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Biomedical subjects

Y Kuwabara

Publications and source records attributed to Y Kuwabara.

At least 19 recordsLinked to original sources

Proteome analysis of human placentae: pre-eclampsia versus normal pregnancy.

Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to obtain placental proteome maps. The identified protein spots (ca. 60% of the total) on the proteome maps included several pregnancy-related proteins (PRPs). Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to pre-eclampsia revealed three immunopositive spots that appeared to correspond to dynactin p-50, a protein related to cell turn-over. The rate of positivity for dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre-eclamptic women than in 58 normally pregnant women. These results indicate that dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.

Adult↗

Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma.

NDRG1 (N-myc downstream regulated gene-1) was reported to be necessary for p53-mediated apoptosis and to be regulated by PTEN (phosphatase and tensin homolog). In several cancers, it was suggested to be a tumor suppressor gene. Its significance in esophageal squamous cell carcinoma (ESCC) has not been studied. The objective of this study was to clarify the relation between clinicopathological and biologic factors in esophageal carcinoma and to determine the prognostic significance of the expression of NDRG1. Expression of NDRG1 mRNA was quantified by real-time reverse transcription polymerase chain reaction using a Lightcycler in 47 esophageal ESCC specimens. The data were analyzed with reference to clinicopathological factors. Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0-I vs. II-IV; P = 0.0027) and local tumor invasion (T1-2 vs. T3-4; P = 0.0136). Patients who had low NDRG1 mRNA expression had a significantly shorter survival after surgery compared with patients who had high NDRG1 mRNA expression (log-rank test, P = 0.0478). Impaired NDRG1 expression may lead to more aggressive invasion of ESCC.

Aged↗

Cerebral hemodynamics in Moyamoya disease: correlation between perfusion-weighted MR imaging and cerebral angiography.

BACKGROUND AND PURPOSE: In Moyamoya disease, the relationship between cerebral hemodynamics and angiographic findings has not been fully evaluated. The purpose of this study is to evaluate hemodynamics in Moyamoya disease with perfusion-weighted MR imaging (PWI) and cerebral angiography. METHODS: Twenty patients with Moyamoya disease were the subjects. Mean transit time (MTT) derived from PWI was calculated in the medial frontal lobes, the posterior frontal lobes, the occipital lobes, and the basal ganglia. From the angiographies, we classified the degrees of internal carotid artery (ICA) and posterior cerebral artery (PCA) stenoses as well as the degrees of Moyamoya vessels and leptomeningeal anastomosis (LMA). MTT in each region was compared with the angiographic findings. RESULTS: MTT positively correlated with the degree of ICA stenosis in the medial frontal (P < .01), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of PCA stenosis in the medial frontal (P < .001), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of Moyamoya vessels in the medial frontal (P < .05) and posterior frontal (P < .01) lobes. A multivariate analysis revealed that ICA and PCA stenoses and Moyamoya vessels were independent factors that prolonged MTT. CONCLUSION: Both ICA and PCA stenoses may influence overall cerebral perfusion in Moyamoya disease. The development of Moyamoya vessels may indicate hemodynamic impairment.

Adolescent↗

Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance and pulmonary complication in thoracic esophagectomy patients.

SUMMARY: In spite of improvements in surgical technique and perioperative care, severe lung complication remains as the leading cause of morbidity in thoracic esophageal cancer patients who undergo esophagectomy. The purpose of this study was to evaluate the safety and effectiveness of postoperative drug therapy using low dose dopamine, gabexate mesilate, and ulinastatin on postoperative lung complication in esophageal cancer patients. Sixty-one patients operated for esophageal cancer from 1996 to 2000 were treated postoperatively with low dose dopamine (300 microg/kg/h), gabexate mesilate (80 mg/h), and ulinastatin (300 000 unit/day) as a study group. Seventy-four patients operated from 1987 to 1994 served as an historical control group. Various preoperative and perioperative medical parameters and water balance were analyzed. Postoperative pulmonary complications were observed in 26 patients (35.1%) in the control group and three patients (4.9%) in the study group, respectively (P < 0.0001). Preoperative and perioperative variables were not significantly different between the groups. Water balance from operation to postoperative day 3 in the study group was significantly lower than the control group. Postoperative use of low dose dopamine, gabexate mesilate, and ulinastatin significantly reduced pulmonary complications after esophagectomy. This may be partly attributable to negative water balance during the early postoperative days.

