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Biomedical subjects

Y Saito

Publications and source records attributed to Y Saito.

At least 91 records · Page 5Linked to original sources
PubMed2002

Development of an aggressive depressed cancer in a case of familial adenomatous polyposis.

In 1977, Kariya et al. reported a case of a small depressed cancer in a patient with familial adenomatous polyposis (FAP) raising the possibility that not all cancers in FAP develop from polypoid adenomas. It is now becoming widely recognized that colonic adenomas may appear as flat or depressed lesions. However, colorectal cancers developing in patients with familial adenomatous polyposis (FAP) are still thought to evolve from adenomatous polyps following the polyp-carcinoma sequence. We report the case of a patient with FAP in whom rectal carcinoma developed 23 years after subtotal colectomy and ileorectal anastomosis. We suggest that this malignancy may have developed de novo because of the depressed shape of the lesion and the aggressive growth pattern. This case raises the possibility that carcinomas may not always evolve from polyps in FAP. Aggressive cancers with a depressed appearance should be searched for when surveying the rectal stump in patients with FAP.

Adenocarcinoma↗
PubMed2002

A case of hyperplastic polyposis of the colon with adenocarcinomas in hyperplastic polyps after long-term follow-up.

A 66-year-old woman had been receiving follow-up since 1990 for hyperplastic polyposis, which remained unchanged endoscopically and radiologically. In 1999, a small (28 x 22 mm) superficial adenocarcinoma was detected in the ascending colon. Histologically, this was a hyperplastic polyp containing a well-differentiated adenocarcinoma invading into the submucosa. A review of the English and Japanese literature identified 32 cases of "hyperplastic polyposis." In about half of the 32 cases, an adenocarcinoma was also found amongst the hyperplastic polyps. Half of the adenocarcinomas were located in the right colon. Although hyperplastic polyposis is uncommon, it warrants regular surveillance, as it appears to be associated with an increased risk of colorectal cancer.

Adenocarcinoma↗
PubMed2002

Effects of lifestyle modifications on patients with type 2 diabetes: the Japan Diabetes Complications Study (JDCS) study design, baseline analysis and three year-interim report.

BACKGROUND: Lifestyle modifications may affect the development of diabetes and prevent complications. However, there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes. OBJECTIVE: The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes. This initial report on a multi-year study describes protocols and the analysis of baseline data and three-year interim results. DESIGN: The study was a randomized, controlled, multi-centre, prospective intervention trial. The trial included patients from 59 Japanese institutes specializing in diabetes care. PATIENTS: The study enrolled 2 205 patients with previously diagnosed type 2 diabetes. INTERVENTION: The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling. The intervention group received educational materials concerning the importance of lifestyle and behavioural changes, a diary to record progress of laboratory and other data, and a pedometer. MEASUREMENTS: Parameters and indices related to glycemic control, diabetic complications, dyslipidemia, hypertension, obesity, and atherosclerosis were measured several times a year. RESULTS: Small but significant differences in HbA1c levels between the intervention (INT) and conventional (CON) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year (CON group, 7.78 +/- 1.27 % vs. INT group, 7.62 +/- 1.20 %, the initial HbA1c level was 7.80 +/- 1.42 % for the CON group and 7.68 +/- 1.28 % for the INT group). Data on differences in occurrence of micro- or macrovascular complications are not yet available. CONCLUSIONS: The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention.

Aged↗
PubMed2002

Recurrent neurological symptoms in a patient following repeat combined spinal and epidural anaesthesia.

A healthy woman developed neurological symptoms after two consecutive Caesarean sections under combined spinal and epidural anaesthesia. Amethocaine was used for spinal anaesthesia and mepivacaine for epidural anaesthesia on both occasions, and a combination of fentanyl and bupivacaine was continuously infused for pain relief after the second. Her symptoms on both occasions were similar, including pain in the buttocks of 7-11 days duration and numbness in the sacral area of 5-6 months.

Adult↗
PubMed2002

Characteristic response of plastic track detectors to 40-80 MeV neutrons.

