Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 361 records · Page 20Linked to original sources

PubMed1999

Liver enriched transcription factors and differentiation of hepatocellular carcinoma.

The development of a complex organism relies on the precise temporal and spacial expression of its genome in many different cell types. The unique phenotype of hepatocytes arises from the expression of genes in a liver specific fashion, which is controlled primarily at the level of mRNA synthesis. By analysing DNA sequences implicated in liver specific transcription, it has been possible to identify members of the nuclear proteins, such as the liver enriched transactivating factors, hepatic nuclear factor 1(HNF-1), HNF-3, HNF-4, HNF-6, CCAAT/enhancer binding protein (C/EBP), and D binding protein (DBP), which are key elements in the liver specific transcriptional regulation of genes. Each of these factors is characterised by DNA binding domains that bind to unique DNA sequences (cis-acting factors) in the promoter and enhancer regions of genes expressed in terminally differentiated hepatocytes (such as, albumin, alpha 1-antitrypsin, transthyretin, alpha-fetoprotein). The determination of the tissue distribution of these factors and analysis of their hierarchical relations has led to the hypothesis that the cooperation of liver enriched transcription factors with the ubiquitous transactivating factors is necessary, and possibly even sufficient, for the maintenance of liver specific gene transcription. With the increase in information about transcriptional regulation, it should be possible to evaluate fully the clinicopathological usefulness of transcription factors in the diagnosis and treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1999

Crazy-paving appearance at thin-section CT: spectrum of disease and pathologic findings.

PURPOSE: To determine the spectrum of disease associated with a fine reticular pattern superimposed on areas of ground-glass opacity (i.e., "crazy-paving" appearance) at thin-section computed tomography (CT) and to determine the underlying pathologic features. MATERIALS AND METHODS: In the in vivo study, the cases of 46 patients (21 male, 25 female; age range, 13-82 years) were retrospectively reviewed, with special attention paid to the size and extent of the reticular network. In the in vitro study, the thin-section CT findings in 20 inflated and fixed lungs were precisely correlated with the gross appearance, contact radiograph findings, stereomicroscopic views, and histologic findings. RESULTS: In the in vivo study, 15 different diseases were identified, including alveolar proteinosis, adult respiratory distress syndrome, acute interstitial pneumonia, diffuse alveolar damage superimposed on usual interstitial pneumonia, and drug-induced pneumonitis. In the in vitro study, the fine networks at pathologic analysis were due to an alveolar filling process (n = 10), an interstitial fibrotic process (n = 7), or a combination of interstitial and intraalveolar processes (n = 3). Twelve (60%) cases did not have thickening of the interlobular septa within the areas of the crazy-paving appearance. CONCLUSION: The crazy-paving appearance is a nonspecific finding seen in a variety of interstitial and airspace lung diseases.

Female↗

PubMed1999

Expression of C-type natriuretic peptide during development of rat lung.

C-type natriuretic peptide (CNP), recently found to be secreted from vascular endothelial cells, is now viewed as a novel endothelium-derived relaxing peptide. However, the distribution and expression of CNP during cardiopulmonary development is unclear. To follow changes in the expression of CNP during lung development, we examined rat embryos and neonates using Northern blot analysis and in situ hybridization for CNP mRNA and radioimmunoassay and immunohistochemistry for CNP protein. A substantial expression of CNP mRNA was first detected on postnatal day 2, and it thereafter remained fairly steady. The level of CNP protein also increased rapidly after postnatal day 1, reaching a settled level on postnatal day 4. CNP protein and mRNA were detected in the endothelium and smooth muscle cells of blood vessels and in bronchial airway and alveolar epithelia. Immunoreactivity for CNP protein in the endothelium of blood vessels increased to an intense level after the saccular stage. These results suggest that the changes in CNP levels may be related to the occurrence of pulmonary vasodilation after birth.

Animals↗

PubMed1999

Basic FGF decreases clearance receptor of natriuretic peptides in fetoplacental artery endothelium.