Carcinoma, Squamous Cell↗

Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy.

BACKGROUND: Impaired regeneration and dysfunction of the cirrhotic liver following partial hepatectomy (PHx) are the most serious risk factors for postoperative liver failure. AIMS: Using naked hepatocyte growth factor (HGF) plasmid by the electroporation (EP) in vivo method, we investigated HGF for its role and mechanism of proliferation and restoration of liver mass in cirrhotic mice following PHx. ANIMALS: Eight week old female mice were used. METHODS: HGF plasmid 50 micro g was injected intramuscularly and transferred by EP in vivo once a week for three weeks. After establishment of carbon tetrachloride induced cirrhosis, mice underwent PHx. The HGF treated group was given naked HGF plasmid four days before PHx, and additional HGF was given once a week until they were killed, while a control group was given only empty plasmid. Mice were killed 2, 4, 10, and 14 days after PHx. Morphological and functional restoration of the liver were examined, as well as activation of mitogen activated protein kinase (MAPK) and mRNA levels of HGF activator (HGFA). RESULTS: The HGF treated group demonstrated a continuous threefold increase in HGF levels in plasma. Therapy with HGF in cirrhotic PHx resulted in effective liver regeneration via restoration of HGFA and activation of MAPK p44/p42, accelerated normalisation of liver function, and increased collagen degradation. CONCLUSIONS: HGF gene therapy by in vivo EP may be useful for hepatic resection in cirrhotic livers by stimulating liver proliferative and collagenolytic capacities, as well as accelerating functional recovery.

Animals↗

Changes in the proportion of T helper 1 and T helper 2 cells in cord blood after premature rupture of membranes.

This study investigated changes in the proportion of T helper (Th)1 and Th2 cells in cord blood after premature rupture of membranes (PROM), and evaluate the effects of PROM on the intrauterine fetal immune status. The proportion of CD3-positive T cells secreting interferon (IFN)-gamma as an index of Th1 cells, and interleukin (IL)-4 as an index of Th2 cells in cord blood of 12 newborns with and without PROM, were analyzed by flow cytometry. In cord blood of newborns with PROM, the proportion of IFN-gamma secreting cells significantly increased, and the proportion of IL-4 secreting cells was rather high but not significantly higher than that of newborns without PROM. These changes eventually caused a shift in the Th1/Th2 ratio to Th1 dominance in PROM. There was no significant correlation between the proportion of IFN-gamma secreting cells and the duration of PROM before the onset of labor. These results suggest that the increase in the proportion of IFN-gamma secreting cells after PROM, which eventually cause the Th1/Th2 ratios to show the Th1 predominance, may reflect in part intrauterine fetal immune responses to PROM.

Adult↗

Serum adenosine deaminase activity and its isoenzyme pattern in women with normal pregnancies.

Adenosine deaminase (ADA) is a purine enzyme which is essential for the proliferation, maturation and function of lymphoid cells, and congenital deficiency of this enzyme is associated with severe combined immunodeficiency disease. The activity of ADA has changed in diseases characterized by the alteration of cell-mediated immunity such as rheumatoid arthritis, systemic lupus erythematosus and tuberculosis, so ADA has been considered as a nonspecific marker of cell-mediated immunity. In this study we examined changes in serum total ADA activity and the patterns of two ADA isoenzymes, ADA1 and ADA2 in normal pregnant women, and evaluated the possible role of the alteration of cell-mediated immunity during normal pregnancy as causes of changes in ADA activity. We measured serum activities of total ADA, ADA1 and ADA2 in normal pregnant women in the third trimester (n=24) and age-matched healthy nonpregnant women (n=24). Peripheral blood lymphocytes and monocytes were also measured. In normal pregnant women, serum total ADA activity averaged 10.5 +/- 0.5 U/L, which was significantly lower than in nonpregnant women (14.0 +/- 0.5 U/L ) (p<0.05), and mean serum ADA2 activity also significantly reduced that of nonpregnant women (p<0.05). There was no significant difference in ADA1 activity in normal pregnant and nonpregnant women. The decrease in total ADA activity was accompanied by the decrease in lymphocyte count. These results suggest that reduced serum total ADA activity reflects decrease in ADA2 activity, and which may be in part associated with depressed cell-mediated immunity during normal pregnancy.