This paper investigates the characteristic response of plastic track detectors to high-energy neutrons. Three types of plastic nuclear track detector (PNTD), Baryotrak made of pure CR-39, TD-1 made of CR-39 containing an antioxidant and TNF-1 made of a copolymer of CR-39/N-isopropylacrylamide, were exposed in quasi-monoenergetic neutron fields generated by p-Li reactions. The total efficiencies for TD-1 and TNF-1 were more than double and triple that of Baryotrak respectively. In addition, the species of particles were classitied into three groups, i.e. proton relatives, alpha particles and heavy ions, by analysing the etch-pit growth curve obtained by step-by-step etching. In a 65 MeV neutron field about half of the tracks recorded in pure CR-39 were due to heavy ions, whereas the TNF-1 detector could effectively register the protons, accounting for 70% of the tracks. The results could be explained by the difference in the sensitivity to high-energy protons.

Aircraft↗
PubMed2002

Pulmonary granulomas of guinea pigs induced by inhalation exposure of heat-treated BCG Pasteur, purified trehalose dimycolate and methyl ketomycolate.

This study was designed to determine the identity of granulomatogenic substances in Mycobacterium bovis BCG Pasteur. When heat-treated BCG Pasteur bacilli were introduced into the lungs of guinea-pigs by an inhalation exposure apparatus, pulmonary granulomas without necrosis developed. Furthermore, when four kinds of mycolates derived from M. tuberculosis Aoyama B strain were introduced into the lungs by the same method, only trehalose 6,6'-dimycolate (TDM) and methyl ketomycolate induced pulmonary granulomas without central necrosis. The pulmonary granulomas consisted of epithelioid macrophages and lymphocytes. When a mixture of TDM and anti-TDM antibody was introduced into the lungs, development of granulomatous lesions was reduced. These data indicate that TDM and methyl ketomycolate are potent granulomatogenic reagents.

Administration, Inhalation↗
PubMed2002

Age related expression of Werner's syndrome protein in selected tissues and coexpression of transcription factors.

AIMS: Werner's syndrome (WS) is an uncommon autosomal recessive disease resulting from mutational inactivation of human WRN helicase, Werner's syndrome protein (WRNp). Patients with WS progressively develop a variety of aging characteristics after puberty. The aim of this study was to determine the distribution of WRNp and the expression of the transcription factors regulating WRN gene expression in a variety of human organs in an attempt to understand the WS phenotype. METHODS: Tissue specimens were obtained from 16 controls aged from 27 gestational weeks to 70 years of age and a 56 year old female patient with WS. The distribution of WRNp and the expression of the transcription factors regulating WRN gene expression-SP1, AP2, and retinoblastoma protein (Rb)- were studied in the various human organs by immunohistochemical and immunoblot analyses. RESULTS: In the healthy controls after puberty, high expression of WRNp was detected in seminiferous epithelial cells and Leydig cells in the testis, glandular acini in the pancreas, and the zona fasciculata and zona reticularis in the adrenal cortex. In addition, the SP1 and AP2 transcription factors, which regulate WRNp gene expression, appeared in an age dependent manner in those regions where WRNp was expressed. In controls after puberty, SP1 was expressed in the testis and adrenal gland, whereas AP2 was expressed in the pancreas. CONCLUSIONS: These findings suggest that the age specific onset of WS may be related to age dependent expression of WRNp in specific organs.

Adolescent↗
PubMed2002

[Reoperation for metachronous pulmonary or tracheal lesions after pneumonectomy].

Although aggressive reoperation for metachronous multiple primary lung cancer or intrathoracic recurrence without distant metastases have been recommended to the patients of primary lung cancer and metastatic lung tumor, surgical indication after a previous pneumonectomy is restricted because of residual pulmonary function. We report about 3 reoperated cases for metachronous pulmonary or tracheal lesions after left pneumonectomy. Case 1: A 61-year old male who underwent left pneumonectomy for primary lung cancer was reoperated for tracheal cancer 41 months after the pneumonectomy. Case 2: A 61-year old male who underwent left pneumonectomy for primary lung cancer was reoperated for metachronous multiple primary lung cancer 59 months after the pneumonectomy. Case 3: A 59-year old male who underwent left pneumonectomy for metastatic lung tumor from rectal cancer was re-operated for intrathoracic recurrence 28 months after the pneumonectomy. All cases are alive without recurrence.

