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Biomedical subjects

T L Wu

Publications and source records attributed to T L Wu.

At least 19 recordsLinked to original sources

Vectorcardiography in experimental myocardial infarction. Serial changes and correlation between QRS loop change and the infarction size.

The objectives of this study were to examine the serial vectorcardiographic changes following acute myocardial infarct and to assess the relationship between QRS loop changes and infarct size. Fifty adult male Long-Evans rats of 250-350 gm body weight were used to study experimental acute myocardial infarction induced by coronary artery ligation. Vectorcardiograms (VCG) of the Frank lead system were recorded before, and 1 day and 7 days after operation. Animals were sacrificed on the 7th day for histological quantitation of infarct area ratios. We found that (1) before operation, rats have ST elevation, probably due to early repolarization. (2) After coronary artery ligation, ECG showed characteristic dome-shaped ST elevation at 1 hr after ligation which returned to normal during the first day. Abnormal Q waves appeared thereafter. (3) After ligation, maximum QRS vector, ST vector and maximum T vector were reduced in magnitude the first day and recovered by the 7th day. The vectors tended to shift their direction to the right and to the posterior. QRS-T angle, however, widened as time went on. About half of the rats revealed changes in the inscription direction of the QRS loop and abnormal QRS morphology also appeared in about half of the ligated rats. (4) Those in whom abnormal QRS loop morphology and/or biting appeared had significantly larger infarct area ratios (p < 0.01). (5) Change in QRS loop inscription direction seemed not to be related to the infarct size. (6) In the LS plane, the difference in max QRS vector magnitude between the 1st and 7th days significantly correlated with the infarct area ratio (r = 0.533, p < 0.05). In the H plane, the change in the max QRS vector magnitude at the 7th day correlated with the infarct area ratio (r = -0.531, p < 0.05). In the F plane, changes in the direction of the max QRS vector were significantly correlated to the infarct area ratio both on the first (r = 0.431, p < 0.05) and 7th days (r = 0.531, p < 0.05). It is concluded that the VCG, like the ECG, had evolutional changes in AMI and that the QRS loop seen on vectorcardiography has only a slight correlation with the histological myocardial infarct size.

Animals

A comparison of antihypertensive effects between two formulations of atenolol: tenolol and tenormin.

BACKGROUND: Atenolol is a cardioselective beta-blocker. Tenolol is a new formulation of atenolol, with bioequivalence to the original atenolol (Tenormin). This study was designed to compare the antihypertensive effects between the two formulations of atenolol, Tenolol and Tenormin. METHODS: Twenty-three patients, with mild to moderate hypertension untreated with any antihypertensive drugs, were recruited. They were randomized to receive two weeks of placebo, four weeks of Tenolol or Tenormin (100 mg once daily) and two weeks of placebo. Then the treatments were crossed over for four more weeks. RESULTS: At two weeks five patients were excluded because their blood pressures (BP) were below 160/90 mmHg. The baseline BPs for the patients receiving Tenormin (162 +/- 18/97 +/- 8 mmHg) and Tenolol (164 +/- 17/97 +/- 9 mmHg) were not distinct. After two weeks of treatment with Tenormin or Tenolol, systolic BPs decreased by 12 +/- 11 mmHg and 13 +/- 14 mmHg, respectively (p < 0.01 for both formulations). Similarly the diastolic BPs decreased significantly (p < 0.01) by 7 +/- 9 mmHg and 7 +/- 10 mmHg, respectively. The hypotensive effects persisted at four weeks of treatment for both formulations. Reductions in systolic and diastolic BPs by treatment with Tenormin and Tenolol were not significantly different by two-way ANOVA analysis. There were no side effects in any patient throughout the study. CONCLUSIONS: The results indicate that the generic formulation of atenolol (Tenolol) has comparable antihypertensive effects as the original formulation (Tenormin).

Adult

Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types.