Atrial natriuretic peptide (ANP) is present in the fetoplacental circulation of humans and sheep. The ANP-A receptor is the specific membrane receptor for ANP, which produces cGMP. The clearance receptor of natriuretic peptide (CR) is postulated to modulate local concentrations of ANP, thereby modulating cGMP production through the ANP-A receptor. Recently we reported that fetoplacental basic fibroblast growth factor (bFGF) and cGMP levels are increased dramatically during the third trimester of ovine gestation. Therefore we hypothesized that bFGF will downregulate CR expression in cultured ovine fetoplacental artery endothelial (OFPAE) cells via the mitogen-activated protein kinase (MAPK) signal cascade mechanism, thereby causing augmentation of ANP-mediated cGMP production. Western analysis and/or RT-PCR of CR expression were performed after treatment of OFPAE cells with bFGF (10 pg/ml-1 microgram/ml) with or without 50 microM PD-98059, a selective inhibitor of MAPK kinase. To investigate the possible effects of CR downregulation on the functional modulation of ANP-A receptor activation, cGMP production (20 min) by OFPAE cells was measured in response to ANP (10 pM-1 microM) with or without pretreatment (24 h) of 10 ng/ml bFGF. CR expression in OFPAE cells was dose dependently downregulated by 1-10 ng/ml bFGF treatment (maximum -69%), which was completely reversed by pretreatment with PD-98059. Treatment of OFPAE cells with 10 ng/ml bFGF (24 h) did not alter maximum ANP-A activity (cGMP production/20 min), but decreased the apparent ED(50) of ANP to stimulate cGMP production from 2.5 to 0.83 nM, suggesting the possibility that bFGF-mediated downregulation of CR may elevate ANP-mediated cGMP production responses. Thus bFGF downregulates CR mRNA and protein expressions via the MAPK cascade in OFPAE cells.

Animals↗

PubMed1999

Expression of mast cell proteases in rat lung during helminth infection: mast cells express both rat mast cell protease II and tryptase in helminth infected lung.

BACKGROUND: The phenotype of proliferated mast cells in Nippostrongylus brasiliensis-infected rat lung has been identified as mucosal mast cells (MMC) but not connective tissue mast cells (CTMC). However, a previous study of ours showed that the expression of rat mast cell tryptase (RMCT) mRNA, which has been reported to be confined to CTMC, significantly increased in rat lung 14 days after infection. METHODS: The expression of four mast cell proteases in rat lung during the course of infection with N. brasiliensis was examined by RNA blot analysis. Immunohistochemical analysis of RMCT and rat mast cell protease (RMCP) II, which has been reported to be confined to MMC was also performed. RESULTS: The number of lung mast cells did not change until 7 days after infection, then gradually increased until 21 days after infection. The expression of the RMCP II gene had increased 14 and 21 days after infection. In addition, the expression of the RMCP I and RMCT genes had also increased at the same time points, but RMCP III had not. By immunohistochemistry, most of the mast cells in infected lung were identified as RMCP II+/RMCT- (MMC), but both RMCP II+ and RMCT+ mast cells were also observed. CONCLUSIONS: The present results suggest that mast cell phenotype alteration or a distinct mast cell subset might be present in N. brasiliensis-infected rat lung, and therefore N. brasiliensis-infected rat lung may be a useful tool for studying the differentiation mechanism of mast cells.

Animals↗

PubMed1999

Carcinoembryonic antigen and carbohydrate antigen 19-9-producing adenocarcinoma of the prostate: report of an autopsy case.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are well known as specific tumor markers of prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-producing adenocarcinoma originating in the prostate is rare. We report here a case of prostatic adenocarcinoma positive for these 4 tumor markers in a 50-year-old man who had initially complained about chest pain due to metastatic bone tumor. In spite of the extensive treatment involving hormone and radiation therapy, the patient died of rapid tumor extension only 4 months after initial diagnosis. Autopsy revealed multiple metastases to the bone, liver, lungs and lymph nodes. Histologically, two types of adenocarcinoma were involved in both primary prostate and metastatic sites: one was a poorly differentiated adenocarcinoma positive for PSA and PAP but not CEA or CA19-9, and the other one was a less differentiated adenocarcinoma partially positive for CEA and CA19-9 but not for PSA or PAP. Based on this case and previous cases by review of the literature, CEA- and CA19-9-producing adenocarcinoma of the prostate was suggested to rapidly progress with multiple metastases and to show poor prognosis with strong resistance to any treatment.

Acid Phosphatase↗

PubMed1999

Pressor response to compression of the ventrolateral medulla mediated by glutamate receptors.

