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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 433 records · Page 24Linked to original sources

Expression and distribution of brain natriuretic peptide in human right atria.

OBJECTIVES: We investigated expression of brain natriuretic peptide (BNP) as well as atrial natriuretic peptide (ANP) and their genes in human right atria. Their relations with atrial pressure were also examined. BACKGROUND: The BNP plays a roll in electrolyte-fluid homeostasis such as ANP. The tissue level is reported to be elevated in the failing ventricles. However, expression and transmural distribution of BNP in the atria remain unclear. METHODS: Expression of ANP and BNP was immunohistochemically investigated in the right atrial (RA) specimens from 21 patients who had undergone cardiac surgery. The mRNA of specimens were quantitatively measured by Northern blot analysis and also evaluated by in situ hybridization. In addition, plasma levels of ANP and BNP were measured in the patients. RESULTS: The BNP immunoreactivity was diffusely seen in RA tissue of patients with mean RA pressure (mRAP) of 5 mm Hg or more, but it was noted only in the subendocardial half of the atria of those with mRAP less than 5 mm Hg. There was a significant correlation between the incidence of BNP-positive myocytes and mRAP (r = 0.850, p < 0.0001). Conversely, ANP-positive myocytes were found diffusely in all cases. In Northern blot analysis, the mRNAs levels of ANP and BNP in the atrial tissue were positively correlated with the mRAP (ANP, p = 0.775, p < 0.005 and BNP, p = 0.771, p < 0.005). In situ hybridization confirmed these findings. The mRNA levels were significantly correlated to each other (r = 0.845, p < 0.0002). Plasma ANP and BNP levels were elevated in the patients compared with that in controls; however, none were significantly correlated with the mRAP. CONCLUSIONS: Expression of BNP and BNP mRNA is augmented in the atria with increased pressure, and distributed predominantly in the subendocardial side. The level of BNP mRNA was well correlated with that of ANP mRNA. Thus, these two genes might be commonly regulated in response to atrial pressure.

Aged↗

Smooth muscle cell migration and proliferation are mediated by distinct phases of activation of the intracellular messenger mitogen-activated protein kinase.

PURPOSE: Mitogen-activated protein kinase (MAPK) is a ubiquitous signaling protein that has been associated with cellular proliferation; however, its role in cellular migration has not been established. In this study, we investigate the role of MAPK in platelet-derived growth factor (PDGF)-induced migration and proliferation of human vascular smooth muscle cells (SMCs). METHODS: SMC migration was measured using a microchemotaxis assay (4 hours), and proliferation was assessed using 3H-thymidine uptake and cell counts. PD098059 was used as a specific noncompetitive inhibitor of MAPK activation. RESULTS: Coincubation of SMCs with PD098059 resulted in significant inhibition of PDGF-BB (5 ng/ml)-induced SMC chemotaxis and proliferation. The IC50 for both processes was approximately 10 mumol/L with complete inhibition at 50 mumol/L. Stimulation of SMCs with PDGF produced an early peak in MAPK activity followed by a plateau of activity that persisted for 24 hours. We hypothesized that variations in the temporal activation of MAPK might explain the action of this enzyme on these two disparate cellular events. By adding PD098059 at intervals after stimulation of SMCs with PDGF, we demonstrated an association between MAPK activity within the first 15 minutes and SMC migration, whereas MAPK activity between 1 and 4 hours was associated with SMC proliferation. CONCLUSIONS: MAPK activity is essential for both SMC migration and proliferation, and distinct phases of enzyme activation are required to stimulate these two discrete cellular events. Inhibition of this signaling protein may prove to be a useful method for preventing intimal hyperplasia.

Becaplermin↗

Effect of mental stress on plasma homovanillic acid in healthy human subjects.

Plasma levels of homovanillic acid (pHVA) have been suggested to provide a measure of dopaminergic activity in the central nervous system. The present study investigated the effect of mental stress by the Kraepelin test, a test of continuous arithmetic addition of single-digit figures for 30 min, on pHVA levels in 13 male psychiatrically normal healthy volunteers. Following an overnight fast and restricted physical activity, plasma samples were collected immediately before and after the administration of the Kraepelin test. Plasma HVA levels following the administration of the Kraepelin test were significantly lower than the pretest pHVA levels. The percent change in pHVA levels by the Kraepelin test positively correlated with pretest pHVA levels. The observed reduction in pHVA levels by mental stress in normal subjects may reflect some aspects of a dopamine-dependent restitutive system in the brain.

Adult↗

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗

Alterative expression of the collagenase and adhesion molecules in the highly metastatic clones of human colonic cancer cell lines.

