An atypical myelodysplastic syndrome with t(9;12)(q22;p12) and TEL gene rearrangement.
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Adult↗
Biomedical subjects
M Iida
Publications and source records attributed to M Iida.
Presence of telomeric G-strand tails in the telomerase catalytic subunit TERT knockout mice.
BACKGROUND: Telomerase consists of two essential subunits, the template RNA (TR; telomerase RNA) and the catalytic subunit TERT (telomerase reverse transcriptase). Knockout mice with a mTR (mouse TR) deletion have been described and well characterized. However, mice with a mTERT (mouse TERT) deletion have not been reported. RESULTS: mTERT-knockout mice have been constructed. The first generation mTERT -/- mice were fertile, and did not show any noticeable macroscopic or microscopic phenotypic change. All tissue cells derived from mTERT -/- mice that were examined lacked telomerase activity, indicating that mTERT is the only gene encoding the telomerase catalytic subunit. Pulse field gel electrophoresis (PFGE) and nondenaturing in-gel hybridization analyses showed that mouse telomeric DNA has G-strand 5'-overhangs, as demonstrated for human and yeast cells. This telomeric single-stranded G-tail was also observed in MEF (mouse embryonic fibroblast) and liver cells derived from mTERT -/- mice. CONCLUSIONS: mTERT-knockout mice show phenotypes that are apparently normal at least during the early generations. This observation is similar to that obtained with the mTR-knockout mice. The presence of the telomeric G-strand tails in mTERT -/- mice suggests that these telomeric 5'-overhangs are produced by telomerase-independent mechanisms, as has been proposed for yeast and human.
Amino Acid Sequence↗
Suppression of default apoptosis in androgen-dependent cells by testosterone-mediated bcl-2 expression.
BACKGROUND: The significance of apoptosis with regard to the development and progression of androgen-dependent cells has not been clearly understood. In the present study we investigated the expression of the bcl-2 proto-oncogene after androgen deprivation and its role in cell growth in an androgen-dependent cell line. METHODS: We used SC2G, an androgen-dependent mouse mammary carcinoma cell line cloned from Shionogi carcinoma 115 (SC115). The expression of bcl-2 mRNA and protein in SC2G cells was measured by reverse transcription-polymerase chain reaction and western blotting, respectively. We also investigated the effects of antisense oligodeoxynucleotides (ODN) complementary to strategic sites in the mouse bcl-2 gene in SC2G cells. RESULTS: When SC2G cells were cultured in serum-free medium, the number of viable cells was significantly larger among cells with testosterone than those without testosterone after 3 days. Apoptosis was demonstrated in approximately 30% of positive-staining nuclei in SC2G cells cultured in testosterone-free medium. The levels of bcl-2 mRNA and protein in SC2G cells started to decrease after testosterone withdrawal. The cell density of SC2G cells decreased after 4 days culture with antisense ODN when compared with cells cultured in the presence of sense control. CONCLUSIONS: These data indicate that bcl-2 proto-oncogene inhibits the self-programmed apoptosis of androgen-dependent cells, suggesting the possibility of an antisense therapy for hormone-refractory prostate cancer, which is reported to express high levels of Bcl-2 protein.
Animals↗
Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation.
We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.
Animals↗
Protective effect of lactosucrose on intracolonic indomethacin-induced small-intestinal ulcers in rats.
BACKGROUND: Little is known about the role of intestinal microflora in the development of indomethacin-induced enteropathy. The aim of this study was to evaluate the effects of lactosucrose, an indigestible oligosaccharide, on intestinal microflora and on indomethacin-induced enteropathy in rats. METHODS: Male Wistar rats were fed either sucrose (SC) or lactosucrose (LS) for 2 weeks. Indomethacin (24 mg/kg/ day) was administered into the colon twice, 24 h apart, and intestinal ulcers in SC and LS groups were compared macroscopically. In another experiment the bacterial composition in the mid-small-intestinal segment was determined in both groups before and after treatment with indomethacin. RESULTS: After indomethacin treatment small-intestinal ulcers were less severe in the LS than in the SC group (ulcer index: median, 0.13 (range, 0.05-0.19) versus 0.23 (0.13-0.34); P < 0.05). Total bacterial count did not differ significantly between the two groups. Indomethacin increased the number of Enterobacteriaceae in both groups, but the increase was less in the LS group. The number of streptococci was also significantly increased in the SC group but not in the LS group. CONCLUSION: These results suggest that LS has some protective effects on indomethacin-induced enteropathy and that this protective effect is in part due to the maintenance of intestinal microflora.
Animals↗
Indispensability of transmembrane domains of Golgi UDP-galactose transporter as revealed by analysis of genetic defects in UDP-galactose transporter-deficient murine had-1 mutant cell lines and construction of deletion mutants.
