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Biomedical subjects

K D Wu

Publications and source records attributed to K D Wu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.

Adenoma↗
PubMed1999

Pentoxifylline inhibits PDGF-induced proliferation of and TGF-beta-stimulated collagen synthesis by vascular smooth muscle cells.

There is growing evidence that pentoxifylline (PTX) may have potential value as an antiproliferative and antifibrogenic agent. To assess whether this drug may be of use in the prevention of atherosclerosis or restenosis after angioplasty, we investigated the ability of PTX to inhibit proliferation and collagen synthesis in rat vascular smooth muscle cells (VSMCs) under both basal and platelet-derived growth factor (PDGF)- or transforming growth factor-beta (TGF-beta)- stimulated conditions. Intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in confluent cells using enzyme immunoassay kits. Cell proliferation was measured by methyltetrazolium assay. Cell cycle distribution was determined by flow cytometry. Total collagen synthesis was measured by 3H-proline incorporation assay. Expression of collagen alpha 1(I) and collagen alpha 1(III) mRNAs was detected by northern blotting. Addition of PTX to VSMC cultures suppressed both basal and PDGF-AB (25 ng/ml)-driven cell proliferation, in conjunction with a cell cycle blockade at the G1/S phase at 24 h. This effect was predominantly cAMP-dependent, as PTX increased cAMP in a dose-dependent manner (0.03 to 0.33 mg/ml) but not cGMP level, and the addition of dibutyryl-cAMP (0.2 to 2 m m) closely mimicked the effect of PTX. Furthermore, co-incubation with a selective inhibitor of cAMP-dependent protein kinase (PKA), H-89 (2.0 microm), or an N -myristoylated PKA pseudosubstrate nonapeptide, m-phi PKA (10 microm), prevented the antimitogenic effect of PTX. PTX also suppressed both basal and TGF- beta 1-augmented collagen alpha 1(I) and collagen alpha 1(III) mRNA levels beginning at 24 h, and attenuated both basal and TGF-beta 1 (5 ng/ml)-stimulated total collagen synthesis at 48 h. Co-incubation with H-89 or m-phi PKA reversed PTX-attenuated collagen alpha 1(I) and collagen alpha 1(III) mRNA levels at 24 h. These data suggest that the antimotigenic and anticollagen effects of PTX were mediated predominantly through a cAMP-PKA effector pathway. The dual effect of PTX on VSMC proliferation and collagen synthesis may form the rationale for animal or clinical trials for the treatment of vascular occlusion due to atherosclerosis and restenosis following angioplasty.

Animals↗
PubMed1999

Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis.

BACKGROUND: Accumulation of glomerular macrophages, proliferation of mesangial cells (MCs), and deposition of extracellular matrix proteins are pathobiological hallmarks of glomerulonephritis. We previously reported that a clinically available nonselective inhibitor of cyclic 3',5'-nucleotide phosphodiesterase, pentoxifylline (PTX), inhibits proliferation of cultured rat MCs, as well as collagen production by these cells. In this study, we investigated the in vivo effects of PTX on rat anti-Thy1 disease, a model of mesangial proliferative nephritis. METHODS: Anti-Thy1 nephritis was induced in Sprague-Dawley rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive PTX (0.1 g/kg/day) or vehicle (phosphate-buffered saline) and were sacrificed at various time points. Paraffin kidney sections were stained with hematoxylin and periodic acid-Schiff reagents for glomerular histology. Frozen kidney sections were stained by monoclonal antibodies against proliferating cell nuclear antigen, ED-1, and alpha-smooth muscle actin and were visualized by color development from a horseradish peroxidase reaction. Monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and various extracellular matrix mRNAs were analyzed by Northern blotting. Urine protein concentrations were determined by Lowry's method. RESULTS: Nephritic rats treated with PTX excreted less urinary protein on day 5 of nephritis than vehicle-treated nephritic rats. In periodic acid-Schiff-stained kidneys from PTX-treated nephritic rats, there was attenuation of both glomerular cellularity and glomerular sclerosis compared with vehicle-treated nephritic rats. PTX decreased the augmented glomerular mRNA levels of MCP-1 and ICAM-1 at two hours and on day 1 of nephritis. Immunoreactive staining showed that PTX reduced the number of proliferating glomerular macrophages on days 1, 2, and 3, but not at two hours of nephritis, compared with vehicle-treated nephritic rats. On day 5, PTX decreased the number of activated proliferating MCs and attenuated the glomerular mRNA levels of type I (alpha1), type III (alpha1), and type IV (alpha1) collagen and fibronectin compared with vehicle-treated nephritic rats. CONCLUSION: The administration of PTX to rats with anti-Thy1 disease reduces accumulation and proliferation of glomerular macrophages, attenuates proteinuria, suppresses activation and proliferation of MCs, and ameliorates glomerular sclerosis. These results suggest that PTX may have a suppressive effect in acute phases or relapses of mesangial proliferative glomerulonephritis.

