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Biomedical subjects

R M Weiss

Publications and source records attributed to R M Weiss.

At least 145 records · Page 8Linked to original sources

Effects of forskolin on contractility and cyclic AMP levels in rabbit detrusor muscle.

Forskolin caused a concentration-dependent relaxation and increase in cyclic AMP levels in rabbit detrusor muscle. Propranolol, a beta-adrenoceptor antagonist, did not affect the relaxation induced by forskolin. 3-isobutyl-1-metylxanthine (IBMX), a cyclic nucleotide phosphodiesterase inhibitor, potentiated the relaxation induced by forskolin. These data suggest that the relaxation of rabbit detrusor muscle induced by forskolin is mediated by cyclic AMP accumulation resulting from activation of adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

Characterization of functional beta-adrenoceptor subtypes in rabbit urinary bladder smooth muscle.

Spontaneous contractile force of muscle strips isolated from male rabbit urinary bladder dome (detrusor) and base (trigonal muscle) was significantly inhibited by isoproterenol (10(-7)-10(-5) M), a non-specific beta-adrenoceptor agonist or by terbutaline (10(-8)-10(-5) M), a selective beta 2-adrenoceptor agonist. The EC50 values for isoproterenol and terbutaline in detrusor were the same as those in trigonal muscle but the maximum relaxant response to isoproterenol or terbutaline was significantly greater in detrusor than in trigonal muscle. Dobutamine (10(-5)-10(-4) M), a relatively specific beta 1-adrenoceptor agonist caused a small but significant relaxant response in trigonal muscle but no change in detrusor. In trigonal muscle the relaxant response to dobutamine was less than that to terbutaline. The relaxant response to 10(-6) M isoproterenol in detrusor was completely blocked by butoxamine (10(-4) M), a selective beta 2-antagonist or by propranolol (10(-6) M), a non-specific beta-antagonist but not by metoprolol (10(-6)-10(-4) M), a selective beta 1-antagonist. Relaxation of trigonal muscle induced by 10(-6) M isoproterenol was inhibited by 10(-5) M metoprolol by 30%, by 10(-4) M butoxamine by 70%, or completely by 10(-6) M propranolol. These findings are consistent with the view that the density of beta-adrenoceptors is higher in the detrusor than in trigonal muscle, and that the relaxant response to beta-adrenoceptor stimulation is mediated by beta 2-subtype in the detrusor and by both of beta 1- and beta 2-subtypes in trigonal muscle of the male rabbit.

Animals↗

Age dependence of adenylate cyclase in guinea pig ureter homogenate.

Adenylate cyclase activity was measured in ureteral homogenates from guinea pigs of five age groups, ranging from neonates to older adults (retired breeders). Isoproterenol stimulation of adenylate cyclase activity is lost completely in ureters from 90 day and older animals. Forskolin activation also declines rapidly with increasing age; there is a significant (39%) decrease in activation at 30 days when compared to 10-day values with a further decline at 90 days. At 90 days, NaF, GTP and 5'-guanylimido-diphosphate stimulation of adenylate cyclase decreases by only 1, 9 and 23%, respectively, from the 10-day values. Prostaglandin E1 stimulation over 5'-guanylimido-diphosphate control does not decrease with age. 5'-Guanylimido-diphosphate in the presence of ethanol, activates adenylate cyclase to a greater extent in the older animals. These data may suggest that the decreased ability to activate adenylate cyclase with age may be due to a loss of the efficiency of coupling in the more rigid aged membranes. Other explanations include loss of catalytic function with age. The loss of adenylate cyclase activity in aging correlates well with our previously reported study showing that isoproterenol causes a greater decrease in contractility of ureters from younger than from older guinea pigs.

Adenylyl Cyclases↗

"On" and "off" responses of guinea pig ureter.

