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Biomedical subjects

C Ryan

Publications and source records attributed to C Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1993

Glucose dynamics and gluconeogenesis during and after prolonged swimming in rats.

Glucose fluxes and, in particular, gluconeogenic rate were examined during and after prolonged submaximal exercise represented by a 4-h swim and 3-h recovery in 12-h-fasted previously catheterized rats. The metabolic clearance rate and production rate of glucose were measured using an infusion of [6-3H]glucose, and gluconeogenesis was assessed from the incorporation of 14C from [14C]bicarbonate into glucose. Immediately after exercise and after the 3-h recovery, liver glycogen was also determined. During exercise, euglycemia was maintained while glucose production and utilization doubled from 1.58 +/- 0.17 to 3.58 +/- 0.21 mg/min. During recovery, glucose concentrations increased to 131.0 +/- 5.8 vs. 110.8 +/- 5.1 mg/dl for controls (P < 0.05), because the decline in glucose production rate lagged behind the decline in metabolic clearance rate. The index of gluconeogenesis coupled with a metabolic correction factor indicates that gluconeogenesis was the primary source of glucose during swimming and recovery and that the principal substrates were at the level of pyruvate. CO2 production rates calculated using plasma CO2 and label concentrations doubled during exercise. Little repletion of liver glycogen was seen after exercise, indicating that the increased production of glucose after exercise is directed primarily toward the repletion of muscle glycogen. Swimming is therefore a useful model of low-intensity exercise easily implemented in untrained animals. [14C]bicarbonate can be used in the estimation of gluconeogenic rates during exercise.

Animals↗
PubMed1993

Influence of plasma glucose rate of decrease on hierarchy of responses to hypoglycemia.

To test the hypothesis that the rate of decrease in plasma glucose concentration may affect the hierarchy of responses to hypoglycemia, we compared plasma couterregulatory hormone concentrations, autonomic and neuroglycopenic symptom scores, and cognitive function test performance in 10 normal volunteers whose plasma glucose concentration was either rapidly (over 30 min) decreased to 3.7 mmol (66 mg/dL) or was slowly decreased in a stepwise manner to plateaus of 4.3 mmol (78 mg/dL), 3.7 mmol (66 mg/dL), 3.0 mmol (54 mg/dL), and 2.3 mmol (42 mg/dL). Comparable plasma counterregulatory hormone concentrations and autonomic symptom scores were observed in both sets of experiments during the 3.7 mmol (66 mg/dL) plateaus. In the stepwise decrement experiments, significant increases in neuroglycopenic symptom scores and deterioration in cognitive performance occurred only during the last glycemic plateau (2.3 mmol, 42 mg/dL). In the rapid decrement experiments, no increase in neuroglycopenic symptom score or deterioration in cognitive performance was observed during the 3.7 mmol (66 mg/dL) plateau. We, therefore, conclude that in normal volunteers the rate of decrease in plasma glucose concentration does not affect the hierarchy of responses to hypoglycemia.

Adult↗
PubMed1993

Vitamin D deficiency found in the diet of the elderly in South Carolina.

Dietary intake of vitamin D was assessed from a 24-hour food recall collected from 293 independent living adults 55 years of age or older who participated in the South Carolina Nutrition Survey. Mean vitamin D intake was only 46 percent of the RDA. The data in this study indicated that insufficient dietary intake of vitamin D is prevalent among older South Carolinians. Possible methods to correct this include: increased exposure to the sun, increased intake of food sources containing this nutrient or prescribing a vitamin D supplement.

Aged↗
PubMed1992

Growth arrest of human B lymphocytes is accompanied by induction of the low molecular weight mammalian heat shock protein (Hsp28).

A large number of protein and molecular markers have been identified that delineate the early stages of human B cell activation and proliferation. In contrast, few if any molecules are transiently expressed precisely as activated B cells stop proliferating and undergo growth arrest. We demonstrate that the low molecular weight heat shock protein (hsp28) exhibits unique induction kinetics that specifically demarcates this interval. After mitogenic activation of unstimulated splenic B cells, hsp28 protein and phosphorylation transiently increase coinciding precisely with the peak of cellular proliferation and the onset of growth arrest. Although most neoplastic B cells constitutively express hsp28, three cell lines were identified that were hsp28-. No differences in phenotype or growth kinetics were detected between hsp28+ and hsp28- neoplastic B cells demonstrating that hsp28 expression is not essential for cell growth. However, when treated with phorbol ester or heat shock, these hsp28- cell lines synthesize hsp28 followed by the onset growth arrest. The consistency with which hsp28 induction transiently delineates the interval from peak proliferation to the onset of growth arrest suggests hsp28 itself is likely to be involved in regulating this process.

B-Lymphocytes↗
PubMed1992

Inhibitory effects of HSP70 chaperones on nascent polypeptides.

