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T M Kelly

Publications and source records attributed to T M Kelly.

65 records · Page 4Linked to original sources
PubMed1984

Partial purification from rat and pig liver of cytosolic stimulators of hormone-sensitive adenylate cyclase: quantitation and resolution of two components.

Procedures were carried out to isolate from liver cytosol the protein activators of hormone-sensitive adenylate cyclase. A method for quantifying amounts of activator protein was used to monitor recovery after each isolation step. The activator proteins were precipitable by ammonium sulfate (30-60% saturation) and partially recoverable from the precipitate. On gel filtration of cytosol, stimulatory activity for glucagon-sensitive adenylate cyclase was recovered in two peaks representing proteins with molecular weights of 49,000 and 25,500. Exposure to GTP-Sepharose reduced liver cytosol's content of stimulatory factors for glucagon-sensitive adenylate cyclase by up to 70%. However, soluble protein adenylate cyclase activators distinct from GTP could not be subsequently eluted from the affinity matrix. Purification efforts were thwarted by factor instability and large losses during simple and conventional steps despite the use of a variety of protein stabilizers and protease inhibitors. If the problem of stimulator instability can be overcome, large-scale purification should be possible using pig liver as a starting material.

Adenylyl Cyclases↗
PubMed1984

Hypogonadism in hemochromatosis: reversal with iron depletion.

Gonadal function was evaluated in 64 persons homozygous for the HLA-linked hemochromatosis allele. Of 41 men, 10 had reduced libido or impotence and 6 had testicular atrophy. Before treatment, 5 men had below normal testosterone concentrations, 4 of whom also had low gonadotrophin levels. Four hypogonadal men were reevaluated after iron depletion treatment. In 2, 1 with primary and another with secondary hypogonadism, testosterone levels returned to normal after phlebotomy and were accompanied by a return of normal sexual function. None of 23 women with hemochromatosis had loss of libido or had a natural menopause before age 45. Our findings indicate that in some men with hereditary hemochromatosis and hypogonadism of either testicular or central origin, sexual function and sex hormone concentrations can be restored to normal after iron depletion therapy.

Adolescent↗
PubMed1983

Thyroid disease in hemochromatosis. Increased incidence in homozygous men.

The thyroid function of 49 patients homozygous for the hemochromatosis allele was studied by measurement of serum thyroxine and thyrotropin concentrations. Of 34 homozygous men, three were found to be hypothyroid (thyroxine, less than 3.0 micrograms/dL and thyrotropin, greater than 40 ImU/mL) and one was hyperthyroid (thyroxine, 24 micrograms/dL). All 15 homozygous women had normal thyroid function. The hypothyroid patients had elevated titers of antithyroid antibodies. Histologic examination of the thyroid at autopsy of one hypothyroid patient showed notable iron accumulation and fibrosis with modest lymphocytic infiltration. The causative importance of iron deposition in thyroid diseases associated with hemochromatosis was suggested by the reversal of the usual sex ratio of thyroid dysfunction. Men with hemochromatosis had a much greater iron load than women, and they also had a surprisingly higher incidence of thyroid disease. Iron may have caused injury to the thyroid, followed by the development of antithyroid antibodies and hypothyroidism. The frequency of thyroid disorders in men with hemochromatosis is about 80 times that of men in the general population.

Adult↗
PubMed1980

Anions and cations as stimulators of liver adenylate cyclase.

The effects of inorganic salts on adenylate cyclase activities were studied in rat liver homogenates, particulates, and purified membranes. Na+ salts of N-3, NO-2, S2O32-, SO42-, and non-F- halides stimulated homogenates by a maximum of 2---5-fold; half-maximal effects were seen at concentrations ranging from 90 mM (Na2S2O3) to 410 mM (NaNo2). NaIO3 stimulated about 2-fold at relatively low salt concentrations (5---20 mM). Na+ salts were stimulatory using both ATP and the ATP analog 5'-adenylyl-beta, gamma-imidodiphosphate (AMP-P(NH)P) as enzyme substrate. The time courses of stimulation by NaCl and NaN3 were linear to at least 10 min with any of the three tissue preparations. Although salt effects clearly varied with the different anions, the magnitude and dose-response of stimulation of homogenates by Cl- salts were also dependent on the accompanying alkali cation (Li+, Na+, K+, Rb+, Cs+). MgCl2 at relatively high concentrations (50 mM) enhanced NaCl-stimulated activity in homogenates only slightly at relatively low concentrations of NaCl and not at high concentrations, suggesting a common mechanism of activation by Mg2+ and Na+ salts. NaCl- and NaN3-stimulated activities were unstable in homogenates kept at 0 degree C for 4 h, falling to 35% and 50% of their respective baseline activities. The effects on homogenates and particulates of maximally stimulatory concentrations of NaCl and NaN3 were further enhanced by GTP and the GTP analog 5'-guanylyl-beta, gama-imidodiphosphate (GMP-P(NH)P).

