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Biomedical subjects

R Chang

Publications and source records attributed to R Chang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Chiloscyllium plagiosum low-density lipoprotein receptor: evolutionary conservation of five different functional domains.

All five functional domains of the low-density lipoprotein (LDL) receptor were assembled in their modern form more than 450 million years ago, as revealed from the cloning and sequencing of an LDL receptor cDNA from Chiloscyllium plagiosum (banded cat shark). The shark LDL receptor has the same overall architecture as the mammalian and amphibian counterparts. Each of the seven cysteine-rich repeats in the ligand binding domain resembles its counterpart in the human LDL receptor more than it does the other repeats in the shark receptor as suggested by the presence of unique "signature" sequences, indicating that these repeats had already acquired their independent structures by the time of shark development. Furthermore, amino acid sequences of the entire ligand binding domain of shark LDL receptor show 35% identity over a stretch of 294 residues with a Lymnaea stagnalis G-protein-linked receptor (LSGLR). The region of homology between these unrelated proteins includes conservation of most of the unique characteristics of the cysteine-rich repeats of LDL receptor at the expected positions in LSGLR. The results presented are consistent with the hypothesis that all seven repeats in the ligand binding domain of LDL receptor may have been lifted directly from an ancestral gene instead of being evolutionary duplications of a single repeat recruited by the primitive LDL receptor from another gene.

Amino Acid Sequence↗
PubMed1996

Hemodynamic effects of epinephrine, bicarbonate and calcium in the early postnatal period in a lamb model of single-ventricle physiology created in utero.

OBJECTIVES: A reproducible fetal animal model of single-ventricle physiology was created to examine the effects of pharmacologic agents commonly used in the perinatal and perioperative intensive care management of patients with a single ventricle. BACKGROUND: Single-ventricle physiology is characterized by parallel pulmonary and systemic circulations, with effective blood flow to each determined by the relative resistances in the pulmonary and systemic vascular beds. Perinatal and perioperative management of these patients is largely based on empiric observations and differs considerably between institutions and is further complicated by the transitional physiology of the newborn. The lack of animal models of single-ventricle physiology has hindered the understanding of this problem. METHODS: A 10-mm, Damus-Kaye-Stansel-type aortopulmonary anastomosis was created in 10 fetal sheep at 140 +/- 1.2 days of gestation. The main pulmonary artery was ligated distally, and pulmonary blood flow (Qp) was provided through a 5-mm aortopulmonary shunt. Eight lambs were delivered at term and placed on cardiopulmonary bypass (30 min) 48 to 72 h after birth. Pharmacologic interventions (0.1 microgram/kg body weight per min of epinephrine, 2 mEq/kg of sodium bicarbonate and 10 mg/kg of calcium chloride) were performed before and after bypass, and hemodynamic responses were observed. The response to the epinephrine bolus was determined only in the postbypass study. RESULTS: Both before and after bypass, epinephrine infusion and calcium and bicarbonate administration increased Qp and systemic blood flow (Qs) (total cardiac output) but produced only small changes in the Qp/Qs ratio (-0.5% to -7.3% change). With the epinephrine bolus, Qp increased enormously, and the Qp/Qs ratio increased by 584% (p < 0.001). CONCLUSIONS: In neonatal lambs with single-ventricle physiology created in utero, epinephrine infusion and calcium and bicarbonate administration increased total cardiac output without significantly compromising the Qp/Qs ratio. However, epinephrine bolus seems to be hemodynamically detrimental in circumstances of single-ventricle physiology and should be used with caution and probably in relatively lower doses in the resuscitation of patients with single-ventricle physiology. Further investigation of the dose-dependent effects and the effects of prolonged administration of common pharmacologic agents will enable better management of patients with single-ventricle physiology.

Animals↗
PubMed1996

Role of tissue diagnosis in pulmonary involvement in pediatric human immunodeficiency virus infection.