UDP-galactose transporter is a membrane protein localized in the Golgi apparatus. It translocates UDP-galactose from the cytosol into the Golgi lumen, thus providing galactosyltransferases with their substrate. We characterized murine UDP-galactose transporter through molecular cloning for the following purposes: (i) to elucidate the molecular bases underlying the genetic defects of murine Had-1 mutants, which are deficient in UDP-galactose transporting activity, and (ii) to obtain information that would help us in planning rational approaches to identify functionally essential regions, based on comparison of primary structures between human and murine UDP-galactose transporters. We identified five nonsense mutations, one missense Gly178Asp mutation, and two aberrant splicing mutations. Although glycine178 is highly conserved among nucleotide-sugar transporters, a Gly178Ala variant was functional. The species-differences between human and murine UDP-galactose transporters were largely confined to the N- and C-terminal regions of the transporters. Substantial deletions in the N- and C-terminal regions did not lead to loss of UDP-galactose transporting activity, indicating that these cytosolic regions are dispensable for the transporting activity. The transporter was fused with green-fluorescent protein at the C-terminal cytosolic tail without impairing the functions of either protein. Our results demonstrate the importance of the transmembrane core region of the UDP-galactose transporter protein.
Amino Acid Sequence↗
Juvenile polyposis occurring in hereditary hemorrhagic telangiectasia.
Various extraintestinal manifestations may occur in juvenile polyposis, but hereditary hemorrhagic telangiectasia has rarely been reported in this type of polyposis. The authors treated a 14-year-old girl with rectal bleeding and anemia who had multiple polyps of the colorectum. Large polyps were removed and histologically diagnosed as juvenile polyps. She was later diagnosed as having telangiectasia of the skin, and arteriovenous malformations in the lung and in the liver, all of which were compatible with the diagnosis of hereditary hemorrhagic telangiectasia. At age 32, she had multiple ulcers in the ileum and in the colon. The coexistence of juvenile polyposis and hereditary hemorrhagic telangiectasia may be a clue for the understanding of the histopathogenesis of juvenile polyposis.
Adolescent↗
Attenuated additional hypocapnic constriction, but not hypercapnic dilation, of spinal pial arterioles during spinal ropivacaine.
UNLABELLED: Ropivacaine constricts spinal vessels. Because the CO2 response of spinal vessels is similar to that of cerebral vessels, we tested to see if hypocapnia would cause further spinal vasoconstriction during ropivacaine administration. In 12 pentobarbital-anesthetized dogs, spinal pial arteriolar diameter was measured using a closed spinal window preparation. Either ropivacaine solution (0.1%; n = 6) or artificial cerebrospinal fluid (n = 6) was infused continuously into the spinal window. After a period of hypocapnia (Paco2, 20-25 mm Hg) had been induced, inspired CO2 levels were adjusted to produce normocapnia (35-40 mm Hg) followed by hypercapnia (55-60 mm Hg). When the desired Paco2 was reached, measurements were made of the arteriolar diameter and physiological variables. During normocapnia, ropivacaine infusion produced a significant constriction of pial arterioles, whereas artificial cerebrospinal fluid caused no change. Hypocapnia induced a much smaller (almost nonexistent) additional vasoconstriction in the ropivacaine group than in the control group (P < 0.01). The final hypercapnic vasodilation was somewhat greater during ropivacaine (P < 0.05 versus control group). Topical ropivacaine induced no change in hemodynamic variables. We conclude that hypocapnia of the magnitude tested did not cause further constriction in spinal vessels during spinal ropivacaine. IMPLICATIONS: During topical application of the local anesthetic ropivacaine in dogs, hypocapnia (Paco2, 20-25 mm Hg) induced almost no additional constriction of spinal arterioles, and the hypercapnic vasodilation was maintained. These data suggest that an additional constriction in spinal vessels is unlikely when hypocapnia occurs during spinal ropivacaine.
Administration, Topical↗
Direct effects of alpha1- and alpha2-adrenergic agonists on spinal and cerebral pial vessels in dogs.
BACKGROUND: The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of alpha2- and alpha1-adrenergic agonists on spinal and cerebral pial vessels in vivo. METHODS: Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 microg/ml; [2.1, 1.9, 2.5, and 2.3] x [10(-6), 10(-5), and 10(-4)] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window. RESULTS: On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 microg/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels). CONCLUSION: Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.
Adrenergic alpha-1 Receptor Agonists↗
Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity.
