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Biomedical subjects

E E Slater

Publications and source records attributed to E E Slater.

At least 37 records · Page 2Linked to original sources
PubMed1986

Stimulation of DNA synthesis in rat A10 vascular smooth muscle cells by threonine-59 insulin-like growth factor I.

The clonal smooth muscle cell line A10, derived from fetal rat aorta, binds 125I-insulin-like growth factor I at a Type 1 insulin-like growth factor receptor. Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin inhibit the binding with IC50 = 10 nM, 84 nM, and 500 nM, respectively. Insulin in high concentrations (greater than 5 microM) completely inhibits 125I-insulin-like growth factor I binding to A10 cells. Threonine-59 insulin-like growth factor I and insulin stimulate [3H]thymidine incorporation into DNA in A10 cells that had been growth arrested by incubation in serum-free media (DMEM/0.1% BSA) for 24-36 hours. The stimulation produced by the peptides is 50-60% of the stimulation produced by 10% fetal calf serum. Low levels of serum (0.1 and 0.5%) also stimulate DNA synthesis, and the effects of Threonine-59 insulin-like growth factor I and low serum are additive. The ED50 for the effects of Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin are 6.8 +/- 0.3 nM, 36 +/- 2.5 nM, and 360 +/- 242 nM, respectively. Incubation of A10 cells for 24 hours with Threonine-59 insulin-like growth factor I or serum increases the protein content per culture dish by 85 +/- 21 and 183 +/- 26%, respectively (mean +/- SEM). Thus, both protein levels and DNA synthesis are increased by incubation with peptides. However, Threonine-59 insulin-like growth factor I does not increase the number of cells in serum starved cultures, although 10% fetal calf serum does.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Hemodynamic effects of synthetic atrial natriuretic factor (ANF) in dogs with acute left ventricular failure.

The hemodynamic and renal electrolyte/function effects of a synthetic peptide (ANF) corresponding to the sequence of the 26 amino acids contained in atrial natriuretic factor (ANF) were assessed in closed-chest dogs in which acute left ventricular failure was produced by coronary artery embolization with 50 micron plastic microspheres. Coronary embolization produced a sustained reduction in cardiac contractility (LV dP/dtmax) and cardiac output which averaged 42 and 44%, respectively. Following a 45 min equilibration period after heart failure induction, most of the hemodynamic functions stabilized. At this time, ANF infused intravenously at 100 pmol/kg per min X 30 min (n = 9) did not lower mean arterial pressure although it increased cardiac output (P less than 0.05) by 17% at only one time period. With the exception of a fall in coronary resistance and an increase in myocardial blood flow, a higher dose of ANF (200 pmol/kg per min) did not consistently alter hemodynamic function. Fractional excretion of sodium (FE Na%) increased 3.4-fold with ANF at 100 pmol/kg per min and 1.8-fold with the 200 pmol/kg per min dose. Neither dose of ANF produced significant effects on renal blood flow (RBF) or glomerular filtration rate (GFR). Plasma angiotensin II which was 91 +/- 20 fmol/ml at baseline increased to 175 +/- 25 fmol/ml (P less than 0.05) 45 min after heart failure induction. However, neither dose of ANF significantly reduced these high circulating angiotensin II levels. These results demonstrate that an infusion of a synthetic ANF stimulated saluresis without altering RBF or GFR, and improved cardiac output in dogs with acute left ventricular failure.

Angiotensin II↗
PubMed1985

The effects of somatostatin and selected analogs on lipid absorption in animals.

