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Biomedical subjects

R Pratt

Publications and source records attributed to R Pratt.

At least 19 recordsLinked to original sources
PubMed1995

Effects of rapamycin on growth factor-stimulated vascular smooth muscle cell DNA synthesis. Inhibition of basic fibroblast growth factor and platelet-derived growth factor action and antagonism of rapamycin by FK506.

Rapamycin (RPM) is a potent and effective immunosuppressant which we have shown previously to inhibit intimal thickening in rat allograft and balloon-injured arteries. In this report, we have examined the effects of RPM on growth factor-induced vascular smooth muscle cell (VSMC) DNA synthesis. RPM potently inhibited platelet-derived growth factor (PDGF) (IC50 = 5 x 10(-9) M) and basic fibroblast growth factor (bFGF) (IC50 = 8 x 10(-10) M)-induced VSMC DNA synthesis. In contrast, only the highest concentrations of FK506 and CsA significantly altered PDGF- or bFGF-induced VSMC DNA synthesis. Addition of RPM (10(-9) M) at as late as 46 hr after growth factor addition still effectively suppressed bFGF- or PDGF-induced DNA synthesis by 76% and 54%, respectively. The extent of the antagonism of RPM's inhibition of bFGF-induced VSMC DNA synthesis by FK506 was inversely proportional to RPM concentration and directly proportional to FK506 concentration.

Animals↗
PubMed1995

Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney.

Natriuretic peptide receptor B (ANP-RGC(B)) has been previously identified in the kidney. It binds C-type natriuretic peptide (CNP) with high affinity and the two other natriuretic peptides (atrial natriuretic peptide and brain natriuretic peptide) with low affinity, and mediates the biological effects of CNP. The purpose of this investigation was to identify sites of ANP-RGC(B) mRNA in the rat renal tubule and to confirm that CNP itself is synthesized in the rat kidney. Kidneys from male Sprague-Dawley rats were removed and divided into cortex, outer medulla, and inner medulla. Using reverse transcriptase and polymerase chain reaction techniques, ANP-RGC(B) mRNA was identified in the three principal regions of the kidney. Individual glomeruli and segments of the renal tubule were microdissected and subjected to reverse transcriptase-polymerase chain reaction. ANP-RGC(B) mRNA was regularly found (>60% of animals) in glomeruli, distal convoluted tubule, and cortical, outer medullary, and inner medullary tubules but not in the proximal convoluted tubule, proximal straight tubule, thin or medullary thick ascending limb. ANP-RGC(B) mRNA was also identified in outer medullary descending vasa recta. Glyceraldehyde-3-phosphate-dehydrogenase and natriuretic peptide A receptor mRNA were present in all segments. In a separate study, CNP mRNA was identified in whole kidney, cortex, and medulla. These findings confirm that CNP and its receptor are present in the rat kidney. The proximity of the ligand and receptor suggests that CNP may have paracrine or autocrine regulatory functions in the rat kidney.

Animals↗
PubMed1994

Vascular injury augments adrenergic neurotransmission.

BACKGROUND: We have observed persistent desensitization to exogenous norepinephrine after balloon injury. We postulated that this desensitization may be due to a local increase in the release of neuronal norepinephrine. METHODS AND RESULTS: New Zealand White rabbits underwent left iliac artery angioplasty; 4 weeks later, both iliac arteries were harvested. Maximal response to exogenous norepinephrine was reduced in injured compared with noninjured vessels (12.3 +/- 1.0 g versus 10.3 +/- 1.5 g; n = 7, P = .056). By contrast, response to electrical stimulation (to induce neuronal norepinephrine release) was significantly greater in injured tissues (36 +/- 7% versus 14 +/- 3%; values expressed as percent of maximal contraction to exogenous norepinephrine; P = .025). Direct measurement of tissue norepinephrine revealed a threefold increase 4 weeks after injury (1236 +/- 410 versus 466 +/- 97 pg/mg; injured versus noninjured). To determine if desensitization to exogenous norepinephrine was due to a persistent increase in neuronal norepinephrine release, the experiments were repeated after chemical sympatholysis using 6-hydroxydopamine (6-OHDA) (65 mg/kg). To determine if activation of vascular angiotensin II contributed to facilitation of adrenergic neurotransmission, other animals received ramipril (RAM; 1 mg/kg per day). Both treatments were initiated 7 days before angioplasty. In the 6-OHDA group there was no evidence of desensitization, judged by maximal response to exogenous norepinephrine (7.5 +/- 0.6 versus 7.5 +/- 0.8, noninjured versus injured). Similar results were obtained in RAM animals (9.9 +/- 0.8 versus 9.6 +/- 1.2, noninjured versus injured). CONCLUSIONS: This is the first study to demonstrate enhanced adrenergic neurotransmission after balloon injury. The facilitation of adrenergic neurotransmission may be due to increased local concentrations of angiotensin II and is associated with desensitization to exogenous norepinephrine.

