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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 109 records · Page 6Linked to original sources
PubMed2001

Participation of ATP in cell volume regulation in the endothelium after hypotonic stress.

1. The role of ATP in the regulatory volume decrease (RVD) after hypotonic cell swelling was examined in cultured endothelial cells isolated from the rat caudal artery. 2. Hypotonic stress increased [Ca2+]i in addition to increasing the overflow of ATP and cell volume. The hypotonicity induced increase in [Ca2+]i was prevented by pyridoxalphosphate-6-azophenyl-1-2',4'-disulphonic acid (PPADS; a P2 purinoceptor antagonist), U-73122 (a phospholipase C inhibitor) and thapsigargin (a Ca2+ pump inhibitor). However, the hypotonicity induced increase in cell volume was potentiated by PPADS, U-73122 and thapsigargin. 3. Similar changes were observed in cells treated with 2-methylthioATP, a P2Y purinoceptor agonist, but not by alpha,beta-methylene ATP, a P2X purinoceptor agonist. Thus, it appears that the responses observed following hypotonic stress are mediated by activation of P2Y purinoceptors. 4. On the basis of these findings, it is suggested that ATP, which is released by hypotonicity, may participate in the RVD as a substantial regulator or initiator via P2 purinoceptor-induced increases in [Ca2+]i.

Adenosine Triphosphate↗
PubMed2001

Macrocystic type of serous cystadenoma with a communication between the cyst and pancreatic duct.

A 42-year-old woman with a cystic lesion in the head of the pancreas was evaluated by using abdominal ultrasonography, a computed tomographic scan, magnetic resonance imaging and endoscopic retrograde pancreatography. Multiple cystic lesions, 5 cm in diameter, which had papillary protrusion inside the cyst in the head of the pancreas and had the communication between the cysts and pancreatic duct, were determined. Pylorus-preserving pancreaticoduodenectomy was performed under the diagnosis of mucinous cystic neoplasm of the pancreas. Although the cut surface of the tumor showed a macrocystic tumor of 3 cm in diameter, part of the cyst wall was cavernous. A histopathological examination showed single-layered cuboidal cells, which lead to the diagnosis as being serous cystadenoma of the pancreas. Serous cystadenoma is a rare, almost benign pancreatic tumor. The macrocystic subtype of serous cystadenoma is even more rare. We describe a patient who had this macrocystic subtype of serous cystadenoma with a communication between the cyst and pancreatic duct. This case illustrates the difficulty in the diagnosis of cystic lesions in the pancreas, and might support the single category of cystic lesions of the pancreas.

Adult↗
PubMed2001

Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters.

BACKGROUND: Oxidative stress during hemodialysis is thought to promote the progression of vascular complications in hemodialysis patients. The protective role of vitamin E as a lipophilic antioxidant against oxidative stress has been widely investigated. Here we investigated the effects of a vitamin E-coated regenerated cellulose hollow fiber dialyzer (CL-EE) on oxidative stress compared with a polysulfone hollow fiber (CL-PS). METHODS: For at least three months before beginning the protocol, 10 nondiabetic (NDM) patients (70.0 +/- 7.5 years; 6 males and 4 females) and 8 diabetic (DM) patients (65.0 +/- 7.4 years; 4 males, 4 females) were dialyzed with CL-PS. After that, we treated all of the patients with CL-EE for six months. Malondialdehyde (MDA), advanced glycation end products (AGEs), and 8-hydroxydeoxyguanosine (8-OHdG) were monitored as biomarkers for oxidative stress at the start and then at one, three, and six months into treatment with CL-EE. RESULTS: Serum MDA, AGE, and 8-OHdG levels increased after the hemodialysis with CL-PS. The increase of the biomarkers was completely prevented by a single use of CL-EE. Long-term hemodialysis with CL-EE for six months significantly reduced the basal levels of the oxidant markers at one month for AGE and at six months for 8-OHdG in both DM and NDM patients. Serum MDA was reduced in only DM patients at three months. The improvement of the oxidative stress with CL-EE was more prominent in the DM patients. CONCLUSIONS: Long-term treatment with CL-EE efficiently improves the oxidative stress associated with hemodialysis and potentially reduces dialysis complications due to oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Pulmonary CT findings in acute mercury vapour exposure.

