Biomedical subjects

R Chang

Publications and source records attributed to R Chang.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1994

Treatment with intralesional granulocyte instillations and interferon-gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses.

We present the case of a 16-year-old girl with p22-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed.

Adolescent↗

PubMed1994

Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis.

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Animals↗

PubMed1994

Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs.

Nitric oxide (NO), a labile humoral factor produced by vascular endothelial cells, is a potent vasodilator and an important mediator of pulmonary vascular tone. Nucleophile/NO adducts are a new class of compounds that spontaneously and predictively release NO. We investigated the hemodynamic effects of intravenous (i.v.) infusions of a recently developed NO-donor drug, the diethylamine-nitric oxide adduct (DEA/NO), in 17 intact newborn lambs. At rest, DEA/NO (1-2 microgram.kg-1.min-1) produced dose-dependent decreases in mean pulmonary (from 10.6 +/- 8.6 to 21.2 +/- 7.9%, p < 0.05) and systemic arterial pressure (from 13.2 +/- 11.7 to 31.0 +/- 15.4%, p < 0.05). Similarly, during pulmonary hypertension induced by infusion of U46619, DEA/NO (0.5-2.0 micrograms.kg-1.min-1) produced dose-dependent decreases in mean pulmonary (from 7.3 +/- 5.6 to 24.1 +/- 13.3%, p < 0.05) and systemic arterial pressure (from 2.2 +/- 3.8 to 20.3 +/- 12.9%, p < 0.05). Cardiac output (CO), heart rate (HR), systemic arterial blood gases, and pH were unchanged; atrial pressures decreased at higher doses. Equimolar infusions of S-nitroso-N-acetyl-penicillamine, nitroglycerin (NTG), and sodium nitroprusside (SNP) produced similar decreases in pulmonary and systemic arterial pressure. The nucleophile/NO adducts are potent vasodilators; their predictable and quantitative release of NO make them potentially useful research tools. In addition, because these compounds may decrease the incidence of tolerance and the risk from toxic metabolites associated with use of other nitrovasodilators, they may be clinically useful.

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

PubMed1994

Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1) in the pathogenesis of severe murine malaria.

Infection of CBA mice with Plasmodium berghei ANKA results in severe malaria, which is characterized by mortality 6 to 10 days after infection and is associated with alterations of the brain microcirculation. These alterations consist of (i) intravascular sequestration of monocytes, (ii) an increase in vascular permeability as documented by Evans blue diffusion, and (iii) microhemorrhages. This syndrome may be due to an increase of production of tumor necrosis factor alpha which upregulates the endothelial expression of ICAM-1 and thus leads to adhesion of CD11a/CD18 (LFA-1)-bearing cells. During severe malaria, we found an important sequestration of the CD11a-bearing polymorphonuclear neutrophil leukocytes (PMN) in the lung but not in the brain. Treatment with a monoclonal antibody (MAb) against PMN, which induces profound neutropenia, prevented mortality and Evans blue diffusion in the brain and the lung, while it unexpectedly increased the occurrence of microhemorrhages. The anti-PMN MAb abolished PMN sequestration in the lung and also partially decreased monocyte sequestration in the brain and the lung. Treatment with an anti-CD11a MAb also prevented mortality, Evans blue diffusion, and PMN and monocyte sequestration. This study shows that PMN contribute to the mortality and the microvascular lesions resulting from severe malaria. This may be due to their CD11a-dependent sequestration in the lung and also to their indirect influence on vascular permeability and the sequestration of monocytes.

Animals↗

PubMed1994

Parkinson's disease in Kin-Hu, Kinmen: a community survey by neurologists.

