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Biomedical subjects

K Fung

Publications and source records attributed to K Fung.

54 records · Page 3Linked to original sources

Renin angiotensin aldosterone axis, including aldosterone binding globulin and blood pressure in three species of nonhuman primates.

Variables of renin-angiotensin-aldosterone axis with inclusion of protein binding to specific plasma globulin (ABG), plasma cortisol, and the blood pressure (BP) were measured in 24 chimpanzees, 4 gorillas, and 16 cynomolgus monkeys. ABG activity was readily detected in plasma from the primates. In chimpanzees and gorillas, all the variables under baseline conditions were similar to those in humans. In cynomolgus (Macaca fascicularis), both the ABG binding capacity for aldosterone and the diastolic or systolic BP were significantly higher (p less than 0.001 and p less than 0.01 respectively) than in chimpanzees and gorillas.

Aldosterone↗

Human salivary or plasma aldosterone- and dehydroepiandrosterone-binding glycoprotein induces hypertension in the rat.

In this study we demonstrated the presence of an aldosterone-binding globulin (ABG) in human saliva. Following ultrafiltration and purification of saliva to electrophoretic homogeneity, this thermolabile globulin called ABG-S appeared to be identical to plasma ABG. It was also shown that both purified ABG-S and plasma ABG bind reversibly, with high affinity (Ka = 1.6 X 10(-9) M, Scatchard plot) to dehydroepiandrosterone sulfate (DHEA-S) to binding sites different from those for aldosterone. Following incubation with human urine both ABG and ABG-S were converted quantitatively into corresponding thermostable forms which appeared to be identical with the human urinary ABG homologue namely ABG-TsU. In addition ABG-S showed the same ability to elevate blood pressure when administered to rats as did ABG-TsU. The fact that an endogenous substance with pressor activity might exist in more than one body fluid suggests further its possible participation in the basic mechanisms of blood pressure regulation.

Animals↗

Peroxybenzoylnitrate: measurements in smog chambers and in urban air.

Peroxybenzoylnitrate (PBzN, C6H5C(O)OONO2), a photochemical atmospheric pollutant and powerful eye irritant, was detected at greater than or equal to 10 ng following aqueous alkaline hydrolysis to benzoate ion and analysis by ion chromatography with ultraviolet detection. Method validation studies and studies of potential interferents including benzaldehyde and benzoic acid are described, together with applications to PBzN measurements in environmental chamber atmospheres and in ambient air.

Air Pollutants↗

Simple reproducible competitive radioligand assay for plasma protein binding of aldosterone.

A simple reliable and specific binding assay for the estimation of plasma (or serum) aldosterone-binding globulins (ABGs) is described. The method is based on the determination of the aldosterone-binding capacity of diluted plasma (with water 1:5), and relating it to the total aldosterone concentration in the same sample. The method distinguishes between the heat-labile and heat-stable ABG, the binding to the latter being determined following heating of plasma at 60 degrees C for 25 min. The binding to the heat-labile protein is determined by subtraction of the value for the binding to the heat-stable protein from the binding of the nonheated diluted plasma. Free aldosterone is separated from the bound fraction by adsorption of the former to dextran-coated charcoal. Two different concentrations of [3H]-aldosterone are used throughout the assay. Data obtained by incorporating chromatographic separation into the cross-reactivity procedure using several steroids are presented as evidence for the specificity of the method. This chromatography separates plasma ABG from corticosteroid-binding globulin. In 316 male or female controls, ABG capacity was 9.7 +/- 0.38% (SE)-range 2-17. Samples in females were taken during the first 8 days from the onset of menstruation. Higher ABG-binding capacity (p less than 0.001) was found during pregnancy.

Adolescent↗

Further studies on human plasma aldosterone-binding globulins: isolation, purification, and evidence for heterogeneity.

