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Biomedical subjects

J M Stewart

Publications and source records attributed to J M Stewart.

At least 127 records · Page 7Linked to original sources
PubMed1992

Chronic elevation of norepinephrine in conscious dogs produces hypertrophy with no loss of LV reserve.

Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak systolic wall stress, LV/end-diastolic diameter, or LV/end-systolic diameter during norepinephrine infusion. Diastolic and systolic wall thickness and chamber weights were increased (P less than 0.05). Indexes of diastolic function, including end-diastolic pressure, end-diastolic pressure-end-diastolic diameter relationship, maximum negative dP/dt, and the time constant (tau) were unchanged after chronic norepinephrine infusion, although maximum end-diastolic pressure during volume loading was increased from 17.7 +/- 2.0 to 21.7 +/- 1.0 mmHg. Chronic norepinephrine infusion did not alter tau, and tau increased equivalently with phenylephrine injection in both normal (36 +/- 1 to 62 +/- 5 ms) dogs and in those chronically infused with norepinephrine (36 +/- 1 to 56 +/- 5 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs.

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and hyperfiltration in the rat.

This study examined the role of tissue kallikrein and kinins in renal vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced total renal vascular resistance and increased glomerular filtration rate (GFR) by 25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated with a two- to threefold increase in urinary kinin excretion rate. Acute treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the rise in urinary kinins and prevented significant increases in GFR and RPF in response to AA. In a second group of rats pretreated with a B2 kinin receptor antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary kinins identically as in untreated controls, but GFR and RPF responses were absent. Aprotinin or the kinin antagonist produced no consistent change in renal function in rats that were not infused with AA.AA-induced increases in kinins were not associated with an increase in renal kallikrein activity. Notably, tissue active kallikrein level fell 50% in AA-infused rats. These studies provide evidence that kinins generated in the kidney participate in mediating renal vasodilation during acute infusion of AA.

Amino Acids↗
PubMed1992

Diversity of B2 bradykinin receptors with nanomolar affinity expressed in passaged IMR90 human lung fibroblasts.

IMR90 human fetal lung fibroblasts express bradykinin receptors activating the pathway for biosynthesis of PGE2. A receptor of the B2 subtype stimulates half-maximal PGE2 production at 4.8 nM bradykinin, and maximal output takes place at 25 nM bradykinin. Radioligand binding studies reveal a population of [3H]bradykinin binding sites whose affinity correlates with this B2 receptor's biologic activity, with a KD of 2.5 nM. As IMR90 cells reach 60% of their defined life span in culture, they spontaneously induce expression of a second site of lower affinity, with half-maximal binding of [3H]bradykinin at 44 nM. This second site displays a characteristic primary B2 receptor recognition profile, but differs from the 2.5 nM site on a secondary level in recognition among different B2 ligands. Bradykinin is the most potent ligand at both sites; they each preferentially recognize an N-terminal extended bradykinin peptide construct having selectivity for the rat myometrial B2 receptor, suggesting that both sites have structural features in common. However, they display diversity in their order of preference for Met-Lys-bradykinin versus Lys-Lys-bradykinin; at the 44 nM site this order is completely reversed from the order of potency exhibited at the 2.5 nM site. Expression of the second site changes the manner in which these fibroblasts control their PGE2 production; it affords a graded response of PGE2 production at bradykinin levels beyond those which would normally saturate the 2.5 nM site. The inducibility of the 44 nM site in cultured fibroblasts addresses in vivo conditions in an inflammatory environment where continuing generation of bradykinin-related peptides takes place and presents a possible mechanism for overriding constraints that would otherwise limit the progression of inflammation.

Amino Acid Sequence↗
PubMed1992

Influence of a kinin antagonist on acute hypotensive responses induced by bradykinin and captopril in spontaneously hypertensive rats.

We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.

Animals↗
PubMed1992

Paraneoplastic syndromes for the primary care physician.

To summarize, we have reviewed the major endocrine, hematologic, neurologic, dermatologic, and miscellaneous paraneoplastic syndromes. These entities are of great importance to the primary care physician because, when recognized, they can permit early diagnosis of the neoplasm. Further, treatment can afford palliation of symptoms. We can expect more definite identification of the causes of the paraneoplastic syndromes in the future because more of the substances that are released by tumors will be identified and analyzed. We need to watch with anticipation for the development of specific treatments for the paraneoplastic syndromes as the causes are identified.

Endocrine System Diseases↗
PubMed1992

Pharmacologic myocardial perfusion stress tests. Adenosine thallium stress test.

Thallium-201 myocardial perfusion scintigraphy assists in detecting coronary artery disease and assessing the significance of known stenoses. An adenosine infusion protocol is discussed in conjunction with presentation of results obtained in a community hospital setting. Primary indications for pharmacologic stress maneuvers include: Evaluation of patients unable or unwilling to exercise to adequate levels of workload and patients undergoing preoperative evaluation (particularly in patients undergoing vascular surgery). Experience in a community hospital setting attests to the safety of this pharmacologic protocol while showing a diagnostic accuracy similar to results reported in peer review literature. The method has been readily received by referring internists and cardiologists and is associated with a 21% increase in nuclear myocardial perfusion stress tests during the first six months of 1991.

