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Biomedical subjects

J H Lin

Publications and source records attributed to J H Lin.

At least 325 records · Page 18Linked to original sources

An improved dispersed adrenal cell assay for corticotropin in rat plasma.

The present study was designed to improve the dispersed adrenal cell technique for determining adrenocorticotrophic hormone (ACTH) concentrations in small amounts of rat plasma. Priming with ACTH, incubation with methyl-isobutylxanthine, or dexamethasone pre-treatment were employed as modifications. Of these, only dexamethasone pre-treatment increased the sensitivity of the assay. The adrenal fragments obtained from 10-12 adult male rats pre-treated with dexamethasone (100 micrograms/kg B.W.) one hour before sacrifice, were digested with collagenase and deoxyribonuclease solution for 30 minutes. The dispersed cells were collected by centrifugation and resuspended in Krebs-Ringer bicarbonate buffer containing 0.2% glucose and 0.5% bovine serum albumin. Aliquots of cell suspension (3-4 X 10(4)/tube) were incubated with various doses of ACTH1-24 or the eluate of plasma samples at 37 degrees C for 2 hours in an atmosphere of 95% O2/5% CO2 in a Dubnoff shaker. The quantity of corticosterone produced was measured fluorimetrically. The assay is precise (lambda = 0.06), extremely sensitive (10 fg/tube), and convenient. One skilled technician can handle 15 to 20 plasma samples per day using 10 rats as the source of assay cells. ACTH can be measured in as little as 10-50 microliters of eluate.

1-Methyl-3-isobutylxanthine↗

Relation of family history of hypertension to platelet aggregation, ratio of total cholesterol to HDL cholesterol and urinary kallikrein excretion.

Some of the relatively easily measurable and possibly hypertension-associated parameters were evaluated in thirty normotensive young subjects divided into the PHT (either parent hypertensive) group and the PNT (both parents normotensive) group. In subjects of the PHT group, the platelet aggregating sensitivity to the arachidonic acid and the ratio of total cholesterol to HDL cholesterol were significantly (p less than 0.05) increased while urinary kallikrein excretion was decreased without simultaneously significant elevation of blood pressure. The enhanced platelet aggregating sensitivity to the arachidonic acid and the increased ratio of total cholesterol to HDL cholesterol suggest that subjects with a positive family history of hypertension might have a greater tendency to atherosclerosis and could contribute to the development of essential hypertension. Decreased urinary kallikrein excretion suggests that the vasodepressive activity of the kallikrein-kinin system might be inhibited in subjects with a positive family history of hypertension.

Adult↗

Corrosion product formation sequence on Cu-rich amalgams in various solutions.

A single particle and four blended Cu-rich amalgam systems were immersed in 37 degrees C solutions for 1-20 months in order to determine the characterization and sequence of corrosion product formation. X-ray diffraction and SEM/EDS were used to characterize the products. The same sequence of formation occurred in all systems in Ringer's and 0.1% Ringer's solutions. The times at which each product formed varied with the brand of the amalgam and the concentration of the solution. The initial products were ZnSn(OH)6 in Zn-containing systems and SnO2 in most other systems. Cu2O formed next, followed by CuCl2 X 3Cu(OH)2. Immersion in 1% Na2S yielded only HgS on all brands. A combination of 1% Na2S and Ringer's solution yielded CaSn(OH)6 after 2 months and Cu2O at later periods. Artificial saliva resulted in a retardation of corrosion product formation and only limited amounts of a Sn-rich product could be found after 20 months. Interactions of the various components appear to alter the nature and rate of corrosion product formation on these systems and additional systematic investigations are necessary to understand the influence of these interactions on corrosion.

Copper↗

Effects of organic anions on the uptake of 1-anilino-8-naphthalenesulfonate by isolated liver cells.