Animals↗
PubMed1998

Low back pain in college athletes. A prospective study correlating lower extremity overuse or acquired ligamentous laxity with low back pain.

STUDY DESIGN: A prospective evaluation of the incidence of low back pain in college athletes was undertaken. OBJECTIVES: To evaluate prospectively leg length discrepancy, hip flexor tightness, and lower extremity acquired laxity or overuse as predictive factors for low back pain in college athletes. SUMMARY OF BACKGROUND DATA: A pilot study found an association between low back pain and the factors to be studied. Several allusions to the kinetic chain theory appear in the literature, but little prospective research has been done in examining the effects of lower extremity involvement on the back. METHODS: Two-hundred fifty-seven college athletes representing nine varsity sports were screened during a preseason sports physical examination. Measures of flexibility, ligamentous stability, leg length discrepancy, and overuse syndromes were recorded. Athletes were observed throughout the ensuing year for low back pain requiring treatment by the athletic trainer. Those athletes with low back pain as the result of direct trauma to the region were excluded from the data. RESULTS: Twenty-four athletes (9.3%) received treatment for low back pain. Thirteen of 87 women (15%) compared with 11 of 170 men (6%) required treatment for low back pain (P = 0.048). Of 57 athletes with lower extremity acquired laxity or overuse, low back pain developed in 14 (P < 0.001). CONCLUSIONS: Athletes with lower extremity acquired ligamentous laxity or overuse may be at risk for the development of noncontact low back pain during athletic competition. Female athletes with lower extremity involvement appeared to have a higher incidence of low back pain treatment compared with their male counterparts. Inflexibility of the lower extremities or leg length discrepancy were not associated with future low back pain treatment.

Adult↗
PubMed1997

Revised cutoff values of serum aminotransferase in detecting viral hepatitis among CAPD patients: experience from Taiwan, an endemic area for hepatitis B.

BACKGROUND: To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD). METHODS: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve. RESULTS: The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria. CONCLUSIONS: Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.

Adolescent↗
PubMed1997

Extracellular matrix proteins modulate human peritoneal mesothelial cell behavior.

Human peritoneal mesothelial cells lie on a basement membrane-like material consisting of fibronectin (FN), type I collagen (CI), type III collagen (CIII) and laminin (LA). To understand how these extracellular matrix (ECM) proteins affect mesothelial cell behavior, we investigated their effect on the adhesion and proliferation of mesothelial cells. A modified methyltetrazolium dye method was used to assess cell number. The results showed that FN, CI, CIII and LA, all increased adhesion of mesothelial cells. The adhesive effect was blocked dose-dependently by a synthetic Arg-Gly-Asp-containing (RGD) peptide. When coated as a substratum (immobilized form), FN, CI, CIII and LA, all enhanced serum-stimulated and epidermal-growth-factor-stimulated cellular proliferation as compared with bovine-serum-albumin-blocked plastic surfaces. When added in a soluble form, all matrix proteins except FN inhibited serum-stimulated and epidermal-growth-factor-stimulated cellular proliferation at high concentrations (CI and CIII: 1-10 micrograms/ml, LA: 3-10 micrograms/ml). We conclude that peritoneal mesothelial cells possess an RGD-sensitive receptor and that the ECM can modulate adhesion and proliferation of peritoneal mesothelial cells. The growth-modulating effect depends on the form and concentration of the ECM proteins.