Humans↗
PubMed2002

[Thrombus entrapped in a patent foramen ovale of the atrial septum].

A 59-year-old women was referred to our hospital due to severe dyspnea and shock status 12 days after intracranial hematoma evacuation for the hypertensive right putaminal hemorrhage. Transthoracic echocardiography revealed right ventricular dilatation and floating structures in the right atrium. Transesophageal echocardiography demonstrated a large, snake-like structure crossing her foramen ovale of the interatrial septum, and impending paradoxical embolism was diagnosed. She did not receive any anticoagulation and surgery due to recent cerebral hemorrhage. Follow-up TEE showed complete disappearance of the thrombus in the atrium two weeks after the onset. Phlebogram of deep vein demonstrated several thrombus in her leg. She underwent placement of inferior vena cava filter and was discharged from our hospital without any symptom of paradoxical embolism.

Echocardiography, Transesophageal↗
PubMed2001

The urotensin II receptor is expressed in the cholinergic mesopontine tegmentum of the rat.

Urotensin II (UII) is a peptide known to be a potent vasoconstrictor. The urotensin II receptor (UII-R) is expressed not only in peripheral tissues but also in the brain of rodents. As a basis for studies of UII central nervous system actions, UII-R localization in the rat brain was analyzed by in situ hybridization and by in situ binding. UII-R mRNA was found in the mesopontine tegmental area colocalizing with choline acetyltransferase. Binding sites were detected throughout the brain with the highest levels found in the pedunculopontine tegmental area, the lateral dorsal tegmental area, and the lateral septal, medial habenular, and interpeduncular nuclei. The majority of these brain nuclei are sites of axonal termination originating from the mesopontine areas, suggesting that UII-R is a presynaptic receptor. This distribution of UII-R in the cholinergic mesopontine area indicates that the UII system may be involved in sensory-motor integration and perhaps in central nervous system blood flow.

Acetylcholine↗
PubMed2001

Endogenous melanin-concentrating hormone receptor SLC-1 in human melanoma SK-MEL-37 cells.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that regulates several physiological functions. The orphan G protein-coupled receptors SLC-1 and MCHR2 were recently found to bind MCH with high affinity. We show here that the human melanoma cell line SK-MEL-37 expresses SLC-1 mRNA but not MCHR2 by RT-PCR analysis and immunofluorescence studies. Using Chinese hamster ovary cells and 293 cells overexpressing SLC-1 by cDNA transfection, it was shown that SLC-1 coupled to both G alpha(i)/G alpha(o) and G alpha(q) proteins. In SK-MEL-37 cells, MCH inhibited forskolin-stimulated cyclic AMP accumulation and induced mitogen-activated protein kinase (MAPK) in a pertussis toxin-(PTX)-sensitive manner. The MAPK activity leads to the production of phosphorylated forms of p42/p44 MAPK. However, an increase in the intracellular free Ca(2+) concentration was not elicited by MCH in SK-MEL-37 cells. These results show that SLC-1 is coupled only to PTX-sensitive G alpha(i)/G alpha(o) in SK-MEL-37 cells. This study provides for the first time a skin-derived cellular model to analyze the molecular mechanism of the MCH signaling pathway.

Animals↗
PubMed2001

Light and electron microscopic study of corticorubral synapses in adult cat: evidence for extensive synaptic remodeling during postnatal development.

