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Biomedical subjects

R W Alexander

Publications and source records attributed to R W Alexander.

At least 217 records · Page 12Linked to original sources
PubMed1981

Angiotensin II stimulates phosphorylation of the myosin light chain in cultured vascular smooth muscle cells.

The vasoactive peptide angiotensin II stimulates phosphorylation of myosin light chain in 32P-labeled confluent cultures of vascular smooth muscle cells derived from rat mesenteric arteries. Myosin light chain was identified and its 32P-phosphorylation level quantitated following selective immunoprecipitation with an antiserum raised against purified human uterine smooth muscle myosin. Following exposure to 0.1 nM angiotensin II, phosphorylation of the light chain peaked at 4 min and then slowly decreased. The stimulation of light chain phosphorylation at 4 min is half-maximal at approximately 0.2 mM angiotensin II; the maximal response is approximately 210% of the unstimulated level. Basal myosin light chain phosphorylation was markedly reduced by incubation of cells with dibutyryl cyclic AMP or the calmodulin-inhibitor chlorpromazine. These data suggest that angiotensin II-mediated contraction in intact blood vessels involves phosphorylation of the myosin light chain, and that phosphorylation is inhibited by a cAMP-mediated process and may be calmodulin-dependent.

Angiotensin II↗
PubMed1981

Mechanisms and implications of vasodilator tolerance in the treatment of congestive heart failure.

Vasodilators play an important role in the treatment of the patient with severe heart failure and increased systemic vascular resistance. However, there are both clinical data and theoretic reasons to anticipate that some degree of tolerance may develop during the long-term use of most agents. The cause of the increased vascular resistance of heart failure is not completely understood, but it appears to be related to a number of neuroendocrine, molecular and physical mechanisms including increased activity of the sympathetic nervous and renin-angiotensin systems, and increased vascular stiffness due to intra- and extracellular sodium and fluid accumulation. Not surprisingly, a lowering of systemic vascular resistance either by direct smooth muscle relaxers or by blockade of specific neuroendocrine systems may result in a number of compensatory responses at the neuroendocrine and/or molecular level. The over-all effectiveness of a particular vasodilator is the net sum of its direct pharmacologic action, and the neuroendocrine and molecular responses to the drug. The specific compensatory mechanisms activated depend on several factors including the type of vasodilator used, the dose employed, the baseline neuroendocrine status of the patient, the severity of heart failure and the functional integrity of various reflex systems. Although not directly applicable to patients with heart failure, much information derived from the use of these agents to treat patients with hypertension and angina pectoris suggests several potential mechanisms by which tolerance may develop to virtually all classes of vasodilators. The major types of vasodilators are discussed with regard to their potential mechanisms of tolerance. Finally, the evidence currently available from long-term studies is reviewed in order to assess the potential relevance of vasodilator tolerance to the clinical management of the patient with heart failure.

Adrenergic alpha-Antagonists↗
PubMed1981

Late hepatic histopathology after jejunoileal bypass for morbid obesity. Relation of abnormalities on biopsy and clinical course.

Late biopsy results in 53 patients after jejunoileal bypass were reviewed and compared with 1 year postoperative biopsies. Patients were divided into groups based on clinical course and liver function tests. Of 24 patients with normal liver function tests and no clinical symptoms of liver failure, 8 (33 percent) had new or progressive lesions on late biopsy, while 1 of these 8 patients had cirrhosis. Thirty percent (6 of 20) of patients with liver function abnormalities but no evidence of liver failure showed evidence of progression on biopsy; 4 of these 6 patients had cirrhosis. Of those with clinical evidence of liver failure in the first year after operation, 44 percent had evidence of progression, but none had cirrhosis. Clinical parameters and liver function tests did not correlate with liver biopsies. In this series of patients, new and progressive lesions were found in the late postoperative period. Long-term serial biopsies are advisable in all patients after jejunoileal bypass to determine whether progressive deterioration in liver histology had occurred.

Biopsy, Needle↗
PubMed1980

Regulation by angiotensin II of its receptors in resistance blood vessels.

The sensitivity of blood vessels to the vasoconstrictor effects of the hormone angiotensin II appears to be modulated by the activity of the renin-angiotensin system. Elevation of circulating angiotensin II levels by sodium depletion or renal artery stenosis is associated with a diminished pressor response to infused angiotensin II (refs 1-3). Conversely, the vasocontrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading or nephrectomy. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth receptor for angiotensin II (refs 5-8). Modification of the interaction between angiotensin II and its vascular receptor, resulting in altered responsiveness to the hormone, could occur either via 'prior occupancy' of receptors by elevated levels of endogenous angiotensin II resulting in fewer free receptors available to respond to circulating angiotensin II (ref. 5), or, elevated levels of angiotensin II could result in a decrease in receptor affinity for the hormone or a decrease in total receptor number in the vascular smooth muscle cell. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature.

Angiotensin II↗
PubMed1980

Primary histiocytic lymphoma of bone: a light and ultrastructural study of four cases.