Cell Adhesion↗
PubMed1996

The milk-alkali syndrome caused by betelnuts in oyster shell paste.

BACKGROUND: The carcinogenic effect of betelnut chewing leading to oral cancer is well known. Betelnut chewing may also affect the autonomic nervous system. In this report, we present another potential hazard of betelnuts, milk-alkali syndrome. CASE REPORT: Two patients who had chewed a large quantity of betelnuts developed hypercalcemia, metabolic alkalosis, and renal insufficiency. They ingested a large amount of calcium carbonate from a local special paste used for betelnut preparation, the main ingredient of which is ground oyster shell. The symptoms and metabolic abnormalities disappeared promptly after abstinence from betelnut chewing and administration of saline solution. Improvement of renal function was observed in both patients. Analysis of the calcium content of the paste suggested that the patients might have ingested 9 g and 6 g of calcium carbonate per day, respectively. CONCLUSION: This is the first report of milk-alkali syndrome not caused iatrogenically, but by recreational usage of oyster shell preparations of betelnuts.

Areca↗
PubMed1995

Quantitative analysis of messenger ribonucleic acid encoding natriuretic peptide receptors in aldosterone-producing adenoma.

There exist conflicting data regarding the inhibitory effect of atrial natriuretic peptide on aldosterone production from aldosterone-producing adenoma (APA). Natriuretic peptides mediate their actions through natriuretic peptide receptors (NPRs). Whether or not NPRs are present in the tumors remains controversial. To elucidate this paradox, gene expression of NPRs was examined by Northern blot analysis and competitive polymerase chain reaction in tumorous and non-tumorous portions of APA, and in normal adrenal gland from patients with renal cell carcinoma. The results of Northern blot analysis showed the presence of messenger ribonucleic acid (mRNA) of three NPRs in all adrenal tissues, including APA. The proportional expression of NPR gene transcripts in APA was type A (0.6%), type B (18.7%), and type C (80.7%). The levels, but not the proportions, of type C and possibly type B NPR mRNAs were lower in tumorous and non-tumorous portions of APA compared to those in normal adrenal gland (type C 190.2 +/- 24.5 [means +/- SEM, normal adrenal gland] > 168.1 +/- 20.8 [non-tumorous portion] > 112.2 +/- 15.5 [tumorous portion] pg/10 micrograms total RNA, F = 3.82, P < 0.05; type B 45.2 +/- 8.5 [normal adrenal gland] > 30.0 +/- 5.2 [non-tumorous portion] > 25.1 +/- 4.1 [tumorous portion] pg/10 micrograms total RNA, F = 3.03, P = 0.065). The mRNA levels of type C, rather than type A or type B, NPR were correlated with the percentage of zona fasciculata-like cells in APA (r = 0.90, P < 0.05). In conclusion we have demonstrated the presence of mRNA encoding the three NPRs in APA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1995

Localization and quantification of endoplasmic reticulum Ca(2+)-ATPase isoform transcripts.

The Ca(2+)-adenosinetriphosphatase pump of the sarcoplasmic or endoplasmic reticulum (SERCA) plays a critical role in Ca2+ signaling and homeostasis in all cells and is encoded by a family of homologous and alternatively spliced genes. To understand more clearly the role the different isoforms play in cell physiology, we have undertaken a quantitative and qualitative assessment of the tissue distribution of transcripts encoding each SERCA isoform. SERCA1 expression is restricted to fast-twitch striated muscles, SERCA2a to cardiac and slow-twitch striated muscles, whereas SERCA2b is ubiquitously expressed. SERCA3 is expressed most abundantly in large and small intestine, thymus, and cerebellum and at lower levels in spleen, lymph node, and lung. In situ hybridization analyses revealed SERCA3 transcripts in cells of the intestinal crypt, the thymic cortex, and Purkinje cells in cerebellum. In addition, SERCA3 was expressed abundantly in isolated rat spleen lymphocytes, in various murine lymphoid cell lines, and in primary cultured microvascular endothelial cells. This analysis demonstrates that SERCA3 is expressed selectively in cells in which Ca2+ signaling plays a critical and sensitive role in regulating physiological processes.

