Biomedical subjects

Y Miyamoto

Publications and source records attributed to Y Miyamoto.

At least 163 records · Page 9Linked to original sources

PubMed1999

KDR/Flk-1 is a major regulator of vascular endothelial growth factor-induced tumor development and angiogenesis in murine hepatocellular carcinoma cells.

Vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors, has been shown to play a pivotal role in tumor angiogenesis, including hepatocellular carcinoma (HCC). The effects of VEGF are mediated mainly through two distinct receptors, flt-1 and KDR/Flk-1. It has been suggested that KDR/Flk-1 plays an important role in tumor development. However, the role of KDR/Flk-1 in HCC has not been examined. We previously reported that VEGF tightly regulated murine HCC development, based on the results of a study using a retroviral tetracycline-regulated (Retro-Tet) gene expression system. This system allows VEGF gene expression to be manipulated in vivo by providing tetracycline in the drinking water. In the present study, we combined the KDR/Flk-1-specific neutralizing monoclonal antibody (KDR/Flk-1mAb) and the Retro-Tet system to elucidate the role of KDR/Flk-1 in VEGF-induced tumor development and angiogenesis in a murine HCC experimental model. In a xenograft study, tumor augmentation induced by VEGF overexpression was almost abolished by means of KDR/Flk-1mAb treatment, with accompanying inhibition of angiogenesis, KDR/Flk-1 autophosphorylation, but not interference of flt-1 activation. This inhibitory effect was achieved even on established tumors and regardless of whether the tumor size was small or large. On the contrary, KDR/Flk-1mAb treatment significantly increased the apoptosis in the tumor. With orthotopic transplantation, KDR/Flk-1mAb also inhibited HCC development in the liver. These results suggest that KDR/Flk-1 is a major regulator of VEGF-mediated HCC development and angiogenesis not only at the initial stage, but also after the tumor has fully developed.

Animals↗

PubMed1999

Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors.

BACKGROUND: A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors. METHODS: Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis. RESULTS: Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines. CONCLUSION: The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.

Adenocarcinoma↗

PubMed1999

Covering the head and face maintains intraoperative core temperature.

PURPOSE: To determine the effect of covering the patient's head and face on the prevention of intraoperative hypothermia (<35.5 degrees C). METHODS: This randomized, prospective trial included 44 adults undergoing elective abdominal surgery. After the induction of anesthesia with thiopental, in 44 patients their extremities and trunk were covered with towels and sheets. In addition, 22 patients (covered group) had their face and head fully covered. Anesthesia was maintained with N2O 50-66% (2-3 L x min(-1)) and isoflurane (<IMAC) in oxygen combined with thoracic epidural anesthesia. Core temperature was measured at the tympanic membrane continuously and was recorded at 15 min intervals from the induction of anesthesia. Heat and moisture exchangers were used in their anesthetic circuit. Ambient temperature was maintained near 25 degrees C. RESULTS: Neither group demonstrated intraoperative hypothermia. However, tympanic membrane temperature at 75, 90, 105 min in the covered group were higher than those of control group (36.7+/-0.4 degrees C vs. 36.5+/-0.4 degrees C, 36.8+/-0.5 degrees C vs. 36.4+/-0.5 degrees C, 36.8+/-0.5 degrees C vs. 36.4+/-0.5 degrees C, respectively, P<0.05). CONCLUSION: Covering the patient's head and face maintains intraoperative core temperature.

Adult↗

PubMed1999

Effects of "body compression" on parameters related to ascites formation: therapeutic trial in cirrhotic patients.

Decreased effective circulating blood volume is an important factor in ascites formation in liver cirrhosis. We designed a "body compression" apparatus as a means to restore effective blood volume and investigated its effectiveness in reducing ascites formation in cirrhotics in terms of its effect on parameters of ascites formation noted below. The subjects, eight cirrhotics with ascites and eight cirrhotics without ascites were given spironolactone (50-75 mg/day) and furosemide (40-80 mg/day) while they received a diet containing 85 mEq of sodium per day. All four limbs and the lower abdomen were compressed with constant pressure [height (cm) divided by 13.6 mmHg] once, for 3h, using stroke rehabilitation splints, while patients lay supine. In cirrhotics both with and without ascites, urine volume, urinary sodium excretion, and creatinine clearance during the body compression were greater than values during control (non-compression) periods (urine volume, means 285 vs 169 ml/3h; P < 0.001, urinary sodium excretion 15.8 vs 9.5 mEq/3h; p < 0.001, creatinine clearance 74 vs 59 ml/min, P < 0.001, respectively). The increased basal plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were significantly decreased by the body compression. In another group of six cirrhotics who received no diuretics or albumin, repeat body compression alleviated ascites in three with well preserved renal function, but was ineffective in three with markedly impaired renal function. These results suggest that the improvement in renal function brought about by the body compression is attributable to an increase in effective circulating blood volume. This maneuver may be a useful complementary therapy in patients with cirrhotic ascites with well preserved renal function.