The in vitro guinea pig ureter responds to 5-s trains of electrical stimuli with two contractions: the first, an "on" response, occurs within 0.1-0.3 s after the onset of the stimulus train; the second, an "off" response, occurs 0.2-1.0 s after the termination of the stimulus train. Force decreases between the two responses during a time when the stimulus is still being delivered. Longer duration and/or higher frequencies of stimuli within the train are required to elicit the off response than the on response. Neither the on nor the off response appears to be neurally mediated, since both responses are unchanged by tetrodotoxin, phentolamine, atropine, and pyrilamine. Decreasing temperature from 37 to 22 degrees C decreases the amplitude of the on response and increases the amplitude of the off response. Calcium-free solution, 2 mM ethylenediaminetetraacetic acid (EDTA), 1 mM Mn2+, and 1 microM verapamil abolish the on response at a time at which the off response continues to persist. Conversely, 0.5 mM caffeine and 0.1 mM theophylline abolish the off response, whereas they only slightly reduce the on response. These data suggest that the on response depends on extracellular free calcium, whereas the off response is more dependent on bound or stored calcium.

Animals↗

The effect of serum dilution on free thyroxine (T4) concentration in the low T4 syndrome of nonthyroidal illness.

Progressive dilution of normal sera causes little change in free T4 concentrations. Similar dilution of sera containing drug inhibitors of T4 binding to serum proteins causes a progressive fall in free T4. The low T4 syndrome of nonthyroidal illness is thought to be associated with a circulating inhibitor(s) of T4 binding. It would be expected, therefore, that dilution of sera from the low T4 syndrome might also result in a fall in free T4 concentrations. We compared the effect of progressive serum dilution on free T4 concentrations in low T4 syndrome sera to those in normal, hyperthyroid, pregnancy, TBG-deficient and salicylate-containing sera. A tracer dialysis method proved inappropriate for studying dilution effects. Using a new dialysate RIA method to measure free T4, we found a progressive fall in free T4 concentrations in sera from patients with the low T4 syndrome similar to that in serum containing salicylate, but not to that in normal sera. The magnitude of the fall varied widely among individual patients. Free T4 methods which use a diluted serum sample will underestimate free T4 concentrations in the low T4 syndrome.

Adult↗

Effect of isoproterenol on contractile force of isolated rabbit renal pelvic smooth muscle.

Isoproterenol produced a concentration-dependent increase in contractile force of rabbit upper renal pelvic smooth muscle. Conversely, isoproterenol produced a concentration-dependent decrease in contractile force of rabbit lower renal pelvic smooth muscle. These data show that in response to isoproterenol upper renal pelvic smooth muscle, which is thought to act as a pacemaker region for pelviureteral peristalsis, resembles cardic muscles, whereas lower pelvic smooth muscle is similar to ureter and other smooth muscles.

Animals↗

Is renal ultrasound a reliable indicator of a nonobstructed duplication anomaly?

Twelve kidneys which had a non-obstructed duplication anomaly on excretory urography were studied sonographically. Ten of the twelve kidneys had a single central renal sinus echo complex; only two kidneys had a split sinus complex typical of duplication. Sonography is not a reliable technique to identify a nonobstructed duplication anomaly.

Adolescent↗

Force-velocity relationships of guinea pig ureter.

Longitudinal force-velocity relationships of the guinea pig ureter were studied in vitro in 3 age groups: 2 to 3 weeks, 2 to 3 months and 2 to 3 years. Velocity of shortening depends on the load lifted and not on the initial length of the muscle. Force-velocity relationships did not change with age, but the isometric force when the velocity is zero and no shortening occurs, increased with age. The shortening of the muscle, expressed as per cent of in vivo length, was independent of age and of preload. Therefore, work performed by a unit length of ureter which is the product of shortening and load lifted, and power which is the product of velocity and load lifted, are unaffected by age or by initial length. Thus there appears to be no significant age-related change in isotonic parameters of contraction such as velocity, shortening, work and power.

Aging↗

The hydrophobic moment detects periodicity in protein hydrophobicity.