The cDNA-predicted amino acid sequence of parathyroid hormone-related protein (PTHrP) contains multiple basic amino acid motifs, suggesting that PTHrP undergoes extensive post-translational processing prior to secretion. The secretory forms of the peptide are currently unknown. To identify these secretory forms, medium was harvested from three cell types: human renal carcinoma (SKRC-1) cells, human keratinocytes, and rat insulinoma cells stably transfected with the cDNA for PTHrP(1-141) (RIN-141 cells). Amino-terminal species were immunopurified using an anti-PTHrP(1-36) column, and mid-region species using an anti-PTHrP(37-74) column. PTHrP peptides in medium and in cell extracts were further resolved by reverse phase high performance liquid chromatography (RP-HPLC) and identified using region-specific immunoassays. SKRC-1 and RIN-141 cells secreted three distinct amino-terminal species and a novel, non-amino-terminal, mid-region fragment. Sequence and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the RIN-141 cell mid-region fragment begins at amino acid 38 of the cDNA-predicted sequence and is approximately 70 amino acids in length. Comparison of RP-HPLC elution patterns suggests that SKRC-1 cells and keratinocytes secrete a similar or identical mid-region fragment. Immunofluorescence studies revealed a Golgi pattern for the amino-terminal species and a secretory granule pattern for the mid-region fragment. These studies indicate that 1) multiple PTHrP species are secreted, including a novel mid-region fragment; 2) Arg37 serves as a cleavage site in at least three cell types; 3) PTHrP(1-36) is likely to be an authentic secretory form of PTHrP; and 4) the mid-region fragment appears to be packaged into secretory granules. The marked interspecies conservation of this mid-region PTHrP suggests that it will have important biological functions.

Amino Acid Sequence

Characteristic abnormal features of body surface potential maps predictive of ventricular tachycardia following coronary artery occlusion in dogs.

In a search for features predictive of ventricular arrhythmias in myocardial ischemia, the body surface potential maps of 17 dogs with coronary artery occlusion were studied. Ventricular tachycardia occurred in 9 (53%) of the 17 dogs. Multiple distribution of the abnormal potential minimum was found in 6 (67%) of the 9 dogs with (group A) and none of the 8 dogs without ventricular tachycardia (group B). The difference was statistically significant (p less than 0.01). The abnormal "early reversal" phenomenon of potential distribution was observed in 6 (67%) of group A and 7 (88%) of group B. The difference was not statistically significant (p greater than 0.05). The area of abnormal negative potential was 28.0 +/- 8.5 cm2 for group A and 14.5 +/- 5.5 cm2 for group B (p less than 0.001). The abnormal negative potential lasted for 25.4 +/- 3.5 ms in group A and 10.1 +/- 5.1 ms in group B (p less than 0.001). The abnormally early appearance of potential minimum lasted for 24.2 +/- 5.1 ms in group A and 10.5 +/- 5.4 ms in group B (p less than 0.001). The data suggest that the distribution, area, and duration of the abnormal negative potential of the body surface potential map are useful in the prediction of ventricular tachycardia associated with coronary artery occlusion.

Animals

Holter monitoring in patients with Wolff-Parkinson-White syndrome: with special reference to intermittent pre-excitation.

To characterize the intermittency of pre-excitation in patients with Wolff-Parkinson-White syndrome (W-P-W), we studied the ambulatory electrocardiograms (ECGs) of 48 patients (32 men and 16 women with a mean age of 38.5 years) with W-P-W. As documentation, at least one ECG for each patient had been performed during the follow-up period at our clinics. All cardiovascular drugs were discontinued for at least two days before Holter ECG monitoring. Through a careful beat-to-beat analysis of the QRS complex morphology, we were able to classify these patients into three groups: persistent pre-excitation in 26 (54.2%); intermittent pre-excitation in 17 (35.4%); and no pre-excitation in five (10.4%). There was no significant difference in sex, frequency of arrhythmias or mean heart rate among the three groups. Among the 17 showing intermittent pre-excitation, type A W-P-W was more prevalent (12 cases), and the ratio of pre-excitation to normal beats tended to decrease with age. Conduction normalized gradually with an increase in heart rate in 12 patients and suddenly in five other cases. There were two patients who showed a period of 2:1 pre-excitation intermingled with 1:1 pre-excitation and 1:1 normalized beats. These changes occurred with equal frequency both during the daytime and at night. These findings suggest that intermittent pre-excitation is a rather frequent phenomenon in patients with W-P-W. It occurs more frequently in type A patients and in older patients. Therefore, it may be an intermediate phase between manifest and concealed W-P-W.