AIM: We describe the pulmonary computed tomography (CT) findings in acute mercury poisoning. MATERIALS AND METHODS: Initial (n= 8) and follow-up (n= 6) chest CT examinations in eight patients exposed to mercury vapour while cutting pipes in a sulphuric acid plant were reviewed. Of the eight patients, two were asymptomatic and had normal CT results, two were asymptomatic but had abnormalities on CT, and four had both acute symptoms and positive CT results. The patients were all men whose ages ranged from 37 to 54 years (mean, 49 years). RESULTS: Poorly defined nodules were present in five of six patients with positive CT findings, present alone in two patients or as part of a mixed pattern in three. They were random in distribution. Alveolar consolidation (n= 3) and areas of ground-glass opacity (n= 4) were observed and were more prominent in the most severely affected patients with the highest blood and urine level of mercury, predominantly in the upper and/or middle zone. These abnormal findings on CT resolved with (n= 1) or without (n= 5) steroid therapy. Pathological findings (n= 1) demonstrated acute interstitial changes predominantly with oedema. CONCLUSION: We report CT findings in eight patients acutely exposed to mercury vapour. The pulmonary injury was reversible on CT in these cases. Hashimoto, M. (2001). Clinical Radiology56, 17-21.

Acute Disease↗
PubMed2001

Functional analysis of RET with Hirschsprung mutations affecting its kinase domain.

BACKGROUND AND AIMS: Many missense mutations in the RET proto-oncogene were found in familial and sporadic cases of Hirschsprung disease (HSCR). The aim of this study was to make clear the mechanisms of RET dysfunction by HSCR mutations identified in its kinase domain. METHODS: Ten kinase domain HSCR mutations were introduced into wild-type RET and constitutively activated RET with a multiple endocrine neoplasia 2A mutation, and the resulting mutant complementary DNAs were transfected into SK-N-MC primitive neuroectodermal tumor cells or NIH 3T3 fibroblast cells. The levels of activation of mutant RET and representative signaling molecules were investigated in the transfectants. RESULTS: E762Q, S767R, R972G, and M980T mutations partially impaired the RET kinase activity and the representative signaling pathways. In particular, these mutations severely impaired the phospholipase C-gamma signaling pathway in SK-N-MC cells. S765P, R873Q, F893L, R897Q, and E921K mutations resulted in a complete loss of the RET kinase activity. The P973L mutation markedly decreased the expression of the RET protein with normal kinase activity. CONCLUSIONS: Hirschsprung disease can result from these distant functional classes of kinase domain mutation of RET.

Cells, Cultured↗
PubMed2001

Atrial fibrillation impairs endothelial function of forearm vessels in humans.

BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Acetylcholine↗
PubMed2001

Investigation on diabetic autonomic neuropathy assessed by power spectral analysis of heart rate variability in WBN/Kob rats.

This article investigates the development of cardiovascular autonomic dysfunction caused by diabetes mellitus. We performed power spectral analysis of heart rate variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of the rats was measured continuously for 24 hours with an implanted telemetric transmitter, and power spectral analysis of heart rate variability was performed on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a tendency toward a decrease in plasma insulin concentration without hyperglycemia. At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm of the blood pressure. By the power spectral analysis of heart rate variability, it became apparent that the circadian rhythm of the low frequency/high frequency ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian rhythms of the high-frequency power level and low frequency/high frequency ratio were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic nervous system in WBN/Kob rats is progressively damaged from the prediabetic to diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized by the appearance of sympathetic overactivity that precedes the impairment of parasympathetic activity.

Animals↗
PubMed2001

Lifting of lesions during endoscopic mucosal resection (EMR) of early colorectal cancer: implications for the assessment of resectability.

BACKGROUND AND STUDY AIMS: This study assessed the indications for and limitations of endoscopic mucosal resection (EMR) for early colorectal cancer, focusing on the way in which the lesion lifts after submucosal injection. PATIENTS AND METHODS: The study included 94 patients with early colorectal cancer who received EMR treatment. The lifting of the lesion after submucosal injection was analyzed (classified as completely lifted/soft; completely lifted/hard; incompletely lifted; and non-lifted) along with the endoscopic findings, pathological findings, and clinical course. RESULTS: Almost all completely lifted/soft lesions were mucosal cancers. Some of the completely lifted/hard lesions were staged as sm2. The incompletely lifted lesions included stages sm1 to sm3. Non-lifting lesions were almost always deeper than sm3. The lifting condition was significantly associated with the depth of invasion, and the lesion type was related to the extent of lifting but not to tumor size or recurrent disease. Recurrent disease was noted in three patients who underwent piecemeal EMR. CONCLUSIONS: The indication for EMR is easily assessed on the basis of the lifting characteristics of the tumor after submucosal injection, which was found to be significantly related to the depth of invasion. The factor limiting the indication for EMR is not the size of a tumor, but its lifting condition.

Aged↗
PubMed2001

IL-18 might reflect disease activity in mild and moderate asthma exacerbation.