Periodicities in the polar/apolar character of the amino acid sequence of a protein can be examined by assigning to each residue a numerical hydrophobicity and searching for periodicity in the resulting one-dimensional function. The strength of each periodic component is the quantity that has been termed the hydrophobic moment. When proteins of known three-dimensional structure are examined, it is found that sequences that form alpha helices tend to have, on average, a strong periodicity in the hydrophobicity of 3.6 residues, the period of the alpha helix. Similarly, many sequences that form strands of beta sheets tend to have a periodicity in their hydrophobicity of about 2.3 residues, the period typical of beta structure. Also, the few sequences known to form 3(10) helices display a periodicity of about 2.5 residues, not far from the period of 3 for an ideal 3(10) helix. This means that many protein sequences tend to form the periodic structure that maximizes their amphiphilicity. This observation suggests that the periodicity of the hydrophobicity of the protein primary structure is a factor in the formation of secondary structures. Moreover, the observation that many protein sequences tend to form segments of maximum amphiphilicity suggests that segments of secondary structure fold at a hydrophobic surface, probably formed from other parts of the folding protein.

Amino Acid Sequence↗

Effect of alpha adrenergic agonists and blockers on Purkinje fiber transmembrane potentials and automaticity in the dog.

Previous studies have shown that alpha adrenergic stimulation can reduce the automaticity of canine Purkinje fibers. In the present study, our interest was to determine whether this is an alpha-1 or alpha-2 adrenergic action. We used standard microelectrode techniques to study the effects of the alpha agonists, phenylephrine and clonidine, and the alpha antagonists, prazosin and yohimbine, on phenylephrine-induced decreases in automaticity. Prazosin and yohimbine, 1 X 10(-5) M, alone, significantly reduced the amplitude and upstroke velocity (Vmax) of stimulated action potentials. In addition, yohimbine, 1 X 10(-5) M, accelerated and prazosin, 1 X 10(-5) M, attenuated repolarization. Prazosin, 1 X 10(-5) M, and yohimbine greater than or equal to 1 X 10(-7) M, alone, decreased automaticity. Phenylephrine, 5 X 10(-8) M, alone, significantly increased the cycle length of automatic Purkinje fibers. The effects of phenylephrine on automaticity were blocked by prazosin but not by yohimbine. Clonidine, alone, 1 X 10(-6) and 1 X 10(-5) M, significantly reduced automaticity, an effect that was not blocked by yohimbine or prazosin. Clonidine, 1 X 10(-6) and 1 X 10(-5) M, also significantly reduced Vmax and prolonged action potential duration of driven Purkinje fibers, an action consistent with direct membrane effects. These experiments suggest that the negative chronotropic effects of phenylephrine on Purkinje fiber automaticity are mediated by alpha-1 adrenergic receptors.

Adrenergic alpha-Agonists↗

Characteristics of normal and refluxing ureterovesical junctions.

In order to quantitatively define the mechanism of urereterovesical junction (UVJ) competence and vesicoureteral reflux, we measured ureteral pressures using a continuously perfused catheter with a single side opening. Studies were performed under general anesthesia on 11 competent and 9 refluxing UVJs. The amplitude of ureteral contractions was essentially the same in refluxing and non-refluxing systems, but peristaltic frequency was significantly lower in the presence of even the milder forms of reflux. With the bladder empty, a high pressure zone was observed at the UVJ in both refluxing and non-refluxing systems, with no significant pressure difference between the 2 groups. No relaxation was observed during urine transport across the UVJ. With bladder filling, a greater increase in profile pressure occurred at the UVJ of non-refluxing than refluxing systems. The UVJ-bladder pressure gradient of non-refluxing systems increased with bladder filling, whereas the gradient in the refluxing systems decreased. It appears that refluxing ureters have a decreased peristaltic frequency and fail to maintain a pressure gradient at the UVJ with bladder filling.

Child↗