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T L Wu

Publications and source records attributed to T L Wu.

At least 55 records · Page 3Linked to original sources
PubMed1995

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↗
PubMed1994

Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing.

Parathyroid hormone-related protein (PTHrP) is expressed by malignant tumors and leads to the syndrome of humoral hypercalcemia of malignancy. It is also expressed by a wide variety of nonmalignant tissues, in which it appears to play distinct paracrine and/or autocrine roles. The human PTHrP gene encodes three cDNA-predicted initial translational products of 139, 141, and 173 amino acids. Most human cell lines contain mRNAs encoding all three PTHrP isoforms. The physiological rationale for the existence of these three highly similar transcripts is unknown. In order to determine whether the protein products derived from these three transcripts differ, we transfected Chinese hamster ovary (CHO) cells and rat insulinoma (RIN) cells individually with cDNAs encoding human PTHrP(1-139), PTHrP(1-141), and PTHrP(1-173). Cell extracts and conditioned medium were then chromatographed using reversed-phase HPLC and analyzed using region-specific PTHrP immunoassays. As we had previously observed in SKRC-1 (renal cell carcinoma) and RIN(1-141) cells, multiple amino-terminal PTHrP species as well as a separate midregion PTHrP species were identified in all six cell lines. In addition, both CHO and RIN cell lines transfected with the PTHrP(1-139) construct contained a previously unrecognized carboxy-terminal fragment that reacted with a PTHrP(109-138) antiserum. This carboxy-terminal fragment was physically distinct from the midregion fragment discovered earlier and was also present in conditioned medium, indicating that it is a secretory form, rather than a biosynthetic intermediate or a degradation product.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Circadian variations of atrial natriuretic peptide in normal people and its relationship to arterial blood pressure, plasma renin activity and aldosterone level.

To investigate the circadian variations of plasma atrial natriuretic peptide (ANP) and its relationship to arterial blood pressure, plasma renin activity and aldosterone level, we determined 24-h blood pressure in 14 healthy volunteers. Plasma ANP concentration, renin activity and aldosterone levels were measured every 3 h by radioimmunoassay. We found no significant circadian variation of plasma ANP level (pg/ml) (daytime level, 62 +/- 24 vs. nighttime level, 57 +/- 19, P = 0.146) and plasma renin level (ng/ml/h) (1.32 +/- 0.78 vs. 1.15 +/- 0.57, P = 0.148), but there was diurnal change of blood pressure (mmHg) (systolic, 122 +/- 7 vs. 116 +/- 11, P < 0.001; diastolic, 80 +/- 11 vs. 72 +/- 11, P = 0.025) and plasma aldosterone level (pg/ml) (86 +/- 42 vs. 62 +/- 37, P < 0.001). The blood pressure and aldosterone levels reached maxima (11:00 h and 08:00 h, respectively) before that of ANP (17:00 h) and then decreased together until the nadir at 02:00 h. This might indicate that elevation of arterial blood pressure and plasma aldosterone level stimulate release of ANP under normal physiological conditions.

Adult↗
PubMed1993

Anomalies in cell wall turnover associated with the growth temperature of Bacillus subtilis.

Cell wall turnover appeared to be anomalously fast in Bacillus subtilis when the cells were grown at temperatures below 29 degrees C. Turnover rates k(generation-1), of exponential cultures at 25 degrees were approximately double those of cells grown at 37 degrees C. When autolysin levels were assayed in cell walls, it was found that the enzyme activities were constant between 25 degrees C and 40 degrees C, suggesting that there was no greater synthesis of autolysin at the lower temperature. Analyses of walls for individual components, extent of aminosugar substitution and extent of crosslinking, did not reveal significant differences between samples obtained from 25 degrees C or 37 degrees C cultures. The N-acetylmuramoyl-L-alanine amidase was stable over the temperature range studied. Lysis of cells, induced by carbonylcyanide-m-chlorophenylhydrazone, occurred at a faster rate for cells obtained at 25 degrees C than for cells obtained at 37 degrees C. In addition, the lysis of cells by hen egg white lysozyme was slightly faster when the cells were obtained from 25 degrees C cultures than from 37 degrees C cultures. It is possible the autolysin(s) responsible for cell wall turnover are cold-activated.

Bacillus subtilis↗
PubMed1993

Mandibulohyoid distance in difficult laryngoscopy.

We studied radiographically 11 patients in whom direct laryngoscopy proved difficult and 100 control (general population) subjects. The vertical distance between the mandible and the hyoid bone (mandibulohyoid distance) was measured and the positions of the mandibular angle and hyoid bone determined in relation to the cervical vertebrae. We found that the mandibulohyoid distance was substantially longer in patients whose trachea was difficult to intubate; the mandibular angle tended to be positioned more rostrally in both men and women, and the hyoid bone tended to be positioned more caudally in women. This suggests that a relatively short mandibular ramus or a relatively caudal larynx may be important, unfavourable anatomic factors in difficult laryngoscopy.

Adult↗
PubMed1993

Body surface potential maps of ventricular depolarization in normal adults.

Body surface potential maps were obtained in 50 normal adults using the heart potential map system designed by Yamada. Group A (younger adult group) consisted of 30 persons whose ages ranged from 20 to 39 years. Group B (middle-aged group) included 20 persons whose ages ranged from 40 to 59 years. Although there were slight variations in the pattern of isopotential distribution among the subjects studied, a consistent pattern with a similar sequence was observed in both study groups. However, there were some parameters which significantly differed between groups A and B, including the earliest appearance time of the anterior negative potential (p < 0.05), the anterior potential minimum (p < 0.001), the posterior positive potential (p < 0.001), the midsternal minimum (p < 0.001), the largest potential minimum (p < 0.05), the largest potential maximum (p < 0.005), the "reversal" pattern (p < 0.001), the multipolar potential distribution in the upstroke (p < 0.001) and the amplitude of potential minimum in the periods 50 msec (p < 0.005) and 60 msec (p < 0.01) of ventricular depolarization. Accordingly, the data obtained regarding the time relationship between the bipolar and multipolar phases, the distribution and time course of the potential as well as the dynamic changes in potential voltage, particularly the age-related potential pattern will serve as a basis for further study of BSPM.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