BACKGROUND: Pulmonary complications occur commonly during HIV infection. The aim of this study was to evaluate the clinical value of lung tissue examination in the diagnosis and treatment of pulmonary disorders in children with HIV infection. METHODS: The medical records of 347 children enrolled between January, 1990, and April, 1994, into various antiretroviral therapy protocols were reviewed to identify patients who underwent a lung biopsy. RESULTS: Fourteen patients underwent diagnostic lung biopsies on 16 separate occasions. The most common radiologic findings were nodular infiltrates which were localized in 7 patients and diffuse in 6. Eight patients presented with fever and progressive respiratory distress unresponsive to empiric therapy, whereas the rest had progressive nodular infiltrates. The pathologic diagnoses included opportunistic infection in 7 patients, lymphocytic interstitial pneumonitis in 5, non-Hodgkin's lymphoma in 3 and interstitial fibrosis in 1. The biopsy led to a major change in the treatment of 7 patients which resulted in a significant improvement of the pulmonary process in all of them. In an additional patient the excisional biopsy proved curative. CONCLUSIONS: When patients are selected appropriately, lung biopsy might have a significant impact on therapy and outcome in HIV-infected children with pulmonary infiltrates.

Adolescent↗
PubMed1996

Functional properties of edible mushrooms.

Edible mushrooms such as shiitake may have important salutary effects on health or even in treating disease. A mushroom characteristically contains many different bioactive compounds with diverse biological activity, and the content and bioactivity of these compounds depend on how the mushroom is prepared and consumed. It is estimated that approximately 50% of the annual 5 million metric tons of cultivated edible mushrooms contain functional "nutraceutical" or medicinal properties. In order of decreasing cultivated tonnage, Lentinus (shiitake), Pleurotus (oyster), Auricularia (mu-er), Flammulina (enokitake), Tremella (yin-er), Hericium, and Grifola (maitake) mushrooms have various degrees of immunomodulatory, lipid-lowering, antitumor, and other beneficial or therapeutic health effects without any significant toxicity. Although the data for this functional food class are not as strong as those for other functional foods such as cruciferous vegetables, because of their potential usefulness in preventing or treating serious health conditions such as cancer, acquired immune deficiency syndrome (AIDS), and hypercholesterolemia, functional mushrooms deserve further serious investigation. Additionally, there is a need for epidemiological evidence of the role of this functional food class.

Food↗
PubMed1996

Metastatic gastrinomas: localization with selective arterial injection of secretin.

PURPOSE: To evaluate localization of hepatic metastases with the intraarterial secretin injection test in Zollinger-Ellison syndrome (ZES). MATERIALS AND METHODS: Results in 74 patients with ZES (aged 15-70 years) were retrospectively studied. All patients had undergone computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin test, in which venous blood is sampled periodically after injection of secretin. RESULTS: Twenty-two patients had liver metastases. An increase in venous gastrin concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection indicated a positive result. Results were positive in 41% of patients with and 2% without liver metastases (P < .0001). Sensitivity of the intraarterial secretin test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%. Intraarterial secretin test results assisted in clinical management in 22% of patients. CONCLUSION: With the criteria developed, the intraarterial secretin test had high specificity but low sensitivity. It should be used when imaging results are unclear.

Adolescent↗
PubMed1996

Parathyroid adenomas in the aortopulmonary window.

