Biomedical subjects

J L York

Publications and source records attributed to J L York.

At least 37 records · Page 2Linked to original sources

PubMed1994

Gender comparisons of alcohol consumption in alcoholic and nonalcoholic populations.

The purpose of this study was to examine the similarities and differences between male and female drinkers in terms of the estimated functional impact of alcohol intake on drinking occasions. Alcohol consumption on drinking occasions was documented in male and female alcoholics and occasional drinkers in face-to-face interviews and also in a general population statewide sample by means of a telephone survey. Expression of ethanol intake in terms of grams of ethanol consumed per kilogram of total body water yielded data consistent with the notion that blood concentrations of ethanol achieved by females on drinking occasions may have been quite similar to the values achieved by males. However, important gender differences were also found in terms of an older age of onset of regular drinking, less frequent alcohol intake and a higher percentage of abstainers among females.

Adult↗

PubMed1994

Glutathione S-transferase activity and isoenzyme concentrations in obese Avy/a and lean a/a mice.

To assist in defining the mechanism(s) by which the activity of hepatic glutathione S-transferase (GST) is decreased in obese rodents, the cytosolic concentrations of individual GST isozymes were determined by high-performance liquid chromatography. For this purpose, liver cytosols from 8- and 16-week-old obese yellow Avy/a and lean black a/a male and female mice of the inbred VY/WffC3Hf/Nctr-Avy strain were assayed. Obese yellow males contained less hepatic GT-9.0 than lean black males; however, there were no differences between the obese and lean females. GT-9.0 concentration, which is induced by testosterone, was several-fold higher in males than in females, regardless of genotype or body weight. No differences in concentrations of other isozymes were detected. Hepatic GST activity towards 1-chloro-2,4-dinitrobenzene was significantly higher in lean males than in obese males; however, there were no differences between obese and lean females. Lean males had higher activity than lean females; but obese males and females had similar enzyme activities. These changes in enzyme activity can be accounted for by the changes in GT-9.0 concentration measured by HPLC. Lung and testes cytosols were also assayed for GST isozyme concentrations. No differences in any isozyme concentration were found between the sexes or the genotypes in the lung or between genotypes in the testes.

Age Factors↗

PubMed1993

GDP-mannose pyrophosphorylase. Purification to homogeneity, properties, and utilization to prepare photoaffinity analogs.

Pig liver GDP-mannose pyrophosphorylase was purified 5,000-fold to apparent homogeneity using standard techniques. The native enzyme showed a single band on gels of about 450 kDa and two subunits of 43 and 37 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 37-kDa (beta-) subunit had only methionine at its amino terminus and a surprisingly hydrophobic sequence: Met-Lys-Ala-Leu-Ile-Leu-Val-Gly-Gly-Tyr-Gly-Thr-Arg-Leu- Arg-Pro-Leu-Thr-Leu-Ser-Ile-Pro-Lys. The 43-kDa (alpha-) subunit was blocked at the amino terminus, but a 29-kDa CNBr fragment had the following sequence: Leu-Asp-Ala-His-Arg-His-Arg-Pro-His-Pro- Phe-Leu-Leu-. Substrate specificity studies done in the direction of formation of nucleoside triphosphate and sugar-1-P indicated that the enzyme was most effective with GDP-glucose as substrate (100%) followed by IDP-mannose (72%) and then GDP-mannose (61%). That GDP-mannose and GDP-glucose activities were indeed catalyzed by the same enzyme was indicated by the following. (i) Various studies indicated that the enzyme was homogeneous. (ii) A staining procedure for production of GTP stained the same single band on native gels when either GDP-mannose or GDP-glucose was the substrate. (iii). GDP-mannose inhibited the utilization of GDP-glucose by the enzyme, and vice versa. When 8-azido-[32P]GTP was incubated with native enzyme and exposed to UV light, both the 43-kDa and the 37-kDa subunits became labeled, although the 37-kDa subunit reacted more strongly. On the other hand, 8-azido-GDP-[32P]mannose only photolabeled the 43-kDa band. Most importantly, the purified enzyme can be utilized to produce 8-azido-[32P]GDP mannose or 8-azido-[32P]GDP glucose.