Adenosine Deaminase↗

Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells.

To determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF) and related compounds on the growth of leukemic cells, human myeloid leukemic cells (HL-60) were exposed to bovine lactoferrin (bLF) and proteolytic hydrolysates of bLF. Pepsin hydrolysates of bLF showed a greater growth suppressive effect than tryptic hydrolysates or mature bLF. Four peptides with proliferation inhibition activity were purified from pepsin hydrolysates by ion-exchange chromatography, reverse-phase HPLC, and gel-filtration. All peptides were from the N-terminal end, in a region where lactoferricin B (Lfcin B), an antibacterial peptide, is located. Among the four peptides, peptide 1 (pep1) was found to exhibit highest activity and corresponded to residues 17 to 38 of bLF, with a molecular weight of 2753.88. The IC50 value of this peptide was 6.3 micrograms/ml. Three other peptides were less active and corresponded to sequences 1 to 16 and 45 to 48, linked by disulfide-bridge (pep2, molecular mass of 2430.13), 1 to 15 and 45 to 46 linked by disulfide bridge (pep3, molecular mass of 2017,92) and from residues 1 to 13 (pep4, molecular mass of 1558.73). Cell proliferation inhibition activity of the peptides was thought to be due to induction of apoptosis, which was evaluated by DNA ladder formation, DNA fragmentation, enhanced expression of phosphatidyl serine, and morphological changes. The IC50 values of the three peptides were confirmed using synthetic peptides and were consistent with those of purified peptides.

Amino Acid Sequence↗

Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome.

Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical hyperplasia (AH) of the endometrium who received conservative treatment to preserve fertility were collected from member institutions of the Japan Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed with EA without myometrial invasion and AH, respectively. We performed a central pathological review to make definite diagnoses, and the diagnosis of EA in 29 cases was changed to AH in ten, complex hyperplasia in three and atypical polypoid adenomyoma in three, and AH in ten was changed to EA in one and simple hyperplasia in one. Nine of 12 women (75%) with EA and 15 of 18 women (83%) with AH had an initial response to medroxyprogesterone acetate (MPA) treatment. Two of nine responders with EA later developed relapse, and one of them had metastasis to the left obturator lymph node. Two became pregnant, and one delivered one full-term infant. One of the responders with AH had a relapse in the endometrium. Five became pregnant, and four delivered four normal infants. The young women with endometrial carcinoma localized in the endometrium who wish to preserve fertility may be treated as successfully with MPA as those with AH.

Adenocarcinoma↗

L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-Serine biosynthesis.

Microglia are well known to become activated during various kinds of neuropathological events. The factors that are responsible for the activation, however, are not fully determined. In the present study, L-Ser was shown to enhance production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) by lipopolysaccharide (LPS)-stimulated cultured rat microglial cells. L-Ser, however, did not enhance the expression of mRNAs encoding inducible NO synthase, IL-6 and TNF alpha. On the other hand, astrocytes did not depend on L-Ser for release of IL-6 and TNF alpha. The expression of an enzyme 3-phosphoglycerate dehydrogenase (3PGDH), which is essential for L-Ser biosynthesis from a glycolytic intermediate 3-phosphoglycerate, was investigated. As revealed by Western blotting and immunocytochemical staining, 3PGDH-protein expression in vitro was the highest in astrocytes, intermediate in neurons and the lowest in microglial cells. Semiquantitative RT-PCR showed that microglial cells expressed 3PGDH-mRNA at a lower level than astrocytes. In frozen sections from rat forebrain, only astrocytes were immunoreactive for 3PGDH. The present study suggested that L-Ser is able to modulate microglial function mainly at the translation level because microglial cells cannot synthesize sufficient amount of L-Ser due to the scarce expression of 3PGDH.