The rostral ventrolateral medulla (RVLM) is considered a major center for the regulation of sympathetic and cardiovascular activities. Several clinical studies have indicated a possible causal relationship between neurovascular contact of the left RVLM and essential hypertension, and some investigators have suggested that the left RVLM is more sensitive to pulsatile compression than the right RVLM. Previously, we reported that pulsatile compression of the RVLM elevates arterial pressure by enhancing sympathetic outflow in rats; however, we have not investigated the laterality of the responses to the compression. In addition, it remains to be elucidated whether RVLM neurons are activated by compression and, if so, how they are activated. Therefore, we performed compression experiments in rats to investigate these issues. Pulsatile compression was performed on the unilateral RVLM with a pulsating probe in anesthetized and artificially ventilated rats. Pulsatile compression of the unilateral RVLM increased arterial pressure, heart rate, and sympathetic nerve activity. The pressor response to compression was inhibited significantly after local microinjection of glutamate receptor antagonists. Pulsatile compression of the RVLM increased Fos immunoreactivitiy, a marker of neuronal activation, within the nuclei of postsynaptic RVLM neurons. All results were observed symmetrically. The data indicate that the responses to pulsatile compression of the unilateral RVLM are similar on both sides. They also suggest that pulsatile compression of the RVLM increases sympathetic and cardiovascular activities by activating postsynaptic RVLM neurons through the stimulation of the local glutamate receptors in rats.

Animals↗

PubMed1999

A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells.

Goblet cells are the major mucus-producing cells of the intestine and are presumed to play an important role in mucosal protection. However, their functional role has not been directly assessed in vivo. In initial studies, a 5' flanking sequence of the murine intestinal trefoil factor (ITF) gene was found to confer goblet cell-specific expression of a transgene. To assess the role of goblet cells in the intestine, we generated transgenic mice in which approximately 60% of goblet cells were ablated by the expression of an attenuated diphtheria toxin (DT) gene driven by the ITF promoter; other cell lineages were unaffected. We administered 2 exogenous agents, dextran sodium sulfate (DSS) and acetic acid, to assess the susceptibility of mITF/DT-A transgenic mice to colonic injury. After oral administration of DSS, 55% of control mice died, whereas DT transgenic mice retained their body weight and less than 5% died. Similarly, 30% of the wild-type mice died after mucosal administration of acetic acid, compared with 3.2% of the transgenic mice. Despite the reduction in goblet-cell number, the total amount of ITF was increased in the mITF/DT-A transgenic mice, indicating inducible compensatory mechanisms. These results suggest that goblet cells contribute to mucosal protection and repair predominantly through production of trefoil peptides.

Acetic Acid↗

PubMed1999

A kinetic model of mitochondrial aspartate aminotransferase transmigration in hepatobiliary disorders.

A hypothetical kinetic model of transmigration of mitochondrial aspartate aminotransferase (m-AST) from liver to blood and its elimination from blood was constructed and assessed for prediction by computer simulation. The elimination of m-AST from plasma in healthy rats followed first-order kinetics. Depletion of m-AST from the liver after induction of hepatobiliary disorders in rats with alpha-naphthylisothiocyanate (ANIT) also followed first-order kinetics. In contrast, the changes in metabolic rate in the liver after ANIT administration, as estimated from the plasma indocyanine green clearance, approximated to a second-order time function. Based on these data, the time-dependent change in plasma m-AST activity after ANIT administration was simulated by computer according to a hypothetical kinetic model. The result of computer simulation of the change in plasma m-AST coincided well with that obtained experimentally, suggesting that continuous measurements of m-AST may be helpful to the clinical diagnosis of liver injury.

1-Naphthylisothiocyanate↗

PubMed1999

Distribution of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in human tissues. Cellular surface localization of HAI-1 in simple columnar epithelium and its modulated expression in injured and regenerative tissues.