Angiotensin II↗
PubMed1994

Angiotensin as local modulating factor in ventricular dysfunction and failure due to coronary artery disease.

Congestive heart failure is the end product of a progressive series of events resulting from acute myocardial damage. Circulatory neurohormonal systems are activated during the acute phase of left ventricular dysfunction resulting from initial myocardial damage and again in the latter phase of decompensated heart failure. However, these neurohormonal mechanisms return to normal during the compensated stage of heart failure. Recent studies have suggested that autocrine/paracrine modulators of cardiovascular function are activated in the preclinical phase preceding the development of overt heart failure. The renin-angiotensin system in particular has been shown to modulate many of the chronic processes involved in the pathophysiology of cardiovascular disorders. Recent studies suggest that locally generated angiotensin II may contribute to the secondary structural changes seen in cardiovascular disorders, such as cardiac hypertrophy and remodelling, coronary artery disease, and atherosclerosis. Thus, inhibition of angiotensin formation with angiotensin converting enzyme (ACE) inhibitors, particularly at the tissue level, may provide valuable cardioprotective effects. Additional evidence points to the efficacy of ACE inhibitors in preventing the progression of asymptomatic left ventricular dysfunction to overt heart failure.

Angiotensin II↗
PubMed1994

Perfluorocarbon distribution to liver, lung and spleen of emulsions of perfluorotributylamine (FTBA) in pigs and rats and perfluorooctyl bromide (PFOB) in rats and dogs by 19F NMR spectroscopy.

Perfluorocarbon emulsion (FCE) particles are reported to be taken up by the reticuloendothelial system (RES) and ultimately eliminated by the lung. This distribution provides an opportunity to measure oxygen partial pressure in vivo with fluorine-19 magnetic resonance imaging (19F MRI). Since the MR image signal-to-noise ratio is directly proportional to the fluorine concentration in the tissue, a greater concentration of perfluorocarbon (PFC) in the tissue will result in a greater confidence in the oxygen image and reduce measurement time. It was postulated that the biodistribution of PFC administered in emulsion form may depend on species RES or FCE composition. The distribution of an emulsion (Oxypherol-E.T.) containing perfluorotributylamine (FTBA) 5 days after administration to pigs (11 g FTBA/kg body weight i.p.) and rats (19 g FTBA/kg i.p.) and an emulsion (Oxygent) containing perfluorooctyl bromide (PFOB) 7 days after administration to dogs (11 g PFOB/kg i.v.) and 5 days after administrations to rats (19 g PFOB/kg i.p.) was analyzed by F-19 NMR spectroscopy of tissue samples. PFC concentrations in spleen are 2 to 3 times those in liver. This pattern appears to be independent of PFC emulsion or species. In contrast, lung PFC content was less than that in the liver and showed a dependence upon both species and PFC emulsion.

Animals↗
PubMed1992

The natriuretic peptides and their receptors.

Atrial natriuretic factor (ANF) is released from the cardiac atrium in response to stretch and acts through receptors to cause an increase in urinary flow and sodium excretion, vasodilatation, and a reduction in blood volume. Recently, two new natriuretic peptides, brain natriuretic peptide (BNP) and C-type natriuretic peptide (C-typeNP), have been isolated, and three different natriuretic peptide receptors have been identified. Two of the receptors, ANP-RGC(A) and ANP-RGC(B), mediate biologic actions. The natural ligand of ANP-RGC(A) is ANF, whereas that of ANP-RGC(B) is C-typeNP. In view of clear differences in ligand specificity and tissue distribution of these receptors, it has been proposed that ANF and its receptor, ANP-RGC(A), and C-typeNP and its receptor, ANP-RGC(B), represent two distinct natriuretic peptide regulatory systems. Whether a separate system exists that incorporates BNP awaits clarification of its natural receptor that mediates a biologic action. The third receptor, ANP-Rc, binds all three natriuretic peptides. Its messenger RNA lacks the guanylyl cyclase sequence present in the mRNA of the other natriuretic peptide receptors, suggesting that the principal function of ANP-Rc is to remove natriuretic peptides from the circulation, that is, to regulate plasma levels of the natriuretic peptides. However, ANP-Rc may also mediate a biologic effect. These findings raise several intriguing questions about the functional role of this family of natriuretic peptides.

Animals↗
PubMed1990

Intrarenal angiotensinogen: localization and regulation.