Animals↗

Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy.

Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 +/- 0.226 vs. 0.057 +/- 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 +/- 0.134 vs. 0.320 +/- 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104-5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer.

Age Factors↗

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung.

OBJECTIVE: We retrospectively assessed and compared the usefulness of 11C-methionine (MET)-PET with that of 18F-FDG-PET for the differentiation between benign lesions and malignant tumors of the lung. METHODS: We examined 101 patients with a suspected lung tumor including 79 patients with primary lung cancer and 22 patients with benign lesions. One hundred and forty PET studies (46 studies with MET-PET and 94 studies with FDG-PET) were performed. Both MET-PET and FDG-PET were performed on 39 patients. The MET-PET was performed 15 minutes after the administration of 67-740 MBq of MET, and FDG-PET 45 minutes after the administration of 30-437 MBq of FDG. The results were then evaluated by the standardized uptake value (SUV). RESULTS: The MET uptake in lung cancer was 3.69+/-1.22 (n = 37) which was significantly higher than that in benign lesions 1.81+/-1.04 (n = 9) (p < 0.001). The sensitivity, specificity and accuracy of MET-PET were 83.8%, 88.9% and 84.8%, respectively, when 2.66 of SUV was used as the cutoff value. The FDG uptake in lung cancer was 5.94+/-2.89 (n = 75) and was also significantly larger than that in benign lesions 2.46+/-1.01 (n = 19) (p < 0.001). The sensitivity, specificity and accuracy of FDG-PET were 81.3%, 78.9% and 80.9%, respectively (cutoff = 3.20). The MET uptake in the lesions correlated significantly with FDG uptake (r = 0.71, p < 0.001). According to an ROC analysis, the area under the curve for MET-PET (area = 0. 833) was higher than that for FDG-PET (area = 0.828), but the difference was not statistically significant. Furthermore, the combined use of MET-PET and FDG-PET did not improve the diagnostic ability. CONCLUSIONS: In conclusion, both MET-PET and FDG-PET were considered to be equally useful for the differential diagnosis of lung tumors. Furthermore, MET uptake in lung lesions was found to correlate significantly with FDG uptake.

Adult↗

Hepatic nodular hyperplasia in a boy with Alagille syndrome: CT and MR appearances.

A boy with Alagille syndrome complicated by hepatic nodular hyperplasia (HNH) is reported. During pre-transplantation evaluation, CT and MRI revealed a large hepatic lesion with multiple small nodular lesions. Angiography demonstrated a large hypervascular lesion and CT arterial portography (CTAP) showed a portal perfusion defect corresponding to the lesion. CTAP also revealed large portal vein branches running through the lesion. Although hepatocellular carcinoma is known to accompany Alagille syndrome, HNH should also be considered when large vessels running through the lesion are demonstrated.

Alagille Syndrome↗

Relapse patterns of localized non-Hodgkin's lymphoma of the head and neck after clinical remission: results of a strict follow-up procedure.

BACKGROUND: No effective follow-up strategy for non-Hodgkin's lymphoma (NHL) has been identified to date. The aim of this study was to assess the value of a strict follow-up procedure in patients with NHL after they showed clinical remission. METHODS: One hundred and twenty-one patients with localized NHL of the head and neck who had achieved clinical remission after radiation therapy and/or chemotherapy were followed with a strict follow-up strategy (consisting of a schedule of frequent office visits, imaging studies, and blood tests, even if the patient was asymptomatic). RESULTS: Thirty-nine patients relapsed after remission. Twenty-two (56.4%) of the relapses were associated with symptoms. In the 17 patients with asymptomatic relapses (43.6%), an abnormal physical examination result initially indicated relapse in 10 patients. The other tests that initially indicated relapse included scheduled computed tomography scans (3 patients), scheduled gallium scans (2 patients), and serum lactate dehydrogenase levels (2 patients). According to the Ann Arbor stage at relapse, 72.7% of the patients with symptomatic relapses were stage III or IV, while 70.6% of the patients with asymptomatic relapses were stage I or II. CONCLUSIONS: These results indicate that a strict follow-up procedure is effective in detecting asymptomatic relapses, which generally involve a smaller tumor load than symptomatic relapses.