Spine-like dendritic protrusions (SLDPs) emanating from developing dendrites have been proposed to play an important role in early synaptogenesis. We previously analyzed synaptic termination sites on soma-dendritic membrane of newborn cats and found that corticorubral (CR) axons form synapses preferentially on SLDPs (Saito et al., 1997). In the present study, we examined CR synapses in adult cats to elucidate the maturation process of CR synapses in relation to SLDPs. Electron microscopic observation of serial thin sections of Phaseolus vulgaris-leucoagglutinin-labeled axons revealed that approximately 60% of CR terminals in adult cats formed synapses on dendritic spines. We also found that CR axons terminate on dendritic spines originating from the intermediate or distal dendrites of rubrospinal cells (more than 200 microm apart from the soma), in contrast to kittens in which CR fibers terminate on SLDPs originating from the proximal dendrites (less than 100 microm apart from the soma) of rubrospinal cells (Saito et al. [1997] J. Neurosci. 17:8792-8803). These results suggest that CR synapses undergo remarkable remodeling after initial termination on SLDP during postnatal development.

Aging↗
PubMed2001

Noninvasive detection of total occlusion of the left anterior descending coronary artery with transthoracic Doppler echocardiography.

OBJECTIVES: The purpose of this study was to evaluate the value of transthoracic Doppler echocardiography (TTDE) for the noninvasive detection of total left anterior descending coronary artery (LAD) occlusion. BACKGROUND: Total coronary occlusion is associated with an adverse long-term prognosis, and mechanical revascularization may be required for the patient with total coronary occlusion. However, a noninvasive diagnosis of total coronary occlusion before coronary angiography (CAG) has been difficult, especially in patients without clinical signs. METHODS: We studied 103 consecutive patients who underwent CAG for the evaluation of coronary artery disease. The study group consisted of 16 patients with total LAD occlusion (group A) and 87 patients without total LAD occlusion (group B). Coronary flow velocity in the mid-portion of the LAD was recorded by TTDE. RESULTS: Adequate spectral Doppler recordings of diastolic flow in the LAD were obtained in 98 study patients (95%; 15 patients in group A and 83 patients in group B). In group A, retrograde LAD flow was obtained in 14 (93%) of 15 patients. The mean diastolic velocity of the retrograde flow was 21.0 +/- 6.1 cm/s. In group B, antegrade LAD flow was obtained in all 83 patients (100%). The mean diastolic velocity of the antegrade flow was 21.5 +/- 7.1 cm/s. Retrograde LAD flow by TTDE had a sensitivity of 93% and a specificity of 100% for the detection of total LAD occlusion. CONCLUSIONS: Retrograde flow in the LAD by TTDE is a highly sensitive and specific finding that can be used to noninvasively diagnose total LAD occlusion.

Aged↗
PubMed2001

Relationship between plasma level of cardiotrophin-1 and left ventricular mass index in patients with dilated cardiomyopathy.

OBJECTIVES: The study evaluated the relationship between plasma cardiotrophin-1 (CT-1) concentration and left ventricular (LV) mass in dilated cardiomyopathy (DCM) patients with congestive heart failure (CHF). BACKGROUND: Cardiotrophin-1 is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, and it has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood. METHODS: We measured the plasma CT-1 level in 51 consecutive patients with DCM. Patients were classified into two groups: small LV mass index group and large LV mass index group, based on the median level of LV mass index. RESULTS: The plasma CT-1 level was increased in DCM patients with the severity of CHF and was significantly higher in the large LV mass group than in the small LV mass group, despite the absence of a difference in LV ejection fraction between the two groups. In addition, there was a significant positive correlation between the plasma CT-1 level and the LV mass index (r = 0.627, p < 0.0001). According to stepwise multivariate analyses among hemodynamic and neurohumoral factors, a high plasma CT-1 level showed an independent and significant positive relationship with a large LV mass index in patients with DCM. CONCLUSIONS: These results indicate that the plasma CT-1 level is increased in patients with DCM and is significantly correlated with the LV mass index, suggesting that CT-1 plays an important role in structural LV remodeling in patients with DCM.

Adolescent↗
PubMed2001

Dramatic phenotypic improvement during pregnancy in a genetic leukodystrophy: estrogen appears to be a critical factor.