Several of the major heat shock proteins (HSPs) function normally as molecular chaperones to prevent aggregation of immature polypeptides and thereby facilitate folding and oligomerization. To determine their effect on nascent polypeptides, we added purified preparations of different isoforms of HSP70 to in vitro translation reactions primed by the 26S mRNA of Sindbis virus, which encodes an autoprotease that functions cotranslationally, or by the mRNA encoding the yeast vacuolar H+ATPase, which is formed by a novel transpeptidase activity that removes the central region of the initial polypeptide. In the presence of HSP70s both the autoprotease and transpeptidase activities were inhibited, indicating that these chaperones can interact with nascent polypeptides and, in the cases studied here, perturb their normal structures.

Animals↗
PubMed1992

Lesion morphology and coronary angioplasty: current experience and analysis.

From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03).

Angioplasty, Balloon, Coronary↗
PubMed1992

Perspective, orientation disparity, and anisotropy in stereoscopic slant perception.

Stereoscopic depth estimates are not predictable from the geometry of point disparities. The configural properties of surfaces (surface contours) may play an important role in determining, for example, slant responses to a disparity gradient, and the marked anisotropy in favour of slant around a horizontal axis. It has been argued that variation in slant magnitude are attributable to the degree of perspective conflict present and that anisotropy is attributable to orientation disparity, which varies with the axis of slant. Three experiments were conducted in which configural properties were varied to try and tease apart the respective roles of orientation disparity and conflicting perspective in determining stereoscopic slant perception and slant axis anisotropy. The results could not be accounted for by the magnitude of the orientation disparities present. Conflicting perspective cues appeared to play a role but only for slant around a vertical axis. It was concluded that there are important configural effects in stereopsis attributable neither to orientation disparity nor to perspective.

Anisotropy↗
PubMed1992

Multicenter evaluation of five commercial rubella virus immunoglobulin G kits which report in international units per milliliter.

In a multicenter study, the consistency of international units expressed by five commercially available rubella virus immunoglobulin G kits was evaluated. The linearity and within-run and between-run precision were determined for each kit. All kits demonstrated good linearity and had within-run and between-run precision coefficients of variation ranging from 5.1 to 21.7% and from 9.5 to 51.0%, respectively. To compare the international units expressed, the results from 40 samples tested in duplicate were compared with the results of a reference enzyme immunoassay calibrated with World Health Organization international standard serum and a hemagglutination inhibition test. The results of the kits were plotted against those of the reference tests, and linear regression analysis was applied. The Pearson correlation coefficient ranged from 0.64 to 0.75 when the commercial kit results were compared with those of the reference enzyme immunoassay, indicating only a moderate degree of correlation. Therefore, the international units expressed by the commercial kits are insufficiently consistent to be of practical use in diagnostic clinical microbiology.

Antibodies, Viral↗
PubMed1992

New controversies in hypertension: questions answered, answers questioned.

Despite multiple, interdisciplinary group recommendations, we are still on uncertain ground when it comes to treatment of most aspects of hypertension. Seven major areas of controversy include mild hypertension, the relevance of hypertension and lipids, hypertensive agents and electrolyte imbalance, treatment and regression of left ventricular hypertrophy, isolated systolic hypertension, ambulatory blood pressure monitoring and overtreatment of hypertension--the "j shaped curve." Although our knowledge of these aspects has advanced tremendously, significant doubts exist as to our present approach. Key publications are reviewed to evaluate our present knowledge and recommendations are made. The 1988 recommendations of the Joint National Committee on Detection, Evaluation and Treatment of Hypertension both answered and raised some questions regarding treatment of high blood pressure. We lack information on the treatment outcomes and many of us remain unconvinced that our present approach is the best we can do. Many other questions abound. Should the treatment of mild hypertension be as aggressive as it is at present or should systolic hypertension in the elderly be treated at all? There are striking variations and recommendations of other groups outside the United States which reaffirm our lack of evidence. Ideally, we ought to be able to reduce or abolish the recognized poor outcomes of treated hypertension: heart attack, heart failure, stroke, renal failure and retinopathy. Adequate control of blood pressure has gone a long way towards preventing stroke, accelerated hypertension and hypertensive encephalopathy. Congestive heart failure has also been reduced. There is a singular lack of evidence of the influence on either total mortality or morbidity from coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1991

Silent ischemia after coronary angioplasty: evaluation of restenosis and extent of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients.

One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Partial purification and substrate specificity of a ubiquitin hydrolase from Saccharomyces cerevisiae.

A ubiquitin hydrolase that removes ubiquitin from a multi-ubiquitinated protein has been purified 600-fold from Saccharomyces cerevisiae. Four different ubiquitin-protein conjugates were assayed as substrates during the purification procedure. Enzymic activities that removed ubiquitin from ubiquitinated histone H2A, a ubiquitin-ubiquitin dimer and a ubiquitin-ribosomal fusion protein were separated during the purification from an activity that removed a single ubiquitin molecule linked by an isopeptide bond to a ubiquitinated protein. The size of the native enzyme was 160 kDa, based on its sedimentation in a sucrose gradient, and the subunit molecular mass was estimated to be 160 kDa, based on a profile of proteins eluted in different fractions by thiol-affinity chromatography. The partially purified hydrolase was not inhibited by a variety of protease inhibitors, except for thiol-blocking reagents. The natural substrate for this enzyme may be the polyubiquitin chain containing ubiquitin molecules bound to each other in isopeptide bonds, with one of them linked to a lysine residue of a protein targeted for intracellular proteolysis.

