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Biomedical subjects

H M Perry

Publications and source records attributed to H M Perry.

At least 91 records · Page 5Linked to original sources
PubMed1989

Partial characterization of a parathyroid hormone-stimulated resorption factor(s) from osteoblast-like cells.

PTH stimulates osteoblast-like cells to produce a product(s) capable of increasing cellular bone resorption. We have investigated this phenomenon using primary cultures of osteoblasts and the clonal osteoblast-like cell line ROS 17/2. Conditioned medium from PTH-stimulated populations of either culture increases bone resorption compared to conditioned medium measured in three independent assay systems; the isolated osteoclast assay system, elicited macrophages, and the fetal bone rudiment system. Characterization of the factor(s) of PTH-stimulated osteoblast-like cell (ROS 17/2) suggests that the compound(s) is not prostaglandin (no inhibition by indomethacin; not extractable in diethylacetate). Rather, it is heat and protease sensitive. In addition, secretion of the product is sensitive to cycloheximide. These findings lead us to the conclusion that the factor(s) is protein. Further work demonstrates the necessity for a divalent cation for retention of factor activity. Finally, we have estimated the molecular radius of the factor as about 110,000 daltons and perhaps a second at about 70,000 daltons using a sizing column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methionine-labeled PTH-stimulated ROS culture supernatants reveals relatively increased secretion of proteins with these approximate molecular radii.

Animals↗
PubMed1988

University of California, Davis, conference: Mild hypertension.

Prevalence of "higher than normal" blood pressures in a community is inversely related to the magnitude of the elevation; the milder grades of elevation are far more prevalent. A multifactorially inherited tendency to develop hypertension is modulated by multiple environmental influences. Autonomic nervous and behavioral factors plausibly appear to contribute to the initiating mechanisms of hypertension; the associated hemodynamic changes and the resulting cardiovascular structural changes interact to perpetuate the process. The complex interaction of hypertension and atherosclerosis is further complicated by direct as well as secondary effects of antihypertensive drugs on atherogenesis. Attributable cardiovascular risk is generally proportional to the degree of hypertension across the entire range of elevated blood pressure; this kind of relationship holds also for normal versus subnormal blood pressure values. Pharmacologic lowering of blood pressure, however, does not confer proportional benefit. Thus, such lowering of blood pressure to normotensive levels does not reduce the risk level to that in the normotensive population. Therapeutic outcome is influenced by the interaction of blood pressure lowering, type of antihypertensive agents used, existing risk factors, and target organ damage. Benefits of lowering blood pressure in established mild hypertension (diastolic blood pressure greater than 95 mm Hg) are confirmed. Drug treatment of patients with lower diastolic blood pressure or with isolated elevations of systolic blood pressures continues to be controversial as does the choice of initial therapeutic agent(s). The large-scale experience of clinical trials encompassing the long-term risks and benefits of the drug treatment of mild hypertension is limited to the use of diuretics and adrenergic beta blockers. A variety of new and promising therapeutic agents for use as alternate choices for initial therapy needs to undergo comparative evaluation.

Adolescent↗
PubMed1988

Increase in the blood pressure of rats chronically fed low levels of lead.

Groups of 15 to 18 female weanling Long-Evans rats fed a rye-based diet low in lead (0.25 ppm) were exposed to 0.1, 1.0, and 5.0 ppm lead in drinking water. No suggestion of clinical lead toxicity was recognized. Systolic pressures were measured at 3-month intervals after weaning. The groups of lead-exposed animals had consistently and significantly higher average pressures than control animals, the increase approximating 15 mm Hg. With the lowest lead exposure (0.1 ppm), the increase in average pressure was gradual, being half minimal at 3 months and requiring 1 year to become maximal. After 1 year, half of these rats had pressures from 0 to 10 mm Hg above the control average; 40, 20, and 10% had pressures that were 20, 30, and 40 mm Hg, respectively, above the control average. Thus, rats exposed to lead in amounts comparable to the environmental exposure of many Americans had an average elevation in systolic pressure comparable to that of human beings with essential hypertension.

Administration, Oral↗
PubMed1987

Adrenal responses to subtotal parathyroidectomy for primary hyperparathyroidism.

Although it is well known that hypertension is often associated with primary hyperparathyroidism and that parathyroidectomy reverses or reduces this abnormality, the etiology of elevated blood pressure in hyperparathyroidism is still conjectural. We have analyzed serum calcium, blood pressure, and metabolites of adrenal cortical hormones before and after surgical therapy for hyperparathyroidism in 10 normotensive and six hypertensive patients with primary hyperparathyroidism. Successful parathyroidectomy lowered serum calcium (P less than 0.01) and diastolic blood pressure (P less than 0.05) in all subjects. Mean urinary aldosterone and Porter-Silber chromagens were within normal limits preoperatively in normotensive as well as hypertensive subjects. After parathyroidectomy, aldosterone levels as well as Porter-Silber chromagens decreased significantly in all patients (P less than 0.01). However, when normotensive and hypertensive subjects were analyzed separately, the decrease in aldosterone levels was significant only in the normotensive group (P less than 0.05) whereas the decrease in Porter-Silber chromagens reached significancy only in the hypertensive group (P less than 0.01). The results indicate that surgical therapy for hyperparathyroidism lowers serum calcium and blood pressure and is associated with a decrease in the excretion of adrenal steroid metabolites. It is suggested that the temporal relationship which exists between ionized calcium and steroidogenesis in hyperparathyroid patients contributes at least in part to the generalized decrease in blood pressure observed after successful parathyroidectomy.