Adolescent

Peripheral and intracardiac concentrations of atrial natriuretic peptide in patients with heart disease.

To study the relationship between the plasma concentration of the atrial natriuretic peptide (ANP) and heart function and to discern the secretion pathway of ANP, we determined the peripheral plasma concentration of ANP in 18 heart patients and the intracardiac concentration of ANP in six heart patients during cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge by acid alcohol. The concentration of ANP was determined by a sensitive and specific radioimmunoassay method. We found that the plasma ANP concentration (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was statistically higher than that in normal adults (ranging from 8 to 20, mean = 12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was inversely correlated with the left ventricular ejection fraction (r = -0.53, p less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107 +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is mainly secreted via the coronary sinus into the atrial cavity. The peripheral plasma ANP concentration is higher in heart patients. It increases as the left ventricular ejection fraction decreases. Therefore, plasma ANP concentration may be a useful indicator for the assessment of cardiac function.

Adolescent

Detection of enterovirus RNA in patients with idiopathic dilated cardiomyopathy by polymerase chain reaction.

The pathogenic role of enterovirus in patients with idiopathic dilated cardiomyopathy has been determined through a molecular biologic approach. Sensitivity in the detection of viral genomes in tissues varied between conventional nucleic acid hybridization and polymerase chain gene amplification. To improve diagnosis, we developed a strategy for reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA. We synthesized two sequence-specific oligonucleotides, primer 1 (5'dACCGACGAATACCACTGTTA3') and primer 2 (5'dCCTCCGGCCCCTGAATGCGGCTAAT3'), complementary to the 5' conserved viral genomic fragments. Viral RNA was amplified by double PCR with these two primers and hybridized with a 32-P labeled inter-primer probe (5'dATGAAACCCACAGGCACAAAG3'). Using this strategy, we detected as little as 10(-8) micrograms of coxsackievirus B3 RNA after amplification with RT-PCR, but detected none in the plasma of eight healthy adults. Among 15 patients with idiopathic dilated cardiomyopathy, viral RNA could be detected in one out of 12 plasmas (8%) and three out of four explanted heart tissues (75%). In contrast, no viral RNA could be detected in six samples of myocardial tissue from patients with other heart diseases. The only patient who had viral RNA in his plasma also had viral RNA in his myocardium. Thus, the high incidence of viral RNA in these patients suggests a possible etiologic link between them. Correct selection of specific PCR primers and the application of double PCR can improve chances of diagnosing enteroviral infection.

Adolescent

Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone-related protein.

Parathyroid hormone (PTH) and PTH-related proteins (PTHrP) interact with a common receptor in rat bone cells and in canine renal membranes with similar affinity, but PTHrP are substantially less potent than PTH in stimulating adenylate cyclase in canine renal membranes; in contrast, PTH and PTHrP are equipotent in stimulating adenylate cyclase in rat bone cells. This discrepancy has been largely viewed as reflecting differences in the relative efficiency of signal transduction of PTHrP between bone and kidney assay systems. To test the alternative (but not mutually exclusive) hypothesis that these differences could reflect interspecies differences in PTH receptors, we have characterized the bioactivity of amino-terminal PTHrP and PTH in rat and human renal cortical membranes (RCM) and compared them to results we previously reported in canine RCM. The stability of PTH and PTHrP peptides under binding and adenylate cyclase assay conditions was greater than 80% for each species. Competitive inhibition of [125I](Tyr36)hPTHrP-(1-36)NH2 binding to rat RCM by bPTH-(1-34) and (Tyr36)hPTHrP-(1-36)NH2 yielded nearly identical binding dissociation constants (3.7 and 3.6 nM, respectively), and binding to human RCM demonstrated slightly greater potency for PTHrP (0.5 nM) than for PTH (0.9 nM). Similarly, adenylate cyclase stimulating activity was equivalent for the two peptides in rat RCM, but PTHrP was twofold more potent than PTH in human RCM. Covalent photoaffinity labeling of protease-protected rat RCM yielded an apparent 80 kD receptor protein, and cross-linking of human RCM labeled an 85 kD receptor, indistinguishable in size from the canine renal PTH receptor. We conclude that rat, canine, and human renal cortical PTH receptors exhibit species specificity. The previously observed differences between rat bone cells and canine renal membranes in the efficiency of signal transduction by PTHrP may be explained, at least in part, by these species differences.