Based upon the clinical finding that a Merck somatostatin-14 (S-14) analog induced steatorrhea in man, we sought to develop animal models to study the effects of S-14 and a series of synthetic analogs on absorption. Rats were trained to eat a diet (preweighed) containing 15% fat. Following the feeding period, the remaining diet was removed and the amount consumed recorded. This food conditioning of the rats was continued until the rats consumed approximately 15 g of the diet per day. Feces were collected and weighed prior to feeding periods. On test days, S-14 or analogs were administered sc to rats immediately prior to feeding. For each compound tested, fat absorption decreased in dose-dependent fashion. For example, S-14 at 0.5 mg/kg did not increase % of dietary fat in feces (% DFF). At 1.0 mg/kg, S-14 increased % DFF from 7.9 to 10.2 (p less than 0.01, pretest day vs test day), and at 10 mg/kg S-14, % DFF increased from 9.1 to 12.8 (p less than 0.001). For each analog, the subcutaneous dose required to decrease fat absorption in rats was several orders of magnitude higher than the intravenous dose required to inhibit insulin and glucagon. Moreover, the threshold for production of statistically significant increases in fecal fat differed among analogs when compared to their endocrine potencies. One analog administered in the model for 14 days was shown to produce consistent fat malabsorption throughout the entire test period; however, this lipid malabsorption was substantially more pronounced on the first three days of the treatment period. When the compound was not administered on day 15, the % DFF significantly decreased. In an attempt to develop a system more suitable for rapid screening, pancreatic secretagogues such as secretin or cholecystokinin, were administered intravenously to anesthetized rats whose duodena had been cannulated and perfused to enable collection of pancreatic secretions. Total amylase, lipase, and protein were determined in single animals in response to a secretagogue, both before and after iv pretreatment by S-14 or an analog. Pancreatic enzyme secretion in response to sequential secretagogue-stimulation was found to be reproducible for up to three injections and behaved in a dose-dependent fashion. In general, secretagogue-induced increases in amylase, lipase, and total protein were comparable. Pretreatment with the S-14 analogs substantially inhibited secretagogue-induced pancreatic exocrine secretion and was dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Renin cleavage of a human kidney renin substrate analogous to human angiotensinogen, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, that is human renin specific and is resistant to cathepsin D.

A synthetic tetradecapeptide, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, which corresponds to the 13 amino terminal residues of human angiotensinogen plus a carboxy terminal serine to replace a suggested site of carbohydrate attachment, has been shown to be a good substrate for human kidney renin. At pH 7.2 and 37 degrees C the KM or Michaelis constant was 8.4 +/- 2.9 microM, and the VM or velocity at infinite tetradecapeptide concentration was 11.3 +/- 2.4 mumol angiotensin I made per hour per milligram renin. The tetradecapeptide was highly resistant to cleavage by mouse submaxillary renin. The tetradecapeptide was also slowly cleaved by human liver cathepsin D, by rabbit lung angiotensin-converting enzyme, and by reconstituted human serum, but did not yield angiotensin I. Thus, this synthetic renin substrate should permit more specific measurement of human kidney renin activity.

Amino Acid Sequence↗
PubMed1984

Long-term survival of patients with treated aortic dissection.

Retrospective data on the treatment of aortic dissection at the Massachusetts General Hospital from 1963 to 1978 are reported. During this period, 160 patients with spontaneous aortic dissection were treated by definitive medical or definitive surgical therapy. Patients were classified according to type (proximal versus distal) and duration (acute versus chronic) of dissection. Long-term follow-up (mean 48 months, range 1 to 147) was available in 156 cases. Hospital and late survival in each of the categories of dissection were evaluated in relation to those features of the dissection itself and of the subsequent therapy that correlated with ultimate survival. Results show that: 1) chronic presentation was the most significant determinant of both hospital and late survival; 2) in acute dissection, prognosis was determined largely by the presence or absence of major complications, regardless of ultimate therapy; the only complication without adverse effect on survival was aortic insufficiency; 3) late survival after discharge from the hospital was similar for patients with all types of dissection and modes of therapy; and 4) the incidence of late complications from aortic dissection was lower than previously reported. Thus, the success of early definitive medical and surgical treatment was sustained on long-term follow-up.

Acute Disease↗
PubMed1984

Renovascular hypertension.

Renovascular hypertension, the most common form of secondary hypertension, continues to present a variety of diagnostic and therapeutic dilemmas. This article briefly reviews the pathogenesis, etiology, natural history, and classification of the forms of renovascular disease and discusses available techniques for its diagnosis and treatment in adults.

