Search PubMed⌕ Search

Biomedical subjects

J M Hartnell

Publications and source records attributed to J M Hartnell.

7 recordsLinked to original sources
PubMed1990

Diabetes-related changes in chromatin structure of brain, liver, and intestinal epithelium.

To determine whether diabetes alters chromatin structure in vivo, fluorometric analysis of alkali-induced DNA unwinding was carried out in various tissues of streptozocin-induced diabetic rats and genetically obese diabetic (db/db) mice. When zero-order kinetics were used to analyze the data, the percentage of double-stranded DNA (%dsDNA) unwinding in brain, liver, and intestinal epithelium of diabetic rats maintained for 4 wk was significantly reduced compared with vehicle-injected control rats (%dsDNA 0.37 +/- 0.05 vs. 0.73 +/- 0.02 for brain, 0.59 +/- 0.1 vs. 0.84 +/- 0.02 for liver, and 0.58 +/- 0.07 vs. 0.90 +/- 0.13 for intestinal epithelium). Insulin treatment of diabetic rats normalized the rate of DNA unwinding in liver (0.82 +/- 0.09 %dsDNA/min) and intestinal epithelium (1.05 +/- 0.09 %dsDNA/min), but the increase in the unwinding rate of brain DNA (0.51 +/- 0.06 %dsDNA/min) did not achieve control values. Similarly, alkali-induced DNA unwinding was significantly slower in brain and liver of db/db mice compared with homozygote controls. When first-order kinetics were used to analyze the data, fractional rate constants of DNA unwinding in brain and liver of diabetic rats or mice were significantly smaller than observed in nondiabetic control animals. The fractional rate constant of DNA unwinding in intestinal epithelium was not altered with diabetes. We conclude that chronic uncontrolled hyperglycemia can alter chromatin structure in vivo.

Animals↗
PubMed1989

The tissue specificity of the age-related changes in alkali-induced DNA-unwinding.

To determine if the age-related changes in chromatin digestibility are tissue-specific, fluorometric analysis of the alkali-induced DNA unwinding technique was adapted for soft-tissue chromatin studies. The rate of DNA unwinding in the brain and liver of young Fischer 344 male rats (3 months of age) was significantly greater than the rates measured in middle-aged (15 months) or aged rats (26 months). In contrast, the rate of DNA unwinding in the intestinal epithelium, a continuously replicating tissue, did not significantly vary with age. Although this assay is capable of detecting DNA strand breaks in vivo following N-nitrosodimethylamine administration, the age-related changes could not be attributed to reduced DNA strand lesions in the aged animals. The % double-stranded DNA at time 0 of incubation in alkali was lower in the brain and liver of aged rats indicating that DNA strand breaks may actually increase with aging. These results indicate that proliferative activity of the tissue is an important determinant of age-related changes in chromatin structure.

Aging↗
PubMed1989

Reduction of alkali-induced white blood cell DNA unwinding rate: a potential biomarker of aging.

The modification of DNA with aging or in diabetes mellitus has been proposed as a possible mechanism of cellular senescence. To test this hypothesis, we measured DNA strand breaks in human white blood cells (WBC) by fluorometric analysis of DNA unwinding in alkaline solutions. In a nondiabetic population with an age range 22-80 years, there was a significant negative correlation between the rate of DNA unwinding and the age of the individual with an r of 0.60 (p less than .001). The rate of alkaline digestion of double-stranded DNA (ds DNA) in the elderly diabetics (n = 26, 65-80 yrs) was significantly lower than that in the nondiabetic, age-matched ambulatory elderly. Within the healthy group studied, there was a statistically significant correlation between the rate of DNA unwinding and plasma glucose concentration (p less than .05) or glycosylated hemoglobin A1C levels (p less than .0001). The availability of WBC and the relative ease and rapidity of the technique employed make this a potentially useful biological marker of aging.

Adult↗
PubMed1987

Comparison of the effects of pulsatile and continuous TRH infusion on TSH release in men.

Pulsatile secretion of hypothalamic releasing factors modulates the release of pituitary hormones. To compare the effects of pulsatile and continuous administration of TRH on TSH secretion, we studied six healthy euthyroid 20- to 38-year-old men by obtaining blood samples every 20 minutes for 12 hours (8 AM to 8 PM) during five days of study. TRH was administered according to the following schedule: day 1 (no TRH, control); day 2 and subsequent day 3 (20 micrograms IV bolus of TRH every 96 minutes); 6 to 17 days rest; then consecutive days 4 and 5 (continuous infusion of 20 micrograms TRH/96 minutes) for 12 hours on and 12 hours off. The highest mean serum TSH levels occurred on the first day of pulsatile TRH. Serum TSH on pulsatile days 1 and 2 and continuous day 1 was significantly greater than on the control day. Similarly, the mean TSH on each day of pulsatile TRH was greater than the mean TSH on the corresponding days of continuous TRH administration. The highest serum T4 and T3 levels were observed on pulsatile day 2, suggesting that the decrease in serum TSH on this day was due to thyroid hormone negative feedback at the pituitary. The mean T4 and T3 values on continuous day 1 and 2 did not differ significantly, suggesting that other factors, including "down-regulation" of the pituitary TRH receptors by the continuous TRH infusion may be involved in the further decline of TSH levels on continuous day 2. We conclude that pulsatile TRH infusion releases more TSH, T3, and T4 than the corresponding amount of TRH administered continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Glyburide does not alter thyroid function.

Goiter and hypothyroidism have been reported as side effects of sulfonylurea therapy. To test the effects of glyburide, a new generation sulfonylurea drug, on thyroid function, we studied 15 male Type 2 diabetic patients before and after 6 weeks of treatment with this drug, and we repeated the studies on 9 of these patients who remained on the drug for at least 24 weeks. All hypoglycemic agents were discontinued for 1 week before the study. Patients had a baseline thyroid examination, serum T4, free T4 index (FT4I), T3, and free T3 index (FT3I), fasting serum glucose (FSG), HbA1c and a TRH test of TSH reserve. The dose of glyburide was adjusted at 2 weeks, and the tests were repeated after 6 weeks and after at least 24 (24-32) weeks of glyburide therapy. Compared to baseline, there was a significant decrease in FSG at 6 weeks and again at 24-32 weeks. Body weight, thyroid size, serum FT4I, FT3I, and TSH did not change significantly. After 6 weeks of therapy, there was no significant correlation of FSG or HbA1c with FT4I, FT3I, basal or peak TSH or TSH response area. The integrated area under the TSH response curve decreased significantly in 8 patients at 24 weeks (p less than 0.05). There was a positive correlation between FSG and the area under the TSH response curve using the combined baseline and 24 week data in these patients (r = 0.73, p less than 0.01). In this study with patients acting as their own controls, there was no effect of glyburide on thyroid function or size.

Aged↗