Human colonic carcinoma cell lines, KM12C, KM12SM and KM12L4, were previously established and their in vivo metastatic potentials have been well evaluated. The highly metastatic cell lines KM12SM and KM12L4 were derived from the parental low metastatic cell line KM12C in vivo. To evaluate the metastatic behavior of these cell lines in vitro, we examined colony formation on monolayers of the pulmonary arterial endothelial (CPAE) cells. On day 4, the highly metastatic cell lines showed an approximately 2-fold increase in number of colonies on CPAE cell monolayers relative to the parental KM12C cell line. To investigate what evidence is correlated with their metastatic and invasive abilities, Northern blot analysis and flow cytometry were performed in all cell lines. According to the results of Northern blot analysis, the levels of matrix metalloproteinase (MMP)-2 and c-met mRNA expression were increased in highly metastatic cell lines as compared with the parental cell line. We also examined the cell-surface expression of several adhesion molecules by flow cytometry. The levels of expression of sialyl Lewisa antigen (sLe(a)) in KM12SM and KM12L4 were twice higher than that in KM12C. However, the levels of expression of E-cadherin in KM12SM and KM12L4 were decreased to half that in KM12C. The alterative expression of the collagenase and adhesion molecules might contribute to their metastatic/invasive abilities of these cell lines both in vivo and in vitro.

Antigens, CD↗

Effect of preinduction of heat-shock proteins on acetic acid-induced small intestinal lesions in rats.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that stress is known to cause the release of endogenous substances such as catecholamine, beta-endorphine, 5-hydroxytryptamine, corticotropin-releasing factor, and thyrotropin-releasing hormone (TRH). However, the role played by these neurohormonal mediators in bowel dysfunction under stress conditions is not well known. We investigated the influence of water-immersion stress or TRH administration on the expression of 60-kDa, 72-kDa, and 90-kDa heat-shock proteins (HSP60, HSP72, and HSP90, respectively) in rat small intestinal mucosa by Western blot and immunohistochemical analyses. The cytoprotective function of preinduced HSPs on experimentally induced mucosal damage also was studied. In order to investigate the influence of preinduction of HSP60 on small intestinal damage, the small intestinal lumen was perfused with 1.5% acetic acid 1 ml/min for 15 min with or without pretreatment with water-immersion stress or TRH administration. Expression of HSP60 was significantly increased by water-immersion stress or TRH administration in the small intestinal mucosa, whereas HSP72 and HSP90 did not increase. Interestingly, expression of this protein showed the biphasic peak pattern after water-immersion stress or TRH administration. Each peak was observed 3-6 hr and 21-24 hr after the initiation of water-immersion stress or TRH administration. Immunohistochemical study also showed a significant increment of HSP60 in both the cytoplasm and nuclei of the small intestinal mucosal cells. No histopathologic alteration was observed in rat small intestinal mucosa after each treatment. Small intestinal damage caused by 1.5% acetic acid perfusion was not influenced by preinduction of HSP60. We demonstrated that water-immersion stress or TRH administration specifically induced HSP60, although preinduction of this protein did not show a cytoprotective function in the small intestinal mucosa.

Acetic Acid↗

Donor lymphocyte infusion at unstable mixed chimerism in an allogeneic BMT recipient for chronic granulomatous disease.

We report a 14-year-old boy who had successfully received allogeneic BMT for chronic granulomatous disease and 3 years later was treated with donor lymphocyte infusion (DLI, 3.3 x 10(8) cells/kg) at unstable mixed chimerism in association with reduced neutrophil function. Following DLI, the patient developed transient acute hepatic GVHD, which was confirmed by liver biopsy and was manageable with cyclosporin A and prednisolone. The patient eventually attained complete chimerism with improved neutrophil function. At the time of writing (2.5 years from the DLI), the patient is doing well, free from infectious episodes and chronic GVHD. Our experience suggests that DLI could be a safe and effective strategy for dissolution of unstable mixed chimerism in BMT recipients for inherited disorders.

Adolescent↗

Plasma concentration of cytokine antagonists in patients with infection following liver resection.

