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Biomedical subjects

Kenji Nakamura

Publications and source records attributed to Kenji Nakamura.

At least 73 records · Page 4Linked to original sources

[A case of pulmonary Langerhans' cell histiocytosis].

A 42-yr-old woman was referred to our hospital because of multiple small nodules in a chest radiograph. She had no symptoms such as dyspnea, cough or sputum. A chest CT revealed many centrilobular small nodules and thin-walled cysts with predominance in the peripheral area of the lungs. The specimens obtained by thoracoscopic surgery showed granulomas with scattered eosinophils and numerous Langerhans' cells. The Langerhans' cells were positive for both S-100 protein and CD1a. These findings are compatible with pulmonary Langerhans' cell histiocytosis (LCH). Since the granulomas showed no fibrotic changes, the LCH may have been in its early stages. However, there were clusters of lymphocytes and macrophages around the terminal and respiratory bronchioles, and cystic lesions without cellular infiltrates, in the specimens. The former histologic findings suggested respiratory bronchiolitis causing interstitial lung disease and the latter are indistinguishable from centrilobular emphysema. Therefore, these smoking-related diseases may have been superimposed on the LCH in this patient.

Adult↗

[A case of advanced gastric cancer with multiple liver metastases responding to TS-1 and CDDP].

A 44-year-old male presented to our hospital with abdominal pain. The upper endoscopy revealed advanced gastric cancer. On the abdominal CT, there was evidence of multiple, massive liver metastases. After total gastrectomy, the patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra-hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had decreased significantly both in size and number after 2 cycles. The current case suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of advanced gastric cancer with multiple liver metastases.

Administration, Oral↗

Evaluation of the performance of polished mirror surfaces for the TAMA gravitational wave detector by use of a wave-front tracing simulation.

We evaluated the performance of polished mirror surfaces for the TAMA interferometric gravitational wave detector by comparing the experimental results with a wave-front tracing simulation. The TAMA mirror surfaces were polished to a roughness of a few nanometer rms. We confirmed that these polished mirrors do not limit the present TAMA sensitivity and that the target shot-noise sensitivity will be achieved with these mirrors, even if a power-recycling technique is introduced in the next stage of the TAMA.

Journal Article↗

Antisense oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury.

Tissue factor (TF) is an initiation factor for blood coagulation and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury. AS-1/TF was delivered intravenously to Lewis rats. After 10 h, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 min and harvested. TF expression was studied using immunohistochemical staining. One of 10 rats survived in a 5-day survival rate and TF was strongly stained on endothelial cells in non-treatment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells. These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver.

Animals↗

Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant.

Mutations of either PKD1 or PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The molecular function of the gene product of PKD1, polycystin-1, in vitro has been elucidated recently, but the molecular pathological consequences of the loss of polycystin-1 in vivo have remained unclear. We have generated a mouse with a targeted deletion of exons 2-6 of Pkd1 to study the molecular defects in Pkd1 mutants. Homozygote embryos (Pkd1(-/-)) developed hydrops, cardiac conotruncal defects and renal cystogenesis. Total protein levels of beta-catenin in heart and kidney and c-MYC in heart were decreased in Pkd1(-/-) embryos. In the kidneys of Pkd1(-/-), the expression of E-cadherin and PECAM in basolateral membranes of renal tubules was attenuated, and tyrosine phosphorylation of epidermal growth factor receptor and Gab1 were constitutively enhanced when cystogenesis started on embryonic day (E) 15.5-16.5. Maternally administered pioglitazone, a thiazolidinedione compound, resolved these molecular defects of Pkd1(-/-). Treatment with pioglitazone improved survival of Pkd1(-/-) embryos and ameliorated the cardiac defects and the degree of renal cystogenesis. Long-term treatment with pioglitazone improved the endothelial function of adult Pkd1(+/-). These data indicated that molecular defects observed in Pkd1(-/-) embryos contributed to the pathogenesis of ADPKD and that thiazolidinediones had a compensatory effect on the pathway affected by the loss of polycystin-1. Pathways activated by thiazolidinediones may provide new therapeutic targets in ADPKD.

Animals↗

Inactivation of Cdc7 kinase in mouse ES cells results in S-phase arrest and p53-dependent cell death.