Adenine Nucleotides↗
PubMed1979

Temporal anticipation of response initiation by mentally retarded persons.

The ability of retarded persons to anticipate a signal to initiate discrete movements of varying complexity was investigated in two experiments. The results revealed an interaction between temporal anticipation and response complexity. Experiment 1 showed no reduction in reaction time (RT) in discrete aiming movements when the foreperiod was changed from a random interval to a fixed interval (1 or 3 seconds). Reaction time did not vary with length of the interval or the difficulty of the movement. Experiment 2 showed a reduction of RT to a simple release response at a fixed 1-second warning interval. The findings reflect the difficulty retarded persons have in programming more complex movements and the interaction of temporal anticipation in this response-initiation process.

Adult↗
PubMed1978

Activation of epinephrine and glucagon-sensitive adenylate cyclases of rat liver by cytosol protein factors. Role in loss of enzyme activities during preparation of particulate fractions, quantitation and partial characterization.

The role of cytosol components in the loss of rat liver adenylate cyclase activity which occurs during the preparation of particulate fractions from crude homogenates was studied. Epinephrine (5 micron)-, glucagon (10 micron)-, and fluoride (5 mM)- stimulated activities of twice-washed particulates were 31%, 58% and 67% of the homogenate activities, respectively. Addition of cytosol (100,000 X g supernatant devoid of adenylate cyclase activity) restored these activities to 82%, 88% and 80%. Cytosol also increased particulate basal activity from 60% of homogenate activity to 98%. The cytosol components capable of increasing adenylate cyclase activity were heat labile, nondialyzable, stable to freezing at -20 degrees, resistant to change of pH between 2 and 12, and unaffected by EGTA and NAD. Pretreatment with pepsin destroyed the effects of cytosol on both epinephrine- and glucagon-sensitive activities, whereas trypsin destroyed the effect of cytosol only on epinephrine-sensitive activity. The cytosol effect on adenylate cyclase was specific, since several purified proteins and ubiquitin, did not stimulate enzyme activity. Only part of the cytosol effect could be attributed to its GTP content. GTP at the concentration present in cytosol stimulated epinephrine-sensitive activity but significantly less than did cytosol, while GTP had no effect on glucagon-sensitive activity. Dialyzed cytosol retained its effectiveness even after removal of most (97%) of its GTP to a concentration where GTP had only a minimal effect on epinephrine-sensitive activity. Cytosol, unlike GTP, stimulated rather than inhibited activation by fluoride. Cytosol thus appears to contain at least two different protein components, which increase the activity of the two hormone-sensitive adenylate cyclases and presumably account in part for losses of adenylate cyclase activities seen during the preparation of particulates from homogenates.

Adenylyl Cyclases↗
PubMedDate not supplied

Method for estimating confidence levels for measurements by blood glucose monitoring systems.

A joint conference on self-monitoring of blood glucose (SMBG) has proposed that all glucose monitoring systems generate values that are within 10% of the actual blood glucose level 100% of the time. To estimate the confidence limits of blood glucose measurements made in a typical university ambulatory care setting and to ascertain whether they met the proposed standard, we performed duplicate determinations of blood glucose using a reflectance meter and applied to the measurements a method for calculating the closeness of measured values to a "true" mean. Based on paired measurements in 100 consecutive diabetic subjects, we were able to show that one measurement would be within 11.9% of a true mean value 95% of the time and within 8.4% of the mean 90% of the time. The 95 and 90% confidence limits for the average of two repeated measurements were calculated to be 8.4 and 5.9%, respectively. Our methodology can be applied to any set of SMBG values to calculate their confidence limits and to determine whether the measurements meet recommended standards.

Blood Glucose Self-Monitoring↗
PubMedDate not supplied

Survival with acute primary coronary artery dissection: a case report and review of the literature.

Primary coronary artery dissection is a rare etiology of acute myocardial infarction (AMI) that often has devastating consequences. We present the case of a 46-year-old male survivor of primary coronary artery dissection who was diagnosed angiographically. He suffered a non-Q-wave MI but had no electrocardiographic (ECG) changes during his course. A review of the literature of primary coronary artery dissection, particularly those diagnosed antemortem, is provided.

Aortic Dissection↗