Adult↗

PubMed1999

Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis C associated with autoimmune hepatitis-like serological manifestations.

We report a 70-year-old woman with chronic hepatitis C associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis C virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.

Aged↗

PubMed1999

Upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

The aim of this study was to compare postprandial hemodynamic changes observed during assumption of the recumbent posture and upright posture in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were studied. Echo-Doppler examinations were performed to measure flow volume in the portal vein (PV), superior mesenteric artery (SMA), and splenic artery (SA) in the fasting condition. Collateral blood flow was indirectly calculated by determining the difference between the sum of SMA, SA, and PV blood flows. After these measurements were done, each patient received a standardized liquid meal and was then randomly assigned to either maintain supine or upright posture, in a crossover design, on 2 different days (recumbent day and upright day). On each study day, the above-mentioned measurements were repeated 30 min and 60 min after the meal. PV blood flow increased significantly after the meal on the recumbent day (P < 0.01) but not on the upright day (P = 0.78). Although there were significant postprandial increases in SMA blood flow on both study days (P < 0.01, P < 0.01), the effect was less pronounced on the upright day than on the recumbent day (P < 0.01). Postprandial SA blood flow showed no change on the recumbent day (P = 0.64), but decreased significantly on the upright day (P < 0.01). The calculated postprandial collateral blood flow increased significantly on the recumbent day (P < 0.05), but showed no change on the upright day (P = 0.53). These results suggest that the upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.

Aged↗

PubMed1999

Evaluation of TMN classification for lung carcinoma with ipsilateral intrapulmonary metastasis.

BACKGROUND: Staging for lung cancer based on the TNM classification is an important predictive factor for prognosis. Recently, lung cancer with ipsilateral intrapulmonary metastasis (PM) was reclassified according to the revision of the TNM classification. To evaluate the prognostic importance of the new staging system for PM, we analyzed the postoperative survival of patients with non-small cell lung carcinoma. METHODS: Of 1,002 consecutive patients who underwent operation for primary lung cancer between June 1984 and December 1996, we reviewed the medical record of 889 patients who underwent complete resection for non-small cell lung cancer. RESULTS: We considered 89 patients (10.0%) to have synchronous ipsilateral PM. After reclassification to the former staging system revised in 1992, 5 patients were classified as stage I, 29 as stage IIIA, 48 as stage IIIB, and 7 as stage IV. In the new staging system revised in 1997, 48 patients were recategorized as stage IIIB, and 41 as stage IV. The 5-year survival of patients without PM (49.5%) was significantly better than that of patients with PM in primary-tumor lobe (29.6%, p = 0.002) or in nonprimary-tumor ipsilateral lobe (23.4%, p = 0.0002). Although the survival of patients with stage IV cancer without PM was significantly worse than that of patients with the new (1997) stage IV cancer with PM (p = 0.02), it was similar to that of patients with the former (1992) stage IV cancer with PM. The survival of PM patients with N0 or N1 disease was significantly better than that of PM patients with N2 or N3 disease (p = 0.001). Furthermore, in patients with the new (1997) stage IIIB cancer, the survival of N0 disease was better than that of N2 disease (p = 0.007). CONCLUSIONS: Inasmuch as the prognosis of non-small cell carcinoma in patients with PM strongly correlated with N factor rather than PM factor, N factor should be reflected in a staging designation. We therefore consider the new TNM classification for PM reclassified in 1997 to be less acceptable for surgical-pathologic staging than the revision in 1992.

Adult↗

PubMed1999

How should interlobar pleural invasion be classified? Prognosis of resected T3 non-small cell lung cancer.

BACKGROUND: The results of surgical treatment for non-small cell lung cancer with interlobar pleural involvement and direct invasion of the other lobe have seldom been documented. METHODS: Of 1,130 consecutive patients who were operated on for primary bronchogenic carcinoma between 1984 and 1997, we studied 132 patients who had complete resection of T3 non-small cell carcinoma. RESULTS: The structures involved were as follows: parietal pleura, 49 patients; chest wall, 45; interlobar pleura, 19; main bronchus within 2 cm of the carina, 11; mediastinal pleura, 6; and diaphragm, 1. Patients with N2 disease had a significantly worse survival than those with N0 (p = 0.0054) and N1 disease (p = 0.0165). The survival of patients with involvement of the interlobar pleura was significantly worse than that of patients with T1 (p = 0.0001) or T2 disease (p = 0.0484), and was similar to that of patients with T3 disease (p = 0.9821). CONCLUSIONS: In patients with T3 disease, mediastinal lymph node involvement influenced survival significantly. Patients with involvement of the interlobar pleura should be regarded as having T3 lesions.

