- 0.5 pulses/10 h (P < 0.02) and increased the mean pulse amplitude from 2.4 +/- 0.5 to 5.0 +/- 1.1 IU/L (P < 0.0005). Alprazolam had no significant effect on LH pulsatility or amplitude in MLP women. To explain this variation in response to alprazolam, we propose that alprazolam accelerates the GnRH pacemaker in SRA women by inhibiting excessive CRH activity, which blocks the GnRH pacemaker in these women. In normal women, we hypothesize that tonic inhibition of the GnRH pacemaker by CRH is minimal, and the reduced pulsatility of LH after alprazolam treatment in EFP women results from inhibition of stimulatory noradrenergic neurons. In MLP women, we propose that preexisting opioid inhibition of noradrenergic neurons by progesterone blocks this effect of alprazolam.

Adolescent↗
PubMed1995

Trout and chicken proglucagon: alternative splicing generates mRNA transcripts encoding glucagon-like peptide 2.

In mammals, the proglucagon gene is transcribed into a single identical mRNA in pancreas, intestine, and brain. The proglucagon mRNA encodes glucagon and two glucagon-like peptides (GLP 1 and GLP 2), whose production is regulated by tissue-specific proteolytic processing. Previously characterized pancreatic proglucagon cDNAs from birds and fish encode glucagon and only one glucagon-like peptide, GLP 1. The isolation of intestinal proglucagon cDNAs from the rainbow trout, Oncorhynchus mykiss, and chicken, Gallus gallus, shows that the proglucagon gene of fish and birds also contains the sequence of a second glucagon-like peptide, GLP 2. In contrast to the proglucagon mRNAs from mammals, fish and bird proglucagon mRNAs from pancreas and intestine have different 3'-ends that are due to alternative mRNA splicing. The intestinal mRNA was found to be spliced to one or more exons, which encode GLP 2, while the pancreatic mRNA terminates within the intron between the exons encoding GLP 1 and GLP 2. These results show that proglucagon gene expression is regulated at the level of mRNA splicing and serve to reemphasize the potential biological importance of GLP 2.

Alternative Splicing↗