PURPOSE: To describe localization studies in nine patients with ectopic parathyroid adenomas in the aortopulmonary window. MATERIALS AND METHODS: Nine patients with ectopic parathyroid tissue (eight adenomas, one hyperplastic gland) in the aortopulmonary window were examined with ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, and scintigraphy. Diagnostic arteriography (n = 4) and venous sampling (n = 3) were performed in the first four patients; arteriography for the purpose of staining was attempted in the last five patients. RESULTS: The results of CT and MR imaging studies were positive in eight of nine patients (89%) and five of eight patients (63%), respectively. The results of thallium/technetium scintigraphy were negative in three patients scanned (0%), but the results of a repeat study in one patient were positive (33%). Sestamibi scans were positive in six of six patients (100%). Single photon emission CT was performed in all six patients and enabled distinction between adenomas in the aortopulmonary window and those in the thymus. CONCLUSION: Ectopic parathyroid glands in the aortopulmonary window are usually detected at sestamibi scintigraphy, and SPECT is helpful in distinguishing these adenomas from more common adenomas in the anterior mediastinum. CT and MR imaging studies can also enable this distinction, but imaging must extend below the aortic arch.

Adenoma↗
PubMed1996

Altered endothelium-dependent responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer.

PURPOSE: We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers, Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine patients refractory to paclitaxel by 3-hour infusion were treated orally with r-verapamil every 4 hours starting 24 hours before the same-dose 3-hour paclitaxel infusion and continuing for a total of 12 doses. Once the maximum-tolerated dose (MTD) of the combination was determined, seven additional patients who had not been treated with either drug were evaluated to determine whether the addition of r-verapamil altered the pharmacokinetics of paclitaxel. Consenting patients had tumor biopsies for P-glycoprotein (Pgp) expression before receiving paclitaxel and after becoming refractory to paclitaxel therapy. RESULTS: The MTD of the combination was 225 mg/m2 of r-verapamil every 4 hours with paclitaxel 200 mg/m2 by 3-hour infusion. Dose-limiting hypotension and bradycardia were observed in three of five patients treated at 250 mg/m2 r-verapamil. Fourteen patients received 32 cycles of r-verapamil at the MTD as outpatient therapy without developing cardiac toxicity. The median peak and trough serum verapamil concentrations at the MTD were 5.1 micromol/L (range, 1.9 to 6.3), respectively, which are within the range necessary for in vitro modulation of Pgp-mediated multidrug resistance (MDR). Increased serum verapamil concentrations and cardiac toxicity were observed more frequently in patients with elevated hepatic transaminases and bilirubin levels. Hematologic toxicity from combined paclitaxel and r-verapamil was significantly worse compared with the previous cycle of paclitxel without r-verapamil. In the pharmacokinetic analysis, r-verapamil delayed mean paclitaxel clearance and increased mean peak paclitaxel concentrations. CONCLUSION: r-Verapamil at 225 mg/m2 orally every 4 hours can be given safely with paclitaxel 200 mg/m2 by 3-hour infusion as outpatient therapy and is associated with serum levels considered active for Pgp inhibition. The addition of r-verapamil significantly alters the toxicity and pharmacokinetics of paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

In vitro cytokine profiles and their relevance to rejection following renal transplantation.

Graft rejection remains an important cause of renal allograft failure, despite improvements in immunosuppression and HLA typing. Although HLA matching is beneficial, ensuring an exact match it is often impractical. Thus, a reliable in vitro method for quantitating and qualitating alloreactivity is an important goal. In this study, we measured in vitro the cytokine secretion profiles of mononuclear cells from patients prior to renal transplantation by stimulating with anti-CD3 monoclonal antibody and suppressing with cyclosporine. Mononuclear cells from patients who subsequently developed acute cellular rejection secreted higher mean levels of interleukin (IL)-2 and gamma-interferon (IFN-gamma) than those from patients who had no rejection episodes. IFN-gamma secretion was significantly associated with rejection (P = 0.002), whereas IL-2 secretion did not quite reach statistical significance. There was no significant correlation between IL-4 levels and rejection. Although cyclosporine suppressed the secretion of both IL-2 and IFN-gamma, there was no difference in sensitivity to suppression between rejectors and nonrejectors. These results further emphasize the importance of the TH1 lymphocyte subset in renal allograft rejection. The IFN-gamma secretory capacity of alloreactive T cells may influence the outcome of a renal allograft by (1) activating graft infiltrating macrophages and/or (2) up-regulating HLA molecules on the graft.