Affinity Labels↗

PubMed1993

Inhibition studies of some serine and thiol proteinases by new leupeptin analogues.

Fifteen tripeptide analogues of leupeptin containing either a C-terminal argininal or lysinal were synthesized. The synthetic analogues were tested, using spectrophotometric assay techniques, as inhibitors of trypsin, kallikrein, thrombin, plasmin, and cathepsin B. The lysinal analogues were fairly selective as inhibitors of cathepsin B activity. Acetyl-L-leucyl-L-valyl-L-lysinal (21) showed a stronger inhibition of cathepsin B (IC50 = 4 nanomolar) than leupeptin. Acetyl-L-phenylalanyl-L-valyl-L-argininal (2i) was found to be a good inhibitor of cathepsin B (IC50 = 0.039 microM), thrombin (IC50 = 1.8 microM), and plasmin (IC50 = 2.2 microM).

Amino Acid Sequence↗

PubMed1993

Enhanced glutathione S-transferase 7-7 expression in rat hepatic cytosol following treatment with pyrrole.

Rat hepatic GST 7-7 expression in cytosol and in the S-hexylglutathione-agarose affinity purified fraction of cytosol from saline- (control) and pyrrole-treated animals was examined using metabolic activity, SDS-PAGE, immunoblot, and HPLC analyses. Metabolic activity of hepatic cytosol from pyrrole-treated animals was assayed using the substrates 1-chloro-2,4-dinitrobenzene, ethacrynic acid, and acrolein, and an approximately 1.5-, 1.2-, and 1.3-fold increase, respectively, was monitored in the rate of GST-catalyzed substrate conjugation to reduced glutathione. SDS-PAGE and immunoblot analysis using Class Pi GST-specific IgG confirmed that the GST 7 subunit was expressed in hepatic cytosol and in the affinity purified fractions from pyrrole-treated rats. In contrast, the GST 7 subunit was below the limit of detection in hepatic cytosol of saline-treated animals. HPLC analysis demonstrated the presence of the GST 7 subunit in the affinity purified fraction from pyrrole-treated rat hepatic tissue and showed that the level of this subunit was increased approximately 8-fold relative to the barely detectable level present in control tissue. N-terminal amino acid sequencing analysis confirmed the identity of the HPLC peak as GST 7-7. GST subunits 3, 1a, and 1b were elevated approximately 1.7-, 2.0-, and 2.4-fold respectively, in response to pyrrole treatment. These data provide evidence that pyrrole treatment results in de novo expression of GST 7-7 in rat hepatic tissue and suggest that pyrrole-containing compounds potentially generated during disease and/or altered heme metabolism, or those ingested in food products, may alter GST expression in hepatic tissue.

Animals↗

PubMed1993

Age-related differences in sensitivity to alcohol in the rat.

Female F344 rats of three different ages (4, 13, and 25 months) were tested for sensitivity to the ataxic, hypothermic, and hypnotic effects of injected ethanol. Challenges with ethanol sufficient to produce similar blood alcohol concentrations (BACs) in all age groups at the time of testing were observed to produce greater ataxia in old rats (25 months > 13 months > 4 months). Old rats also were observed to recover the righting reflex at lower BACs than those present in young or middle age rats. BAC at a target rectal temperature of 36 degrees C was observed to be lower in old than in young or middle-age rats when measured as body temperature was falling after doses of 3.0 g/kg to old and 3.5 g/kg to young and middle rats. However, no differences among groups in BAC at target temperature (36 degrees C) were observed as body temperature was recovering from peak hypothermia back up to 36 degrees C. With the exception of the last observation cited, these findings appear to confirm and extend earlier reports of increased target tissue sensitivity to ethanol with advancing age in rodents.