Uptake of the fluorescent probe, 1-anilino-8-naphthalene-sulfonate (I) into isolated rat liver cells was studied using both fluorescence and filtration methods. The time course of the fluorescence enhancement of I after addition to the isolated liver cells was analyzed in terms of rapid, medium, and slow phases. The slow phase (half-time approximately 7 min) was characteristic of viable cells. The fluorescence enhancement was proportional to the amount of I taken into the cells, as measured by the filtration method. The uptake of I followed Michaelis-Menten kinetics with an apparent Km of 39 microM and Vmax of 1.4 nmole/10(6) cells/min. The temperature coefficient (Q10) of the uptake of I was found to be approximately 1.9. No pH optimum was observed, and various metabolic inhibitors did not affect the uptake of I. Among the amino acid reagents used, only 2,4-dinitrofluorobenzene decreased the uptake of I (by approximately 45%). The effects of various organic anions on the uptake of I were measured. The inhibition of the uptake of I by sulfobromophthalein could be analyzed in terms of competitive inhibition; the slight inhibition by sodium taurocholate could not. It is concluded that the uptake of I is a carrier-mediated facilitated process, and that the carrier is common to both I and sulfobromophthalein.

Amino Acids↗

Effect of pregnancy on the pharmacokinetics of acetaminophen in rats.

Acetaminophen (A), in single doses of 15 mg/kg and 300 mg/kg, was administered by i.v. injection to nonpregnant (180-240 g) and 20 days pregnant Lewis rats (250-330 g). Blood samples (for plasma) and urine were collected serially and analyzed by high-performance liquid chromatography for A, A glucuronide and A sulfate. Serum inorganic sulfate concentrations were determined in a separate study. With respect to the 300-mg/kg dose, pregnant animals exhibited a significant decrease in relative (body weight normalized) total clearance and no change in absolute total clearance, no change in relative apparent volume of distribution and a significantly increased biological half-life. As a fraction of the administered dose, pregnant animals excreted more A, less A sulfate and the same fraction of A glucuronide as did nonpregnant animals. Pregnancy had no apparent effect on base-line serum inorganic sulfate concentration. Both normal and pregnant rats became inorganic sulfate-depleted after injection of A, 300 mg/kg. The relative total clearance of the 300-mg/kg dose of A decreased with increasing litter size, whereas the relative apparent volume of distribution was unaffected. The relative total clearance of a 15 mg/kg dose of A was much higher than that of the 300-mg/kg dose and approximated liver plasma flow rate; it was not changed by pregnancy. The relative renal clearances of A glucuronide, A sulfate and creatinine were decreased in pregnancy, whereas the absolute renal clearances of the two conjugates and creatinine were unaffected. Comparative assessment of the effect of pregnancy on the pharmacokinetics of A and other drugs in different species requires consideration of possible dose dependence and of the implications of normalizing clearance and volume of distribution values.

Acetaminophen↗

A case of leukemic reticuloendotheliosis responding to oxymetholone.

A 63-year-old man presented with fever, easy bruisability, splenomegaly and pancytopenia. Bone marrow aspiration was unsuccessful, and marrow biopsy revealed crowding by sheets of mononuclear cells; a diagnosis of leukemic reticuloendotheliosis (LRE) was made and the patient underwent splenectomy. There was no hematologic improvement, and the patient continued to have a significant requirement for erythrocytes and platelet transfusions. Within two months of beginning oxymetholone therapy (50 mg orally three times a day) the patient's platelet count had normalized, followed by improved erythrocyte and leukocyte counts. When the drug was discontinued, the peripheral blood counts deteriorated drastically; he again demonstrated hematologic improvement when oxymetholone therapy was reinstated. We feel that by demonstrating a hematologic response to oxymetholone, relapse when it was withdrawn, and another remission upon readministration, that we have provided stronger evidence than previously reported for the efficacy of this drug in LRE.

Adult↗

Cu2O and CuCl2 . 3Cu(OH)2 corrosion products on copper rich dental amalgams.

In addition to Sn-rich corrosion products found in conventional amalgams, Cu-rich amalgams also form Cu-containing corrosion products. The nature of these Cu-rich products was investigated by immersion of samples of 13 Cu-rich amalgam systems in Ringer's solution for prolonged periods. SEM/EDS and x-ray diffraction studies were used to identify the compounds formed and their morphology. Two products were identified: Cu2O, a red product, and CuCl2 . 3Cu(OH)2, a green product.

Copper↗

In vitro and in vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models.

