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Biomedical subjects

M Kung

Publications and source records attributed to M Kung.

15 recordsLinked to original sources
PubMed2001

Ultrasonography of the fetal thyroid: nomograms based on biparietal diameter and gestational age.

OBJECTIVE: To describe gestational age-dependent and -independent nomograms for fetal thyroid size. METHODS: Two hundred fetuses were evaluated between 16 and 37 weeks' gestation in this cross-sectional study. RESULTS: Nomograms of fetal thyroid size were created by using the 5th, 10th, 50th, 90th, and 95th percentiles based on biparietal diameter and gestational age. A second-order polynomial fit for biparietal diameter and a linear fit for gestational age best described thyroid circumference measurements. Variations in thyroid circumference measurements increased with both larger biparietal diameter and advancing gestational age. There was no intraobserver or interobserver variability in thyroid circumference measurements (P > .20). CONCLUSIONS: Both biparietal diameter and gestational age serve as good predictors of fetal thyroid circumference. When the biparietal diameter is difficult to measure, gestational age can be used to assess thyroid size.

Cross-Sectional Studies↗
PubMed2000

A novel serotonin transporter ligand: (5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol.

The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans would provide a useful tool for understanding how alterations of this system are related to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [(125)I]ODAM [(5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide and sodium[(125)I]iodide, the radiolabeled [(125)95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K(i) = 2.8 +/- 0.88 nM. Using LLC-PK(1) cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT (K(i) = 0.12 +/- 0.02 nM). Inhibition constants for the other two transporters were lower (K(i) = 3.9 +/- 0.7 microM and 20.0 +/- 1.9 nM for DAT and NET, respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [(125)I]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0. 86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection, respectively. The specific uptake in hypothalamus can be effectively blocked by pretreatment of known SERT ligands. The results suggest that this novel ligand displays desirable in vitro and in vivo properties as a potential SERT imaging agent.

Animals↗
PubMed1998

Mutagenesis studies of human red opsin: trp-281 is essential for proper folding and protein-retinal interactions.

Human red and green opsins contain a strikingly large number of tryptophan residues. These tryptophans are highly conserved among all red and green opsins. To investigate possible roles of these tryptophans in folding and structure, we have systematically replaced each tryptophan of human red opsin. When expressed in COS cells, wild-type red opsin undergoes N-linked glycosylation, forms a light-sensitive pigment with absorption maximum at 560 nm upon reconstitution with 11-cis-retinal, and is transported to the plasma membrane. We used the extent of glycosylation, pigment generation, and intracellular localization of mutant red opsins as our criteria for assessing the effect of substitution. Replacement of eight tryptophans, Trp-59, Trp-90, Trp-149, Trp-152, Trp-183, Trp-191, Trp-195, and Trp-243, with Phe or Ala did not affect the wild-type phenotype significantly. However, replacement of Trp-5 and Trp-51 in the putative N-terminal domain and Trp-142, Trp-177, Trp-179, and Trp-281 in the transmembrane domain with Phe had profound effects, indicating that these substitutions affected red opsin folding. Judged by the severity of the effects, we propose that Trp-5, Trp-51, Trp-177, and Trp-281 are important for red opsin folding. Although substitution of Trp-281 with Phe and Cys did not permit normal glycosylation and transport, substitution with Tyr and His permitted these processes but resulted in blue-shifted pigment. Thus, polar aromatics appear to substitute for Trp-281 to allow red opsin folding. The large spectral shift indicates that Trp-281 is essential for the proper interaction of the protein with 11-cis-retinal.

Amino Acid Sequence↗
PubMed1995

Alcohol modulation of human normal T-cell activation, maturation, and migration.

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4+ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and beta-endorphin pretreatment on the activation of CD4+ lymphocytes endowed with the homing receptor CD62L.

Alcoholic Intoxication↗
PubMed1994

Direct mutation analysis of 495 patients for fragile X carrier status/proband diagnosis.