Aging↗

PubMed1993

Recovery of respiratory sinus arrhythmia in detoxified alcoholic subjects.

Although most alcoholic subjects show little autonomic dysfunction, severe alcoholic subjects may have pathological changes in autonomic nerves. We asked if respiratory sinus arrhythmia amplitude (RSA), an index of vagal cardiac control, is decreased in alcoholism and, if so, whether the decrease is reversed with abstinence. RSA was assessed in 17 normotensive alcoholic subjects (A) at 1, 4, 12, and 24 wk of abstinence after detoxification and at similar intervals in 17 controls (C) matched for age, race, and gender. Subjects were studied in both supine and seated positions while breathing in a prescribed deep (> 50% vital capacity) and slow (5-7/min) pattern. Mean heart rate (HR) was determined over 30 s from the electrocardiogram; RSA (the difference between maximum and minimum instantaneous HRs after inspiratory onset) was determined from 10 consecutive breaths. In C, both HR (supine: 61.5 +/- 2.2 beats/min; seated: 71.3 +/- 1.7 beats/min; P < 0.002) and RSA (supine: 22.5 +/- 1.0 beats/min; seated: 28.4 +/- 1.4 beats/min; P < 0.003) were higher when seated than when supine, but neither HR nor RSA varied over 24 wk. At week 1 of abstinence, HRs for A were higher than those for C (supine: 74.2 +/- 2.3 beats/min, P < 0.001; seated: 83.2 +/- 2.7 beats/min, P < 0.003), but by week 24, both seated and supine values returned to control levels. RSA in A at week 1, was only one-half that of C (supine: 11.1 +/- 1.4 beats/min, P < 0.001; seated: 14.7 +/- 1.9 beats/min, P < 0.001) and independent of body position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice.

These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation.

4-Nitroquinoline-1-oxide↗

PubMed1991

Hand movement speed and accuracy in detoxified alcoholics.

Detoxified alcoholics (n = 192) were found to be 9.3% slower than age-matched controls (n = 112) with regard to the composite speed (movement time, MT) with which they were able to strike targets of various sizes and distances with a hand-held stylus at onset of a light stimulus (Fitts's Task). Females (n = 102) were 8% slower than males (n = 202), and blacks (n = 103) about 15.6% slower than whites (n = 201). Gender was the only significant factor with regard to errors (target misses), with women committing 28% fewer errors than men. Women, in contrast to men, appear to trade speed for accuracy in this task. Favorable socioeconomic/medical status and target misses were directly related to movement speed. Thus, when the MT data were corrected for lifestyle variables, the significance of the alcohol effects on MT disappeared, but gender differences persisted. The alcohol effect became statistically significant, the ethnic group differences remained statistically significant, and the gender effect became insignificant when MT scores were corrected for accuracy of performance (target misses). The slope of the linear function relating MT to target difficulty was similar for all subgroups. Prior knowledge of the direction of movement was found to affect MT performance more in white than in black subjects. With regard to reaction times, ethnic group and alcohol use effects remained statistically significant after corrections for lifestyle and errors were made, with values for blacks about 5% slower than values for whites, and values for alcoholics about 4.6% slower than those for controls. Prior knowledge of the direction of movement significantly improved (shortened) reaction time in all subgroups (14%-19%).

Adult↗

PubMed1991

Works in progress #7. Age-dependent fibrin clot invasion by human meniscal fibrochondrocytes. A preliminary report.

This study was performed to determine whether human fibrochondrocytes possess the same biologic potential for initiating a reparative response in a meniscal defect as that found in lower vertebrates. Small, circular defects were created in meniscal fragments obtained from nine men aged 14 to 72 years. The defects were filled with purified fibrin and placed in a culture medium. By 4 weeks, there was excellent cellular penetration into all clots. This study suggests that human meniscal fibrochondrocytes are also capable of initiating a reparative response, and the rapidity of this response appears to be age dependent. The 14- and 16-year-old menisci mounted a more rapid healing response in vitro than did those obtained from skeletally mature individuals.