Antibodies, Monoclonal↗
PubMed1995

Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.

OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

Adult↗
PubMed1995

Affinity purification of human plasma vitamin D-binding protein.

During the course of our studies to probe the vitamin D ligand-binding domains of vitamin D-binding protein and vitamin D receptor, we developed a synthetic procedure to modify the 3 beta-hydroxyl group of vitamin D3 and its 25-hydroxy- and 1,25-dihydroxy metabolites with a 3'-aminopropylether group. In the present study we have coupled 25-hydroxyvitamin D3-3 beta-3'-aminopropylether to an activated Sepharose matrix. Using this stable and reusable affinity matrix we have purified human vitamin D-binding protein from human plasma to homogeneity.

Binding Sites↗
PubMed1995

Impact of recounting trauma stories on the emotional state of Cambodian refugees.

Twenty Cambodian refugees with premigration histories of trauma received an average of 16 sessions of individual therapy from a Cambodian bicultural counselor at a trauma treatment center in Sydney, Australia. Nineteen of the 20 patients reported that during treatment they had been willing to talk about their trauma histories, a finding that raises doubts about the commonly held belief that Asians are not psychologically minded and avoid disclosing emotionally sensitive information to health care workers. However, self-disclosing therapy alone did not appear to benefit these patients. Only four patients found talking about their trauma story directly helpful in improving their emotional state, and three of the four found the relief to be transitory.

Adaptation, Psychological↗
PubMed1995

Selective venous sampling from the cavernous sinuses is not a more reliable technique than sampling from the inferior petrosal sinuses in Cushing's syndrome.

The purpose of this study was to compare ACTH levels in unstimulated samples obtained from the cavernous sinuses (CS) to unstimulated and CRH-stimulated samples obtained from the inferior petrosal sinuses (IPS) in 15 patients with surgically proven Cushing's disease. After unstimulated samples were obtained through 5-French catheters placed in both IPS, tracker catheters were introduced into both cavernous sinuses, and unstimulated samples were obtained within 5 min of the initial set. The Tracker catheters were removed, CRH was administered, and CRH-stimulated samples were obtained from the IPS. We compared the central to peripheral ACTH ratios in unstimulated samples from the cavernous sinuses to unstimulated and CRH-stimulated samples from the IPS as a basis for distinguishing pituitary from ectopic ACTH production. In addition, we compared the ability of the intercavernous and interpetrosal ACTH ratios to correctly predict the site of the microadenoma. Unstimulated levels of ACTH in the cavernous sinuses were generally higher than unstimulated levels of ACTH in the petrosal sinuses. However, 3 of 15 patients failed to show central to peripheral ACTH ratios greater than 2 in unstimulated samples from the cavernous sinuses and were thus falsely negative for the diagnosis of Cushing's disease (test sensitivity, 80%). By comparison, the test sensitivity for the petrosal sinus samples was 87% for the unstimulated samples and 100% for the CRH-stimulated samples. Lateralization was correct in 6 of 15 patients based on CS samples and in 9 of 15 patients based on IPS samples. Because of the 20% false negative rate, CS sampling without CRH stimulation is not recommended for the differential diagnosis of ACTH-dependent hypercortisolism.

Adenoma↗
PubMed1995

Effects of carbohydrate type and concentration and solution osmolality on water absorption.