OBJECTIVE: Mucosal inflammation in ulcerative colitis (UC) is presumed to be regulated by Th2-like cytokines. The aim of this study was to characterize local expression of various cytokines mRNA. METHODS: Total RNA was extracted from rectal biopsy specimens in 61 patients with UC, 18 inflammatory controls, and 16 noninflammatory controls. Reverse-transcription polymerase chain reaction (RT-PCR) was used to determine mRNA expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, IL-13, and IL-15. RESULTS: Expression of IL-10 was more frequent in UC (75.4%) than in noninflammatory controls (37.5%, p < 0.01). IL-4 was more frequently positive in UC (41%) than in inflammatory controls (5.6%, p < 0.01) and in noninflammatory controls (6.3%, p < 0.01). Positive expressions of IL-4 (66.7% vs 20.6%, p < 0.01) and IL-13 (63.0% vs 29.4%, p < 0.01) were higher in active UC than in inactive UC. The positive rate of IL-2, interferon (IFN)-gamma, and IL-15 expression showed no difference among the groups divided by clinical, endoscopic, and histological grade of inflammation. CONCLUSIONS: These findings suggest that in active UC, IL-4 is pivotal, in combination with other Th2-like cytokines. In contrast, Th1-like cytokines and IL-15 bear no definite relation to local inflammation of UC.
Adolescent↗
In vivo observation of the ileal microadenoma in familial adenomatous polyposis.
Microadenomas or aberrant crypt foci (ACFs) are regarded as early neoplastic lesions that precede the development of macroscopic adenomas. The aim of this study was to characterize surface features of ileal microadenomas in patients with familial adenomatous polyposis (FAP). Magnifying ileoscopy was performed in 19 patients with FAP. A histologically verified adenomatous tubule, the existence of which was suggested by magnified observation, was regarded as a microadenoma. Magnifying ileoscopy detected microadenoma in five patients. In four of the five cases, the ileal microadenomas were identified as areas with tiny crypt openings or serrated surfaces, which were distinctive of nonneoplastic, diminutive protrusions. Magnifying ileoscopy seems to be useful in the detection of ileal microadenomas.
Adenoma↗
Bamboo-joint-like appearance of the stomach: a histopathological study.
A bamboo joint-like (BJL) appearance is an endoscopic finding characterized by swollen longitudinal folds transversed by erosive fissures or linear furrows, and it seems to be associated with Crohn's disease (CD). We performed gastroduodenoscopy in 1781 patients, and found BJL lesions in 15 (65.2%) of 23 CD patients and 20 (1.1%) of 1758 non-CD patients. Histological examination of the biopsy specimens showed sharp, fissure-like erosion or mucosal cleft in 7 (50%) out of 14 CD patients and one (20%) out of 5 non-CD patients. All cases with fissure-like erosion or, mucosal cleft revealed lymphoid aggregates, eosinophilic infiltration and edema in the superficial portion of the surrounding lamina propria. Epithelioid granuloma was seen at the base of the fissure-like erosion in two cases with CD. Our results indicated that fissure-like erosion or mucosal cleft in gastric biopsy specimens reflects the BJL appearance, and that such findings may provide a diagnostic clue to CD.
Adult↗
Clinicopathological features of serrated adenoma of the colorectum: comparison with traditional adenoma.
AIM: Serrated adenoma is a recently described category of colorectal adenoma. The aim of this study was to determine whether serrated adenomas have clinicopathological findings distinct from "traditional" adenoma. METHODS: Colonoscopy records for 1995-1998 were reviewed, and all traditional adenomas and serrated adenomas identified. Tumour site and endoscopic configuration were compared between the two types of adenoma. In polypectomised lesions, size and grade of dysplasia were compared between the two groups. RESULTS: There were 3305 traditional adenomas and 43 serrated adenomas. Serrated adenomas were more often found in the rectosigmoid colon than the traditional adenomas (67.5% v 41.2%, p = 0.0008). Polypectomy was more often done for serrated adenomas (27 of 43 lesions, 62.8%) than for traditional adenomas (626 of 3305 lesions, 18.9%, p < 0.0001). Size (mean (SD) maximum dimension, 12 (6) mm v 13 (3) mm) and incidence of high grade dysplasia (14.8% v 13.6%) in endoscopically removed specimens were not different between the two types. CONCLUSIONS: The therapeutic judgement applied to the management of traditional adenoma seems to be appropriate for serrated adenoma.
Adenoma↗
Experimental enteropathy in athymic and euthymic rats: synergistic role of lipopolysaccharide and indomethacin.
The aim of this study was to investigate the immunologic and microbiological bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen-free (SPF) rats were reared under conventional or SPF conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously described ulcer index and tissue myeloperoxidase activity. Both euthymic and athymic nude rats developed intestinal ulcers to the same degree under conventional conditions but no or minimal ulcer under SPF conditions. Pretreatment of conventional rats with intragastric kanamycin sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a dose-dependent fashion. Interestingly, when lipopolysaccharide was injected intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in these rats in a dose-dependent manner. We confirmed that kanamycin decreased the number of gram-negative bacteria and endotoxin concentration of the small intestine in a dose-dependent fashion. These results indicate that indomethacin enteropathy is bacteria dependent and does not require a T cell function. Synergy between indomethacin and bacterial lipopolysaccharide may play a major role in this enteropathy.
