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Biomedical subjects

M Yasui

Publications and source records attributed to M Yasui.

At least 73 records · Page 4Linked to original sources

[Features of colorectal cancer with fecal-occult-blood tests--comparison with colorectal cancer with no screening].

BACKGROUND: There is now evidence from three randomized controlled trials (from Minnesota, Nottingham and Funen) that screening average-risk individuals for colorectal cancer (CRC) with fecal-occult-blood tests (FOBT) can reduce mortality from CRC. In Japan, mortality rates from CRC have increased and mass screening with FOBT has been performed since 1992. Although there is growing proportion of CRC with FOBT, there is no conclusive evidence that they reduce mortality from this cause. We evaluated the feature of CRC with FOBT, as one of the methods for evaluation of the efficacy of screening with this test. METHODS: Between January, 1982 and December, 1996, 2071 cases with CRC resected in our hospital were considered. We evaluated the clinicopathological findings about age, sex, location of tumor, size depth, incidence of lymph node metastasis, stage and prognosis of CRC with FOBT (376) compared with CRC with no screening (controls; 1695). RESULTS: CRC with FOBT were earlier stage and smaller-sized cancers than controls. No significant difference was found in the incidence of lymph node metastasis at each depth and prognosis in each stage. CONCLUSIONS: By screening with FOBT, we can detect at an earlier stage and with a smaller cancer, with the same biological behavior as controls. Now, we must encourage colon screening, continuing to research ways to improve identification of high-risk subgroups and increase complicance.

Colorectal Neoplasms↗

[A case of neurologic type of Wilson's disease with increased aluminum in liver: comparative study with histological findings to metal contents in the liver].

Histological findings and metal contents in the liver were studied in a patient with neurologic type of Wilson's disease. Copper and aluminum contents in the biopsied liver of the patient with Wilson's disease were measured simultaneously by neutron activation analysis at Research Reactor Institute, Kyoto University. Four cases of adult cirrhosis were selected as the control for cirrhosis and five cases of adult liver as the control for neurologically normal. The biopsied liver showed markedly increase in the copper content (814.4 micrograms/g: dry weight) and extremely high content of aluminum (479.4 micrograms/g: dry weight), compared to those of the controls. On the other hand, macroscopically no cirrhosis was observed and the characteristic appearances of macronodular cirrhosis failed to detect histologically. Interestingly the fibrosis or inflammation of the liver was seen faintly. It is likely that toxic metals in the liver such as aluminum, copper and manganese might be implicated in the pathogenesis of neurologic type of Wilson's disease.

Adult↗

[Comparative studies of breath-hold magnetic resonance cholangiopancreatography (MRCP) between different two sequences and between 1.0T and 1.5T units].

In this article, a comparative study in the diagnostic ability of a breath-hold MRCP between thin slice half-Fourier acquisition single-shot turbo spin-echo (HASTE) and thick slice rapid acquisition with relaxation enhancement (RARE), and between 1.5T and 1.0T units was made. Although thin slice HASTE sequence might be more excellent in the diagnostic ability than thick slice RARE, the ability of depiction of pancreaticobiliary system on MRCP was not statistically different between these two sequences and between 1.0T and 1.5T units. Thick slice RARE sequence was inferior to thin slice HASTE in the depiction of gallbladder stone. However, thick slice RARE sequence was useful for MRCP because a projection image of pancreaticobiliary system could be easily obtained without postprocessing and without misregistration. Thick slice RARE sequence should be used in combination with thin slice HASTE sequence for the diagnosis of pancreaticobiliary system.

Adult↗

Perinatal changes in expression of aquaporin-4 and other water and ion transporters in rat lung.