Adult↗

PubMed1999

Extended sleeve lobectomy for lung cancer: the avoidance of pneumonectomy.

OBJECTIVE: We have tried atypical bronchoplasties in patients with noncompromised lung function with centrally located cancers to avoid pneumonectomy. We evaluated the efficacy of extended sleeve lobectomy in such patients. METHODS: Among 157 patients undergoing bronchoplasty for primary non-small cell lung carcinoma, 15 patients underwent extended sleeve lobectomy. RESULTS: According to the mode of reconstruction, the 15 patients were classified into 3 groups: (A) anastomosis between the right main and lower bronchi with resection of the upper and middle lobes (n = 6), (B) anastomosis between the left main and basal segmental bronchi with resection of the upper lobe and superior segment of the lower lobe (n = 4), and (C) anastomosis between the left main and upper division bronchi with resection of the lingular segment and lower lobe (n = 5). The tumors were completely resected in all patients. Pulmonary angioplasty was carried out in 8 patients. Bronchial reconstruction was successful in all patients. Pulmonary vein thrombosis resulting from overstretching of the inferior pulmonary vein occurred in 1 patient of group A and was relieved by completion pneumonectomy. There was neither operative mortality nor local recurrence. Although all patients with stage IIB disease and half of patients with stage IIIA disease were alive without recurrence (12-106 months), half of the patients with stage IIIA disease died of distant metastases within 1 year. CONCLUSIONS: We suggest that this extended sleeve lobectomy, which is technically demanding, should be considered in patients with centrally located lung cancer, because this lung-saving operation is safer than pneumonectomy and is equally curative.

Aged↗

PubMed1999

Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival?

OBJECTIVE: We analyzed the effect of the station of mediastinal metastasis with regard to the location of the primary tumor on the prognosis in patients with non-small cell lung cancer. METHODS: Of 956 consecutive patients who underwent operation for primary lung carcinoma between 1986 and 1996, 760 patients (79.5%) were diagnosed as having non- small cell carcinoma and were subjected to complete removal of hilar and mediastinal lymph nodes together with the primary tumor. RESULTS: The status of lymph node involvement was N0 in 480 patients (63.2%), N1 in 139 patients (18.3%), and N2 in 141 patients (18.6%). The 5- and 10-year survival of patients with N2 disease were 26% and 17%, respectively. Neither cell type nor the extent of procedure was a significant survival determinant. Patients having involvement of subcarinal nodes from upper-lobe tumors had a significantly worse prognosis than those patients with metastases only to the upper mediastinal or aortic nodes (P =.003). Patients with nodal involvement of the upper mediastinum from lower-lobe tumors had a significantly worse survival than those patients with metastases limited to the lower mediastinum (P =.039). Furthermore, patients with involvement of the aortic nodes alone from left upper-lobe tumors had a significantly better survival than those patients with metastasis to the upper or lower mediastinum beyond the aortic region (P =.044). CONCLUSIONS: When mediastinal metastasis is limited to upper nodes from upper-lobe tumor, to lower nodes from lower-lobe tumor, or to aortic nodes from left upper-lobe tumor, acceptable survival could be expected after radical resection.

Adult↗

PubMed1999

Involvement of the serotonergic neuronal system in phencyclidine-induced place aversion in rats.

The possible involvement of the serotonergic neuronal system in aversive motivation produced by phencyclidine [1-(1-phenylcyclohexyl)piperidine; PCP] was investigated using a place-conditioning paradigm in rats. PCP (4 mg/kg, i.p.) produced place aversion in this task as reported previously (Kitaichi K, Noda Y, Hasegawa T, Furukawa H, Nabeshima T. Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats. Eur J Pharmacol 1996;318:7-9). The blockade of serotonin2A (5-HT2A) receptors using the antagonist ritanserin (3 and 10 mg/kg, p.o.) significantly attenuated this aversive property of PCP whereas lesions of serotonergic neurons using 5,7-dihydroxytryptamine (5,7-DHT, 100 microg/animal, i.c.v.) failed to affect it. Repeated PCP treatment (10 mg/kg, i.p. for 14 days), which is enough to diminish the stereotyped 5-HT2A receptor-mediated head-twitch behavior, also decreased the place aversion. These results suggest that the serotonergic neuronal system, specifically the 5-HT2A receptor, may play a critical role in producing PCP-induced place aversion.