With the cloning of the FMR-1 gene, direct mutation analysis is possible for fragile X syndrome. We have analyzed 495 patients using the StB12.3 probe/EcoRI/EagI system of Rousseau et al. [N Engl J Med 325:1673-1681, 1991] and 167 of these also with PCR analysis according to Brown et al. [JAMA 270:1569-1575, 1993]. For 28 patients requesting carrier status due to a family history of fragile X, 10 were shown to have either premutations or full mutations; for the remainder with varied backgrounds, 1 in 182 was shown to carry a premutation. For proband diagnosis, 7 of 14 with a fragile X family history carried a full mutation; 11 of 271 with other family histories carried the full mutation.

Blotting, Southern↗
PubMed1988

Differential behaviour of 25-hydroxyvitamin D3 24-hydroxylase and 1-hydroxylase in response to protein synthesis inhibitors and cytochrome P-450 inhibitors.

To characterize 25-hydroxyvitamin D3 24-hydroxylase and 25-hydroxyvitamin D3 1-hydroxylase, the activities of the two enzymes were measured in the presence of two types of inhibitors. The effect of protein synthesis inhibitors on 25-hydroxyvitamin D3-stimulated 24-hydroxylase activity in 1-hydroxylating rat kidneys perfused in vitro was tested. Actinomycin D (4 microM) and cycloheximide (10 microM) each abolished 25-hydroxyvitamin D3 24-hydroxylase synthesis when added at the start of perfusion but not when added 4 h later; they did not affect 25-hydroxyvitamin D3 1-hydroxylase activity. The effects of cytochrome P-450 inhibitors on the two enzyme activities were then studied in vivo. Metyrapone and SKF-525A (50 mg/kg body weight) each inhibited 25-hydroxyvitamin D3 24-hydroxylase at 6 and 24 h; in contrast 1-hydroxylase increased and was 5 times the control value at 24 h. Finally, the in vitro effects of six cytochrome P-450 inhibitors at concentrations ranging from 10(-7) to 10(-3) M on enzyme activities in renal mitochondrial preparations were compared. Both enzymes were inhibited by all of the inhibitors, but inhibition of 25-hydroxyvitamin D3 24-hydroxylase was consistently greater than that of 25-hydroxyvitamin D3 1-hydroxylase. These studies demonstrate that 24-hydroxylation and 1-hydroxylation respond differently to protein synthesis inhibitors and to cytochrome P-450 inhibitors. The findings are consistent with the hypothesis that the two enzyme activities are associated with different cytochrome P-450 moieties.

Animals↗
PubMed1988

Effects of acute carbon tetrachloride poisoning on vitamin D3 metabolism in the rat.

To achieve biologic potency, vitamin D must undergo two successive hydroxylations, first, in the liver and then, in the kidney. Carbon tetrachloride is known to cause extensive damage to the liver, but its effect on vitamin D metabolism has not been studied thoroughly. The effect of carbon tetrachloride on renal hydroxylation of 25-hydroxyvitamin D3 has not been studied. To evaluate the acute effect of carbon tetrachloride on vitamin D metabolism in the liver, vitamin D depleted rats received a single intraperitoneal injection of carbon tetrachloride (2.0 mL/kg body weight). After 24 h, they were given 55, 550, or 5050 pmol [3H]vitamin D3 intravenously. Twenty-four hours after injection of [3H]vitamin D3, aliquots of serum and liver were analyzed for [3H]vitamin D3 and its metabolites by high performance liquid chromatography. Sera of carbon tetrachloride treated rats had higher [3H]vitamin D3 and [3H]25-hydroxyvitamin D and lower [3H]1,25-dihydroxyvitamin D3 concentrations than did control sera. Livers of carbon tetrachloride treated rats contained more [3H]vitamin D3, [3H]25-hydroxyvitamin D3, and more fat. Liver histology showed massive centrilobular necrosis in the treated rats. Thus, our experiment in rats given an acute dose of carbon tetrachloride provided no evidence of impairment of vitamin D metabolism by the liver, but offered a suggestion that 25-hydroxyvitamin D3 metabolism by the kidney might be impaired. To determine the acute effect of carbon tetrachloride on metabolism of vitamin D3 by the kidney, we studied hydroxylation of [3H]25-hydroxyvitamin D3 in isolated perfused kidney. Kidneys from the treated rats showed a 66% reduction in [3H]1,25-dihydroxyvitamin D3 production.

