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Biomedical subjects

Hideki Shima

Publications and source records attributed to Hideki Shima.

At least 19 recordsLinked to original sources

Altered renin-angiotensin system gene expression causes renal hypoplasia in the rats with nitrofen-induced diaphragmatic hernia.

The association between renal hypoplasia and pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) has become recently appreciated. However, the underlying mechanisms responsible for this association are still unknown. Renin-angiotensin system (RAS) plays an important role in renal and somatic growth, angiogenesis and reproduction. We hypothesized that abnormal expression of RAS components may be responsible for renal hypoplasia in CDH. We therefore designed this study to examine the gene expression of main components of RAS in the kidney of nitrofen-induced CDH in the rat. Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9.5 of gestation. Foetuses were recovered at term and divided into three groups: control (n=8), nitrofen without CDH (n=8) and CDH (n=8). Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of angiotensinogen (AGT), angiotensin II type 1 receptor with 1a and 1b subtypes (AT(1a)R and AT(1b)R), angiotensin II type 2 receptor (AT(2)R), angiotensin-converting enzyme (ACE) and renin expression in the kidney. AT(1a)R, AT(1b)R, AT(2)R, AGT and renin levels were significantly decreased in the kidney of CDH rats compared with controls. We did not find a significant difference in ACE between CDH animals and controls. Our data show that the downregulation of RAS may play an important role in the pathogenesis of renal hypoplasia in the nitrofen-induced CDH.

Abnormalities, Multiple↗

A case of Henoch-Schönlein purpura with rare complications: necrosis of the small intestine, neurological symptoms, and pericardial tamponade.

A case of Henoch-Schönlein purpura (HSP) with necrosis of the small intestine, neurological symptoms, and pericardial tamponade after frequent recurrence is described. Neurological symptoms were controlled well with steroid pulse therapy, and pericardial tamponade was treated successfully with pericardiocentesis and steroid pulse therapy. To treat necrosis of the small intestine, the necrotic tissue was excised and artificial anuses were constructed. Five months later, the small intestine was anastomosed in a curative operation. Periodic administration of coagulation factor XIII was required from the onset of symptoms until curative surgery, but the activity of this factor returned to normal levels after surgery operation. We report a case of Henoch-Schönlein purpura with extremely rare complications: necrosis of the small intestine, neurological symptoms, and pericardial tamponade.

Abdominal Pain↗

Ovarian fibroma (fibrothecoma) with extensive cystic degeneration: unusual MR imaging findings in two cases.

Two cases of ovarian fibroma (fibrothecoma) with extensive cystic degeneration are described. One case revealed a large multiloculated cystic mass with a small solid part. Each locule showed variable signal intensity on both T1- and T2-weighted magnetic resonance (MR) images. The other case revealed a parviloculated cystic mass with a small solid part. In both cases, the solid parts were located at the periphery of the mass and showed distinct low signal intensity on both T1- and T2-weighted MR images and slight enhancement. It should be noted that ovarian fibromas (fibrothecomas) with extensive cystic degeneration are a rare exception to the rule that solid components in a cystic adnexal mass imply malignancy.

Aged↗

Noncardiogenic pulmonary edema as the first manifestation of pheochromocytoma: a case report.

We report here a case of pheochromocytoma presenting with noncardiogenic pulmonary edema, which is an unusual first manifestation of pheochromocytoma. Chest radiograph showed diffuse consolitaion and ground-glass opacity on both lungs. Neither pleural effusion nor cardiomegaly was present. High-resolution computed tomography (HRCT) showed widespread ground-glass opacity with fine intralobular reticular opacity (so-called "crazy-paving" appearance) and consolidation in a strikingly dependent distribution. The areas of ground-glass opacity and consolidation were sharply marginated by interlobular septa, showing a geographic appearance. The pulmonary edema and dyspnea resolved over three days without cardioactive or diuretic treatment. Noncardiogenic pulmonary edema is an unusual first manifestation of pheochromocytoma. It is important to recognize this unusual manifestation in the emergency situation.

Adrenal Gland Neoplasms↗

Expression of vasoactive mediators during mechanical ventilation in nitrofen-induced diaphragmatic hernia in rats.