Adenosine↗
PubMed1991

Position effect on apparent helical propensities in the C-peptide helix.

A search has been made for position effects on apparent helix propensities when another amino acid is substituted for alanine in the C-peptide helix of ribonuclease A. Three internal alanine residues (Ala4, Ala5, Ala6) are used as sites for substitution. Five amino acids, Glu, His, Arg, Lys and Phe, are substituted singly in individual peptides at each of these three positions, and the pH profiles of helix content for the substituted peptides have been determined. The effect of using an acetyl or a succinyl amino-terminal-blocking group has also been determined for each substitution. A strong position effect is found at Ala5: the helix content of the substituted peptide is significantly higher for substitution at position 5 than at positions 4 or 6 in almost all cases. The reason for the position 5 effect is unknown. The results also show that electrostatic interactions often influence substitution experiments, and they provide data on the variability of substitution experiments made with a natural sequence peptide.

Amino Acid Sequence↗
PubMed1991

Antagonist binding reveals two heterogenous B2 bradykinin receptors in rat myometrial membranes.

In rat myometrial membranes, two bradykinin binding sites with K1 values of 18 pM and 5.6 nM were identified. Three potent bradykinin antagonists were tested for their ability to compete for [3H]bradykinin binding. Two of them, D-Arg[Hyp3,Thi5.8,D-Phe7]bradykinin and [Hyp3,Thi5.8,D-Phe7]bradykinin, also bound to both the high- (KH) and the low-affinity (KL) site whereas [Thi5.8,D-Phe7]bradykinin identified only the low-affinity bradykinin receptor. There is a close correlation between the antagonistic potencies and the KL site affinities.

Animals↗
PubMed1991

Fatty-acid-binding protein facilitates the diffusion of oleate in a model cytosol system.

The proposed function of fatty-acid-binding proteins in facilitating the diffusion of their ligand has been examined in a cytosolic model using a steady-state diaphragm cell apparatus. The white muscle of ocean pout (Macrozoarces americanus) does not have a fatty-acid-binding protein: nor does it exhibit detectable beta-oxidative capacity, and as such is a good source of cytosol preparation. After determining the diffusion coefficient of oleate in this medium, fatty-acid-binding protein, isolated from the ventricle of this animal, was added and the apparent diffusion coefficient was again determined. The presence of the fatty-acid-binding protein increased the apparent diffusion coefficient of this long-chain fatty acid about 6-fold, from 0.087 x 10(-5) cm2.s-1 to 0.58 x 10(-5)cm2.s-1. This confirms the facilitated diffusion hypothesis as one role of fatty-acid-binding protein. The diffusion coefficients of oleate in 50 mM-sodium phosphate buffer, pH 7.4, at 10 degrees C and 25 degrees C (0.15 x 10(-5) cm2.s-1 and 0.28 x 10(-5) cm2.s-1 respectively) were also measured.

Animals↗
PubMed1991

Calorimetric determination of the enthalpy change for the alpha-helix to coil transition of an alanine peptide in water.

The enthalpy change (delta H) accompanying the alpha-helix to random coil transition in water has been determined calorimetrically for a 50-residue peptide of defined sequence that contains primarily alanine. The enthalpy of helix formation is one of the basic parameters needed to predict thermal unfolding curves for peptide helices and it provides a starting point for analysis of the peptide hydrogen bond. The experimental uncertainty in delta H reflects the fact that the transition curve is too broad to measure in its entirety, which precludes fitting the baselines directly. A lower limit for delta H of unfolding, 0.9 kcal/mol per residue, is given by assuming that the change in heat capacity (delta Cp) is zero, and allowing the baseline to intersect the transition curve at the lowest measured Cp value. Use of the van't Hoff equation plus least-squares fitting to determine a more probable baseline gives delta H = 1.3 kcal/mol per residue. Earlier studies of poly(L-lysine) and poly(L-glutamate) have given 1.1 kcal/mol per residue. Those investigations, along with our present result, suggest that the side chain has little effect on delta H. The possibility that the peptide hydrogen bond shows a correspondingly large delta H, and the implications for protein stability, are discussed.

Alanine↗
PubMed1991

Parameters of helix-coil transition theory for alanine-based peptides of varying chain lengths in water.

Thermal unfolding curves have been measured for a series of short alanine-based peptides that contain repeating sequences and varying chain lengths. Standard helix-coil theory successfully fits the observed transition curves, even for these short peptides. The results provide values for sigma, the helix nucleation constant, delta H0, the enthalpy change on helix formation, and for s (0 degree C), the average helix propagation parameter at 0 degree C. The enthalpy change agrees with the value determined calorimetrically. The success of helix-coil theory in describing the unfolding transitions of short peptides in water indicates that helical propensities, or s values, can be determined from substitution experiments in short alanine-based peptides.