Cdc7-related kinases play essential roles in the initiation of yeast DNA replication. We show that mice lacking murine homologs of Cdc7 (muCdc7) genes die between E3.5 and E6.5. We have established a mutant embryonic stem (ES) cell line lacking the muCdc7 genes in the presence of a loxP-flanked transgene expressing muCdc7 cDNA. Upon removal of the transgene by Cre recombinase, mutant ES cells cease DNA synthesis, arresting growth with S-phase DNA content, and generate nuclear Rad51 foci, followed by cell death with concomitant increase in p53 protein levels. Inhibition of p53 leads to partial rescue of muCdc7(-/-) ES cells from cell death. muCdc7(-/-)p53(-/-) embryos survive up to E8.5, and their blastocysts generate inner cell mass of a significant size in vitro, whereas those of the muCdc7(-/-)p53(+/-) embryos undergoes complete degeneration. These results demonstrate that, in contrast to cell cycle arrest at the G(1)/S boundary observed in yeasts, loss of Cdc7 in ES cells results in rapid cessation of DNA synthesis within S phase, triggering checkpoint responses leading to recombinational repair and p53-dependent cell death.

Animals↗

Relation of biliary bile acid output to hepatic adenosine triphosphate level and biliary indocyanine green excretion in humans.

We have previously demonstrated that there are two subgroups of patients with different types of biliary bile acid output after relief of obstructive jaundice by percutaneous transhepatic biliary drainage (PTBD). The reason for two groups is not clear but is possibly the difference in hepatic reserve function. The aim of this study was to examine the relation of biliary bile acid output to the hepatic ATP level and biliary excretion rate of indocyanine green (ICG) in humans. Patients whose bile could be collected through a PTBD tube participated in this study. The mean serum total bilirubin concentration was 12.7 mg/dl at the time of PTBD, decreasing to 1.1 mg/dl before surgery. These patients underwent curative resection for cancer of the bile duct, duodenal papilla, or pancreatic head after the relief of hyperbilirubinemia. Bile was collected at 1-hour intervals for 5 hours after intravenous administration of ICG (0.5 mg/kg) within a few days before surgery, and a small liver tissue sample was obtained immediately after laparotomy without using ischemic procedures. The concentrations of total bile acid and ICG in bile, the bile flow rate, and the bile acid output and ICG excretion rate in bile over 5 hours were determined. ATP concentrations in liver tissue were determined by high performance liquid chromatography. Results of hepatic ATP levels were correlated with the bile acid output and ICG excretion rate into bile. Both the biliary bile acid output (micromoles per 5 hours) and ICG excretion rate (percent of injected dose of ICG) over 5 hours were significantly correlated with the hepatic ATP level (p = 0.0190 and p = 0.0084, respectively). Neither the bile flow rate nor the serum liver function tests were related to the hepatic ATP level. Significant correlation was found between the bile acid output and the ICG excretion rate (p = 0.0127). Biliary bile acid output reflects the hepatic ATP level. Determination of the biliary bile acid output and ICG excretion may provide useful parameters for evaluating the hepatic energy status, which is essential for organ viability.

Adenosine Triphosphate↗

The role of tissue factor in renal ischemic reperfusion injury of the rat.

BACKGROUND: Tissue factor (TF) is a membrane-bound glycoprotein that is the primary cellular initiator of the blood clotting cascade and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit tissue factor activity. We studied the role of TF in the kidney following warm ischemic reperfusion and studied the effect of TFPI in vivo. MATERIALS AND METHODS: After laparotomy of Lewis rats, the right kidney was harvested and left renal artery and vein were clamped. The kidney was reperfused after 60, 120, and 180 min of ischemia. Rats were sacrificed at 0, 1.5, 5, 12, and 24 h after reperfusion with or without TFPI treatment, and the kidney was harvested. Blood samples were collected at 0, 5, 12, and 24 h after reperfusion from the abdominal aorta. Blood urea nitrogen and kalium were monitored. TF expression was also studied by immunohistochemical staining with a monoclonal antibody (HTF-K108). RESULTS: Histologically, the necroses of the tubular epithelial cells were observed 1.5 h after reperfusion. Immunohistochemically, TF staining was positive on the glomerular endothelial cells and stimulated monocytes but negative on the tubular epithelial cells. The necrotic area extended and encompassed almost all of the ischemic kidney by 12 h after reperfusion. TF was stained on the glomerular base membrane, the glomerular endothelial cells, and the stimulated monocytes but was not evident on the necrotic tubular epithelial cells. Fibrinogen was also observed in the glomerular endothelial cells at 5-12 h after reperfusion, while it was slight in normal tissue. With TFPI treatment, the necrotic area was narrow and TF was slightly stained on the endothelial cells. CONCLUSIONS: These results suggest that TF plays an important role in the development of renal injury after ischemia and reperfusion. The microcirculatory incompetence due to microthrombus might cause the formation and development of the necrosis. These results also suggest that TFPI plays a key role in modulating tissue factor-dependent blood coagulation, therefore TFPI is a strong medication for prevention of ischemic reperfusion injury.