Animals↗
PubMed1995

Zona fasciculata-like cells determine the response of plasma aldosterone to metoclopramide and aldosterone synthase messenger ribonucleic acid level in aldosterone-producing adenoma.

The different responses of plasma aldosterone to ACTH and angiotensin II in aldosterone-producing adenoma (APA) is thought to be due to the various cellular compositions of the tumors. To investigate whether the dopaminergic regulation of aldosterone in APA is also dependent on the cellular types, we studied the effects of metoclopramide on plasma aldosterone in six patients with APA. The messenger RNA (mRNA) levels of aldosterone synthase (P450aldo), 11 beta-hydroxylase (P450(11) beta), and 17 alpha-hydroxylase (P450(17) alpha) of APA and normal adrenal glands were determined by competitive polymerase chain reaction. After administration of metoclopramide (an antagonist of dopamine-2 receptor), the increment of plasma aldosterone correlated inversely with the percentage of zona fasciculata cells of APA. The mRNA level of P450aldo in the tumorous portion was much higher, whereas the levels of P450(11) beta and P450(17) alpha mRNAs were lower, than those of the nontumorous portion and normal adrenals. There was a correlation of the percentage of zona fasciculata cells in APA with the levels of P450aldo and P450(11) beta mRNAs, but not with P450(17) alpha mRNA. These results suggest that differential responsiveness of plasma aldosterone to metoclopramide may be due to various proportions of different cell types in APA that may have different expression of dopamine-2 receptor. In addition, this histologically dependent expression was present at the transcriptional level of the gene responsible for aldosterone biosynthesis.

Adenoma↗
PubMed1995

Diagnostic value of plasma aldosterone/potassium ratio in hypoaldosteronism.

The diagnosis of hypoaldosteronism usually depends upon a combination of abnormal clinical and laboratory findings. The most common abnormality in hypoaldosteronism is hyperkalemia, which may be combined with sodium depletion. In the present study, 5 of 16 patients diagnosed with isolated hypoaldosteronism (IHA) had sodium depletion due to renal salt wasting, and four patients had normokalemia. Of these 16 IHA patients, 70% had subnormal baseline and stimulated plasma renin activity (PRA). Six patients diagnosed with type I pseudohypoaldosteronism (PHA) had normal or high PRA and plasma aldosterone concentrations (PAC). In 11 control subjects, supine PAC correlated positively with serum potassium (SK), and PAC stimulated by furosemide and ambulation correlated with the 24-hour urinary potassium excretion (UK). However, these correlations were not found in IHA and PHA patients. The ratio of UK/UNa+K and UNa/UK correlated with the stimulated PAC when the IHA and control subjects were taken as a whole. However, these electrolyte excretion parameters bore no relationship to the supine PAC. The stimulated PAC/SK ratio was used to discriminate the three groups; all IHA patients had a ratio below 3. The results indicate that stimulated PAC reflects the bioactivity of aldosterone on the collecting tubule, and the stimulated PAC/SK ratio is useful for the diagnosis of hypoaldosteronism and pseudohypoaldosteronism.

Adult↗
PubMed1994

Blood pressure, circulating atrial natriuretic peptide and sodium excretion responses during acute saline infusion in patients with essential hypertension.