The present study further characterizes the aldosterone-binding globulin (ABG) in human plasma. Isolations were performed by ultrafiltration, Blue Sepharose CL-6B, or ion-exchange chromatography and gel filtration. New ABG species were identified: interconvertible with ABG in plasma is a thermolabile (MW less than 70,000) and a thermostable ABG macromolecule (MW 27,500). All forms were extensively purified to electrophoretic homogeneity (SDS-PAGE) showing microheterogeneity in isoelectric focusing (pI 4.76 and 4.8) and reversible high-affinity binding for aldosterone. Chromatography of lipoprotein-free plasma in DEAE-Sephadex A-50 gel (ionic gradient) revealed the presence of a dimer of ABG (MW 55,000) which was found to be interconvertible with ABG and was the main carrier of aldosterone in normal fresh plasma. Selective adsorption of albumin from lipoprotein-free plasma on Blue Sepharose CL-6B permitted in a single novel step the complete resolution of bound aldosterone (binding ABG) and bound cortisol (binding corticosteroid-binding globulin). Both ABG and the dimer can be separated from corticosteroid-binding globulin by Blue Sepharose chromatography. A new homeostatic mechanism in which ABG participates in blood pressure regulation by interacting with aldosterone is postulated.

Aldosterone↗

Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma.

Tumor cells were recovered from the right atrium in three of five patients during hepatic resection for hepatocellular carcinoma. Mechanical factors during blunt mobilization and rotation of the hepatic tumor appeared to be responsible for tumor dislodgement into the venous circulation. Tumor embolization to the lungs may be one of the important reasons for the poor results of surgery in this disease. Two possible technical and therapeutic modifications are suggested to prevent or neutralize this phenomenon.

Blood↗

Experimental essential hypertension in the rat?

1. A human urinary thermostable glycoprotein (ABG-TsU) believed to be a homologue of the plasma aldosterone-binding globulin (ABG) was isolated and purified by differential ultrafiltration, ion-exchange chromatography and gel filtration to electrophoretic homogeneity; it showed a charge heterogeneity in electrofocussing. 2. ABG-TsU was administered intraperitoneally to male rats in small daily doses (7 microgram/day per rat). Sustained hypertension developed in 5--8 days. 3. The treated rats showed no changes in plasma electrolytes, aldosterone or plasma renin activity; however, a significant increase in heart weight was observed. 4. This hypertension appears to be adrenal dependent since it is prevented by bilateral adrenalectomy or administration of an aldosterone antagonist, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU.

Animals↗

Differences in physicochemical and antigenic properties of chlamydial strains.

Antigenic analysis of Chlamydia psittaci, C. trachomatis, and Lymphogranuloma venereum (LGV) revealed basic physicochemical differences among the three chlamydial strains. These were manifested in structural, isoelectric points, absorption spectra, and in the characteristics of the chromophobe-containing proteins. The effective period of sonication for C. psittaci and C. trachomatis is around 60 min during which the linkages most susceptible to external sonication forces were broken, releasing all attainable cellular components. Denaturation studies demonstrated that less than 50% of protein content of C. psittaci was denatured after 1 h of sonication, only 5% in the case of C. trachomatis. The protein and carbohydrate content of the most reactive fractions in macrophage-spreading inhibition test were different for LGV and C. trachomatis. The structural differences appear to determine the antigenic properties observed among the chlamydial strains as well as the specificity and probably the mechanisms (s) of cellular immune reactivity to Chlamydiae. This in turn may explain the failure of chlamydial vaccines, prepared from stock strains, to protect immunized children against 'wild' chlamydial strains.

Antigens, Bacterial↗

Esophageal reconstruction: an experimental approach to the control of reflux after esophageal resection.

A study of the properties of replacement gastric tubes and colonic segments, and their use in the prevention of reflux after esophageal resection indicates that, in order to prevent reflux, these tubes must be maintained in a subdiaphragmatic position. Gastric tubes have a higher intrinsic pressure barrier than colonic tubes--a 2.5- to 6-cm segment prevents reflux and the tube maintains a pressure barrier 10 cm H2O higher than stomach presure, whereas colonic segments require 12 cm of subdiaphragmatic length to control reflux and maintain a pressure barrier only 2 cm H2O above gastric pressure. Removal of the intrinsic pressure barrier by myotomy allows free reflux in tubes that previously had prevented reflux.