A door-to-door survey by neurologists in Kin-Hu township, Republic of China, of a sample of the Chinese population of 683 persons aged 50 years and over was performed in August, 1992. A total of 482 subjects (70.6%) completed the study. Kin-Hu, a township of Kinmen, is predominantly rural with agriculture as the main occupation. Six subjects (5 men, 1 woman) were diagnosed with Parkinson's disease (PD). Of these six, five were newly diagnosed; one of the five also had dementia. The crude prevalence rate per 1,000 persons over 50 years of age of PD in Kin-Hu was 6.2. The age-specific prevalence rates per 1,000 persons (95% confidence intervals) were 0 for age 50-59, 7.8 (0-22.9) for age 60-69, 17.5 (5.2-29.8) for age 70-79, and 25.4 (10.9-39.9) for age > or = 80. These rates are considerably higher than those reported in the People's Republic of China, and similar to rates found in Western countries. The higher prevalence of PD found in this pilot study suggests that environmental factors may be more important than racial factors in the pathogenesis of PD. If confirmed, the results suggest that epidemiologic studies looking for environmental risk factors might be of value.

Aged↗

PubMed1993

Expression cloning of a cDNA encoding a novel murine B cell activation marker. Homology to human CD38.

A rat mAb (NIM-R5) has recently been prepared against a novel murine B cell activation marker. We report here isolation of a cDNA (1-19) encoding the B cell-derived protein recognized by NIM-R5 antibody. This cDNA contains an open reading frame that encodes a polypeptide of 304 amino acids with a predicted molecular weight of 34,500. The existence of a 22-amino acid hydrophobic region located 23 amino acids from the amino terminal of the deduced protein, together with four potential N-linked glycosylation sites, characterize the deduced protein encoded by I-19 cDNA as a typical type II transmembrane glycoprotein. Although I-19 cDNA appears to encode a novel murine protein, its nucleotide sequence and deduced amino acid sequence show approximately 70% homology to the previously reported sequence of human CD38, suggesting that I-19 cDNA encodes either the mouse homologue of CD38 or a closely related protein. Northern blot analysis of the expression of this cDNA product in a variety of cell types, together with immunoprecipitation of the recombinant protein expressed in BaF3 cells, indicated that I-19 cDNA encodes not only the epitope recognized by NIM-R5 but also a protein that is indistinguishable biochemically and in terms of distribution from the murine B cell activation marker recognized by NIM-R5 antibody. Chromosomal mapping studies have localized this locus to the proximal region of mouse chromosome 5. We anticipate that the availability of probes for the murine B cell activation marker recognized by NIM-R5, and the recombinant protein itself, will greatly aid efforts to define the role of this molecule in murine B cell development.

ADP-ribosyl Cyclase↗

PubMed1993

Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells.

Interleukin-6 (IL-6) has been suggested to play a major role in multiple myeloma. To investigate the source and target cells of IL-6 activity in multiple myeloma, expression of the cytokine and its receptor genes by myeloma plasma cells was studied. Tumor cells were sorted from bone marrow aspirates of myeloma patients using 4-parameter gating. Myeloma cells were identified as CD38high CD45negative-intermediate and by their light-scatter characteristics. Sorted cells contained only myeloma plasma cells. No contaminating cells were present as determined morphologically, by monoclonal cytoplasmic Ig analysis, and by polymerase chain reaction (PCR) amplification of marker genes. Myeloma cells from 45% of patients expressed IL-6. IL-6 receptor transcripts were found in 68% of the specimens. IL-6 gene expression correlated with expression of the IL-6 receptor gene (P < .005). Correlations observed between the expression of CD45, a protein tyrosine phosphatase expressed by B lymphocytes but not by plasma cells, and the expression of the IL-6 and IL-6-receptor genes (P < .0002 and P < .005, respectively) suggest that an autocrine IL-6 loop is functioning in myeloma in preplasma cells.

Adult↗

PubMed1993

Antibodies to murine CD40 stimulate normal B lymphocytes but inhibit proliferation of B lymphoma cells.