Angioplasty, Balloon↗
PubMed1984

Antisera to human renin normalize renin-dependent hypertension in the monkey: therapeutic implications.

Polyclonal antisera raised against pure human renin normalize renin-dependent blood pressure elevation in the monkey (M. fascicularis). In vitro, comparable inhibition of either human or monkey plasma renin by the antisera was demonstrated. In vivo, intravenous infusion of 2 ml of antisera did not change mean arterial pressure of salt-repleted monkeys, however, its administration to salt-depleted monkeys with elevated plasma renin activity lowered mean arterial pressure 10 Torr. A 25 Torr rise in mean arterial pressure and increase in plasma renin activity occurred promptly after inflation of a suprarenal aortic cuff in conscious uninephrectomized monkeys. Administration of 2 ml of antisera to these monkeys normalized mean pressure, which was reduced by an additional 10 Torr if the animals were previously salt-depleted. Maximal hypotension occurred within 1 hour and was sustained for approximately 10 hours. Because of the differing specificities of polyclonal antisera, sera raised in two laboratories against human renin purified from different sources were employed. Identical results were obtained. This is the first demonstration of the use of antisera to inhibit endogenous renin activity in primates and predicts the in vivo efficacy of renin antisera as experimental, diagnostic and therapeutic agents.

Animals↗
PubMed1983

Adrenocortical hormone levels during cardiopulmonary bypass with and without pulsatile flow.

To determine the effect of hypothermic pulsatile and nonpulsatile cardiopulmonary bypass (CPB) with hemodilution on adrenocortical function we measured plasma levels of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin in two groups of patients. Group I, comprising 11 patients had routine CPB (nonpulsatile), and Group II, comprising 12 patients, had pulsatile flow during CPB (pulsatile). Both groups demonstrated comparable increases in cortisol, ACTH, and aldosterone with operation. Levels for all three hormones appeared to decline during CPB and then rose again in the post-CPB period. There were no significant differences between groups. Plasma renin activity gradually declined in a comparable manner in both groups. In the post-CPB period, renin activity was slightly higher in the nonpulsatile group (1.7 +/- 0.5 versus 0.8 +/- 0.2 ng/ml/hr, p less than 0.05). Correction for the effect of hemodilution demonstrated no decrease in cortisol and a slight increase in ACTH in both groups during CPB. Significant increases occurred in both groups during CPB in urinary Na+ excretion rate and urinary Na+/K+ ratio, more so for the nonpulsatile group. There was no correlation between urinary Na+/K+ ratios and either plasma cortisol or aldosterone levels. Thus routine CPB demonstrates no evidence of adrenocortical hypofunction and the addition of pulsatile flow produces little improvement.

Adrenal Cortex Hormones↗
PubMed1982

Cathepsin B from human renal cortex.

Cysteine-proteinase activity was observed in homogenates of human-cadaver renal cortex. This activity co-purified with renin enzymic activity until separation by aminohexyl-Sepharose--pepstatin affinity chromatography. The cysteine proteinase was purified 1780-fold after the following successive chromatographic procedures: Sephadex G-75, DEAE-cellulose DE-52, and an organomercurial affinity resin. The proteinase activity was dependent upon activation by thiol-containing compounds such as dithiothreitol, as well as by EDTA, and was inhibited by the thiol-group-specific alkylating reagents iodoacetic acid and N-ethylmaleimide. DE-52 cellulose chromatography resolved the cysteine proteinase into two components. On the basis of molecular size (26 000 daltons), activity as a function of pH, stability as a function of pH, substrate specificity and thermal lability, the major component (95%) has been identified as cathepsin B. The DE-52 cellulose elution pattern of the minor component (5%) is suggestive of cathepsin H [Schwartz & Barrett (1980) Biochem. J. 191, 487-497] Enzymic activity was determined with synthetic substrates, in particular alpha-N-benzoyl-DL-arginine 2-naphthylamide (Bz-Arg-NNap), thus precluding the detection of cathepsin L [Kirschke, Langner, Wiederanders, Ansorge, Bohley & Broghammer (1976) Acta Biol. Med. Germ. 35, 285-299]. Inhibition by dimethyl sulphoxide was observed in the determination of Km = 7.0 +/- 0.4 mM for the substrate Bz-Arg-NNap, and care must therefore be taken in the preparation of substrate solutions.