Animals↗

Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction.

A subepicardial aneurysm became evident in a male patient after anticoagulant therapy. On admission, it appeared to be an old anterior infarction accompanied by a mural thrombus. After warfarin administration, the thrombus disappeared and an echo-free space emerged outside the apical myocardial wall. The echo-free space communicated with the left ventricular cavity through the apical myocardial wall. Emergency surgery was undertaken and the patient survived. The aneurysm was covered with epicardium and there was an endomyocardial rupture of the muscle in the apical wall, which was the entrance of the aneurysm. This case suggests that cautious follow-up with echocardiography is necessary when anticoagulant therapy is selected for thrombi following myocardial infarction.

Anticoagulants↗

Inhibition of neointimal hyperplasia by heat stress in an experimental model.

PURPOSE: To evaluate the potential effect of heat stress in inhibiting neointimal hyperplasia after angioplasty in an experimental model. MATERIALS AND METHODS: In vitro, proliferation and migration of heat-stress-induced and noninduced cells were compared with use of an endothelial cell/smooth muscle cell coculture model (five culture dishes in each experiment). Mild heat stress was induced via exposure of cultures to a temperature of 42 degrees C for 2 hours. In vivo, the neointimal thickness of ear arteries of Japanese white rabbits 7 days after denudation of endothelium was histologically evaluated in the control and heat-stress-induced groups (three rabbits in each group). RESULTS: Proliferation of heat-stress-induced smooth muscle cells declined significantly compared with that of noninduced cells in single-culture and coculture models. The migration rates of neither endothelial cells nor smooth muscle cells were significantly affected by heat stress. In vivo, the mean neointimal thickness was 13.8 micro m +/- 8.0 in the control group and 3.9 micro m +/- 2.1 in the induced group (P <.05). CONCLUSION: Induction of mild heat stress has great potential to reduce neointimal hyperplasia after angioplasty because it inhibits smooth muscle cell proliferation without inhibiting endothelial migration in vitro and suppresses neointimal growth in vivo.

Angioplasty↗

Frequent seizures with elevated interleukin-6 at the eruptive stage of exanthema subitum.

A 15-month-old girl developed frequent seizures at the eruptive stage of exanthema subitum. The eruption persisted for 2 weeks. Serum immunoglobulin G antibody to human herpes virus type 6 (HHV-6) increased markedly. Interleukin-6 was elevated whereas HHV-6 deoxyribonucleic acid was not detected in cerebrospinal fluid. These findings suggest that immune-mediated reactions after HHV-6 infection rather than direct action of active HHV-6 are responsible for frequent seizures in this case.

Acute Disease↗

Efficacy and safety of balloon-occluded endoscopic injection sclerotherapy as a prophylactic treatment for high-risk gastric fundal varices: a prospective, randomized, comparative clinical trial.

BACKGROUND: No single effective method has yet been established for the prophylactic treatment of gastric fundal varices at high risk for bleeding. A prospective, randomized trial was conducted to compare the efficacy and safety of a new technique, balloon-occluded endoscopic injection sclerotherapy (BO-EIS), to balloon-occluded retrograde transvenous obliteration (B-RTO) for treatment of high-risk gastric fundal varices. METHODS: Twenty consecutive patients with gastric variceal diameters of over 5 mm by color Doppler EUS were randomized to undergo either BO-EIS or B-RTO. All patients underwent color Doppler EUS 2 weeks after treatment and EGD every 3 months for assessment of sclerosing effect. RESULTS: The gastric varices in all patients except one in the B-RTO group were eradicated with either treatment. The volume of sclerosant used was significantly smaller in patients who underwent BO-EIS (p < 0.05). The endoscopic grade of esophageal varices in 4 of 9 patients worsened after treatment with B-RTO (p < 0.05). The method of randomization used resulted in an uneven distribution of women, although the difference between the groups was not statistically significant. When only men were compared, the results of the study were unchanged. CONCLUSIONS: BO-EIS is a safe and effective for treatment of high-risk gastric fundal varices. In contrast to B-RTO, it can be used even in patients without a gastrorenal shunt.

Aged↗

A prematurely terminated phase III trial of intraoperative intrapleural hypotonic cisplatin treatment in patients with resected non-small cell lung cancer with positive pleural lavage cytology: the incidence of carcinomatous pleuritis after surgical intervention.