Adenylyl Cyclases

Immunoaffinity purification of parathyroid hormone-related protein from bovine milk and human keratinocyte-conditioned medium.

Parathyroid hormone-related proteins (PRHrP) are a novel family of proteins that appear to be responsible for humoral hypercalcemia of malignancy. Although PTHrP derived from human tumors have been purified and their N-terminal amino acid sequence determined, and although the structure of the PTHrP gene and its alternatively spliced mRNA transcripts have been defined, the secretory and circulating form(s) of the protein are unknown. Purification of PTHrP in the past has been difficult, requiring multiple chromatographic steps and months or years to complete. To define naturally occurring PTHrP species we have developed a rapid and efficient immunoaffinity purification method. Bovine milk (250 ml) and human keratinocyte-conditioned medium (3000 ml) were affinity purified using a 300 microliters affinity-purified polyclonal anti-PTHrP-(1-36) antibody column and a single RP-HPLC step. Purification required only 7-10 days and yielded a 3-4% recovery. Quantities of PTHrP sufficient for silver-stained SDS-PAGE, Western analysis, and N-terminal amino acid sequence were obtained. In contrast to conventional purification schemes, affinity purification of PTHrP is rapid and efficient and can be applied to biologic samples that contain PTHrP in low abundance. These methods can be applied to the purification and characterization of the as yet undefined secretory and circulating forms of PTHrP.

Animals

Glycosylation of parathyroid hormone-related peptide secreted by human epidermal keratinocytes.

While the gene and mRNA transcripts encoding PTH-related peptide (PTHrP) have been well characterized, the actual secretory form(s) of the peptide is unknown. Accordingly, synthetic and recombinant PTHrPs employed to date for biological and immunological characterization have necessarily been of arbitrary lengths. No prior evidence for glycosylation of PTHrPs has been described. To define the naturally occurring form(s) of this peptide secreted by human epidermal keratinocytes, we have affinity purified, using an anti-PTHrP-(1-36) antibody column, human PTHrP secreted under conditions of protease protection. Human keratinocyte-conditioned medium collected without measures to protect against proteolytic degradation contains multiple PTHrP immunoreactive and bioactive species. In contrast, under conditions of protease protection, human keratinocyte-conditioned medium contains a single 18,000 mol wt (Mr) form of the peptide. In contrast to recombinant and synthetic PTHrPs, which migrate as distinct, well focussed bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, this 18,000 Mr PTHrP displays the broad electrophoretic profile of a glycoprotein. Treatment of this peptide with trifluoromethanesulfonic acid, an agent that deglycosylates both O- and N-linked saccharides from their core proteins, shifted the Mr of the protein to approximately 10,000. In contrast, exposure of recombinant PTHrP-(1-141) to the same agent results in no change in electrophoretic mobility. These studies indicate that the 18,000 Mr species of PTHrP secreted by human epidermal keratinocytes is a glycoprotein.

Blotting, Western

Molecular cloning of complementary deoxyribonucleic acid (cDNA) for the rat atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) is a cardiac hormone with an important role in fluid, electrolyte and hemodynamic homeostasis. Rat ANP cDNA was cloned from the cDNA library constructed using 1 microgram of atrial mRNA from the heart of Wistar rats. Eight positive clones were isolated with an ANP oligonucleotide probe. One of them with about a 0.8 kb insert was selected for further subcloning and sequencing analysis. The rat ANP cDNA had 813 base pairs with a concensus sequence for transcription initiation, termination and poly A tailing. The deduced amino acid sequence contains a potential glycosylation site and two putative protease cleavage sites. Northern blot analysis showed that the ANP gene was specifically transcribed in the rat atria rather than the ventricles. The results suggest that ANP gene expression is differentially and developmentally controlled.