Cathepsin B↗
PubMed1981

Renin and angiotensin: the complete system within the neuroblastoma x glioma cell.

Cells of the homogeneous hybrid line neuroblastoma x glioma (NG108-15) have many neuronal properties. Immunocytochemical tests show that they contain both immunoreactive renin and angiotensin; direct radioimmunoassays show that they are positive for renin, angiotensin I, and angiotensin II; enzymatic assays show that they contain angiotensinogen and converting enzyme as well. The renin appears to be present in an enzymatically inactive form that can be activated by trypsin and then blocked by antiserum to purified mouse submaxillary renin. Renin concentration and activity are increased by enhancing cellular differentiation with dibutyryl cyclic adenosine monophosphate or by serum withdrawal. These findings demonstrate a complete renin-angiotensin system within these neuron-like cells, and suggest that activation of intracellular renin could generate angiotensin II.

Angiotensin I↗
PubMed1981

Pure human renin. Identification and characterization and of two major molecular weight forms.

Human renal renin was purified from normal kidney by either of two protocols which combined sequential DEAE-cellulose chromatography, pepstatin affinity chromatography, gel filtration, and a final step of affinity chromatography using either the synthetic octapeptide renin inhibitor (D-Leu6] or antirenin immunoglobulin as ligand. An approximate 500,000-fold purification and a yield of 1 mg of protein or 7% enzymatic activity from 10 kg were obtained by either method. Maximum specific activity was 1170 Goldblatt units/mg. Amino acid composition and kinetic properties were determined. Using purified angiotensinogen substrate, optimum pH was 5.5-6.0 and the Km was 1.54 X 10(-6) M. Two major forms of renin possessing similar enzymatic and immunologic properties, but differing in apparent molecular size and charge were purified and characterized. One form, the major form obtained after antibody affinity chromatography, had an apparent molecular size of 50 kilodaltons by sodium dodecyl sulfate-gel electrophoresis and migrated more slowly (RF = 0.32) on polyacrylamide disc gel electrophoresis at pH 7.8. The other form had an apparent molecular size of 39 kilodaltons and migrated more rapidly (RF = 0.76) on polyacrylamide disc gels. This smaller form predominated in protocols which allowed the persistent presence of acid protease activity throughout purification. Moreover, renin molecular size was demonstrated to change from 50 to 40 kilodaltons in the presence of this protease, which was subsequently isolated from the penultimate step of renin purification and tentatively identified as a renal cathepsin D. These findings help reconcile certain disparate characteristics for pure human renin obtained by others, explain the marked instability of the human enzyme, and suggest that the apparent molecular size of human renin is somewhat larger than had been previously reported.

Amino Acids↗
PubMed1981

Renin.

Explore the source record for details and available documents.

Animals↗
PubMed1981

Attenuation of the stress response to cardiopulmonary bypass by the addition of pulsatile flow.

The effect of pulsatile flow during cardiopulmonary bypass on the hormonal stress response was studied in 26 patients. Thirteen had routine and 13 had pulsatile bypass with an average pulse pressure of 30 mm Hg. Plasma vasopressin levels were significantly elevated during bypass in both groups, but were lower with pulsation (66 +/- 11 vs 36.3 pg/ml, p less than 0.05). Epinephrine levels increased in both groups during bypass, but were higher after bypass (1179 +/- 448 vs 713 +/- 140 pg/ml, p less than 0.05) and in the recovery room (1428 +/- 428 vs 699 +/- 155 pg/ml, p less than 0.05) in the nonpulsatile group. The same response was noted in the norepinephrine levels (924 +/- 225 vs 465 +/- 90 pg/ml, p less than 0.05; 1015 +/- 491 vs 717 +/- 112 pg/ml, p less than 0.05). There were no significant changes in renin activity in either group, but the increase after cardiopulmonary bypass was greater in the nonpulsatile group (2.0 +/- 0.7 vs 1.36 +/- 0.4 ng/ml/hr, NS). These data suggest that pulsatile flow significantly attenuates the vasopressin and catecholamine stress response to cardiopulmonary bypass. This may explain the increased flow requirements and better tissue perfusion and organ function and the decreased incidence of postoperative hypertension after bypass using pulsatile flow.