We studied intestinal absorption of solutions containing either one (glucose, Glu, or maltodextrin, Mal) or two (fructose, Fru, and Glu or sucrose, Suc) transportable carbohydrate (CHO) substrates using segmental perfusion technique in eight healthy male subjects. These CHO were either free or directly transportable monosaccharides (Glu, Fru), bound as the disaccharide (sucrose, Suc), or as oligomers (maltodextrins, Mal). [CHO] was varied from 6% to 8% (120-444 mmol.1(-1)). All solutions contained low [Na+] (15-19 mEq) and [K+] (3-4 mEq). Solutions osmolalities varied from 165 to 477 mOsm.kg(-1). Osmolalities in the test segment ranged from 268 to 314 mOsm.kg(-1). The regression line of osmolality with water absorption differed for single as compared with multiple substrate solutions. The significantly different intercepts of these two regression lines suggest that solutions with multiple substrates produce greater water absorption at a given osmolality than those with one. Comparing all solutions, test segment solute flux (partial r = 0.69) was more important than mean osmolality (partial r = 0.32). In conclusion, solutions with multiple substrates stimulate several different solute absorption mechanisms yielding greater water absorption than solutions with only one substrate.

Amino Acids↗
PubMed1994

Interleukin-6 prevents dexamethasone-induced myeloma cell death.

The effects of dexamethasone on the growth of four human multiple myeloma cell lines were studied. In addition, the effects on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by the use of reverse-transcriptase polymerase chain reaction. Dexamethasone (Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene expression in three of four cell lines studied, whereas the higher concentration of the hormone inhibited also IL-6R gene expression. Dex effects were modulated through the glucocorticoid receptor (GR). Dex treatment resulted in killing of sensitive cells associated with DNA fragmentation, which could be reversed by concomitant treatment with IL-6. The reversal of Dex-mediated effects by IL-6 did not result from an inhibition of GR function as measured by receptor nuclear translocation or Dex-regulated reporter gene function. These results indicate that blockage of the IL-6 signaling pathway is essential for effective myeloma cell kill by Dex.

Base Sequence↗
PubMed1994

Inefficient processing of human protein C in the mouse mammary gland.

Vitamin K-dependent plasma protein, human Protein C (HPC) has been expressed in transgenic mice, using a 4.2 kb mouse whey acidic protein (WAP) promoter, 9.0 kb HPC gene and 0.4 kb 3' flanking sequences. Expression was mammary gland-specific and the recombinant human Protein C (rHPC) was detected in milk at concentrations of 0.1 to 0.7 mg ml-1. SDS-PAGE revealed that the single, heavy and light chains of rHPC migrated with increased electrophoretic mobility, as compared to HPC. Enzymatic deglycosylation showed that these molecular weight disparities are in part due to differential glycosylation. The substantial increase observed in the amount of single chain protein, as well as the presence of the propeptide attached to 20-30% of rHPC, suggest that mouse mammary epithelial cells are not capable of efficient proteolytic processing of rHPC. The Km of purified rHPC for the S-2366 synthetic substrate was similar to that of plasma-derived HPC, while the specific activity was about 42-77%. Amino acid sequence analyses and low anticoagulant activity of purified rHPC suggest that gamma-carboxylation of rHPC is insufficient. These results show that proteolytic processing and gamma-carboxylation can be limiting events in the overexpression of fully biologically active rHPC in the mouse mammary gland.

Amino Acid Sequence↗
PubMed1994

Dilation of lower ureteral strictures with Van Andel catheters.

We present a simple method to dilate ureteral strictures, which was performed in 7 patients with metastatic cancer (1 breast, 1 lymphoma, 2 ovarian and 3 colorectal tumors) who presented with newly discovered obstruction in the distal ureter. The obstruction was due to tumor in the pelvis in 5 patients and to pelvic radiotherapy in 2. A 0.035-inch guide wire was passed beyond the stricture cystoscopically. In each case a double pigtail stent could not be passed beyond the stricture over the guide wire. The strictures were then dilated with progressively larger Van Andel catheters passed over the guide wire through the cystoscope. Following dilation a 7.5F to 8.5F soft double pigtail catheter was easily advanced. All patients had good drainage on followup radiographic studies. The method is presented as an alternative to balloon dilation of lower ureteral strictures when the goal is placement of an adequate diameter indwelling ureteral stent.

Adult↗