Amino Acid Sequence

Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer.

Tumors from patients with humoral hypercalcemia of cancer produce a parathyroid hormone-related protein (PTHRP). We have developed two region-specific immunoassays capable of measuring PTHRP in plasma: an immunoradiometric assay directed toward PTHRP amino acid sequence 1 to 74 and a radioimmunoassay directed toward PTHRP amino acid sequence 109 to 138. Sixty normal subjects had low or undetectable plasma PTHRP (1 to 74) concentrations (mean, 1.9 pmol per liter) and undetectable PTHRP (109 to 138) concentrations (less than 2.0 pmol per liter). Patients with humoral hypercalcemia of cancer (n = 30) had elevated levels of both PTHRP (1 to 74) (mean, 20.9 pmol per liter) and PTHRP (109 to 138) (mean, 23.9 pmol per liter). The plasma concentrations of immunoreactive PTHRP correlated with the levels of urinary cyclic AMP excreted; in some patients, the concentrations decreased after the tumors were resected. Patients with chronic renal failure (n = 15) had plasma PTHRP (1 to 74) concentrations similar to those in the normal subjects, but their plasma PTHRP (109 to 138) concentrations were elevated (mean, 29.6 pmol per liter). The levels of both peptides were normal in patients with hyperparathyroidism and those with hypercalcemia due to various other causes. Breast milk contained high concentrations of PTHRP. An anti-PTHRP (1 to 36) immunoaffinity column failed to extract PTHRP (109 to 138) immunoactivity from plasma, suggesting that the C-terminal region circulates as a separate peptide. We conclude that plasma PTHRP concentrations are high in the majority of patients with cancer-associated hypercalcemia and that the circulating forms of PTHRP in such patients include both a large N-terminal (1 to 74) peptide and a C-terminal (109 to 138) peptide. Measuring the concentrations of PTHRPs may be useful in the differential diagnosis of hypercalcemia.

Adult

The value of body surface potential maps in detecting abnormal ventricular wall motion.

In an effort to enlarge the clinical application of body surface potential maps (BSPMs), the authors studied the relationship between abnormal ventricular wall motion and BSPMs in 98 consecutive patients with angiographically proven coronary artery disease (CAD). Forty-nine of the patients (50%) had wall motion abnormalities as seen on single-plane left cine ventriculograms. During early ventricular depolarization, normal BSPMs have a potential maximum that is greater than the absolute value of the potential minimum; this reverses in late depolarization such that the absolute value of the potential minimum is the greater. The patients showed a significantly early reversal (p less than 0.001), and 55 (56.1%) had abnormal "early reversal" BSPMs. This abnormal "early reversal" is closely related to abnormal ventricular wall motion. Using it as an indicator of abnormal wall motion, the authors obtained the sensitivity, specificity, positive predictive value, and negative predictive value of the following conditions: LAD lesions, LCX, RCA, LAD and RCA lesions, LAD and LCX, and three-vessel disease, and for all patients. A relatively high sensitivity (85%) and specificity (80%) was found in patients with LAD lesions only or multivessel lesions in addition to LAD lesions.

Adult

The value of body surface potential maps in assessment of experimental myocardial infarction.

Body surface potential maps (BSPMs) and the pathology of 32 dogs with coronary artery ligations were analyzed to research the application of BSPMs to acute myocardial infarction (AMI). The group consisted of 18 dogs with left anterior descending coronary artery (LAD) ligations, 8 with right coronary artery (RCA) ligations and 6 with left circumflex coronary artery (LCX) ligations. The abnormal distribution of negative potential and minimal potential were observed in all of the dogs. In dogs with RCA ligations, the abnormal negative potential displayed on the right-superior, right-inferior or right portion of the anterior thorax. In those with LAD ligations, the abnormal potential appeared on the left-superior, left-inferior, middle-superior or middle portion of the anterior thorax. In those with LCX ligations, the abnormal potential showed on the left-superior or left-middle portion of the thorax. A good correlation was observed between the area of myocardial lesion and the extent of abnormal negative potential distribution (r = 0.82, p less than 0.001). A close correlation was also found between the area of myocardial lesion and the duration of abnormal negative potential (r = 0.61, p less than 0.05). This study suggests that BSPMs are useful in the assessment of AMI in terms of diagnosis, location and extent of myocardial infarct.