The high mortality in patients with congenital diaphragmatic hernia (CDH) has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Endothelin-1 (ET-1), nitric oxide (NO), and calcitonin gene-related peptide (CGRP) have been reported to be important vasoactive mediators in the perinatal pulmonary circulation. The exact mechanism by which these vasoactive mediators interact to regulate the perinatal pulmonary vascular tone in CDH with PPH is not fully understood. We hypothesized that the altered pulmonary vascular reactivity in CDH is due to imbalance in vasoactive mediators. This study was designed to investigate mRNA expression of ET-1, eNOS, and CGRP in CDH lung in the perinatal period. A CDH model was induced in pregnant rats following administration of nitrofen. In control animals, the same dose of olive oil was given without nitrofen. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated and ventilated, and ventilation was continued for 1-6 h. Left lungs were collected from both groups at 0, 1, and 6 h after ventilation (n=8 in each group). Reverse transcriptase-polymerase chain reaction on lung tissue was performed to evaluate the relative level of ET-1, eNOS, and CGRP mRNA expression. The results showed a significant increase in ET-1 mRNA in CDH lung at 1 and 6 h after ventilation compared with controls. In CDH lung, eNOS mRNA and CGRP mRNA levels were significantly increased at 1 h but were similar to control values at 6 h after ventilation. The increased expression of vasoconstrictor ET-1 mRNA and vasodilators eNOS mRNA and CGRP mRNA in the CDH lung at 1 h after ventilation suggests that pulmonary vascular tone is rapidly changing after birth. An imbalance in the production of vasoconstrictors and vasodilators by the CDH lung may contribute to high pulmonary vascular resistance.

Animals↗

Increased expression of EGFR and TGF-alpha in segmental renal dysplasia in duplex kidney.

Renal dysplasia (RD) is a disorganised development of renal parenchyma that results in a deficit of functional renal tissue. It is known that the epidermal growth factor (EGF) and the transforming growth factor-alpha (TGF-alpha) enhance renal cell proliferation, migration and differentiation during kidney development through binding to the same EGF receptor (EGFR). The aim of the study was to analyse the expression of TGF-alpha and EGFR in the dysplastic kidney. The specimens of dysplastic upper poles duplex kidneys were surgically resected from 19 patients. Indirect immunohistochemistry was performed using the ABC method employing antibodies against EGFR and TGF-alpha, and gene expression using primers specific to the human genes. There was absent or weak EGFR and TGF-alpha immunoreactivity in normal kidney tissue. In dysplastic kidneys, there was strong TGF-alpha and EGFR immunoreactivity in the epithelium of primitive tubules and strong EGFR immunoreactivity in the connective tissue around the primitive tubules. Our findings of markedly increased local expression of EGFR and TGF-alpha in primitive tubules suggest that EGFR and TGF-alpha may play an important role in altering renal morphogenesis resulting in renal dysplasia.

Child↗

Intracorporeal electrohydraulic lithotripsy for intrahepatic bile duct stone formation after choledochal cyst excision.

An 18-year-old girl who had undergone excision of a choledochal cyst and Roux-en-Y hepatico-jejunostomy at another hospital when 23 months old was referred to our department because of recurrent cholangitis. Radiological investigations showed stones lying in minimally dilated, right posterior intrahepatic bile ducts (IHBD). At laparotomy, the hepatico-jejunostomy site was incised, and a flexible endoscope inserted into the IHBD. Multiple stones packed in the IHBD were easily fragmented using an electro-hydraulic lithotripsy (EHL) device inserted through the endoscope, and removed. There were no EHL-related complications, and her postoperative progress was uneventful. She is currently well with no episodes of cholangitis after a follow-up period of 3 years. EHL is a simple, effective alternative method for removing IHBD stones after choledochal cyst excision. To the best of our knowledge, this is the first report of EHL being used to remove stones that developed in the IHBD after choledochal cyst excision.

Adolescent↗

Upregulated expression of EGF and TGF-alpha in the proximal respiratory epithelium in the human hypoplastic lung in congenital diaphragmatic hernia.