A rat anti-mouse CD40 antiserum has been prepared by hyperimmunisation of Lewis rats with a highly purified preparation of the recombinant extracellular domain of murine CD40. This antiserum specifically binds CD40-expressing L cell transfectants, but not untransfected L cells, and induces vigorous proliferation of highly purified small dense B cells obtained from the spleens of unstimulated mice. Anti-CD40-induced B cell proliferation can be augmented by the addition of IL-4 and is inhibited by purified recombinant soluble mouse CD40. Interestingly the same anti-CD40 antiserum specifically inhibits the in vitro growth of A.20 murine B lymphoma cells. The specificity of this inhibition can be demonstrated by reversing the effect with purified recombinant soluble mouse CD40. These data implicate CD40 as a possible target for therapeutic intervention in the treatment of B lymphomas.

Animals↗

PubMed1993

HIV-related emergencies: frequency, diagnoses, and outcome.

OBJECTIVE: To study the clinical epidemiology and outcome of HIV-related emergencies, and to identify clinical predictors of HIV-related emergency hospitalizations. DESIGN: Case series. SETTING: Emergency facility of a tertiary care teaching hospital. PATIENTS: 350 HIV/AIDS patients followed at the authors' center. MEASUREMENTS AND MAIN RESULTS: 69 of 356 patients made 92 emergency visits with a frequency of 8% per month and 20% per quarter in a three-month study period. Forty-three visits (47%) resulted in hospitalization and contributed to 70% of total AIDS hospitalizations in the period. The five most common acute diagnoses were pneumonia (n = 22; 24%), fever (n = 15; 16%), upper respiratory infection (n = 9; 10%), cellulitis (n = 6; 7%), and gastroenteritis (n = 6; 7%). Three diagnoses accounted for 70% of acute HIV hospitalizations: pneumonia (n = 19), fever (n = 4), and sepsis (n = 4). Analysis of patient disposition as it relates to the patient's clinical presentation and HIV history using multivariate analysis yielded 1) the presence of dyspnea or cough (p = 0.015) and 2) fever with an abnormal chest x-ray (p = 0.008) as independently predictive of hospitalization. CONCLUSION: The findings indicate that HIV/AIDS patients have a frequent need for emergency care and most HIV/AIDS hospitalizations are emergency-related. The acute problems of these patients are related to a limited number of diagnostic categories, and the presence of respiratory or constitutional symptoms with an abnormal chest radiograph are the only reliable factors predictive of hospitalization.

Adult↗

PubMed1993

Infected hepatic Echinococcus cyst presenting as recurrent Escherichia coli empyema.

An 81-year-old man, previously a shepherd in Italy, presented with recurrent Escherichia coli empyema over an 8-month period. His empyema was caused by an infected, nonviable hepatic Echinococcus cyst that eroded the diaphragm and led to intermittent spillage and pleural seeding. This case demonstrates that when dealing with Escherichia coli empyema, a subdiaphragmatic source ought to be suspected, and among immigrants from areas with prevalent hydatid disease, infected hepatic Echinococcus cyst might rarely be the cause.

Aged↗

PubMed1993

Endothelin-1 does not mediate acute hypoxic pulmonary vasoconstriction in the intact newborn lamb.

The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. Previous studies suggest that hypoxia-induced vasoconstriction is endothelium-dependent and is associated with the release of endothelin-1 (ET-1), a potent vasoactive paracrine hormone produced by vascular endothelial cells. The vasoconstrictive effects of ET-1 are likely to be mediated by ETA receptors located on vascular smooth-muscle cells. BQ-123 is a selective ETA receptor antagonist. To determine the role of ET-1 and ETA receptors on resting tone and hypoxic pulmonary vasoconstriction, we studied the effects of ET-1 and BQ-123 at rest and during hypoxia-induced pulmonary vasoconstriction in 12 intact newborn lambs (< 1 week old). At rest, the intrapulmonary infusion of BQ-123 did not change resting pulmonary arterial pressure but completely blocked the rapid increase in pulmonary artery pressure produced by high doses of ET-1 (2,000 ng/kg) (23.0 +/- 10.8% versus -12.6 +/- 27.5%; p < 0.05). During mechanical ventilation there was no difference in the increase in mean pulmonary arterial pressure and pulmonary vascular resistance induced by alveolar hypoxia before and after BQ-123 (34.0 +/- 8.9% versus 30.5 +/- 10.9% and 25.3 +/- 11.6% versus 35.2 +/- 22.4%). This study suggests that the pulmonary vasoconstrictive effects of ET-1 are mediated by ETA receptors and that ET-1 does not mediate acute hypoxic pulmonary vasoconstriction in intact newborn lambs.