17-Hydroxycorticosteroids↗
PubMed1986

Diurnal variation of serum calcium and phosphorus in postmenopausal women.

Serum calcium, ionized calcium, and phosphorus have been obtained at hourly intervals in nine healthy postmenopausal women. The hourly means of ionized calcium and phosphorus demonstrate significant diurnal variation with a similar apogee, nadir, and periodicity (24 hours). These results are distinct from the diurnal variation of ionized calcium and phosphorus previously reported for young men and provide more evidence of an altered mineral hemostasis in postmenopausal women.

Aged↗
PubMed1986

Parathyroid hormone-lymphocyte interactions modulate bone resorption.

The biologically active PTH fragment 1-34 induces mononuclear leukocytes to produce a substance(s) capable of increasing bone resorption, as assayed in an organ culture system. The onset of the effect is evident at 2 days and lasts at least 7 days. The cell responsible for this effect appears to be an activated nonadherent lymphocyte (probably T-cell). PTH-(1-34) induces these cells to secrete this factor(s). The presence of adherent mononuclear leukocytes or appropriate conditioned medium appears to augment this response. Secretion of this factor(s) is specific for PTH-(1-34); it is not induced by biologically inactive PTH fragments, nor can it be induced by incubating mononuclear leukocytes with other hormones, including human PRL or lysine vasopressin. On the other hand, PTH-(1-34), human PRL, and lysine vasopressin all activate mononuclear leukocytes, as determined by [3H]thymidine incorporation. Biologically inactive PTH fragments do not. Thus, while lymphocyte activation may be a necessary prerequisite to lymphocyte modulation of bone resorption, it is not sufficient of itself. The PTH fragment 1-34 activates mononuclear leukocytes and specifically induces nonadherent lymphocytes to produce a substance(s) capable of increasing bone resorption. Preliminary characterization of this substance(s) shows that cellular components of the organ culture are necessary to demonstrate the increased resorptive capacity of PTH-stimulated lymphocyte supernatants. Secondly, this resorptive capacity is heat sensitive. Finally, this substance(s) appears to have a nominal molecular radius greater than 14,000 daltons, but less than 50,000 daltons.

Bone Resorption↗
PubMed1986

Use of diuretics in treatment of hypertension in the elderly.

Men and women with isolated systolic hypertension who were at least 60 years of age were treated for 1 year with chlorthalidone (25-50 mg daily) or matching placebo as the step I drug. Most patients reached goal blood pressure without requiring a step II drug. The blood pressure response was similar in all age, sex and race subgroups, with an overall difference between the randomised groups of 17 mm Hg for systolic blood pressure (p less than 0.001) and 6mm Hg for diastolic blood pressure (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum concentrations of potassium (0.5 mmol/L lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001), and creatinine (0.08 mg/dl higher, p = 0.02). Compliance was good, and more than 80% of participants were still taking the study medications at the end of the year.

Aged↗
PubMed1986

Systolic Hypertension in the Elderly Program, Pilot Study (SHEP-PS): morbidity and mortality experience.

SHEP-Pilot Study, a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension, followed 551 participants aged 60 years or more with untreated blood pressures of greater than or equal to 160/less than 90 mmHg for an average of 34 months. Mean age was 72 years, 63% were female and 82% white. Pretreatment blood pressures averaged 172/75 mmHg. As their Step I drug, 443 participants were assigned chlorthalidone and 108 placebo. Of 512 surviving participants, 80% and 84% of the chlorthalidone and placebo groups, respectively, attended their last clinic visit; 71% and 60% were still taking blinded drug; and 60% and 33% had systolic blood pressures less than 160 mmHg. Final blood pressures averaged 140/67 and 154/72 mmHg for the chlorthalidone and placebo groups, respectively. All-cause mortality rates were 25 and 23 deaths per 1000 participant-years of risk, respectively; rates for 'definite' first strokes were 8.3 and 13 deaths. Differences between chlorthalidone and placebo groups were significant for blood pressure but not for event rates.

Aged↗
PubMed1985

The evolution of antihypertensive therapy.

Beginning in the early 1950s, when a ganglioplegic agent and a vasodilator were used in combination to provide long-term control of severe hypertension, which neither drug alone could control, much has been learned about the management of hypertension from the use of new antihypertensive agents in man and from clinical trials of antihypertensive regimens. Some of this information includes: the unexpected yet very real hazards as well as benefits associated with the long-term use of powerful drugs, in particular the original description of hydralazine-induced lupus, its relation to genetic markers and its association with control of hypertension; the apparently decreasing need for antihypertensive drugs in subjects with well-controlled severe and moderate hypertension; the identification of risk factors for the complications of hypertension and the quantitation of their effects; the decrease in the incidence of hypertensive complications associated with the pharmacologic treatment of severe, moderate and, at least, the upper ranges of mild hypertension; the possibility of designing a chemical to block a specific reaction and the realization that it would have broader than expected effects; and the primary prevention of myocardial infarction in very high risk subjects.