Animals↗
Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese.
BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.
Aged↗
Dynamic changes in serum leptin concentrations during the fetal and neonatal periods.
We investigated the dynamics of the leptin concentration throughout the perinatal period. Serum leptin concentrations in venous cord blood at different gestational ages were measured in 20 preterm and 139 term newborns, as well as in 143 pregnant women and 24 term newborns at approximately 6 d of life. Leptin concentrations in preterm newborns (mean 4.6+/-6.9 ng/mL) were lower than those in term newborns (mean 19.6+/-14.3 ng/mL) and tended to increase according to gestational age and birth weight, especially from the late stage of gestation. Leptin concentrations in pregnant women increased from the first trimester and then remained higher than those in non-pregnant women throughout the remainder of pregnancy even after controlling for body mass index. The leptin concentrations of newborns declined rapidly and were extremely low by approximately 6 d of life (mean 1.9+/-1.1 ng/mL). These results suggest that fetuses might produce a part of circulating leptin in their own adipocytes and that the relatively high leptin concentrations at birth and their rapid decline in the early neonatal period might reflect the dramatic changes of the hormonal and nutritional state during the perinatal period.
Body Mass Index↗
(+)-[3H]isradipine and [3H]glyburide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertension.
We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel ligand, (+)-[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (K(ATP)) channel ligand, [3H]glyburide, to heart, lung and brain membranes isolated from Sprague-Dawley rats made pulmonary hypertensive by monocrotaline, a pyrrolizidine alkaloid. A single subcutaneous injection of monocrotaline increased right ventricular systolic pressure, a measure of pulmonary arterial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[3H]PN200-110 and [3H]glyburide binding site densities (Bmax) were reduced in hypertrophied right ventricles when normalized per unit protein in comparison with those of age-matched control (sham) rats, whereas the values of the dissociation constant (Kd) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [3H]PN200-110 binding to the lung membranes of the monocrotaline-induced pulmonary hypertensive rats was increased. The results indicate that the change in the binding of 1,4-dihydropyridine Ca2+ and K(ATP) channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.
ATP-Binding Cassette Transporters↗
[Cohort study on risk factors for subarachnoid hemorrhage among Japanese men and women].
PURPOSE: To examine the risk factors for subarachnoid hemorrhage, for few prospective data have been available on risk factors of subarachnoid hemorrhage among Japanese. METHODS: A 9.4-year cohort study was conducted on 12,372 men and women, aged 40-69 years, free of history of stroke in six communities in Japan. RESULTS: During the follow-up, seventy-one incidents of subarachnoid hemorrhage occurred. After adjusting for age, serum total cholesterol, body mass index, history of diabetes mellitus, blood pressure category and drinking category, current smokers had a significantly increased risk of subarachnoid hemorrhage compared with 'never-smokers': multivariate relative risk (RR) [95% confidence interval (95% CI)] = 3.1(1.4-6.9) for women, 1.5(0.4-5.3) for men and 2.7(1.3-5.5)for men and women. Hypertensives had a significantly increased risk of subarachnoid hemorrhage compared with normotensives: multivariate RR(95% CI) = 3.1(1.6-6.0) for women, 4.3(1.5-12.0) for men and 3.4(2.0-5.9) for men and women. For men, heavy drinkers (> = 69 g per day ethanol), had a significantly increased risk of subarachnoid hemorrhage compared with 'never-drinkers': multivariate RR(95% CI) = 4.3(1.1-16.8). For women, the relationship between heavy drinking and risk was not examined due to the small number of heavy drinkers (n = 13). Multivariate RR(95% CI) for men who smoked currently and drank heavily compared with men who did not smoke currently nor drink heavily was 6.0(1.8-20.1). Multivariate RR(95% CI) for hypertensive men who drank heavily compared with normotensive or borderline hypertensive men who did not drink heavily was 13.0(3.9-43.9). Multivariate RR(95% CI) for hypertensive men and women who smoked currently compared with normotensive or borderline hypertensive men and women who did not smoke currently was 6.1(1.3-28.7) for men and 6.3(1.4-28.0) for women. Furthermore, the combination of smoking, hypertension and heavy drinking raised the risk of subarachnoid hemorrhage substantially: multivariate RR(95% CI) = 17.5(3.4-90.2). CONCLUSION: Smoking and hypertension appeared to increase the risk of subarachnoid hemorrhage. For men, although the association of smoking with the risk of subarachnoid hemorrhage was weak compared with women, the combination of smoking, hypertension and heavy drinking increased the risk substantially. For women, smoking appeared to be an independent risk of subarachnoid hemorrhage, and the combination of smoking and hypertension increased the risk in additive fashion.
Adult↗