BACKGROUND: IL-18, identified as an IFN-gamma-inducing factor, is a proinflammatory cytokine that plays an important role in TH1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines. OBJECTIVE: The aim was to evaluate the contribution of IL-18 to asthma exacerbation. METHODS: Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-gamma levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy. RESULTS: Significantly higher serum IL-18 levels were found in patients with acute asthma (215 +/- 33 pg/mL, mean +/- SE; P = .02) and pulmonary sarcoidosis (239 +/- 27 pg/mL, P = .008) than in control subjects (127 +/- 11 pg/mL), but the plasma IFN-gamma level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-gamma levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy. CONCLUSION: It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation.

Acute Disease↗
PubMed2001

Feasibility of cryopreserved tracheal xenotransplants with the use of short-course immunosuppression.

OBJECTIVE: We evaluated the feasibility of discordant xenotransplantation of the cryopreserved trachea with intermittent immunosuppression to help solve the shortage of donor tracheas. METHODS: Two experiments were performed with heterotopic transplantation models in 14 guinea pigs and 85 rats. So that the minimal dose of FK506 for viable fresh xenografts could be determined, FK506 was given in escalating doses (0, 1.5, 2.5, and 3.5 mg/kg) for recipient animals after xenogeneic transplantation. With the goal of obtaining a long-term survival of the xenografts, the effect of cryopreservation on xenografts was assessed and thereafter different cycles of immunosuppression every third week were evaluated in fresh or cryopreserved xenografts in the second experiment. RESULTS: An FK506 dosage of more than 2.5 mg/kg per day was much more effective than smaller dosages, as demonstrated by morphologic assessment. A higher dosage of FK506 potentially delayed the rejection of xenografts and can thus maintain tracheal xenograft viability for less than 4 weeks in rat recipients. In experiment 2, the cryopreserved xenografts showed less histologic viability than fresh xenografts but greater patency of the lumen. The patency of cryopreserved xenografts was favorably maintained for a longer period than that of fresh xenografts with either the same number or more cycles of immunosuppression. CONCLUSIONS: We conclude that the synergistic effect of cryopreservation and adequate intermittent immunosuppression may enable tracheal xenografts to remain viable over longer periods.

Animals↗
PubMed2001

Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow DNA in aged rats and its relation to antioxidant vitamins.

We compared the influence of docosahexaenoic acid (DHA) supplementation on oxidative DNA damage in bone marrow between young and aged rats. As a marker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone marrow in the aged DHA group was significantly higher than that in the other groups. Vitamin E concentrations, however, did not differ among the groups regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations in the aged control group were approximately 1/2 those in the young control group. The concentrations of vitamin C tended to be higher in the young DHA group and lower in the aged DHA group when compared to their respective control groups. Changes in the concentrations of vitamin C and vitamin E in plasma were similar to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the concentrations of vitamin C in the bone marrow and the plasma. These results suggest that in aged rats, but not young rats, excess supplementation of DHA induces oxidative DNA damage in bone marrow and that the decrease in vitamin C synthesis in aged rats is involved in the mechanisms of DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Preventive effects of Juzen-taiho-to on N-methyl-N-nitrosourea and estradiol-17beta-induced endometrial carcinogenesis in mice.

Two experiments were conducted to determine effects of Juzen-taiho-to on endometrial carcinogenesis in mice. In the first experiment, Juzen-taiho-to treatment (2 weeks) decreased the levels of estradiol-17beta (E(2))-stimulated expression of c-fos/jun mRNA and their oncoproteins, determined by reverse transcription-polymerase chain reaction and Southern blot analysis, and the immunohistochemical method, in the uteri of ovarectomized mice. For the second experiment, 93 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and were divided into four groups. Group 1 was given a diet containing 0.2% Juzen-taiho-to and 5 p.p.m. E(2). Group 2 was given a diet containing 5 p.p.m. E(2) alone. Group 3 was given a diet containing 0.2% Juzen-taiho-to alone. Group 4 was kept on the basal diet alone and treated as a control. Juzen-taiho-to treatment significantly decreased incidences of the uterine endometrial atypical (P<0.01), complex (P<0.05) and simple hyperplasias (P<0.01), under estrogenic stimulation. It is suggested that Juzen-taiho-to has an inhibitory effect on E2-related endometrial carcinogenesis in mice, relevantly through suppression of estrogen-induced c-fos/jun-expression.

Animals↗
PubMed2001

Protective effect of OK-432 on mice against endotoxemia and infection with Pseudomonas aeruginosa and Salmonella enteritidis.