Abdomen↗

Bile aspiration: an experimental study in rabbits.

It has been shown that bile injected intratracheally in rabbits produces severe pulmonary edema, atelectasis, and focal hemorrhages. The authors investigated the effect of a number of solutions, including physiological concentration of bile, hydrochloric acid pH 1.0, bile salt diluted to 1%, and bile at 100% concentrations. Whenever the bile concentration exceeded 3%, none of the test animals survived. It is not possible to apply directly the results of an experimental animal study to humans. However, the severity of the pulmonary changes produced force the conclusion that bile is a potentially dangerous aspirate in humans.

Animals↗

Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control.

BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, delivered to a target volume encompassing gross disease and suspected microscopic disease with a 2 cm margin. Treatment breaks arising during concurrent ChT+RT were used to manage severe symptomatic or hematologic toxicities. We used the interruptions in thoracic RT as the 'marker' for any concurrent break and measured 'break duration' by the total length of time (in days) RT was interrupted, since that also signaled that ChT could be re-initiated. Patient results were analyzed for the impact of interruptions/treatment prolongation on overall and disease-free survival. RESULTS: For all patients, 2-year and 5-year overall and disease-specific survivals were 22.7 and 7.2, 27.6 and 9.3%, respectively; overall and disease-specific median survivals were 14.7 months each. A total of 56 patients (26%) had treatment breaks due to toxicity. Hematologic depression caused the majority of breaks (88%). The median duration of breaks was 5 days (range 1-18). Patients with and without interruptions were compared for a range of prognostic factors and were not found to have any significant differences. Comparing interrupted/uninterrupted courses, median survivals were 13.8 versus 15.6 months, respectively, and 5-year overall survivals were 4.2 versus 8.3%, respectively. There was a statistical difference between overall survival curves which favored the uninterrupted group (P=0.01). When comparing a series of prognostic variables, multivariable analysis found that the most significant factor influencing survival in the present study was the presence of treatment breaks (P=0.006). There was a trend for development of any recurrence in the patients with breaks (P=0.08). When controlling for the use of prophylactic cranial irradiation (PCI) in the two groups, the rate of failure in the chest was higher in the patients with RT breaks (58 vs. 33%). The rate of failure in the brain was dependent on the use of PCI only. CONCLUSIONS: Interruptions in treatment to palliate the toxicity from concurrent chemoradiation result in poorer local control and decreased survival.

Adult↗

A survey of personal exposures to benzene in Mexico City.

Benzene is a widely distributed environmental contaminant that causes leukemia. It is an important component in gasoline, it is used frequently as a solvent or chemical feedstock in industry, and it is emitted as a product of incomplete combustion. In Mexico City, investigators suspect that benzene exposure might be elevated and may pose a risk to the population; however, no published data are available to confirm or disconfirm this suspicion. We, therefore, conducted a survey in 3 occupational groups in Mexico City. Forty-five volunteers who used portable passive monitors measured their personal exposure to benzene during a workshift. None of the participants smoked during the monitoring period. Benzene exposure was significantly higher among service-station attendants (mean = 359.5 microg/m3 [standard deviation = 170.4 microg/m3]) than among the street vendors (83.7 microg/m3 and 45.0 microg/m3, respectively) and office workers (45.2 microg/m3 and 13.3 microg/m3, respectively). However, the benzene exposure levels observed among office workers were substantially higher than levels reported elsewhere for general populations. Our results highlight the need for more complete studies by investigators who should assess the potential benefits of setting environmental standards for benzene in Mexico.

Adolescent↗

A study of the nonprescription drug consumer's understanding of the ranitidine product label and actual product usage patterns in the treatment of episodic heartburn.