An important parameter used in physiologically based pharmacokinetic models is the partition coefficient (Kp), which is defined as the ratio of tissue drug concentration to the concentration of drug in the emergent venous blood of the tissue. Since Kp is governed by reversible binding to protein and other constituents in blood and tissue, an attempt was made here to estimate the Kp values for a model drug ethoxybenzamide (EB) by means of in vitro binding studies and to compare these Kp values to those obtained from in vivo kinetic parameters observed following the administration of EB by two different routes, i.e., i.v. bolus injection and constant rate infusion. The Kp values obtained by using these three different methods were in reasonably good agreement suggesting that binding data obtained in vitro can successfully be used to estimate in vivo distribution.

Animals↗

Physiological pharmacokinetics of ethoxybenzamide based on biochemical data obtained in vitro as well as on physiological data.

Ethoxybenzamide (EB) concentrations in plasma and various tissues were simulated using a physiological pharmacokinetic model. The biochemical parameters, such as plasma and tissue binding constants and Michaelis-Menten constants for EB deethylation, which were needed for these simulations, were, however, obtained from in vitro data. The simulations predicted well the observed data in plasma and various tissues of the rat. Furthermore, animal scale-up predicted reasonably well the concentrations of EB in plasma and various tissues of the rabbit from data gathered in rats.

Animals↗

Computed tomography of the normal and abnormal superior sagittal sinus.

The appearances on computed tomography (CT) of the normal and abnormal superior sagittal sinuses are presented. The varied patterns of non-enhanced and enhanced normal superior sagittal sinuses are correlated with and reflect the findings of anatomical dissection. Cases of abnormal superior sagittal sinus include thrombosis, brain death and sinus displacement.

Adolescent↗

Effect of experimental renal failure on sulfate retention and acetaminophen pharmacokinetics in rats.

The investigation was designed to determine the effect of experimental renal failure on the retention of free (inorganic) sulfate and on the pharmacokinetics of acetaminophen in rats. Adult male Sprague-Dawley rats with renal failure produced by uranyl nitrate treatment or ligation of ureters had much higher serum free sulfate concentrations (about 2 and 5 mM, respectively) than normal animals (about 1 mM). The time-averaged total clearance of a 100-mg/kg dose of acetaminophen was higher in animals with renal failure than in normal rats and was positively correlated with serum free sulfate concentration (r = 0.76, P less than .001). Renal failure had no effect on the total clearance of a 15-mg/kg dose of acetaminophen, apparently because free sulfate was not appreciably depleted by this small dose. A 6-hr infusion of acetaminophen, at 36 mg/kg/hr, produced steady-state plasma concentrations of about 20 micrograms/ml within 2 hr in renal failure (ureter-ligated) animals, whereas in normal animals the plasma concentrations increased continuously to about 100 micrograms/ml at 6 hr. Free sulfate concentrations in serum at the end of the infusion were about 0.2 mM in normal animals and generally greater than 1 mM in the renal failure animals. The rats with renal failure converted most of the administered dose to acetaminophen sulfate, whereas normal animals metabolized much of the drug to acetaminophen glucuronide. These observations demonstrate the important effect of the endogenous free sulfate level in the body on the elimination kinetics and metabolic fate of a drug that is subject to conjugation with sulfate.

Acetaminophen↗

Atypical measles syndrome: pathologic and serologic findings.

The clinical course of measles occurring in 17 adolescents who had previously received killed measles vaccine is described. All adolescents had a peripheral dermatitis. Fifteen had characteristic pulmonary infiltrates. Serologic study in six adolescents using immunoprecipitation of 35S-methionine-labeled measles virus antigens revealed that 5/6 acute sera lacked antibody to the hemolysin antigen whereas 5/6 sera contained antibody to hemagglutinin antigen. Skin biopsies, obtained from three patients, demonstrate a combination of an Arthus reaction and delayed hypersensitivity. The typical measles histologic complex was absent. Measles virions were seen in the deep dermal blood vessels. The serologic and histopathologic presentation of this disease indicates that killed vaccine does not adequately induce antibody to the hemolysin (F) which is necessary to prevent cell-to-cell spread of paramyxoviruses. Killed vaccine does, however, produce hemagglutinin antibody and simultaneously incites later hypersensitivity to wild virus infection, producing the unusual dermatopathologic reaction seen.

Adolescent↗