BACKGROUND: The prognosis of patients with resected non-small cell lung cancer without carcinomatous pleuritis whose intrapleural cancer cells were detected by means of a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy has been reported to be poor. METHODS: The Japan Clinical Oncology Group conducted a phase III trial for a 3-year period starting from October 1994 to determine whether intraoperative intrapleural hypotonic cisplatin treatment could effectively control pleural disease and thereby prolong the survival of these patients. The patients were randomized to receive either intraoperative intrapleural hypotonic cisplatin treatment or no treatment before closure of the open thorax. The intraoperative intrapleural hypotonic cisplatin treatment consisted of exposing the entire thorax to cisplatin (50 microg/mL) in distilled water for 15 minutes. RESULTS: Because of the slow registration pace, the study was prematurely terminated in January 1998. During the 41-month period from the start of the registration, 49 patients were entered into the study, and all were eligible. Twenty-five and 24 patients were randomly assigned to the treatment and control groups, respectively. No statistically significant difference in the overall survival and disease-free survival between the 2 groups was observed. However, the appearance of carcinomatous pleuritis was suppressed by the hypotonic cisplatin treatment (42% of the control group vs 8% of the treatment group, P =.008). CONCLUSIONS: Although the randomized trial was prematurely terminated, the intraoperative intrapleural hypotonic cisplatin treatment was found to effectively suppress the appearance of carcinomatous pleuritis in resected patients who demonstrated a positive pleural lavage cytology finding.

Aged↗

[Macroscopic indices of psychiatric hospital functions: evaluation based on data of remaining hospitalized patients].

In recent years, mental health administration in Japan has been changing its orientation from institutional care to community-based care. For this reason, we need new macroscopic indices evaluating psychiatric hospital functions. The most notable indices are data of the remaining hospitalized patients. In this paper, we discuss the macroscopic indices evaluating psychiatric hospital functions focusing on the data of the remaining hospitalized patients. The data are based on a survey of the number of monthly discharged patients who had been admitted to 1,617 psychiatric hospitals in the month of June 1998. The result shows that 1. 70.4% of admitted patients are discharged to communities within a year, 2. 18.3% of patients remain hospitalized one year after admission, and 3. 50% of admitted patients are discharged within 74.2 days. Examination of these data showed it is very useful to evaluate psychiatric hospital functions by categorizing psychiatric hospitals based on the rate of patients remaining hospitalized one year after admission. We also found that "the rate of admissions discharged to communities within a year", "the rate of patients remaining hospitalized after one year", "transition in the rate of patients remaining hospitalized", and "the number of days until 50% of admitted patients are discharged" can be used as effective and practical indices evaluating psychiatric hospital functions.

Community Mental Health Services↗

Alterations to hepatic microcirculation in thioacetamide-induced cirrhotic livers of rats.

In liver cirrhosis, increased resistance of intrahepatic microvasculature contribute to the development of portal hypertension. This study aimed to reveal the alterations to hemodynamics in microvasculature of thioacetamide-induced fibrotic and cirrhotic rat livers, using in vivo microscopy. In fibrotic livers, although intrahepatic blood flow remained unaltered, area percentage of sinusoids was significantly decreased. In cirrhotic livers, intrahepatic blood flow was significantly increased concurrently with decrease in area percentage of sinusoids. The flow velocity and volume flow were significantly increased in terminal portal venules (TPVs) without changes in vascular diameters, whereas all these parameters were not altered in terminal hepatic venules (THVs). Intrahepatic shunts which emerged from TPVs and ran toward THVs, and anastomoses between neighboring THVs were formed in cirrhotic livers. These data indicate that the first occurring alteration of microcirculation in liver cirrhosis is decrease in sinusoidal beds.

Animals↗

Brachytherapy for the prevention of neointimal hyperplasia in the canine inferior vena cava after stent placement.

The aim of this study was to evaluate the efficacy of brachytherapy for preventing neointimal hyperplasia in the inferior vena cava (IVC) after stent placement. Sixteen beagles underwent Z-stent placement in the IVC and the aorta. For 8 of 16 beagles, irradiation (15 Gy) was delivered endoluminally to the stented segments of each vessel immediately after stent placement using the 192Ir. All animals were sacrificed after 6 weeks for morphometric and histopathologic examination. Morphometrically, neointimal thickness in the IVC of the radiation group was significantly decreased compared with the control group as well as that in the aorta (p < 0.05). Histopathologic findings showed the neointima in the IVC of the control group contained markedly organization of thrombus and neovascularization though that in the IVC of the radiation group consisted mainly of smooth muscle cells without organization of thrombus and neovascularization. From these data intravenous irradiation may prevent clinical restenosis after stent placement.

Animals↗