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Biomedical subjects

J P Cain

Publications and source records attributed to J P Cain.

17 recordsLinked to original sources
PubMed2004

Exploring Ramachandran and chi space: conformationally constrained amino acids and peptides in the design of bioactive polypeptide ligands.

Ligand binding and concomitant changes in receptor structure provide the means to target signal transduction pathways. With appropriate refinement of the ligand's interaction with the "receptor," one in theory could produce ligands that have greater therapeutic benefits. This review will discuss how, when these ligands are amino acids and peptides, the introduction of appropriate conformational constraints provides a powerful strategy for improved drug design. This review will discuss how various constraints on amino acids can provide a powerful tool for ligand design, determination of the three dimensional pharmacophore and new insights into receptor systems and information transduction. Through the use of constrained ligands, new information regarding their interaction with their "receptor" systems, and further refinement of the use of constraints, scientists can produce more beneficial drugs for mankind.

Amino Acids↗
PubMed1986

Cardiac dysfunction during abdominal aortic operation: the limitations of pulmonary wedge pressures.

The mortality rate for elective abdominal aortic operations remains between 3% and 8% despite careful hemodynamic monitoring, and half of these deaths are cardiac in origin. An extensive evaluation of ventricular function was performed during abdominal aortic operation to detect subtle abnormalities in systolic or diastolic ventricular function that could precipitate progressive ischemic cardiac injury. Twenty-three patients undergoing elective abdominal aortic operations (14 patients with abdominal aortic aneurysm [AAA] and nine patients with aortoiliac occlusive disease [AIOD] ) had hemodynamic and nuclear ventriculographic measurements performed preoperatively, during aortic clamping, and immediately after aortic declamping. No differences were found in the hemodynamic response to operation between patients with AAA or AIOD. Volume loading was performed at each time period to assess ventricular function. Myocardial performance (the relation between cardiac index and end-diastolic volume index) and systolic function (the relation between systolic blood pressure and end-systolic volume index) were depressed during aortic clamping (p less than 0.05), suggesting decreased contractility, but returned to baseline values after declamping. Diastolic compliance (the relation between pulmonary capillary wedge pressure and end-diastolic volume index) decreased after declamping (p less than 0.05), suggesting early myocardial ischemia. The decrease in diastolic compliance rendered pulmonary capillary wedge pressure a poor index of left ventricular preload after declamping. Higher pressures were required to maintain adequate diastolic volumes. Despite careful hemodynamic monitoring, potentially ischemic ventricular dysfunction was found during abdominal aortic operation.

Aged↗
PubMed1976

Nelson's syndrome: frequency, prognosis, and effect of prior pituitary irradiation.

Previous reports differ regarding the frequency and course of pituitary tumors occurring after adrenalectomy for bilateral adrenal hyperplasia (Nelson's syndrome). In this report, 120 patients who were adrenalectomized for bilateral adrenal hyperplasia were followed for 2 to 20 years. Nine of the 120 developed Nelson's syndrome (8%), the tumors appearing 6 months to 16 years after adrenalectomy. In the majority of cases, the course was benign; seven patients are living an average of 9.7 years after discovery of their tumors. Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelson's syndrome. Twenty of 120 patients had pituitary irradiation as the initial treatment for bilateral adrenal hyperplasia and two subsequently developed pituitary tumors. Thus, after adrenalectomy for bilateral adrenal hyperplasia, all patients, regardless of previous pituitary irradiation, should be followed indefinitely with periodic X rays of the sella turcica for the possible occurrence of Nelson's syndrome.

Adolescent↗
PubMed1972

Glucagon-initiated human growth hormone release: a comparative study.

Human growth hormone (HGH) responses in 20 healthy adults to subcutaneous glucagon, arginine infusion and tolbutamide and insulin hypoglycemia were compared. HGH rose in all four tests. HGH response to glucagon was also studied in 49 patients with suspected pituitary insufficiency, of whom 25 also later received an arginine infusion; an abnormal response to glucagon was the most frequent functional abnormality and often HGH was the only anterior pituitary hormone of which a deficiency was detectable. In seven subjects (two healthy controls and five patients with suspected hypopituitarism) there was a subnormal HGH response to arginine but a normal response to glucagon. It is concluded that glucagon is a simple and effective stimulus to HGH release, equal or superior to arginine, tolbutamide and insulin, and is an important test of anterior pituitary function.

17-Hydroxycorticosteroids↗
PubMed1972

Studies of the control of plasma aldosterone concentration in normal man. I. Response to posture, acute and chronic volume depletion, and sodium loading.

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.

Adult↗