BACKGROUND: The interactions between endogenous cytokine antagonists, surgical injury and perioperative infection are poorly understood. METHODS: Perioperative plasma concentrations of soluble tumour necrosis factor receptor p55 (STNFR p55), interleukin (IL) 1 receptor antagonist (IL-1ra) and IL-6 were measured by immunoassay in 29 consecutive patients undergoing liver resection. RESULTS: Plasma concentrations of STNFR p55, IL-1ra and IL-6 showed a striking increase immediately after operation (day 0) and on postoperative day 1. STNFR p55 concentrations correlated significantly with operating time (P< 0.05); IL-1ra levels with operating time, blood loss and weight of resected liver (P < 0.05); and IL-6 concentrations with operating time and blood loss (P< 0.05). Eight of the 29 subjects developed postoperative infections, of whom four had positive cultures of enteric organisms. Plasma STNFR p55 and IL-6 concentrations were significantly higher in the infected group than in the uninfected group (P < 0.05). STNFR p55 and IL-6 concentrations on day 0 differentiated between the two groups with a diagnostic accuracy of 79 and 83 per cent respectively. CONCLUSION: These results suggest that STNFR p55, IL-1ra and IL-6 are produced during operation in response to surgical stress. This production of STNFR p55 and IL-6 may be enhanced further by intraoperative bacterial translocation. Measurement of plasma STNFR and IL-6 concentrations may predict the development of postoperative infectious complications.

Adult↗

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure.

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5 +/- 3.4, mean +/- SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres, Ohmeda, Englewood, CO, USA) and urine was collected for determining volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P < 0.01, ANOVA). Baseline BNP levels were not significantly correlated with patient's clinical and polysomnographic parameters. However, in the latter half of the sleep period (02:00-06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r = 0.784 P < 0.01, diastolic: r = 0.587 P < 0.01) and with apnoea duration (r = 0.582 P < 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P < 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P < 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.

Atrial Natriuretic Factor↗

Over-expression of a tobacco homeobox gene, NTH15, decreases the expression of a gibberellin biosynthetic gene encoding GA 20-oxidase.

Ectopic expression of the homeobox gene, NTH15 (Nicotiana tabacum homeobox 15) in transgenic tobacco leads to abnormal leaf and flower morphology, accompanied by a decrease in the content of the active gibberellin, GA1. Quantitative analysis of intermediates in the GA biosynthetic pathway revealed that the step from GA19 to GA20 was blocked in transgenic tobacco plants overexpressing NTH15. To investigate the relationship between the expression of NTH15 and genes involved in GA biosynthesis, we isolated three cDNA clones from tobacco encoding two types of GA 20-oxidase and a 3 beta-hydroxylase. RNA gel blot analysis revealed that the expression of one gene (Ntc12, encoding GA 20-oxidase), which in wild-type tobacco plants was abundantly expressed in leaves, was strongly suppressed in the transformants. The expression level of Ntc12 decreased with increasing severity of phenotype of transgenic tobacco leaves. The abnormal leaf morphology was largely overcome by treatment with GA20 or GA1 but not by GA19. These data strongly suggest that overexpression of NTH15 inhibits the expression of Ntc12, resulting in reduced levels of active GA and abnormal leaf morphology in transgenic tobacco plants. In situ hybridization in wild-type tobacco revealed that expression of Ntc12 occurred mainly in the rib meristem, cells surrounding the procambium and in leaf primordia. Expression was not seen in the tunica, corpus and procambium, tissues in which NTH15 was predominantly expressed. The contrasting expression patterns of these genes may reflect their antagonistic functions in the formation of lateral organs from the shoot apical meristem.

Amino Acid Sequence↗

Clinical features of circadian rhythm sleep disorders in outpatients.

The clinical data of 86 cases of primary circadian rhythm sleep disorder (primary CRSD) were retrospectively examined and compared to 40 cases of secondary circadian rhythm sleep disorder (secondary CRSD), who had presented with some kind of psychiatric or medical disorder, and had exhibited sleep-wake rhythm disorders that were judged to be secondary CRSD based on sleep logs. The comparison of cases found that: (i) the mean age at first presentation to the clinic was significantly younger for primary CRSD compared to secondary CRSD; (ii) more secondary CRSD cases were unemployed than were Primary CRSD cases; (iii) more cases in the secondary CRSD group had a clear trigger for sleep-wake rhythm disorder onset than cases in the primary CRSD group; and (iv) the types of sleep-wake rhythm disorders in the primary CRSD group consisted of delayed sleep phase syndrome (DSPS), 72 (83.7%), non-24 pattern, 11 (12.8%), and irregular, 3 (3.5%). In the secondary CRSD group there were 25 (62.5%) cases of DSPS pattern, 1 (2.5%) of non-24 pattern and 14 (35.0%) with irregular pattern. The 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.

Adolescent↗

Oral administration of tritiated water (HTO) in mouse. III: Low dose-rate irradiation and threshold dose-rate for radiation risk.