Newborn infants with congenital diaphragmatic hernia (CDH) still have a high mortality rate. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are peptide growth factors involved in the fetal lung growth and development. The EGF and TGF-alpha have been reported to promote pulmonary branching activity and alveolar type-II pneumocyte proliferation. Epidermal growth factor and TGF-alpha immunoreactivity and mRNA expression in the bronchial and bronchiolar epithelium is maximal during early fetal life and barely detectable in the proximal airways of neonatal lung. The purpose of this study was to determine protein and gene expression of EGF and TGF-alpha in CDH lung in order to elucidate the potential role of these growth factors in the pathogenesis of pulmonary hypoplasia in CDH. Lung tissue specimens were obtained from archival lung tissue from 11 patients with CDH and 5 controls. Indirect immunohistochemistry was performed using ABC method with anti-EGF and anti-TGF-alpha antibodies. In situ hybridization was performed using EGF and TGF-alpha specific digoxigenin-labeled oligonucleotide probes. The most striking difference between hypoplastic CDH lung and control lung was the strong EGF and TGF-alpha mRNA expression and immunoreactivity in the bronchial and bronchiolar epithelium in CDH lung. The upregulated protein and gene expression of EGF and TGF-alpha in the proximal airways in the CDH hypoplastic lung suggests persistence of fetal stage of pulmonary airway development in CDH.

Epidermal Growth Factor↗

Increased expression of ICAM-1 and VCAM-1 in the lung of nitrofen-induced congenital diaphragmatic hernia in rats.

Recently, increased expression of inflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been reported in both humans and animal models with CDH and the decreased TNF-alpha expression in CDH lung after antenatal dexamethasone (Dex) treatment. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are induced by several inflammatory cytokines such as TNF-alpha. The aim of this study was to investigate pulmonary ICAM-1 and VCAM-1 expression in CDH lung in rats and to determine the effect of antenatal glucocorticoid. CDH model was induced in pregnant rats following administration of nitrofen on day 9.5 of gestation. In control animals, the same dose of olive oil was given without nitrofen. Dex (0.25 mg/kg) was given on day 18.5 and 19.5 of gestation. RT-PCR was performed to evaluate the relative amount of ICAM-1 and VCAM-1 mRNA expression. Fluorescein immunohistochemistry using anti-ICAM-1 and anti-VCAM-1 antibody was performed using light and confocal microscopy. ICAM-1 and VCAM-1 mRNA expression and ICAM-1 and VCAM-1 immunoreactivity were markedly increased in CDH lung compared to controls. Dex downregulated the expression of both adhesion molecules in the hypoplastic lung. Increased ICAM-1 and VCAM-1 mRNA expression in hypoplastic lungs would suggest that the increased local synthesis of pulmonary adhesion molecules may induce respiratory distress in CDH. Decreased expression of adhesion molecules in CDH lungs after Dex treatment suggests that antenatal glucocorticoids therapy may improve pulmonary immaturity and associated respiratory distress in nitrofen-induced CDH lung.

Animals↗

ICAM-1 expression is upregulated in reflux nephropathy.

Reflux nephropathy (RN) is a major cause of end-stage renal failure in children and young adults. Intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein, has a role in the regulation of interaction among immune cells. It has been demonstrated that increased levels of tubular ICAM-1 correlate with an extent of tubular damage in diabetic nephropathy. We hypothesized that ICAM-1 local synthesis is altered in reflux nephropathy and therefore designated this study to investigate ICAM-1 expression in RN. The kidney specimens from six patients with severe reflux nephropathy secondary to primary vesicoureteral reflux were obtained at the time of nephrectomy. Control materials included normal kidney specimens obtained from three adult patients during partial nephrectomy for an incidentaloma. Fluorescent immunohistochemistry was carried out using monoclonal antibodies to ICAM-1 utilizing confocal laser scanning microscopy. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of ICAM-1. In the control kidneys, there was lack of ICAM-1 immunoreactivity in the interstitium and proximal tubules and moderate immunoreactivity in the glomerulus. In the refluxing kidney there was strong ICAM-1 immunoreactivity in the glomerulus, interstitium and proximal tubules. The RT-PCR showed strong ICAM-1 mRNA expression in the refluxing kidneys and absent or weak ICAM-1 expression in the controls. Our findings of increased expression of ICAM-1 in the severe reflux nephropathy kidney suggests that ICAM-1 may play a role in the pathogenesis of renal parenchymal damage associated with RN.

Adult↗

Increased c-Met tyrosine kinase expression in segmental renal dysplasia.