1. At birth, rapid removal of lung liquid from potential airspaces is required to establish pulmonary gas exchange. To investigate the role for water channels, aquaporins (AQP) and ion transporters in this process, the mRNA expression of AQP, Na+,K(+)-ATPase and the amiloride-sensitive Na+ channel (ENaC) were studied in the fetal and postnatal rat lung. 2. The mRNA expression of all transporters studied increased postnatally. 3. The following water channels were expressed in the lung, AQP1, 4 and 5. The most specific perinatal induction pattern was observed for AQP4. A sharp and transient increase of AQP4 mRNA occurred just after birth coinciding with the time course for clearance of lung liquid. This transient induction of AQP4 mRNA at birth was lung-tissue specific. Around birth there was a moderate increase in AQP1 mRNA, which was not transient. AQP5 increased continuously until adulthood. 4. Fetal lung AQP4 mRNA was induced by both beta-adrenergic agonists and glucocorticoid hormone, which are factors that have been suggested to accelerate the clearance of lung liquid. 5. Immunocytochemistry revealed that AQP4 was located in the basolateral membranes of bronchial epithelia in newborn rats, consistent with the view that this is the major site for perinatal lung liquid absorption. 6. The Na+,K(+)-ATPase alpha 1 subunit and ENaC alpha-subunit mRNA also increased around birth, suggesting that they co-operatively facilitate lung liquid clearance at birth. 7. These data indicate that removal of lung liquid at birth is associated with pronounced and well-synchronized changes in the expression of AQP and the ion transporters studied. The transient perinatal induction of AQP4, which could be prenatally induced by beta-adrenergic agonists, and the localization of this water channel strongly suggest that it plays a critical role for removal of lung liquid at the time of birth.

Adrenergic beta-Agonists↗

Carcinogenicity test of 50 Hz sinusoidal magnetic fields in rats.

Male and female F344 rats, 48 per exposure group, were sham exposed (Group A) or exposed to 0.5 (Group B) and 5 mT (Group C) magnetic fields for two years. Animals were exposed from 5-109 weeks of age in SPF conditions according to the OECD test guideline No. 451. Average exposure was 22.6 hr/day. No significant differences in body weight and food consumption were observed between the sham and exposed groups. At the end of the exposure period, survival rates of the male rats were 73, 83, and 79%, and those of the females, 77, 79, and 75% for Groups A, B, and C, respectively, with no significant differences between groups. Differential counts of leukocytes were measured at the 52nd, 78th, and 104th weeks of exposure and no significant differences were observed between the exposure groups. All survivors were euthanized on schedule, and all the organs and tissues suspected of tumoral lesions were examined histopathologically. Incidences of mononuclear cell leukemia in the male and the female rats were 5, 4, 4 and 8, 6, 7 for Groups A, B and C, respectively; incidences of malignant lymphoma in the female rats were 0, 1 and 1. Neither significant increases nor acceleration of incidence of leukemia were observed. Incidences of brain and intracranial tumors did not increase in the exposed groups. Incidences of both benign and malignant neoplasms showed no significant difference between the exposed and sham exposed groups with one exception: fibroma of the subcutis in the male rats, which was considered not to be a statistically significant when evaluated with respect to the historical control data in our laboratory.

Animals↗

Potentially multicentric hepatocellular carcinoma: clinicopathologic characteristics and postoperative prognosis.

When multiple hepatic tumors are present, it is sometimes difficult to distinguish between metastatic and multicentric hepatocellular carcinoma (HCC). To identify the important clinicopathologic features of multicentric HCC, we evaluated the clinical characteristics of patients with multicentric HCC and examined the usefulness of surgical treatment in those patients. A total of 99 patients with multiple HCCs were classified into one of the following two groups according to whether their tumors were multicentric or metastatic: Group MO consisted of 18 patients with tumors thought to have developed synchronously from multicentric origins. Group IM consisted of 64 patients with intrahepatic metastases. In this study 18% of the patients with multiple HCCs were thought to have presented with multicentric tumors. This study revealed that synchronous multicentric HCCs often affected multiple segments of the liver and responded relatively well to partial hepatectomy of individual tumor-affected areas. To appropriately treat potentially multicentric HCC, it is important to understand the histopathologic characteristics of multicentric HCC and diagnose during preoperative and intraoperative ultra-sonography, so surgical treatment may be useful.