Acute Disease↗

PubMed1993

Joint impairment and ambulation in the elderly.

OBJECTIVE: To test the impact of joint impairment on ambulation in the elderly, using a multivariate model. DESIGN: Cross-sectional observational study (baseline data from an ongoing longitudinal study). SUBJECTS: Five hundred thirty-two persons over age 60, including continuing care retirement community (CCRC) (n = 222), homebound (n = 63), and ambulatory (n = 247) respondents. Mean age at assessment = 76.6 (SD = 6.6). MEASUREMENT: Independent variables included sociodemographics, physician measures of lower joint impairment, an index of cormorbidities derived from physical examination or chart abstract, self-assessed arthritis pain, depression, and anxiety. The dependent variable, ambulation, was measured as walk-rate, based on the time required to walk 50 feet. MAIN RESULTS: For the total sample, 61% of the subjects were impaired in more than one lower joint group, with almost 50% of the homebound impaired in more than three joint groups. Demographics (particularly age and education) explained much of the variance in walk-rate. After controlling for demographics and membership in the groups purposely sampled (CCRC, homebound, ambulatory), lower joint impairment accounted for an additional 7% of the variance in walk-rate. Total amount of variance explained by the model was 56% (Adjusted R2 = .56). A 3-point change in lower joint impairment score, equivalent to the maximum impairment score for a single joint group, is associated with a 4-second change in the mean time required to walk 50 feet. The knee and lower spine joints contributed most to the impact of the lower joint impairment measure. CONCLUSIONS: Among the elderly, age and education are strong predictors of performance on a walk-rate test. Independent of demographics and non-musculoskeletal conditions, joint impairment is associated with diminished walking ability in this population.

Activities of Daily Living↗

PubMed1993

M&B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs.

To investigate the hypothesis that pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in the vascular smooth muscle cell concentration of cGMP, we studied the hemodynamic effects of M&B 22948, a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, in eight intact newborn lambs. At rest, M&B 22948 (1.0-2.5 mg/kg) selectively decreased pulmonary arterial pressure (by 8.5 +/- 6.6 to 10.3 +/- 4.5%, P < 0.05). Similarly, M&B 22948 (0.5-5.0 mg/kg) produced selective dose-dependent decreases in pulmonary arterial pressure during pulmonary hypertension induced either by U46619 (by 7.7 +/- 4.2 to 44.2 +/- 4.4%, P < 0.05) or by alveolar hypoxia (by 9.5 +/- 6.2 to 29.0 +/- 11.0%, P < 0.05). In addition, M&B 22948 augmented the pulmonary vasodilating effects of acetylcholine and ATP (both endothelium- and cGMP-dependent vasodilators) but not isoproterenol (an endothelium-independent and cAMP-dependent vasodilator). Because M&B 22948 inhibits the breakdown of cGMP, this study supports the in vitro data that changes in the vascular smooth muscle cell concentration of cGMP, in part, may regulate pulmonary vascular tone and mediate endothelium-dependent vasodilator responses in the pulmonary circulation. In addition, N omega-nitro-L-arginine (an inhibitor of endothelium-derived relaxing factor synthesis) blocked the vasodilating effects of M&B 22948, suggesting that the majority of endogenous cGMP is generated by the release of endothelium-derived relaxing factor.

3',5'-Cyclic-GMP Phosphodiesterases↗