Animals

Hemodynamic significance of vectorcardiographic pattern in patients with mitral stenosis.

Vectorcardiographic (VCG) studies were conducted in 71 patients with pure mitral stenosis (MS) documented by clinical findings, echocardiograms and cardiac catheterization. Among them, 31 were males and 40 females, with ages ranging from 20 to 58 (mean age 36.3) years. The Frank lead system was adopted for the VCG study. By VCG, 67 patients (94.4%) showed right ventricular hypertrophy (RVH), among whom 15 (21.2%) were type A, 30 (42.3%) type B and 22 (31.0%) type C. Forty-five patients (63.4%) were in sinus rhythm (NSR), while the remaining 26 (36.6%) were in atrial fibrillation (AF). Patients with type A RVH had a significantly higher pulmonary wedge (PAW) and main pulmonary arterial (MPA) pressures than those with type B or C. Patients with type C had a higher mean MPA pressure (39.0 +/- 11.3 mmHg) than those with type B (32.3 +/- 10.1 mmHg) (p less than 0.05). Among the 3 types of RVH, the mean right atrial (RA) pressures were similar (p greater than 0.05). Patients with AF had a lower mean MPA pressure, but a higher RA pressure than those with NSR (p less than 0.05). The maximal anterior force and maximal rightward force at the horizontal plane were significantly correlated with the mean MPA pressure (r = 0.54 and 0.49, respectively, both p less than 0.01), but they did not correlated well with the PAW and RA pressures (p greater than 0.05). We conclude that in patients with MS, as pulmonary hypertension progresses, VCG seems to begin with type B RVH, then emerges into type C and finally becomes type A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Characterization of canine renal receptors for the parathyroid hormone-like protein associated with humoral hypercalcemia of malignancy.

Parathyroid hormone-like proteins (PTHLP) display actions in the kidney which are similar to those of parathyroid hormone (PTH). We compared the binding properties of PTHLP and PTH in canine renal cortical membranes to determine if they interacted with the same or different receptors. Radioiodination to high specific activity (greater than 400 microCi/micrograms) of [Nle8,18,Tyr34]human PTH-(1-34)amide and [Tyr36]PTHLP-(1-36)amide was performed using the lactoperoxidase method. Complete enzymatic digestion of both radioligands demonstrated that the peptides were monoiodinated. Both radioligands retained full biological activity in the renal adenylate cyclase assay, and neither was significantly degraded during incubation with highly purified canine renal membranes under binding assays conditions. Specific binding reached equilibrium by 20 min at 20 degrees C. Competition binding studies using unlabeled [Nle8,18,Tyr34]human PTH-(1-34)amide, [Tyr36] PTHLP-(1-36)amide, and bovine PTH-(1-34) with either radioligand revealed similar binding affinities for all three peptides. Biologically inactive PTHLP fragments did not show significant displacement. In contrast to its similar binding affinity, [Tyr36]PTHLP-(1-36)amide was 6-15-fold less potent than bovine PTH-(1-34) in the renal adenylate cyclase assay, suggesting less efficient receptor-effector coupling. Photoaffinity cross-linking using either radioligand in canine renal membrane labeled indistinguishable 70,000-dalton proteins. In the presence of multiple protease inhibitors, binding to an 85-kDa component was observed. Labeling of both receptor forms was specifically abolished by an excess of either cold peptide and dose-response curves using affinity cross-linked membranes corroborated the apparent binding affinities determined by conventional radioligand binding assays. We conclude that PTHLP-(1-36) and amino-terminal PTH analogues bind to indistinguishable receptors in canine renal cortical membranes, but display differential coupling to post-receptor events.

Affinity Labels