Adult↗

Use of omentum for mediastinal tracheostomy after total laryngoesophagectomy.

BACKGROUND: Carcinomas of the cervicothoracic esophagus frequently invade the trachea and complete removal of the tumor often requires mediastinal tracheostomy. Traditionally, this surgical management was associated with high morbidity and mortality. Several types of myoctaneous flaps have been used for mediastinal tracheostomy to reduce the complication. We present our experience with a new technique for construction of mediastinal tracheotomy after total laryngoesophagectomy and reconstruction with the stomach. METHODS: The anterior chest wall was amply resected and the distal end of the trachea was placed low between the superior vena cava and aortic arch. We mobilized the entire omentum with the stomach and brought them up to the neck through the posterior mediastinum. The omentum was put around the trachea, main arteries, and the anastomosis. RESULTS: Seven mediastinal tracheostomies were performed using this method. There was no hospital death. Complications included respiratory failure (2 patients) and pyothorax (1 patient). Anastomotic leakage and inominate artery rupture were not experienced. Postoperative survival was disease dependent. All patients were discharged with satisfactory oral food intake, good airway condition, and excellent cosmetic appearance. CONCLUSIONS: We suggest the use of the omentum as a simple and reliable technique in constructing mediastinal tracheostomy following total laryngoesophagectomy for cervicothoracic esophageal cancer.

Esophageal Neoplasms↗

Mesenchymal stem villous hyperplasia of the placenta and fetal growth restriction.

BACKGROUND: Mesenchymal stem villous hyperplasia of the placenta is a rare placental anomaly characterized by placental vascular malformation and the appearance of a partial mole. CASE: A multiparous woman presented with fetal growth restriction (FGR) at 35 weeks' gestation. Ultrasonographic examination showed multiple anechoic lesions on the placental surface. Cesarean delivery was performed at 37 weeks' gestation, and a healthy 1536-g female was delivered. The placenta had aneurysmal dilatations of the chorionic vessels. Unlike other cases, it also showed subamniotic hemorrhage and had no features of a partial mole. Histologic examination established the diagnosis of mesenchymal stem villous hyperplasia of the placenta with severe thrombosis. CONCLUSION: Fetal growth restriction can be caused by severe thrombosis in this placental anomaly.

Chorionic Villi↗

Depressed cerebral oxygen metabolism in patients with chronic renal failure: a positron emission tomography study.

To elucidate brain oxygen metabolism in uremic patients, regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and oxygen metabolism (rCMRO(2)) were measured by positron emission tomography (PET) in 10 hemodialysis (HD) patients and 13 predialysis patients with chronic renal failure (CRF). Data were compared with 20 nonuremic patients (controls) without neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. In the hemisphere, rCMRO(2) in both HD (1.82 +/- 0.10 mL/min/100 g) and CRF patients (1.95 +/- 0.09 mL/min/100 g) showed significantly lower values compared with controls (2.23 +/- 0.05 mL/min/100 g; P < 0.01). Hemispheric rCBF in HD (35.6 +/- 2.1 mL/100 g/min) and CRF patients (36.1 +/- 2.1 mL/100 g/min) was not different from controls (31.8 +/- 1.4 mL/100 g/min). Hemispheric rOEF in CRF patients (45.7% +/- 1.6%) was significantly greater than that in controls (40.5% +/- 1.2%; P < 0.02), but rOEF in HD patients (43.7% +/- 1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially cerebral cortices. All PET parameters in frontal cortices tended to show the lowest values in patients with renal failure. For all HD patients, rCBF in both the frontal cortex and white matter correlated inversely with HD therapy duration (P < 0.05). In conclusion, brain oxygen metabolism is depressed in patients with renal failure on or before the start of HD therapy. The cause for depressed brain oxygen metabolism is considered to be either dysregulation of cerebral circulation or lower brain cell activity.

Brain↗