We used a specific monoclonal antibody to human hepatocyte growth factor activator inhibitor type 1 (HAI-1) in immunohistochemical procedures to determine the distribution and localization of HAI-1 in human tissues. In normal adult tissues, HAI-1 was predominantly expressed in the simple columnar epithelium of the ducts, tubules, and mucosal surface of various organs. In all cases, HAI-1 was localized predominantly on the cellular lateral (or basolateral) surface. By contrast, hepatocytes, acinar cells, endocrine cells, stromal mesenchymal cells, and inflammatory cells were hardly stainable with the antibody, and stratified squamous epithelium showed only faint immunoreactivity on the surface of cells of the basal layer. In the gastrointestinal tract, the surface epithelium was strongly stained. RNA blot analysis confirmed the presence of specific mRNA transcript in the gastrointestinal mucosa, and in situ hybridization revealed that HAI-1 mRNA showed a similar cellular distribution pattern. Although HAI-1 was not expressed in normal hepatocytes, strong immunoreactivity was observed on the epithelium of pseudo-bile ducts and on the surface of scattered hepatocytes in fulminant hepatitis. The enhanced expression was also noted in regenerating tubule epithelial cells of the kidney after infarction. We conclude that HAI-1 is preferentially expressed in the simple columnar epithelium of the mucosal surface and duct, that the predominant localization of HAI-1 is the cell surface, and that the expression of HAI-1 can be modulated by tissue injury and regeneration.

Antibodies, Monoclonal↗

PubMed1999

Effect of Dai-kenchu-to on levels of 3 brain-gut peptides (motilin, gastrin and somatostatin) in human plasma.

We examined the effect of Dai-kenchu-to (DKCT), a traditional Chinese (Kampo) medicine, on the levels of 3 brain-gut peptides (motilin, gastrin and somatostatin) in plasma from 24 healthy subjects. A single oral administration of DKCT, at a dose of 7.5 g, caused significant increases in plasma motilin levels (about 12 pg/ml) at 60 to 90 min, compared with a placebo-treated group. Transient elevations of gastrin levels were noted after administration of both DKCT (25.9+/-1.4 pg/ml) and placebo (23.5+/-1.3 pg/ml). DKCT did not alter the levels (about 5.7 pg/ml) of somatostatin. In conclusion, these results indicate that the action of DKCT closely relates to changes in motilin-immunoreactive substance levels in human plasma.

Administration, Oral↗

PubMed1999

The time from anaerobic threshold (AT) to respiratory compensation point reflects the rate of aerobic and anaerobic metabolism after the AT in chronic heart failure patients.

The significance of the time from anaerobic threshold to respiratory compensation point (RCP-AT time) in patients with chronic heart failure was investigated. Thirty-seven patients with chronic heart failure (New York Heart Association class II or III) were enrolled into the study. Cardiopulmonary exercise testing was performed using breath-by-breath gas sampling. A bicycle ergometer was used, and incremental exercise testing was carried out. Anaerobic threshold, respiratory compensation point (RCP), and the slope of oxygen uptake (VO2) as a function of work rate (deltaVO2/deltaWR) were measured. A positive correlation (r=0.53) between RCP-AT time and deltaVO2/deltaWR was found. RCP-AT time was corrected for the whole exercise period (ramp exercise-RCP point), and the correlation between corrected RCP-AT time and deltaVO2/deltaWR was still present (r=0.46). There was no correlation between RCP-AT time and anaerobic threshold. These findings suggest that RCP-AT time is a new parameter that reflects the rate of the aerobic and anaerobic metabolism after AT.

Anaerobic Threshold↗

PubMed1999

Exercise-induced changes in plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in healthy subjects with chronic sleep deprivation.

Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.

Adult↗

PubMed1999

Effects of exercise training on the recovery of the autonomic nervous system and exercise capacity after acute myocardial infarction.

This study investigated the effects of aerobic exercise training on the early phase of the recovery process following acute myocardial infarction (AMI) in terms of the autonomic nervous system, cardiac function and exercise capacity. Twenty-eight patients in the first week after the onset of AMI were assigned randomly to either a training group or a control group. The training group performed aerobic exercise for 2 weeks. Cardiopulmonary exercise testing was performed 3 times during the 3 months after the onset. Heart rate variability, plasma norepinephrine (NE) levels, and cardiac index (CI) during exercise were measured. In the training group, plasma NE level and deltaCI (peak CI-rest CI) were significantly improved from 1 to 3 weeks after the onset, and the high frequency of heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset. In the control group, the plasma NE level and the deltaCI during the 1-3 weeks post-AMI, the high frequency of heart rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset. These results indicate that sympathetic nervous activity improves soon after the onset of AMI, in conjunction with improvement in cardiac function, and that this improvement is not affected by exercise training. In contrast, the recovery of parasympathetic nervous activity requires a longer period, along with the recovery of exercise capacity, which is facilitated by even short-term aerobic exercise training.