Blood Gas Analysis↗
PubMed1981

Renal function and stress response during halothane or fentanyl anesthesia.

The effects of anesthesia on hormonal stress response and renal function were measured before institution of cardiopulmonary bypass in two groups of patients undergoing elective coronary artery surgery. Group 1 (10 patients) received fentanyl, 100 microgram/kg, and N2O/O2; group 2 (12 patients) received halothane and N2O/O2. Patients in group 1 showed no significant changes in plasma levels of vasopressin, renin, or aldosterone during anesthesia or operation. This same group, however, demonstrated significant decreases in plasma levels of cortisol (8.4 +/- 1 to 4.2 +/- 1 microgram%, p less than 0.01), epinephrine (260 +/- 72 to 97 +/- 28 pg/ml, p less than 0.05), and norepinephrine (715 +/- 177 to 322 +/- 46 pg/ml, p less than 0.05) during operation. This was accompanied by an increase in urine volume (2.1 +/- 0.8 to 7.6 +/- 2 ml/min, p less than 0.05), a decrease in urine osmolality (610 +/- 82 to 166 +/- 60 mOsm/kg, p less than 0.01), and urine Na+ (54 +/- 12 to 16 +/- 4 meq/L, p less than 0.01) and no change in creatinine clearance. In contrast, in the group 2 patients during operation plasma levels of cortisol (11.7 +/- 2 to 31.1 +/- 2 microgram%, p less than 0.01), aldosterone (60 +/- 14 to 106 +/- 2 pg/ml, p less than 0.01), and vasopressin (10.4 +/- 1 to 23.3 +/- 3 pg/ml, p less than 0.01) all increased. This was accompanied by a significant decrease in creatinine clearance (148 +/- 52 to 92 +/- 12 ml/min/m2, p less than 0.05). The data demonstrate that high dose fentanyl anesthesia can significantly attenuate the hormonal stress response to operation and preserve renal function. They also suggest that decreases in renal function observed with anesthesia and operation may be a reflection of the hormonal changes associated with surgical stimulation.

Aldosterone↗
PubMed1980

Wide distribution of immunoreactive renin in nerve cells of human brain.

By use of the indirect peroxidase-antiperoxidase complex immunocytochemical technique, antibody to purified human renal renin was applied to formalin-fixed paraffin sections of human cadaver brain. Immune reaction products were observed in most nerve cells in all areas of the brain examined; staining was limited to the soma and proximal dendrites. These experiments have confirmed the presence of a renin-like substance in central nervous tissue and suggest a more generalized function for "brain renin" than was previously anticipated.

Adolescent↗
PubMed1980

Renal artery angioplasty versus surgery: a hypertensionologist's dilemma.

Percutaneous transluminal angioplasty for renovascular hypertension offers the potential for simple, safe, and relatively inexpensive therapy in certain categories of patients. The technique should be performed only under these conditions: (1) in centers with experience in angiography and angioplasty of peripheral vascular lesions; (2) with an experienced vascular surgical team standing by in case of surgical complications; (3) on lesions anatomically amenable to catheter dilation; and (4) on patients with prior proof of increased renin production on the affected side. Angioplasty is limited by the anatomy of the stenoses. Complications are similar to those of percutaneous angiography and occur with an estimated frequency of 5%-10%. Short-term patency is considered 70%-80%, somewhat lower than the surgical repair result. In all but certain cases where angioplasty offers a relative advantage, randomized controlled studies will be required to determine whether angioplasty or surgery should be the preferred method of therapy.

Adult↗