Renal dysplasia (RD) is a disorganized development of renal parenchyma that results in a deficit of functional renal tissue. It has been suggested in the animal model that increased expression of HGF receptor, c-Met tyrosine kinase in the epithelial cells during kidney development may induce a growth of dysplastic epithelia and result in RD. The aim of this study was to investigate the immunoreactivity of c-Met tyrosine kinase in the dysplastic kidney in order to further understand the pathogenesis of RD. Specimens of dysplastic upper pole kidney were obtained from 19 patients during upper pole partial nephrectomy for non-functioning upper moiety of duplex kidney. In the dysplastic kidney, there was strong c-Met immunoreactivity in the epithelium of primitive tubules. In contrast, c-Met immunoreactivity was barely detectable in the normal kidney. Markedly increased expression of HGF receptor, c-Met tyrosine kinase in renal dysplasia suggests that HGF may be involved in the development of renal dysplasia.

Child↗

Bronchoarterial ratio and bronchial wall thickness on high-resolution CT in asymptomatic subjects: correlation with age and smoking.

OBJECTIVE: The purpose of this study was to determine whether the values of the bronchoarterial ratio and bronchial wall thickness, as viewed during high-resolution CT, relate to age and smoking status in asymptomatic healthy subjects. SUBJECTS AND METHODS: High-resolution CT was performed prospectively in 85 subjects without cardiopulmonary disease. The subjects were divided into three groups according to age: 29 subjects were 21-40 years old; 29 subjects, 41-64 years old; and 27 subjects, 65 years or older. Both bronchoarterial ratios, defined as the diameter of the bronchial lumen divided by the diameter of its accompanying artery, and the T/D ratio, defined as wall thickness (T) divided by the total diameter of the bronchus (D), were measured at the segmental and subsegmental levels of the apical and posterior basal segments. Each calculated ratio was evaluated according to age and smoking status. RESULTS: Significant correlation was found between the bronchoarterial ratio and age (r = 0.768, p < 0.0001), with the bronchoarterial ratio increasing with age and exceeding 1 in 41% of subjects older than 65 years. No significant correlation was seen between the T/D ratio and age. No significant differences in bronchoarterial ratio and T/D ratio were seen between smokers and nonsmokers in subjects overall; but in the elderly group, the T/D ratio was significantly higher in smokers than in nonsmokers (p = 0.021). CONCLUSION: The bronchoarterial ratio is influenced by aging. The normal bronchoarterial ratio in a substantial number of subjects older than 65 years overlaps with the ratio considered to represent bronchiectasis. Thus, when this ratio is used for the quantitative analysis of pulmonary and cardiovascular disease, the influence of age should be considered.

Adult↗

Effect of the rate of gadolinium injection on magnetic resonance pulmonary perfusion imaging.

PURPOSE: To determine whether the injection rate of contrast agent affects the dynamics of enhancement of the pulmonary parenchyma on magnetic resonance (MR) pulmonary perfusion imaging. MATERIALS AND METHODS: Fifteen healthy volunteers underwent enhanced MR pulmonary perfusion imaging to evaluate the effects of different injection rates. Injection rates were 1, 3, or 5 mL/second. Regions of interest (ROIs) were chosen in the lung and aorta to analyze the change in signal intensity over time. RESULTS: As the injection rate increased, the peak enhancement occurred significantly earlier (P = 0.0012), but the peak enhancement signal-to-noise ratio (SNR) value was not affected (P = 0.25). With the 3- and 5-mL/second injection rates, images of both the pulmonary circulation and systemic circulation were obtained separately. However, with 1 mL/second, higher enhancement of the aorta was overlapped with peak enhancement of the lung tissue. CONCLUSION: The injection rate affects the enhancement profiles of the pulmonary parenchyma.

Adult↗

Selective chemical ablation of the enteric plexus in mice.