Aged↗

PubMed1999

A case of endobronchial endometriosis treated by subsegmentectomy.

We present a case of endobronchial endometriosis with catamenial hemoptysis. The lesion was diagnosed as endobronchial endometriosis using helical CT, and the patient underwent a subsegmentectomy of the upper part of the lateral basal segment. A histopathologic examination of the resected specimen revealed findings typical of endobronchial endometriosis with intimal hyperplasia within the bronchus. Since the operation, the patient has been asymptomatic for 11 months with no recurrence of hemoptysis.

Adult↗

PubMed1999

Myotonic dystrophy associated with insulinoma.

We describe a 51-year-old man with myotonic dystrophy (MyD) associated with insulinoma. In addition to the typical symptoms of MyD, he showed hypoglycemic attacks after meals. The radiological examination and selective blood sampling revealed an insulinoma in the head of the pancreas. The tumor was resected and histopathologically diagnosed as an insulinoma. In Southern blot analysis, CTG repeat of the myotonin protein kinase gene in the insulinoma showed the longest expansion, followed by normal tissue of the pancreas, muscle and white blood cells. Therefore, microsatellite instability was the most prominent in the tumor cells.

Biomarkers, Tumor↗

PubMed1999

Expression of 90-kDa heat shock protein within regenerative tubular cells in a patient with acute oliguric renal failure due to malignant hypertension.

A 29-year-old man developed acute oliguric renal failure with severe hypertension and microangiopathy. He was treated with hemodialysis and anti-hypertensive drugs, but oliguria was prolonged. A renal biopsy was performed on the 29th hospital day. Small arteries and arterioles were characterized by marked intimal thickening, and most of the glomeruli showed ischemic changes. Although there was extensive tubular loss and atrophy, regenerative changes were occasionally observed in some tubules, in which 90-kDa heat-shock protein was induced. He was diagnosed as having malignant nephrosclerosis, and was treated with a prostaglandin I2 analog, in addition to anti-hypertensive drugs. Thereafter, his renal function recovered gradually, and hemodialysis was discontinued on the 49th hospital day. Functional recovery lasts more than five years. We suggest that the expression of HSP90 in regenerative tubular cells is a useful histological indicator for predicting recovery from acute oliguric renal failure due to malignant hypertension.

Acute Kidney Injury↗

PubMed1999

Treatment of cervical compressive myelopathy with a new dorsolateral decompressive procedure.

OBJECT: A new dorsolateral decompressive procedure involving a unilateral approach has been devised for the treatment of cervical compressive myelopathy. In this operation, the posterior spinal elements of the contralateral side are not disturbed, and thus, postoperative deformity of the cervical spine can be avoided. Following decompressive surgery via the unilateral approach, the cervical spine was kept more stable compared with the results obtained after wide laminectomy or other expansive laminoplasty procedures. METHODS: Twenty-six patients underwent dorsolateral decompressive surgery, and the patients' clinical and radiological results were examined during the follow-up period to evaluate neurological function and postoperative deformities of the cervical spine. The underlying conditions for myelopathy were cervical spondylosis (19 patients), ossification of posterior longitudinal ligament (three patients), and ossification of yellow ligament (four patients). The follow-up period ranged from 6 to 110 months (average 35.5 months). Functional recovery, which was rated by using the Japanese Orthopaedic Association scoring system, was an average of 56% in all patients (100% being equal to full recovery). The recovery rate was compatible with those attained after other expansive laminoplasty procedures. Radiographically, progression to swan-neck or kyphotic deformity was not observed in any patient. No postoperative spinal instability was noted. Based on computerized tomography myelograph evaluation, the average transectional area of the dural tube at the C4-5 level was expanded from 122 mm2 to 169 mm2, and the transectional area of the spinal cord at the C4-5 level was expanded from 39.6 mm2 to 52.9 mm2 after surgery. CONCLUSIONS: The authors conclude that this operative procedure could be used as a new option for the treatment of cervical compressive myelopathy.

Adult↗