In order to examine whether changes in circulating atrial natriuretic peptide (ANP) and sodium excretion during saline infusion in patients with essential hypertension (EH) could be modulated by the severity of resting arterial blood pressure (BP), 30 subjects with EH and nine normotensive subjects were given 2 L of isotonic saline infusion at a rate of 500 mL/hour. Plasma ANP concentrations in EH increased significantly from 64.9 +/- 5.1 (mean +/- SEM) to 92.5 +/- 12.8 pg/mL at the first hour and peaked at the second hour. In normotensives, the increase of plasma ANP was not significant until the fourth hour of infusion. Hypertensive subjects sustained a greater percentage increment of mean BP (MBP) than normotensives at the end of infusion. Those with pre-saline MBP exceeding 107 mmHg (group A) exhibited a faster and greater rise in plasma ANP after saline loading than those having less than or equal to 107 mmHg (group B). The post-saline four-hour natriuresis was appreciably higher in group A than group B, while the percentage increment of MBP at the fourth hour was significantly greater in the latter as compared to normal controls. These results indicate that patients with higher basal arterial pressure attain a faster and greater ANP response following saline infusion than those with lower BP. This phenomenon may be responsible for the maintenance of short-term fluid-volume and BP homeostasis during acute sodium loading in established EH.

Adult↗
PubMed1993

Molecular cloning and quantification of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in rat muscles.

A cDNA encoding the full-length adult rat fast-twitch muscle Ca(2+)-adenosinetriphosphatase (ATPase) was cloned. The deduced amino acid sequence of this molecule has 97 and 90% identity with those of rabbit fast-twitch muscle and chicken skeletal muscle Ca(2+)-ATPases, respectively. Specific probes from the 3'-untranslated region of each sarcoplasmic or endoplasmic reticulum Ca(2+)-ATPase (SERCA) gene product and full-length cRNA transcript standards were used to determine the quantity of mRNA encoding each isoform in various rat muscles. Quantitative immunoblotting was also used to determine the protein content of each SERCA isoform. Fast-twitch fibers expressed both SERCA1 mRNA and protein at a level two- to fivefold higher than SERCA2 was expressed in slow-twitch fibers. We observed a protein-to-mRNA ratio that varied from approximately 500,000 molecules per molecule in the fast-twitch muscles to approximately 200,000 in cardiac and smooth muscles. There was no difference, however, between the ratio for different isoforms in the same muscle. The content of Ca2+ pump in a given muscle therefore depends on at least three factors: 1) the efficiency of gene transcription and message stability (fiber type dependent), 2) the efficiency of translation and protein stability (muscle identity dependent), and 3) fiber composition of the muscle.

Amino Acid Sequence↗
PubMed1993

The acute effect of nicardipine on the renin-angiotensin-aldosterone system in salt-sensitive essential hypertension.

To determine the role of the renin-angiotensin-aldosterone (RAA) system in the acute effect of calcium channel blockers, we examined the acute effect of 40 mg nicardipine in 21 essential hypertensive patients. Nine patients whose mean blood pressure (MBP) decreased more than 5% at 2 hours after 20 mg furosemide i.v. were classified as salt-sensitive (SS); the remainder as salt-resistant (SR). The percentage decrease of MBP with nicardipine was not different between the two subgroups (12.4 +/- 2.5% for SS, and 17.7 +/- 4.1% for SR). The percentage decrease of MBP correlated with the pretreatment MBP (r = 0.67, p < 0.001), but not with the basal plasma renin activity (PRA), plasma aldosterone concentration (PAC), or natriuretic response. A significant increase of heart rate was noted in SR (31.2%) but not in SS (6.5%), and was associated with a higher increase of PRA in SR (90.7%) than in SS (25.5%). A correlation between the increase of PRA and the percentage increase of heart rate was noted (r = 0.77 p < 0.001). Decrease of PAC was observed in SS but not in SR until the third hour. The 3-hour sodium excretion was slightly greater in SR than in SS (59.9 +/- 9.1 vs. 35.1 +/- 3.0 mEq; p < 0.05). In summary, the acute hypotensive effect of nicardipine is dependent upon the vascular tone regardless of the status of the RAA system. An increase in PRA by nicardipine resulting from a baroreflex mechanism may counteract the inhibitory effect of aldosterone secretion by nicardipine. The unchanged PRA in SS is due to their blunted baroreflex control of heart rate. Mechanisms other than the change in the RAA system by nicardipine may account for the acute natriuretic effect.

Adult↗