Adolescent↗

PubMed1990

Body composition in detoxified alcoholics.

Body composition was evaluated in healthy detoxified alcoholics (aged 20-39) and lifestyle controls, with the expectation that prolonged, excessive consumption of alcohol may bring about nutritional or toxicologic alterations in the relationship between body fat and lean body mass. Body fat was assessed by measurements of skin-fold thickness and by means of bioelectric impedance methodology. No noteworthy differences were observed between alcoholics and controls with regard to the relationship between lean body mass and body fat or in the relationship between extracellular and intracellular water. It would appear that 15-20 years of heavy alcohol consumption does not necessarily alter body composition in healthy, young alcoholics.

Adult↗

PubMed1990

Effects of age and sex on reciprocal tapping performance.

Using a reciprocal tapping task (Fitts's task), the speed and accuracy of small-amplitude motor movements of the hand were measured for 62 men and 84 women, 20 to 89 yr. of age. Men and women in their 20s and 30s performed similarly, although men in their 20s displayed a tendency to trade accuracy in favor of speed. Movement time increased noticeably for both men and women beginning with the 40s decade and continued to increase through the 80s decade. Error rates were lower for women than men and were relatively uniform for both men and women across all age decades past 30 yr. Older subjects of both sexes appeared to sacrifice speed (slowed down) to maintain accuracy on the task. The slope of the linear regression relating movement time to task difficulty was steeper for men than for women and increased more for men than women with advancing age, indicating that older men slowed down relatively more than older women on more difficult tasks.

Adult↗

PubMed1989

Mouse hepatic glutathione transferase isoenzymes and their differential induction by anticarcinogens. Specificities of butylated hydroxyanisole and bisethylxanthogen as inducers of glutathione transferases in male and female CD-1 mice.

GSH transferase isoenzymes of class Mu (two forms), class Pi (one form) and class Alpha (two forms) were purified from liver cytosols of female CD-1 mice pretreated with an anticarcinogenic inducer, 2(3)-t-butyl-4-hydroxyanisole. GSH transferases GT-8.7, GT-8.8a and GT-8.8b, GT-9.0, GT-9.3, GT-10.3 and GT-10.6 contained a minimum of six types of subunits distinguishable by structural, catalytic and immunological characteristics. H.p.l.c. analysis of the subunit compositions of affinity-purified GSH transferases from liver cytosols of induced and non-induced male and female CD-1 mice showed that two anticarcinogenic compounds, 2(3)-t-butyl-4-hydroxyanisole and bisethylxanthogen, differed markedly in their specificities as inducers of GSH transferase.

Animals↗

PubMed1988

A soluble factor produced by bone marrow natural suppressor cells blocks interleukin 2 production and activity.

We previously reported that a population of Fc gamma-receptor+ (Fc gamma R+) suppressor cells present in normal unstimulated rabbit bone marrow inhibited the growth of autologous rapidly proliferating bone marrow cells devoid of Fc gamma R. It is now reported that the Fc gamma R+ bone marrow cells produced a soluble, nondialyzable suppressor factor(s) (SF) which blocked the proliferation of Fc gamma R- bone marrow cells. In addition, the Fc gamma R+ cells and SF significantly inhibited spleen cell proliferation in response to concanavalin A (Con A), phytohemagglutinin, and pokeweed mitogen. The bone marrow SF exhibited a dose-dependent suppression of the growth of IL-2-dependent T lymphocytes in the presence of IL-2. SF also completely blocked the production or release of IL-2 by Con A-stimulated T cells. Thus, these bone marrow natural suppressor cells produced a soluble factor, which regulated the growth of rapidly proliferating bone marrow cells and also regulated T cell reactivity by modulating IL-2 production and activity.