OK-432 has been used clinically as a biological response modifier for cancer therapy. We investigated here the protective effects of OK-432 against endotoxic shock and infectious death caused by Pseudomonas aeruginosa and Salmonella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endotoxic shock in D-(+)-galactosamine-sensitized C3H/HeN mice. OK-432 did not affect the TNFalpha production in blood, but it did decrease the susceptibility to TNFalpha. Furthermore, an acceleration of LPS clearance from blood was detected. The pretreatment of OK-432 also decreased the lethality of mice in bacterial infection caused by P. aeruginosa and S. enteritidis. The rapid decrease of the viable bacteria from the circulating blood and in spleen and liver in mice was observed in a manner similar to LPS clearance. These findings indicate that the protective effect of OK-432 against the endotoxemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNFalpha.

Animals↗
PubMed2001

Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice.

The effects of isoflavones (genistein and daidzein) on endometrial carcinogenesis in mice were investigated in two experiments. In the short-term experiment (2 weeks), single subcutaneous (s.c.) administration of genistein [1 mg / 30 g body weight (b.w.)] significantly decreased the levels of estradiol-17beta (E(2)) (5 ppm in diet)-induced expression of c-jun, interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) mRNAs in the uteri of ovariectomized mice (P < 0.005, P < 0.05 and P < 0.01, respectively). Daidzein significantly inhibited E(2)-induced expression of c-fos and IL-1alpha (P < 0.01, P < 0.01 respectively). In the long-term experiment (30 weeks), 140 female ICR mice were given N-methyl-N-nitrosourea-containing solution (1 mg / 100 g b.w.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into six groups; group 1 was given E(2) (in diet) alone. Group 2 was given E(2) and genistein (1 mg / 30 g b.w., s.c., every four weeks). Group 3 was exposed to E(2) and daidzein (1 mg / 30 g b.w., s.c., every four weeks). Groups 4 and 5 respectively received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical endometrial hyperplasia of the group given E(2) and genistein or daidzein were significantly lower than of the group with E(2) alone (P < 0.01 and P < 0.05, respectively). It is suggested that both genistein and daidzein have an inhibitory effect on estrogen-related endometrial carcinogenesis in mice, possibly by suppressing expression of estrogen-induced estrogen-related genes c-fos and c-jun, and internal cytokines IL-1alpha and TNF-alpha through a cytokine and estrogen receptor-mediated pathway.

Adenocarcinoma↗
PubMed2001

The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA.

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural progenitor cells, including neural stem cells. In this study, the RNA-binding sequences for Msi1 were determined by in vitro selection using a pool of degenerate 50-mer sequences. All of the selected RNA species contained repeats of (G/A)U(n)AGU (n = 1 to 3) sequences which were essential for Msi1 binding. These consensus elements were identified in some neural mRNAs. One of these, mammalian numb (m-numb), which encodes a membrane-associated antagonist of Notch signaling, is a likely target of Msi1. Msi1 protein binds in vitro-transcribed m-numb RNA in its 3'-untranslated region (UTR) and binds endogenous m-numb mRNA in vivo, as shown by affinity precipitation followed by reverse transcription-PCR. Furthermore, adenovirus-induced Msi1 expression resulted in the down-regulation of endogenous m-Numb protein expression. Reporter assays using a chimeric mRNA that combined luciferase and the 3'-UTR of m-numb demonstrated that Msi1 decreased the reporter activity without altering the reporter mRNA level. Thus, our results suggested that Msi1 could regulate the expression of its target gene at the translational level. Furthermore, we found that Notch signaling activity was increased by Msi1 expression in connection with the posttranscriptional down-regulation of the m-numb gene.

3T3 Cells↗
PubMed2001

Genetic polymorphism of the MxA gene promoter and interferon responsiveness of hepatitis C patients: revisited by analyzing two SNP sites (-123 and -88) in vivo and in vitro.

We have previously reported a single nucleotide polymorphism (SNP) at nucleotide (nt) position -88 (G or T) within an interferon-stimulated response element-like sequence in the promoter region of the MxA gene, which correlated with responsiveness of hepatitis C patients to interferon. Upstream of it, we then identified another SNP (C or A at nt -123) and investigated whether this SNP also correlates with interferon responsiveness. The two SNPs showed a high linkage to each other: all the individuals having G at -88 had C at -123, and 73% of those having T at -88 had A at -123. As was expected from this observation, the SNP at -123 also exhibited a correlation with interferon responsiveness (C/C homozygotes were more frequent among nonresponders than among responders: 65% of 107 vs. 40% of 52, p = 0.0028). These in vivo data from patients were further supported by results from in vitro experiments. The MxA promoter sequence with A at -123 and T at -88 showed about 4-fold higher activity of upregulating the downstream reporter gene than that with C at -123 and G at -88, in a luciferase reporter assay.

GTP-Binding Proteins↗