Although genetically aganglionic mice such as piebald lethal and lethal spotted mice exhibit striking similarities to the human condition of Hirschsprung's disease (HD), the aganglionic segment is very short and always located in the distal part of the rectum. Topical application of benzalkonium chloride (BAC) to the rectum of rats has been reported to result in segmental aganglionosis. To induce chemical ablation of the enteric plexus in mice to produce an aperistaltic narrow segment simulating HD, 32 mice were divided into three groups: (1) abdominal (n=12), for sigmoid colon treatment; (2) rectal (n=10), for rectum treatment; and (3) controls (n=10). For groups 1 and 2, 0.1% BAC was applied to a 1-cm serosal surface of the bowel for 15 min. In the controls, isotonic saline was applied in this fashion. A detailed histologic examination was performed using hematoxylin and eosin staining and acetylcholinesterase histochemistry. Ten animals (9 in group 1 and 1 in group 2) died 1 to 9 weeks after BAC treatment. Autopsy revealed a narrow segment of bowel at the site of BAC treatment and marked dilatation of the bowel proximal to the narrow segment. The remaining animals were killed 12 weeks after BAC treatment. Histologic examination demonstrated normal myenteric and submucous plexuses in the controls, whereas there was a total lack of innervation in the BAC-treated segments.Topical application of BAC thus successfully produced a narrow aganglionic segment of bowel in normal mice. This model provides the basis for future studies to investigate the pathophysiology of HD and megacolon and for comparison with genetically aganglionic mice.

Animals↗

Nitric oxide, enhanced by macrophage-colony stimulating factor, mediates renal damage in reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) is a major cause of end-stage renal failure in children and young adults. Nitric oxide (NO) is an important mediator of tissue injury and inflammation. NO production is enhanced by hematopoietic growth factor including macrophage colony stimulating factor (M-CSF). M-CSF plays a pivotal role in the development of nephritis via macrophage activation. The aim of this study was to investigate the expression of inducible NO synthase (iNOS) and M-CSF in the refluxing kidney, in order to further understand the pathogenesis of RN. METHODS: The kidney specimens from 6 patients with severe RN and 6 controls were examined by NADPH-diaphorase histochemistry and immunohistochemistry using ABC method with anti-M-CSF antibody. Double staining using NADPH-diaphorase histochemistry/M-CSF immunohistochemistry and M-CSF/iNOS fluorescence immunohistochemistry also was performed. In situ hybridization was performed using digoxigenin labeled M-CSF specific probe. RT-PCR was performed to evaluate the relative amount of iNOS mRNA expression. Apoptosis was determined using the in situ end-labeling technique. RESULTS: The most striking difference between tissues from RN patients and controls was the marked increase in NADPH-d activity, iNOS immunoreactivity and mRNA and M-CSF immunoreactivity and mRNA expression in the kidneys of RN patients, particularly in the distal tubules, collecting system. Apoptotic cells were markedly increased in RN compared to controls. CONCLUSIONS: Our findings suggest that the increase in M-CSF-stimulated local production of nitric oxide may be a major mediator in the development of reflux nephropathy.

Adolescent↗

Effect of mechanical ventilation on the pulmonary expression and production of elastin in nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Hypolastic lung in congenital diaphragmatic hernia (CDH) shows markedly thickened alveolar walls, increased interstitial tissue, and markedly diminished alveolar air space, showing morphologic immaturity. Decrease in lung compliance and distensibility often is seen in human CDH as well as experimentally produced CDH. Collagen and elastin, critical components of the lung connective tissue, have been suggested to have important influence on lung compliance and maximal expansion. The barotrauma caused by mechanical ventilation is known to produce structural changes in the pulmonary architecture. The aim of this study was to investigate the expression and production of elastin in the lung in newborn rats with CDH during mechanical ventilation. METHODS: CDH was induced in rat embryos after administration of nitrofen to pregnant dams on day 9.5 of gestation. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated using a 24-gauge Teflon catheter. After ligation of the umbilical cord, the intubated animals were transferred immediately to a warm plate and connected to a modified ventilator. Ventilation was continued for a maximum of 6 hours. The relative amount of soluble elastin in the lung was assessed using an enzyme-linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of tropoelastin mRNA expression in the lung. RESULTS: Elastin mRNA in the CDH lung was increased significantly (P <.01) at one hour after ventilation compared with ventilated controls. Elastin protein significantly increased in the CDH lung at one hour (P <.01) and 6 hours (P <.01) after starting ventilation compared with controls. CONCLUSION: The data show that during mechanical ventilation, elastin production is increased significantly in the CDH lung, and this may further affect lung compliance.

Animals↗