Carcinoma, Hepatocellular↗

Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow transplantation (BMT). Its prediction, diagnosis and treatment remain unclear. Examination was made of changes in hemostatic parameters in patients with or without VOD after BMT. Twenty-seven children were studied following BMT. Eight of them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin-antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC), antithrombin III (AT-III), protein C, N-terminal propeptide for type III procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG significantly fell during the post-transplant period (P < 0.05). Significantly low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD. The coagulation-fibrinolysis system following endothelial cell damage may contribute to the onset of VOD.

Adolescent↗

Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.

Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.

Adenylyl Cyclases↗

The role of tissue-fixed macrophages in apoptosis in the developing kidney.

Programmed cell death (PCD) and cell type involving dying cells in the developing mouse and human fetal kidneys were investigated using the modified TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method in combination with immunohistochemistry. We identified many TUNEL-positive apoptotic cells mainly in the nephrogenic region in the developing mouse and human fetal kidneys. Tissue-fixed macrophages were widely distributed throughout the developing mouse and human fetal kidneys, including the nephrogenic zone. Most of the apoptotic cells in the nephrogenic zone were phagocytosed by tissue-fixed macrophages, suggesting that tissue-fixed macrophages play an important role in the process of PCD in the developing mouse kidney and human fetal kidney.

Animals↗

Elevated chemokine levels in bronchoalveolar lavage fluid of tuberculosis patients.

In pulmonary tuberculosis, the proportion of lymphocytes, particularly that of CD4+ T lymphocytes, was increased in bronchoalveolar lavage fluid (BALF), reflecting their protective role against mycobacterial infections. In order to elucidate the mechanisms of lymphocyte accumulation in lungs, we measured the levels of chemokines with potent lymphocyte chemotactic activities, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and, regulated on activation, normal T-cell expressed and secreted (RANTES) present in BALF from patients with pulmonary tuberculosis in acute (n = 10) and convalescent phases (n = 6), as well as normal subjects (n = 10). During the acute phase of the disease, the proportions of lymphocytes and neutrophils were increased, as reported in previous studies. The levels of IL-8, MCP-1, and RANTES in the acute phase of pulmonary tuberculosis were also markedly elevated as compared with those of normal subjects. MCP-1 and RANTES, but not IL-8 levels present in BALF, decreased in the convalescent phase. Moreover, the concentration of RANTES correlated significantly with the absolute number of CD4+ cells in BALF. These data suggest that chemotactic cytokines are differentially produced and participate in the host response to Mycobacterium tuberculosis infection.

Bronchoalveolar Lavage Fluid↗

A specific elevation of RANTES in bronchoalveolar lavage fluids of patients with chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is a rare, idiopathic lung disorder characterized pathologically by massive eosinophil infiltration into lung. In the bronchoalveolar lavage fluid (BALF) of patients with CEP, eosinophil numbers were markedly increased but returned to normal-levels upon the resolution of clinical symptoms, which suggests the crucial role of eosinophils in the pathogenesis of CEP. To clarify the mechanism of eosinophil accumulation in CEP, we determined the BALF levels of RANTES and macrophage inflammatory protein-1 alpha, two chemokines that predominantly exhibit in vitro eosinophil chemotactic activities. RANTES (106.7 +/- 27.2 pg/mg albumin; n = 16) concentrations in BALF from patients with CEP were significantly elevated in comparison with those of normal control subjects (1.4 pg/mg albumin; n = 13), whereas BALF macrophage inflammatory protein-1 alpha levels were not. In addition, eosinophils, lymphocytes, and macrophages in BALF were positively stained with a specific anti-RANTES antibody, which suggests that RANTES was produced locally in the lungs of CEP patients. Moreover, BALF-RANTES levels correlated significantly with the proportion of eosinophils in BALF. Furthermore, nearly half of the eosinophil chemotactic activities in BALF were abrogated by the anti-RANTES antibody in vitro. Collectively, these data suggest that locally produced RANTES is involved in eosinophil accumulation in the pulmonary alveolus and interstitium of patients with CEP.