Globoid cell leukodystrophy is one of the classical genetic leukodystrophies in humans. The typical infantile disease in man (Krabbe disease) is caused by deficiency of lysosomal galactosylceramidase. We recently generated a new mouse model of a late-onset, chronic form of the disease by inactivating saposin A, the essential activator of galactosylceramidase. The phenotypic features of saposin A(-/-) mice are qualitatively identical but milder than those of twitcher mice, which is caused by genetic galactosylceramidase deficiency. During intercrossing of saposin A(-/-) mice, we observed that affected females that are continually pregnant showed greatly improved neurological symptoms compared to affected females that do not experience pregnancy, or affected males. The pathological hallmark of globoid cell leukodystrophy, demyelination with infiltration of globoid cells, largely disappeared. The immune-related gene expression (MCP-1, TNF-alpha) was significantly down-regulated in the brain of pregnant saposin A(-/-) mice. In addition, we found intense expression of the estrogen receptors (ER alpha and ER beta) on the globoid cells, activated astrocytes and microglia in the demyelinating area of saposin A(-/-) mice. When saposin A(-/-) mice were subcutaneously implanted with time-release 17 beta-estradiol (E2) pellets from 30 to 90 days, the pathology was vastly improved. These findings suggest that a higher level of estrogen during pregnancy is one of the important factors in the protective effect of pregnancy. While we should be cautious in extrapolating these observations in the mouse to human disease, the phenomenon is spectacularly dramatic and estrogen administration might be worth a consideration as a supplementary treatment for some chronic genetic leukodystrophies.

Animals↗
PubMed2001

Furanodictine A and B: amino sugar analogues produced by cellular slime mold Dictyostelium discoideum showing neuronal differentiation activity.

We investigated the constituents of Dictyostelium discoideum to clarify the diversity of secondary metabolites of Dictyostelium cellular slime molds and to explore biologically active substances that could be useful in the development of novel drugs. From a methanol extract of the multicellular fruit body of D. discoideum, we isolated two novel amino sugar analogues, furanodictine A (1) and B (2). They are the first 3,6-anhydrosugars to be isolated from natural sources. Their relative structures were elucidated by spectral means, and the absolute configurations were confirmed by asymmetric syntheses of 1 and 2. These furanodictines potently induce neuronal differentiation of rat pheochromocytoma (PC-12) cells.

Amino Sugars↗
PubMed2001

ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts.

We recently reported that angiotensin II (Ang II) induced IL-6 mRNA expression in cardiac fibroblasts, which played an important role in Ang II-induced cardiac hypertrophy in paracrine fashion. The present study investigated the regulatory mechanism of Ang II-induced IL-6 gene expression, focusing especially on reactive oxygen species (ROS)-mediated signaling in cardiac fibroblasts. Ang II increased intracellular ROS in cardiac fibroblasts, and the increase was completely inhibited by the AT-1 blocker candesartan and the NADH/NADPH oxidase inhibitor diphenyleneiodonium (DPI). We first confirmed that antioxidant N-acetylcysteine, superoxide scavenger Tiron, and DPI suppressed Ang II-induced IL-6 expression. Because we observed that exogenous H(2)O(2) also increased IL-6 mRNA, the signaling pathways downstream of Ang II and exogenous H(2)O(2) were compared. Ang II, as well as exogenous H(2)O(2), activated ERK, p38 MAPK, and JNK, which were significantly inhibited by N-acetylcysteine and DPI. In contrast with exogenous H(2)O(2), however, Ang II did not influence phosphorylation and degradation of IkappaB-alpha/beta or nuclear translocation of p65, nor did it increase NF-kappaB promoter activity. PD98059 and SB203580 inhibited Ang II-induced IL-6 expression. Truncation and mutational analysis of the IL-6 gene promoter showed that CRE was an important cis-element in Ang II-induced IL-6 gene expression. NF-kappaB-binding site was important for the basal expression of IL-6, but was not activated by Ang II. Ang II phosphorylated CREB through the ERK and p38 MAPK pathway in a ROS-sensitive manner. Collectively, these data indicated that Ang II stimulated ROS production via the AT1 receptor and NADH/NADPH oxidase, and that these ROS mediated activation of MAPKs, which culminated in IL-6 gene expression through a CRE-dependent, but not NF-kappaB-dependent, pathway in cardiac fibroblasts.

Angiotensin II↗