Antihypertensive Agents↗
PubMed1985

Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Aged↗
PubMed1985

Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion.

Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.

Anesthetics↗
PubMed1984

Parathyroid hormone receptors in circulating human mononuclear leukocytes.

In this article we demonstrate receptors for parathyroid hormone in circulating mononuclear leukocytes using the radioiodinated analogue (8,18 norleucine, 34 tyrosine) bPTH 1-34 (bovine parathyroid hormone 1-34). Specific binding, which is reversible and saturable, equilibrates within 5 min at 0-4 degrees C with a calculated KD of 8.9 X 10(-11) M. This binding has a pH maximum of 7.0, is magnesium-dependent, and is inversely related to medium calcium concentration. Such binding is completely inhibited by simultaneous addition of 4 ng/ml of bovine parathyroid hormone 1-34, 5 ng/ml of bovine parathyroid hormone 1-84, or 5 ng/ml (8,18 norleucine, 34 Tyr) of 3-34 bPTH, but is unaffected by a biologically inactive parathyroid hormone fragment or other unrelated peptide hormones. Cyclic AMP accumulation increases 3-fold after 5 min exposure of mononuclear leukocytes to bPTH 1-34 in concentrations as low as 1 X 10(-9) M. Lymphocytes appear to be the circulating cells which interact with PTH as indicated by the observations that: 1) lymphocyte-enriched preparations bind three times as much radioligand/cell as do mixed mononuclear leukocytes, 2) monocytes, platelets, granulocytes, and erythrocytes do not bind PTH, and 3) monocytes, but not lymphocytes, degrade the hormone.

Cell Separation↗
PubMed1984

Long identical repeats in the mouse gamma 2b switch region and their implications for the mechanism of class switching.

A computer sorting method was used to construct a dictionary by which long identical repeats of nucleotides could be identified and all available sequences of immunoglobulin switch regions were examined. The genomic mouse gamma 2b switch region contains two sets of four long identical repeats comprising 102, 72, 98 and 109 nucleotides respectively. The first is separated from the second by 347 nucleotides which contain the first 46 nucleotides of the 98 nucleotide set as a third partial repeat. These sets overlap the 49-bp separation between identical five nucleotide repeats GAGCT, GGGGT, ACCAG and CGAGC. Switches from S mu to S gamma 2b in and between these sets involve deletions of all or part of a set. Frequencies and locations of short repeats show differences between S mu, S epsilon, and S alpha and the other switch regions; these could determine specificity and locations of switches.

Animals↗
PubMed1984

Survival of treated hypertensive patients as a function of compliance and control.

In the 1950s, 223 white patients had varyingly severe hypertension controlled in hospital with ganglioplegic agent and hydralazine. At home, each was instructed to take and record his/her blood pressure (BP) four or five times per day and to bring all BP records to the next treatment visit. Our file of home BP records exactly one year after treatment began was used to divide the patients into: non-compliant; compliant but uncontrolled; controlled. There were 56 non-compliant, 60 compliant but uncontrolled, and 107 controlled patients. Their respective median survival times after beginning therapy were 56.5, 134, and 153 months. Thus, survival was a strong function of compliance and a significant but weaker function of control. The non-compliant quarter of the group survived an average of less than five years, while the controlled half survived an average of more than 12 years.

Blood Pressure Determination↗
PubMed1984

Alternate calcitonin and etidronate disodium therapy for Paget's bone disease.

The efficacy of salmon calcitonin and etidronate disodium was compared in the therapy of Paget's bone disease in 37 patients. Nineteen patients received etidronate for six months with a mean alkaline phosphatase reduction to 53% of initial values. Bone scintophotographs improved in 12 and were unchanged in seven. Symptoms improved in 11 subjects, were unchanged in seven, and worsened in one. Twelve of these patients were then treated with calcitonin for six months with continued improvement in alkaline phosphatase values to 36% of initial values. All bone scintophotographs improved compared with initial studies. Seven patients continued to improve symptomatically; five described no change. Eighteen individuals were treated initially with calcitonin for six months. During therapy, the alkaline phosphatase level fell to 76% of initial values. Bone scintophotographs were worse in two patients, did not change in seven, and improved in nine. Eleven patients reported improvement in symptoms and seven reported no change. Seventeen of these patients were then treated with etidronate for six months with a decrease in alkaline phosphatase levels to 64% of initial values. Compared with initial tests, bone scintophotographs were worse in three with no change in five and improvement in nine. Symptomatically, three patients reported improvement; four noted no change, and ten reported increasing pain. Although the reason for the poor response to initial calcitonin therapy and/or subsequent etidronate therapy is not apparent, we have concluded that patients fare better when treated with an etidronate calcitonin sequence when compared with those treated with a calcitonin/etidronate sequence.

Aged↗