Centrifugation, Density Gradient↗
PubMed1991

Hypertension in the elderly patient.

Several trials have demonstrated a significant reduction in morbidity from cardiovascular disease with the treatment of diastolic hypertension in elderly persons. The pilot trial of the Systolic Hypertension in the Elderly Patient study showed a reduction in morbidity and mortality from stroke with less of a reduction in death from cardiac conditions in elderly patients who were treated. Isolated systolic hypertension in elderly persons has a particularly hazardous connection with morbidity and mortality from stroke and cardiovascular disease. The mechanisms of hypertension are different, if not greatly so, in the elderly population. Peripheral vascular resistance plays a major role. However, reduction in peripheral vascular resistance can still be demonstrated with exercise in older patients. Two major studies are ongoing--the Systolic Hypertension European trial and the Systolic Hypertension in the Elderly Patient trial. We await the outcome of these trials to learn more about the treatment of isolated systolic hypertension in elderly patients.

Aged↗
PubMed1991

Alteration of a nuclease in Fanconi anemia.

Fanconi anemia is a cancer-prone disease characterized by progressive loss of blood cells, skeletal defects and stunted growth. Studies of a nuclease acting on double-stranded DNA have revealed an enzyme alteration in cells derived from Fanconi patients. A particulate fraction isolated from cultured human lymphoblasts and fibroblasts was solubilized with detergent and subjected to isoelectric focusing. Nuclease activity observed in four normal cell lines bands in a pH gradient with a pI of 6.3. Four cell lines belonging to complementation group A exhibit an increase in the pI of that nuclease to 6.8. These observations provide a new diagnostic for this disorder. Analysis of this enzyme in tetraploid cultures derived from fusion of normal and Fanconi cells suggest that the normal phenotype is dominant. That observation supports the hypothesis that the Fanconi A gene is required for modification of the nuclease pI. Definition of the molecular basis of this enzyme alteration should provide insight into the primary genetic lesion in this disorder.

Cell Fractionation↗
PubMed1991

Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction.

To define glycemic thresholds for activation of counterregulatory hormone secretion, initiation of symptoms (autonomic and neuroglycopenic), and onset of deterioration of cognitive function, we measured indexes of these responses during glycemic plateaus of 90, 78, 66, 54, and 42 mg/dl in 10 normal volunteers, with the use of the hyperinsulinemic glucose clamp technique. Activation of glucagon, epinephrine, norepinephrine, and growth hormone secretion began at arterialized venous plasma glucose concentrations of 68 +/- 1, 68 +/- 1, 65 +/- 1, and 67 +/- 2 (SE) mg/dl, respectively. Autonomic symptoms (anxiety, palpitations, sweating, irritability, and tremor) began at 58 +/- 2 mg/dl, which was significantly (P = 0.0001) lower. Neuroglycopenic symptoms (hunger, dizziness, tingling, blurred vision, difficulty thinking, and faintness) and deterioration in cognitive function tests began at 51 +/- 3 and 49 +/- 2 mg/dl, respectively, values that were both significantly (P = 0.018 and 0.004, respectively) lower than that for initiation of autonomic symptoms. We therefore conclude that there is a distinct hierarchy of responses to decrements in plasma glucose, such that the threshold for activation of counterregulatory hormone secretion occurs at higher plasma glucose levels than that for initiation of autonomic warning symptoms, which in turn occurs at higher plasma glucose levels than that for onset of neuroglycopenic symptoms and deterioration in cerebral function. Such a hierarchy would maximize the opportunity to avoid incapacitating hypoglycemia.

Adult↗
PubMed1990

Fluorescence studies with potato carboxypeptidase inhibitor.

Potato carboxypeptidase inhibitor (CPI) is a 39-residue globular protein whose X-ray structure is known. The protein's two tryptophan residues (W22 and W28) appear to be on the surface in the crystal structure. The fluorescence spectrum of CPI has a maximum at 344 nm. Acrylamide solute quenching yields an upward curving Stern-Volmer plot with KSV approximately 9 M-1. KI quenching yields a linear plot with KSV approximately 5.5 M-1. These studies indicate that emission occurs from a solvent exposed residue(s). Fluorescence lifetime measurements were fitted to a biexponential decay law with tau 1 = 0.9 ns. f1 = 0.22 and tau 2 = 3.9 ns. Anisotropy decay data were described by a single rotational correlation time of 1.2 ns. This value is somewhat small for the global rotation of a protein of this size. The low temperature phosphorescence of CPI shows a biexponential decay, with a rapidly decaying 0.5-1.0 second component. The triplet state of at least one of the two tryptophan residues must be perturbed by interaction with nearby disulfide bonds.

Acrylamides↗
PubMed1990

Usefulness of tomographic thallium-201 imaging for detection of restenosis after percutaneous transluminal coronary angioplasty.

The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization.

Angioplasty, Balloon, Coronary↗