Alanine↗
PubMed1991

Bradykinin-induced burst of prostaglandin formation in osteoblasts is mediated via B2 bradykinin receptors.

The receptor subtype mediating the bradykinin (Bk)-induced burst of prostaglandin formation in osteoblasts has been studied. Bk, but not des-Arg9-Bk, induced the formation of prostaglandin E2 and prostacyclin in neonatal mouse calvarial bones incubated for 30 minutes. Bk-induced prostaglandin synthesis is neonatal mouse calvarial bones was significantly inhibited by the B2 Bk receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk. The B2 Bk receptor agonists Bk and Lys-Bk, but not the B1 Bk receptor agonist des-Arg9-Bk, caused a rapid burst (5 minutes) of prostaglandin E2 and prostacyclin formation in isolated osteoblast-like cells from neonatal mouse calvarial bones and in the murine osteoblastic cell lineage MC3T3-E1. When comparing the relative potency of different kinin analogs on their stimulatory effect on prostaglandin formation in isolated osteoblast-like cells and in MC3T3-E1 cells, we found that Bk = Lys-Bk greater than Met-lys-Bk much much greater than Des-Arg9-Bk. Bk-induced prostaglandin synthesis in isolated osteoblast-like cells and in MC3T3-E1 cells was inhibited by D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk, whereas the B1 Bk receptor antagonist des-Arg9-Leu8-Bk had no effect. Total binding of 3H-Bk (3-20 nM; 4 degrees C) to whole MC3T3-E1 cells reached a maximum after 4-5 h. An excess of nonradioactive Bk (1 microM) reduced cell-associated radioactivity by 20-30%. The B2 Bk receptor agonist Bk and the B2 Bk receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]-Bk were able to reduce specific binding, but the B1 Bk receptor agonist des-Arg9-Bk was unable to reduce the specific binding of 3H-Bk to whole MC3T3-E1 cells. These findings indicate the presence of B2 Bk receptors on osteoblasts coupled to enhanced prostaglandin synthesis.

Amino Acid Sequence↗
PubMed1991

Noncardiac chest pain in adolescents and children with mitral valve prolapse.

Chest pain in adolescents and children is usually not of cardiac origin. Of cardiac conditions commonly linked to chest pain in childhood, mitral valve prolapse (MVP) is the most prevalent, but this association has recently been questioned. In light of recent reports of gastroesophageal sources of chest pain in adults with MVP, we performed a comprehensive gastroesophageal evaluation of 17 preadolescents and adolescents with mitral valve prolapse who had chest pain as their presenting symptom. Evaluation consisted of esophageal manometry, Bernstein test, esophageal pH probe, and/or esophagogastroscopy. Fourteen of the 17 patients had at least one abnormal finding. Five patients had esophagitis, five had gastritis, one had high-amplitude esophageal contractions, one had abnormal esophageal manometry with positive Bernstein test, one had esophageal reflux and positive Bernstein test, and one had abnormal manometry with esophageal reflux. The 13 patients with esophagitis, gastritis, reflux, or positive Bernstein test were treated with antacid, with resolution of chest pain in 12 patients. Two of these patients underwent follow-up endoscopy with documentation of improvement. The patient with high-amplitude esophageal contractions was treated with dicyclomine, which resulted in resolution of chest pain. The observation that the chest pain was not related to mitral valve prolapse is important in clinical practice and raises further questions as to whether mitral valve prolapse causes chest pain.

Adolescent↗
PubMed1991

Atrial compliance determines the nature of passive atrial stretch and plasma atrial natriuretic factor in the conscious dog.

STUDY OBJECTIVE: The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. DESIGN: Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. EXPERIMENTAL MATERIAL: Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. MEASUREMENTS AND MAIN RESULTS: During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. CONCLUSIONS: Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.

Animals↗
PubMed1991

Giardia lamblia and Cryptosporidium infections in child day-care centers in Fulton County, Georgia.

Risk factors for the introduction, spread and persistence of Cryptosporidium and Giardia lamblia infections in child day-care centers are not well understood. In 1989 and 1990 stool specimens were obtained from 292 diapered children attending 17 randomly selected day-care centers in Fulton County, GA; 8 (2.7%) children in 2 centers were infected with Cryptosporidium and 21 (7.2%) children in 7 centers were infected with Giardia. In 1986 the prevalence of Cryptosporidium and Giardia in these same centers had been 0.4 and 11.0%, respectively; the prevalence of Cryptosporidium, but not Giardia, increased significantly (P = 0.04) between 1986 and 1989 to 1990. Risk factors for Giardia infection included day-care attendance for greater than 3 months, the presence of toddlers in the classroom and the presence of other children in the household. Day-care centers with a Giardia-positive child in 1986 were not more likely to have an infected child in 1989 to 1990. Cryptosporidium, like Giardia, may be endemic in day-care centers in Fulton County.

Child Day Care Centers↗