Bronchoalveolar Lavage↗

Regional adjuvant chemotherapy after partial hepatectomy for metastatic colorectal carcinoma.

The prognostic factors after hepatic resection for metastases from colorectal carcinoma were examined, and the results of adjuvant hepatic arterial chemotherapy are presented. Hepatic resection was undertaken in 57 patients with metastatic liver tumor from colorectal cancer. Adjuvant hepatic arterial chemotherapy using 5-fluorouracil, doxorubicin or epirubicin, and mitomycin C was administered to 31 patients. The 3- and 5-year survival rates for the 57 patients were 53% and 23%, respectively. The significant prognostic factors were solitary liver tumor and metachronous liver tumor. However, type of hepatectomy, surgical margin, site of the primary tumor, and histologic differentiation of the carcinoma did not relate to the prognosis. The 3- and 5-year survival rates for the patients given adjuvant arterial chemotherapy were 57% and 57%, respectively, indicating a significantly better survival rate than in the nontreated patients. These results suggest that hepatic arterial chemotherapy is effective treatment in patients with hepatic resection for metastases from colorectal carcinoma. However, recurrence in the lung is relatively high. Further improvement might be achieved by administering hepatic arterial chemotherapy as well as effective systemic chemotherapy.

Adult↗

[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy].

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.

Brain Diseases↗

[Similarities in calcium and magnesium metabolism between amyotrophic lateral sclerosis and calcification of the spinal cord in the Kii Peninsula ALS focus].

Current epidemiological surveys in the Western Pacific area and Kii Peninsula have suggested that low calcium (Ca), magnesium (Mg) and high aluminum (Al) and manganese (Mn) in river, soil and drinking water may be implicated in the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). The condition of unbalanced minerals was experimentally mimicked in this study using rats. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. In the groups maintained on unbalanced mineral diets, calcium and magnesium contents of the bones were lower than those fed with standard diet. On the other hand, Ca content of CNS showed higher values in the unbalanced diet groups (especially in spinal cord of the low Ca-Mg plus high Al diet group) than those in the standard diet group. This was determined by neutron activation analysis (NAA) at Research Reactor Institute, Kyoto University. Also, Ca content in soft tissues of rats given unbalanced mineral diets was higher than those on standard diet. Mg content of soft tissues and spinal cord of rats was markedly lower in the low Ca-Mg plus high Al diet group than the other three groups as determined by inductively coupled plasma emission spectrometry (ICP). Six Kii cases with amyotrophic lateral sclerosis (ALS) also showed higher Ca and lower Mg contents in the CNS tissues than those of neurologically normal controls. As of today, calcification of the spinal ligaments (CSL) has been reported in only 120 cases in the world and 28 cases of CSL in the Kii Peninsula have been found in the same foci as ALS. We analyzed Mg content of 7 spinal bones and 10 ligaments of the CSL and Ca content of 5 spinal bones compared with controls. The CSL showed lower values of Mg contents in bones and ligaments compared to controls. The Ca content in bones of CSL was significantly lower than that of controls. These results suggest that the environmental factor may contribute to the pathogenesis of CSL due to low Ca and Mg intake as well as for ALS.

Aged↗

Effects of low calcium and magnesium dietary intake on the central nervous system tissues of rats and calcium-magnesium related disorders in the amyotrophic lateral sclerosis focus in the Kii Peninsula of Japan.