INTRODUCTION: A study of the consumer's understanding of the product label instructions and the resulting product use were conducted to support the switch of a product from prescription to nonprescription status. H2 receptor antagonists have recently been approved for nonprescription use. This study evaluated the consumer's understanding of the product label for ranitidine hydrochloride (Zantac 75) and the product usage pattern in the treatment of episodic heartburn. OBJECTIVES: Our objectives were to evaluate each aspect of the communication of labeled indications, contraindications, and directions for use of two label formats (old and new) for a new nonprescription preparation of ranitidine (Zantac) and to evaluate nonprescription consumers' use of ranitidine 75-mg tablets (as Zantac 75) in a medically unsupervised, at-home setting to observe whether these consumers used the product appropriately and followed directions as written on the package label. METHODS: Adult male and female consumers (n = 1405) in a shopping mall environment who were attracted to a poster asking, "Do you have stomach problems?" were recruited for the label comprehension phase (two different label formats) and the 3-week usage phase if after reading the Zantac 75 package label they decided the product was appropriate for them. No instructions regarding the use of Zantac 75 were provided beyond what was printed on the package label. Subjects recorded use in a diary and tablet counts were performed at the end of the study period. A medical history was also taken at this time and an assessment of product use was performed by a physician. RESULTS: In at least 84% of all subjects, both formats were effective in the communication of label objectives for the contraindication against concurrent prescription stomach ulcer medication, maximum daily dose, and maximum duration of dosing at maximum daily doses. The direction to take one tablet per dose was adhered to by 90% of consumers, and 90% of consumers followed the instructions to take no more than two tablets in 24 hours. Ninety-six percent of consumers complied with the direction not to take the maximum daily dose for more than 14 consecutive days. Notably, the maximum daily dose was taken for < or =3 consecutive days by 79% of consumers. The most frequently reported adverse events were headache, acute nasopharyngitis, upper respiratory tract infection, diarrhea, nausea, and menstrual cramps. CONCLUSION: The study demonstrated that the vast majority of a large sample of unsupervised consumers understood the package label and fully complied with the package directions by not exceeding the maximum daily dosage and length of use. Nonprescription consumers safely used Zantac 75 without medical supervision.

Adult↗

Aldosterone-binding globulin-induced hypertension in the rat. A new experimental model.

A thermostable urinary homologue of the plasma aldosterone-binding globulin (ABG), designated ABG-TsU, was isolated and purified by differential ultrafiltration, ion exchange chromatography, and gel filtration to electrophoretic homogeneity. Scatchard plot analysis using highly purified ABG-TsU demonstrated reversible high-affinity low-capacity binding at separate sites for aldosterone and dehydroepiandrosterone sulfate (DHEA-SO4). ABG-TsU injected intraperitoneally (i.p.) in male rats resulted in sustained hypertension after 5 to 8 days, characterized after 12 days by no changes in plasma Na+ K+, aldosterone, or plasma renin activity (PRA). No histological changes could be detected in the kidneys, brains, or hearts, nor evidence of adrenocortical hyperplasia. This hypertension appears to be aldosterone-dependent since it is prevented by bilateral adrenalectomy or administration of a spironolactone, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU. Hemodynamic characterization of this hypertension was carried out in rats after treatment with ABG-TsU or saline i.p. for 14 days. Cardiac output (CO) was measured using the reference sample microsphere method. ABG-TsU-treated rats had significantly higher mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and CO, while no difference in total peripheral resistance (TPR) was detected. This new animal model of borderline essential hypertension (EH) induced by ABG-TsU, which has a reversible high-affinity binding for aldosterone, results in adrenal-dependent hypertension due at this early phase to an increase in CO without any change in TPR, which remains inappropriately normal.

Adrenalectomy↗

Lowering patient dose on single-phase X-ray units.

In this study, entrance skin doses for AP pelvis and lateral lumbar spine examinations were measured with single-phase, three-phase and medium frequency x-ray generators. Results showed that for equal tube voltage (kVp) exposure to achieve similar film density, the ESD was significantly higher with the single-phase generator than the other two generators. Further research showed that by increasing kVp, the single-phase generator could achieve the lower ESD values obtained with the three-phase and medium frequency generators while maintaining similar film density and contrast.

Humans↗