Animals↗
PubMed1986

Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo.

The antihistaminic effect of loratadine (160 mg) was compared in twenty-four normal male volunteers to chlorpheniramine maleate (4 mg) and placebo in a double blinded 3-way cross-over study of latin square design. After receiving single oral doses of each medication, the wheal response to serial 0.1 ml intradermal histamine (2 micrograms) and saline (control) injections were recorded over a 24-h period. The calculated wheal areas were compared to base-line measurements. The results were analyzed by analysis of variance. Loratadine exhibited a more pronounced inhibition of histamine wheal formation than placebo or chlorpheniramine maleate (p less than 0.003). In contrast to chlorpheniramine maleate which had a duration of action of only 3 h, loratadine inhibited the response for the entire observation period between 1 and 24 h post-dose. Although sedation was observed less frequently with loratadine (Placebo, n = 2; chlorpheniramine, n = 3; and loratadine, n = 1), the relative incidence were not statistically significant.

Adult↗
PubMed1983

The isolation and identification of two new metabolites of 25-hydroxyvitamin D3 produced in the kidney.

We have demonstrated in this paper the isolation and identification of two new metabolites of 25-hydroxy-vitamin D3 (25(OH)D3) from the kidney of the vitamin D-replete rat. These are 24-oxo-23(25-(OH)2D3 and 24,25,26,27-tetranor-23(OH)D3. Both compounds logically fit on the same metabolic pathway. 25(OH)D3 leads to 24(R),25-(OH)2D3 leads to 24-oxo-25(OH)D3 leads to 24-oxo-23,25-(OH)2D3 leads to leads to 24,25,26,27-tetranor-23(OH)D3 Each metabolite on this pathway was isolated and identified from kidneys perfused with pharmacological concentrations of 25(OH)D3. All metabolites were identified by techniques involving high performance liquid chromatography, UV spectrophotometry, and mass spectrometry. Use of 24(R),25-(OH)2D3 as the substrate gave rise to increased amounts of 24-oxo-25(OH)D3, 24-oxo-23,25-(OH)2D3, and 24,25,26,27-tetranor-23(OH)D3. In vitro studies involving perfusion of a vitamin D-replete kidney with 25(OH)D3 at a concentration of 25 nM suggest that 24-oxo-23,25-(OH)2D3 is also formed under physiological conditions. At this substrate concentration, 24(R),25-(OH)2D3 represented the major metabolite accumulating in the perfusate over the initial 2-h period but at subsequent times the concentration of 24-oxo-23,25-(OH)2D3 increased so that by the end of 6 h it was the major product remaining in the perfusate. Our work also suggests that the rate of synthesis of 25(OH)D3-26,23-lactone is measurable in the intact mammalian kidney but that it is slower than the synthesis of 24(R),25-(OH)2D3 and its metabolites.

Animals↗
PubMed1983

Avian phosphoenolpyruvate carboxykinase: effect of age, starvation and photoperiod.

Computer analysis of the subcellular distribution of phosphoenolpyruvate carboxykinase in adult female (Gallus domesticus) chicken liver indicates that the activity is distributed between the mitochondria and nucleus in the ratio 70: 30%. There was no activity found in the cytosol. Newly hatched chicks and 8-week-old juveniles were found to have a significant soluble hepatic PEPCK activity. The particulate activity of PEPCK in the livers of juveniles raised in continuous light (24L:0D) decreased over the course of a 7-day fast while no such decrease was seen in juveniles raised in a 12-hr daylength photoperiod (12L:12D).