Animals↗

PubMed1988

Motor performance in detoxified alcoholics.

Detoxified male and female alcoholics (aged 20-49 years) and age-matched controls performed a series of 15-sec target-tapping tasks in which they alternatively marked two target strips with a felt marker as rapidly and as accurately as possible. Consistent with "Fitts' Law" (Fitts PM: J Exp Psych 47:381-391, 1954), a highly linear relationship between movement time and task difficulty was observed in all four groups. Overall, the alcoholics were slower and made more errors than the controls, although the pattern of deficit differed for males and females. Accuracy, but not speed, was impaired in male alcoholics. The production of undershoot errors was increased more in alcoholics than nonalcoholics in targets of narrower width, whereas the production of overshoot errors was increased more in alcoholics as target separation decreased. Female alcoholics displayed impairment in speed of movement, but not accuracy. However, both alcoholic groups displayed elevated error rates for the more difficult targets. It is thus possible that detoxified alcoholics might mimic the speed functions of nonalcoholic individuals at the occasional cost of an erroneous response at a difficult target.

Adult↗

PubMed1984

The role of congeners in the effects of different alcoholic beverages.

Five different alcoholic beverages were tested in rats to determine if congener content contributed to the hypothermia or motor impairment produced by the beverages. Solutions of cognac, scotch, tequila, vodka, and commercially supplied ethanol were diluted with physiological saline to form solutions containing 16% w/v ethanol, as verified by gas chromatographic analysis. All beverages were administered in doses containing 0 (saline), 1.6, 3.2, 4.8, or 6.4 g/kg ethanol (gastric intubation) in test sessions separated by 7 days (repeated measures design, N = 8 rats per group). Measurements of rectal temperature and motor impairment (rotarod performance) made at 0, 60, and 120 minutes postinjection revealed no noteworthy differences in either measure at 60 or 120 minutes postinjection at any of the 4 doses tested. Thus, no evidence for a contribution of congeners to beverage effects was observed.

Alcoholic Beverages↗

PubMed1983

Comparative study of the iodination of tyrosines in the amino terminal domain of fibrinogen and in N-DSK and fibrin-N-DSK.

Lactoperoxidase catalyzed iodination has been used to probe for differences in surface orientation of tyrosine residues in the amino-terminal disulfide knot (N-DSK) domain of fibrinogen, in N-DSK and in Fb-N-DSK prepared from fibrin. The central region of N-DSK containing the beta chain Tyr 41 and gamma chain Tyr 18 and 32 are much more susceptible to iodination than when an integral part of the fibrinogen molecule. Cleavage of the N-DSK domain from fibrinogen "loosens" up the tertiary structure of N-DSK and allows iodination of its central region. The iodination pattern of comparable tyrosine residues did not change between N-DSK and Fb-N-DSK. This result implies that no significant change occurs in the tertiary structure of N-DSK upon thrombin activation. These results favor the concept that removal of the fibrinopeptides removes a steric hindrance or exposes a binding site for polymerization.

Amino Acid Sequence↗

PubMed1983

Increased responsiveness to ethanol with advancing age in rats.

Male CD strain rats of three different ages (young-5 months; middle-15 months; old-27 months) were tested for their responsiveness to doses of ethanol sufficient to produce hypothermia or hypnosis. Comparison dosages of ethanol across age groups were based upon the estimated equivalent dilution of the drug into the body water compartments of subjects. In the hypnosis study, there were no statistically significant differences among the groups with regard to the time elapsed until the righting reflex was lost or in total sleep time. However, old animals recovered the righting reflex in the presence of lower blood ethanol concentrations than those observed for young and middle animals, suggesting a greater sensitivity of target tissues to the hypnotic effects of ethanol in old rats. The responsiveness of old rats to the hypothermic effect of ethanol was greater than that of younger rats only when the experiment was conducted at an ambient room temperature of 10 degrees C.

Aging↗