Current epidemiological investigations in the Western Pacific including the Kii Peninsula of Japan, have suggested that environmental factors contribute to the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism dementia (PD). The condition of unbalanced minerals (a low content of calcium and magnesium, and a high content of aluminum) found in soil and drinking water in all three ALS foci was experimentally mimicked in our studies using rats. In rat groups maintained on unbalanced mineral diets, the calcium and magnesium contents of bones were lower than those fed a standard diet. In addition, the calcium content of CNS tissues showed higher values in the unbalanced diet groups (especially in the spinal cord of the low calcium and magnesium plus high aluminum diet group) than those in the standard diet group. The calcium content of other soft tissues as well as the CNS of rats fed unbalanced mineral diets was also higher than those on the standard diet. The magnesium content of soft tissues and spinal cord of rats was markedly lower in the low calcium and magnesium plus high aluminum diet group than in the other groups. Examination of tissues from six Kii Peninsula patients with ALS showed an average magnesium concentration in 26 CNS regions (cortical gray matter, white matter, basal ganglia, brain stem, spinal cord) significantly lower than that for five neurologically normal controls. The average calcium concentration in gray matter of ALS cases was significantly higher than that of controls. Interestingly, only 120 cases of calcification of spinal ligaments have been reported worldwide, and of these, 26 of 28 cases of calcification of spinal in the Kii Peninsula have been found to overlap the same geographic focal region as ALS. We analyzed the magnesium content of seven spinal vertebrae and 10 spinal ligaments of patients with calcification of spinal ligaments and the calcium content of five spinal bones compared with controls. The calcification of spinal ligaments patients had lower values for magnesium contents of bones and ligaments compared to controls and the calcium content of bones in these patients was significantly lower than that of controls. These data suggest that low dietary intake of calcium and magnesium over an extended period of time may contribute to the pathogenesis of patients with ALS and calcification of spinal ligaments.

Amyotrophic Lateral Sclerosis↗

A novel benzodiazepine inverse agonist, S-8510, as a cognitive enhancer.

1. Pharmacological actions of a novel benzodiazepine receptor ligand, S-8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano+ ++[4,3-b] pyridine monophosphate monohydrate), were examined in in vitro and in vivo studies. 2. S-8510 was characterized as a partial inverse agonist with a modest GABA ratio and low efficacy. 3. S-8510 ameliorated memory impairment induced by cholinergic deficit in the water maze paradigm of Wistar rats. 4. S-8510 augmented LTP of the Schaffer collateral/commissural fiber-CA1 synapses in the hippocampal slice preparations of SD rat. 5. S-8510 increased the extracellular levels of acetylcholine and noradrenaline in the hippocampus of Wistar rat. 6. S-8510 selectively potentiated pentylenetetrazol-induced convulsion without affecting minimal electroconvulsive shock- or strychnine-induced convulsion in ddY mice. 7. S-8510 failed to induce any sign of anxiety in the Wistar rat pro-conflict test. 8. S-8510 showed antidepressant-like pharmacological actions in ddY mice. 9. These results suggest that S-8510 can be used as a therapeutic drug for senile dementia, including Alzheimer's disease with little risk for inducing anxiety or convulsion.

Animals↗

Development of urinary concentrating capacity: role of aquaporin-2.

The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP)-activated water channel aquaporin-2 (AQP-2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24-h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e., days 15-20. A similar developmental pattern was observed for AQP-2 mRNA levels in the renal medulla. AQP-2 protein levels also increased markedly from day 10 to 40. Immunohistochemistry revealed that AQP-2 was exclusively located in collecting duct principal cells both in infant and adult rats but that the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP-2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs. Twenty-four hours after treatment, there was an increase in urine osmolality, renal medullary AQP-2 mRNA, and AQP-2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 h significant increase of AQP-2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na(+)-K(+)-ATPase alpha-subunit, Na-K-2Cl cotransporter, and epithelial chloride channel also increased during the weaning period and were upregulated by glucocorticoids. We conclude that there is a well-synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP-2 is one of the limiting factors for low concentrating capacity in infants.

Aging↗