Aging↗
PubMed1979

Determination of pulmonary blood flow by the rebreathing technique in airflow obstruction.

To test the hypothesis that the effect of nonuniform gas distribution on the uptake of inhaled soluble gases in the lung is minimized by rebreathing, we measured pulmonary blood flow by the thermodilution technique, and pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, and alveolar volume by a rebreathing technique in conscious sheep before and immediately after inhalation of a histamine aerosol (4% solution). We also measured pulmonary resistance, distribution of ventilation by multiple-breath N2 washout, and arterial blood gases to monitor airway responses. Histamine inhalation produced a mean pulmonary resistance increase to 621% of baseline accompanied by uneven distribution of ventilation and a decrease in arterial Po2. Despite these alterations in airway function, there were no concomitant changes in pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, alveolar volume, or the ratio of diffusing capacity for CO to alveolar volume. Mean pulmonary capillary blood flow and pulmonary blood flow did not differ from each other before and after histamine inhalation. We conclude that the rebreathing technique for noninvasive measurement of pulmonary hemodynamics is satisfactory in the presence of airflow obstruction.

Airway Obstruction↗
PubMedDate not supplied

Cocaine blunts human CD4+ cell activation.

Cocaine is reported to be immunotoxic. The biochemical mechanisms responsible for the immunopharmacological outcomes of cocaine in vivo and in vitro remain, however, to be fully elucidated. Our experimental data confirm that exposure of normal human T cells to micromolar concentrations of cocaine modulates T-cell responses to stimulation by a variety of stimuli, and indicate that cocaine impairs early activation events during CD4+ but not CD4- T-cell stimulation. Pre-incubation of enriched CD4+ T-cell subpopulations that express the homing receptor CD62L with nanomolar concentrations of the endogenous opioid peptide beta-endorphin leads to a more severe impairment of activation than that noted following pre-incubation with micromolar concentrations of cocaine alone. These findings begin to elucidate the molecular and cellular mechanisms of the immunopathology of cocaine. Our data support the proposition that cocaine abuse may place cocaine-abuser HIV-seropositive individuals at increased risk of opportunistic infections.

Antigens, CD↗
PubMedDate not supplied

Effect of acute dietary restriction on the colonization of MADB106 tumor cells in the rat.

The effects of acute food restriction (i.e. 24-72 h) on (1) the colonization of MADB106 tumor cells; (2) the response of specific T cell subsets in peripheral blood (i.e. CD4+ and CD8+ cells), and (3) natural killer cell activity (NKCA) in the spleen were studied in the Fischer 344 rat. Previous studies have demonstrated that the spread of this tumor cell is enhanced by exposure to an acute stressor within 24 h of tumor inoculation. Consistent with these reports, 72-hour food restricton after tumor inoculation enhanced colonization of tumor cells to the lungs when assessed 4 weeks after inoculation. Food restriction was found to markedly influence the percentage of T cell subsets (i.e. CD4+ and CD8+ cells) and NKCA in the early (24-72 h) postinoculation stage. At 72 h after inoculation, food restriction was associated with a significant reduction in the percentage of CD4+ cells in tumor- or saline-inoculated animals. The percentage of CD8+ cells was significantly increased at 24 and 72 h after tumor inoculation in ad libitum, but not in food-deprived animals. NKCA at 72 h was significantly reduced in saline-treated food-deprived animals compared to animals fed ad libitum. Given that glucocorticoids are typically increased during acute food deprivation and that glucocorticoids are in some instances associated with depressed NKCA, the present study investigated whether there was a relationship between plasma glucocorticoid levels (i.e. corticosterone) and NKCA; however, no significant relationship was found. In conclusion, the present findings demonstrate that 72-hour food deprivation is associated with enhancement of tumor metastasis. This outcome is mediated, at least in part, by the modulatory effect of the physiological response to acute food restriction upon the distribution of circulating T cells and NKCA in the spleen during the early (24-72 h) postinoculation phase.

Adenocarcinoma↗