Multiple lines of evidence (physiologic, immunohistochemical, and molecular biologic) support the presence of a complete intrarenal renin-angiotensin system (RAS). Localization of angiotensinogen messenger ribonucleic acid (mRNA) within the proximal tubule, together with demonstration of renin and converting enzyme mRNAs within the kidney, provide the most persuasive evidence for local, independent synthesis. Data from a combination of in situ hybridization studies, Northern analysis, and physiologic manipulations lead us to propose that a major site for action of a local RAS is the proximal tubule. There, locally generated angiotensins may regulate sodium reabsorption and urine pH. A variety of factors appear to regulate renal angiotensinogen. For instance sodium depletion increases the expression of renal angiotensinogen (as well as renin mRNA), as does high potassium intake and androgen administration. In pathologic states, such as experimental heart failure, and certain models of hypertension, such as the spontaneously hypertensive rat, expression of renal angiotensinogen mRNA levels is altered. It is proposed that changes in the intrarenal RAS may play a role in the maintenance of homeostasis and in the pathophysiology of various disease states.

Angiotensinogen↗
PubMed1988

Effects of sodium dodecylsulphate, dye concentration and paraprotein on coomassie blue dye-binding assays for protein in urine.

Various Coomassie Blue reagents, containing either increased dye concentration or added sodium dodecylsulphate, were compared with a biuret method for the assay of total protein in urine. When immunoglobulin free light chain protein or immunoglobulin paraprotein were present, results from the Coomassie Blue methods were up to 50% lower than with the biuret method; increased dye concentration did not improve comparability substantially, but the addition of sodium dodecylsulphate reduced the bias to about 20%. When neither free light chain protein nor immunoglobulin paraprotein was present, results from the Coomassie Blue methods were only about 30% lower. The addition of sodium dodecylsulphate reduced this bias to 10%. Correlations between the biuret and the Coomassie Blue method were best when the Coomassie Blue reagent contained 40 mg/L sodium dodecylsulphate (r better than 0.98 in all groups; p less than 0.001).

Binding, Competitive↗
PubMed1987

Mitochondrial creatine kinase in cancer patients.

We have developed a quantitative immunoassisted enzyme assay to screen for creatine kinase isoenzymes BB (CK-BB) and mitochondrial (CK-m) using commercial antibodies and reagents. Presence of CK-m activity was subsequently confirmed by electrophoretic separation of samples with elevated values. A prospective clinical trial was undertaken in 117 subjects: Normal (30), cirrhosis patients (30), myocardial infarction patients (30), and untreated oncology patients with metastatic malignancy (27). In 12 patients with malignancy CK-m activities were elevated; all had adenocarcinomas. No significant activity was detected in patients with other malignancies. CK-m positive tumour patients had a significantly higher mortality rate, and in two instances death was preceded by a sudden rise in CK-m activity. We suggest CK-m is a marker of adenocarcinoma and its presence in serum signifies increased mortality.

Adenocarcinoma↗
PubMed1986

Thyroid function tests in acutely ill patients. Comparison of analogue based free thyroid hormone assays with free thyroxine index.

A prospective study of 100 acutely ill patients was carried out to assess the value of the free thyroxine (FT4) assay as a replacement screening procedure for the free thyroxine index (FTI). We found that the FT4 assay was significantly influenced by the albumin concentration, so that the number of follow-up tests required increased markedly. This was especially true at the low end of the FT4 range where the need for thyrotropin assays increased by 162%. The free triiodothyronine (FT3) assay was also shown to be albumin dependent. It is not useful to replace one set of difficulties due to protein binding with another, and overall it was concluded that it is not cost-effective to screen hospital patients for thyroid dysfunction using free hormone assays based on labelled analogue techniques.

Humans↗
PubMed1984

Use of private offices in education of residents in internal medicine.

Of the 440 accredited residency programs in internal medicine, 129 assign residents to private offices. From this group, 29 program directors with 47 resident-preceptor teams matched to the same offices submitted a complete set of questionnaires for analysis. The results provide information concerning the selection process for this assignment, its design and development, the nature of the educational activities, and evaluation and financing. The results suggest that the private office may be an effective learning experience for medical residents and an underused educational resource. A particular strength of the experience may be the frequent and effective resident-preceptor interactions, which seem to focus mostly on problem identification and clinical decision making.

Ambulatory Care Facilities↗
PubMed1982

Functional hyposplenism, a diagnostic clue in amyloidosis. Report of six cases.

Six cases of functional hyposplenism associated with amyloidosis are presented. This association has been infrequently reported. Typical erythrocytic changes were found at initial presentation in five patients, and provided an early clue to the correct diagnosis. Extensive amyloid effacement of the splenic cords was the anatomic basis of the functional hyposplenism. Comments are made on the etiology and infective consequences of adult-acquired functional hyposplenism. A more sensitive method of screening peripheral blood for changes of functional hyposplenism is discussed.

Aged↗