5,7-Dihydroxytryptamine↗

PubMed1999

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS: Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS: In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS: These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

Aged↗

PubMed1999

Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells.

The aim of this study was to examine Bax, Bcl-2 and Bcl-XL proteins in human pancreatic cancer cell lines and to clarify the mechanism of radiation resistance. PANC-1 and AsPC-1 pancreatic cell lines were used, both having mutated p53. Radioresistant PANC-1/Rad cells and AsPC-1/Rad cells were obtained by repeated 5 Gy irradiation of PANC-1 cells and AsPC-1 cells, respectively. Radiation was found to inhibit the growth of PANC-1 cells and AsPC-1 cells. After exposure to radiation, detached cells were subjected to FITC-TUNEL staining to calcualte the ratio of apoptosis. TUNEL positive ratios increased dose-dependently in both cell lines. Western blotting showed that the basal level of the Bax/Bcl-2 ratio reflected the radiosensitivity of these cell lines, and Bax expression was obviously upregulated after irradiation in the presence of mutated p53, but Bcl-2 expression remained almost constant. Both PANC-1/Rad and AsPC-1/Rad cells had greater Bcl-XL expression than the parental cells, and the basal level of the Bax/Bcl-2 ratio was no longer predictive of radiosensitivity. Upregulated expression of Bax protein after irradiation was not related to induction of apoptosis in these cells, suggesting that overexpression of Bcl-XL and functional reconstruction of Bcl-2 family proteins are important factors in acquired radioresistance.

Blotting, Western↗

PubMed1999

Heptakis(2,6-di-O-methyl-3-O-acetyl)-beta-cyclodextrin: A water-soluble cyclodextrin derivative with low hemolytic activity.

Acetyl groups were introduced to the hydroxyl groups of heptakis(2, 6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD), and the resulting heptakis(2,6-di-O-methyl-3-O-acetyl)-beta-CyD (DMA-beta-CyD) was evaluated for the inclusion property and hemolytic activity. It was confirmed by means of NMR and mass spectroscopies that in the DMA-beta-CyD molecule, all seven hydroxyl groups at the 3-position were substituted by acetyl groups. Thus, it has the degree of substitution (DS) of 7, whereas DMA4-beta-CyD with the lower substitution (DS 3.8) was a mixture of components with different DS. The aqueous solubility of DMA-beta-CyD was higher than those of beta-CyD, DM-beta-CyD, and heptakis(2,3,6-tri-O-methyl)-beta-CyD (TM-beta-CyD). The hydrophobicity of the whole molecule, assessed from measurements of surface tension, increased in the order of DM-beta-CyD < DMA-beta-CyD < TM-beta-CyD. The half-life of DMA-beta-CyD for hydrolysis in pH 9.5 and 60 degrees C was about 19 h, and there was only slight liberation of acetic acid in rabbit plasma and carboxylesterase (EC 3.1.1.1) at 37 degrees C. DMA-beta-CyD had an inclusion ability similar to that of TM-beta-CyD for p-hydroxybenzoic acid esters with different alkyl chain lengths and an antiinflammatory drug, flurbiprofen, although it was inferior to that of DM-beta-CyD. The hemolytic activity and rabbit muscular irritation of DMA-beta-CyDs were much weaker than those of DM-beta-CyD: no hemolysis was observed even in the presence of 0.1 M DMA-beta-CyD with DS 7. The results suggest that the water-soluble CyD derivative with superior bioadaptability and inclusion ability can be prepared by properly designing substituents at the 3-position and by optimally controlling their degree of substitution.

Animals↗

PubMed1999

A new biflavonoid from Calophyllum panciflorum with antitumor-promoting activity.

A new biflavonoid named pancibiflavonol (1) was isolated from an EtOH extract of the stem bark of Calophyllum panciflorum, along with six known biflavonoids, and its structure was elucidated by spectroscopic methods. These biflavonoids all exhibited significant inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells.

Antineoplastic Agents↗

PubMed1999

Role of pleural lavage cytology before resection for primary lung carcinoma.

OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance of PLC before manipulation is still controversial. METHODS: Cytology of pleural lavage immediately after thoracotomy but before any manipulation of the lung was examined in 500 consecutive patients with lung cancer with no pleural effusion who underwent pulmonary resections. Eighteen patients who already had pleural dissemination were excluded from this study. RESULTS: Eighteen of 482 patients (3.7%) had positive cytologic findings. The positivity of PLC was significantly correlated with histology, extension of tumor to pleura, and presence of lymphatic permeation or vascular involvement by tumor. Positive lavage findings were seen only in adenocarcinoma. Because 6.3% of the patients with adenocarcinoma had positive cytologic findings, it is vital to perform PLC before curative resections for lung cancer, especially adenocarcinoma. The 5-year survival rates of the patients having negative and positive lavage findings were 52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage findings was as poor as that of the patients with stage IIIB disease and that of the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC indicate exfoliation of cancer cells into the pleural cavity, which is an essential prognostic factor. In addition, we should regard positive cytologic findings as a subclinical malignant pleural effusion that is pathologic stage T4.

Bronchoalveolar Lavage↗

PubMed1999

A heart-specific increase in cardiotrophin-1 gene expression precedes the establishment of ventricular hypertrophy in genetically hypertensive rats.

OBJECTIVE: Cardiotrophin-1 is a cytokine, a novel member of the interleukin-6 superfamily, which is isolated from mouse embryoid bodies. It is known to bind a gp130/ leukemia inhibitory factor (LIF) receptor heterodimer and to induce myocyte hypertrophy. Accumulating evidence indicates that a gp130 signaling pathway is involved in cardiac development and ventricular hypertrophy. METHODS: In order to elucidate the pathophysiologic significance of cardiotrophin-1 in ventricular hypertrophy associated with hypertension, we examined the level of cardiotrophin-1 mRNA in the ventricle of spontaneously hypertensive rats/Izm stroke-prone (SHRSP/Izm) in neonates, and at 4-, 12- and 20-weeks of age by Northern blot analysis. We also examined the gene expression of LIF by Northern blot and reverse transcription-polymerase chain reaction analyses. RESULTS: No significant difference was observed in the level of cardiotrophin-1 mRNA in the ventricle between SHRSP/ Izm and Wistar-Kyoto/Izm (WKY/Izm) neonates. However, the level of cardiotrophin-1 mRNA in the ventricle was significantly augmented in 4-week-old SHRSP/Izm, which did not yet show overt ventricular hypertrophy, and its augmented expression lasted for the duration of the experimental period. The difference in the level of cardiotrophin-1 mRNA between the two strains was most prominent at the age of 4 weeks. This augmented expression of the cardiotrophin-1 gene was not related to the severity of left ventricular hypertrophy. The level of cardiotrophin-1 mRNA in other organs, including the kidney and lung, showed no significant change with aging and was not different between the two strains. After long-term treatment with lisinopril, levels of cardiotrophin-1 mRNA were not changed, although it morphologically prevented the development of left ventricular hypertrophy. LIF mRNA was not detected in any ventricles examined by Northern blot analysis. CONCLUSIONS: The present study demonstrates that the expression of cardiotrophin-1 mRNA is increased in the early stage of ventricular hypertrophy in SHRSP/Izm and it remains elevated after hypertrophy has been established. However, it is unlikely that cardiotrophin-1 plays a mechanistic role in the development and maintenance of left ventricular hypertrophy in SHRSP/Izm. The present study also suggests that cardiotrophin-1, but not LIF, is a possible candidate for natural ligand of a gp130 signaling pathway in the heart.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Phase-dependent heartbeat modulation by muscle contractions during dynamic handgrip in humans.

The influence of cardiac phase on the response of the cardiac pacemaker to dynamic hand contraction in eight healthy young men was studied to determine whether heart rate response to muscle contraction varied as a function of timing within the cardiac cycle. Changes in R-R interval (RRI) in response to muscle contraction were measured at various cardiac phases during heartbeat-synchronized handgrip at a rate of one contraction per two heartbeats. To extract the direct effect of the muscle contraction on the RRI, spontaneous slow variations and respiratory sinus arrhythmia were removed from the total RRI fluctuations in the frequency domain. Cross-correlograms between the extracted RRI fluctuations and muscle contraction showed that the coupling was strong when the muscle contraction occurred at the middle phase of the cardiac cycle. Muscle contraction at the systolic phase of the cardiac cycle had a tendency to produce a phase advance (shortening of RRI), whereas muscle contraction at the middle phase or later had a tendency to produce a phase delay (prolongation of RRI). The results showed the presence of a neuronal circuit that modulates the cardiac pacemaker activity depending on the timing of muscle contraction in the cardiac cycle.

Adult↗