The light and ultrastructural features of primary histiocytic lymphoma of bone are indistinguishable from similar studies of respective cell types of nodular and diffuse large cell nodular and extranodal lymphomas. These ultrastructural features add further support to their lymphocytic histogenesis. There was no relationship between increasing nuclear clefts and convolutions in individual cases and the ultrastructural presence of increasing "histiocytic" features. Primary histiocytic lymphoma of bone is not a completely uniform monomorphic tumor cell population, but may vary in percentage of large noncleaved, large cleaved, large convoluted lymphocytic, histiocytic, and small atypical lymohocytic cells. Detailed study of four cases enabled division into two primary subgroups: Type I, consisting of a predominance of large noncleaved cells; and Type II, consisting of a mixture of cleaved, noncleaved, and convoluted cells. Further cases are being studied to determine whether these two groups are distinct or merely represent part of a continuous spectrum of cellular pleomorphism. In contrast to nodal lymphomas, there is no evidence at this time that proportional variations in the tumor cell population bear any relationship to biologic behavior or survival. Glycogen may be present in histiocytic lymphomas but was very rare (less than 1% total cells). Therefore, this feature as an isolated observation will not differentiate histiocytic lymphoma from Ewing's sarcoma.

Adult↗
PubMed1980

Reversible acute renal failure secondary to acute pyelonephritis.

We have described a case of reversible acute renal failure caused by acute pyelonephritis. In this entity, the kidneys are swollen by an interstitial infiltrate and edema, and white cell tubular casts and microabscesses may be present. Fractional excretion of sodium is high, and nephrotic proteinuria may occur without glomerular abnormalities. Recovery of renal function may occur if antibiotics are promptly instituted. Renal size generally decreases after recovery.

Acute Disease↗
PubMed1980

Inhibition of platelet function by organic nitrate vasodilators.

There is evidence that platelet activation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Since organic nitrate vasodilators are commonly used in coronary artery disease, we have studied the in vitro effects of these drugs on platelet function. Nitroglycerin, isosorbide dinitrate, and their biotransformation product, inorganic nitrite, inhibited platelet aggregation with collagen, epinephrine, arachidonate, and ionophore, and blocked both primary and secondary aggregation in response to ADP. Nitroglycerin was studied in more detail. Its inhibitory effect was reversible and not dependent on external calcium concentration. It inhibited arachidonic acid oxygenation as measured by the arachidonate-induced oxygen burst and malonaldehyde production. These effects were not due to an increase in intracellular cyclic AMP. This unusual generalized inhibition of platelet function by nitroglycerin possibly contributes to its beneficial effect in myocardial ischemia in part by attenuating platelet reactivity in the coronary circulation.

Adenylyl Cyclases↗
PubMed1980

Nodular pulmonary amyloidosis. Description of a case with ultrastructure.

A 64-year-old man with a suspicious asymptomatic coin lesion received a thoracotomy that showed two foci of isolated nodular pulmonary amyloidosis. Ultrastructural analysis verified the amyloid nature of the lesion and suggested that the fibrils were produced by plasma cells and processed by macrophages. The pathogenesis of this lesion is discussed in light of recent studies.

Amyloidosis↗
PubMed1980

Proliferative glomerulonephritis with crescent formation in behcet's syndrome.

Behcet's syndrome is a multisystem disease complex, the major manifestions of which are oral and genital ulcers, arthritis, uveitis, and skin eruptions. Less frequently, CNS disturbances, colitis, thrombophlebitis, large-vessel vaculitis, and myocarditis occur. If renal involvement does occur, it is usually manifested by asymptomatic microhematuria and/or proteinuria. Recently, renal amyloidosis and focal necrotizing glomerulonephritis with immune complex deposition have been described. We describe a patient with Behcet's syndrome who experienced diffuse proliferative glomerulonephritis with epithelial cell crescent formation in 75% of glomeruli examined. Immune complexes were not identified. Renal function, impaired on admission, improved with no therapy.

Behcet Syndrome↗
PubMed1979

Focal nodular hyperplasia of the liver with alcoholic hyalin bodies and cytologic atypia.

Focal nodular hyperplasia is an uncommon hepatic lesion in which the component hepatocytes are usually histologically normal. A case of focal nodular hyperplasia with cytologically atypical hepatocytes is presented. Light and electron microscopic evidence is given for the presence of alcoholic hyalin in these cells. A review of cytologic changes reported in focal nodular hyperplasia by others is included. To our knowledge, the presence of alcoholic hyalin in focal nodular hyperplasia has not previously been reported.

Aged↗
PubMed1979

Intravascular clotting preceding crescent formation in a patient with Wegner's granulomatosis and rapidly progressive glomerulonephritis.

Rapidly progressive glomerulonephritis is thought to be a proliferative reaction common to a number of disorders. Animal experiments implicate clotting or a product of it as its cause. In the human, the presence of fibrin in crescents, as well as the response to heparinization in some cases, support the role of coagulation in the genesis of extracapillary cell proliferation. We describe the clinical and histologic course in a patient with Wegener's granulomatosis who presented with a picture of intracapillary clotting which evolved into rapidly progressive glomerulonephritis. The patient had a remarkable return of renal function.

Adult↗
PubMed1979

Immunity to cell surface antigens and immune complex glomerulonephritis in hamsters bearing human epithelial tumors.

A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularity, electron-dense mesangial deposits, and mesangial deposits of immunoglobulin G and C'3. Renal eluates obtained from the tumor-bearing animals contained substantial amounts of immunoglobulins. Our immunopathological studies demonstrated that virtually all of the eluate immunoglobulin G was tumor-specific antibody directed exclusively against surface determinants of the MA160 cells. There was no demonstrable activity against cytoplasmic or nuclear constituents of the MA160 cells or against certain hamster antigenic determinants. The antibody in the eluate could be removed by repetitive absorptions with viable MA160 cells but not with similar absorptions with either normal human diploid fibroblasts, human heteroploid HeLa cells, or BHK21 hamster cells. Our data support the concept of a specific nephritogenic immunopathological process occurring as a result of immunity to tumor-specific surface determinants.

Adenoma↗