PURPOSE: To investigate the biological effect of tritium on mouse at low dose-rates. MATERIALS AND METHODS: Mice ([C57BL/6N x C3H/He]F1) were exposed to beta-rays by continuous administration of tritiated drinking water throughout their lives at low dose-rates of 3.6, 0.9, and 0.2 mG/day. RESULTS: Including the previous study, the tumour frequency was 70 to approximately 80% for exposure in the range 240 mGy/day to 9.6 mGy/day. Frequency of tumours decreased with decrease of dose-rate to 50% comparable to the controls. Restricting to thymic lymphomas, a linear relationship in a semi-log plot was found between the frequency and the dose-rate above a threshold dose-rate of 12 mGy/day. There was a 'tail' to this relationship down to 0.9 mGy/day. A similar pattern resulted for the relationship between the life-shortening and the dose-rate. The threshold dose-rate of 3H beta-rays, 2 mGy/day (with a tail down to 0.2 mGy/day), was much lower than that of gamma-rays, 20 mGy/day (tail down to 2 mGy/day) derived from other studies. CONCLUSIONS: These studies suggest that there exists the threshold dose-rate in the biological effects of radiation, and that the threshold dose-rate for 60Co gamma-irradiation is higher than that for 3H beta-irradiation.

Administration, Oral↗

Reduction of 8-hydroxyguanine in human leukocyte DNA by physical exercise.

We investigated the effect of physical exercise on the level of 8-hydroxyguanine (8-OH-Gua), a form of oxidative DNA damage, and its repair activity in human peripheral leukocytes. Whole blood samples were collected by venipuncture from 21 healthy male volunteers (10 trained athletes and 13 untrained men), aged 19-50 years, both before and after physical exercise. Trained athletes showed a lower level of 8-OH-Gua (2.4+/-0.5/10(6) Gua, p = 0.0032) before exercise when compared to that of untrained men (6.2+/-3.5). The mean levels of 8-OH-Gua of untrained subjects decreased significantly (p = 0.0057) from 6.2+/-3.5/10(6) Gua (mean+/-SD/10(6) Gua) to 3.3+/-1.4/10(6) Gua after physical exercise. On the other hand, the mean levels of repair activity of untrained subjects significantly increased after exercise (p = 0.0093) from 0.037+/-0.024 (mean DNA cleavage ratio+/-SD) to 0.056+/-0.036. In the trained athletes 8-OH-Gua level and its repair activity were not changed before and after the exercise. We also observed inter-individual differences in 8-OH-Gua levels and its repair activities. These results suggest that physical exercise causes both rapid and long-range reduction of oxidative DNA damage in human leukocytes, with individually different efficiencies.

Adult↗

Routes of hepatic metastasis of gallbladder carcinoma.

This clinicopathologic study aims to clarify routes of hepatic metastasis of gallbladder carcinoma. Nineteen liver specimens obtained by extensive hepatectomy performed for the treatment of advanced gallbladder carcinoma were analyzed. We defined hepatic metastasis as a discrete hepatic lesion separate from the primary tumor and paid special attention to portal tracts at the margins of direct hepatic invasion. Eleven early metastatic foci were demonstrated histologically in 6 cases, most commonly in segments adjacent to the gallbladder. All cases with hepatic metastasis had direct hepatic invasion. Nine of the 11 metastatic lesions were located within the portal tracts or accompanied by invasion into the portal tracts. Because they are in continuity with areas of direct hepatic invasion, the portal tracts at the invasive margin often were involved by cancer cells that spread along these tracts. These results suggest that the most important route in development of hepatic metastasis from gallbladder carcinoma is along the portal tracts after direct hepatic invasion.

Aged↗

Phyllodes tumor showing intracystic growth: a case report.

A phyllodes tumor often grows rapidly and occasionally contains microcysts; however, the tumor rarely shows a morphologically intracystic pattern. We experienced a rare case of a phyllodes tumor with a solid mass growing into the cyst. A 62-year-old female noticed a tumor in her right breast in January 1995. The tumor grew rapidly and she visited our out-patient clinic in February 1995. On physical examination, a 10 x 8 cm, well defined and movable mass with a smooth surface was palpated in the upper outer quadrant of the right breast. Mammography showed a large tumor shadow in the upper outer quadrant of the right breast without any microcalcification. Ultrasonography revealed a large cystic shadow with a low echoic lesion and solid component with heterogeneous internal echo in the cyst. Under general anesthesia, the tumor was widely excised. The resected specimen was 11.5 x 11 x 11 cm in size and the tumor was not invasive to surrounding tissues. Old bloody fluid was contained within the cyst. The gross appearance showed papillary process protrusions into a central cystic cavity. Histological examination revealed a borderline case of phyllodes tumor. Two years after the operation, she is doing well without any recurrence.

Breast Neoplasms↗

Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition.

Adult↗