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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 37 records · Page 2Linked to original sources
PubMed2005

Topically administered timolol and dorzolamide reduce intraocular pressure and protect retinal ganglion cells in a rat experimental glaucoma model.

AIMS: This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat. METHODS: Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears (vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number. RESULTS: Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p<0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p<0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r = -0.908, p<0.005), but not in other groups (p>0.05). CONCLUSIONS: Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP.

Animals↗
PubMed2005

Polymorphism of the 5' flanking region of the IL-12 receptor beta2 gene partially determines the clinical types of leprosy through impaired transcriptional activity.

BACKGROUND: Individual differences in T cell responsiveness to interleukin 12 (IL-12), resulting from inherited factors, may be responsible for differences in the intensity of cell mediated immune (CMI) responses in patients with leprosy, a disease with a wide clinical spectrum. AIM: Polymorphisms in the 5' flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model. METHODS: Polymorphisms in the 5' flanking region of IL12RB2 were examined using direct sequencing techniques, and allele frequencies between patients with lepromatous leprosy and patients with tuberculoid leprosy were compared. The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells. RESULTS: Several SNPs, including -1035A>G, -1023A>G, -650delG, and -465A>G, were detected within the 5' flanking region of IL12RB2. The frequency of haplotype 1 (-1035A, -1023A, -650G, -464A) was high in the general Japanese population, but was significantly lower in lepromatous patients compared with tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNP exhibited a lower transcriptional activity compared with haplotype 1. CONCLUSION: SNPs within the 5' flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.

5' Flanking Region↗
PubMed2005

Possible link between glycolysis and apoptosis induced by sodium fluoride.

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

Apoptosis↗
PubMed2005

[Modified Komeda-David operation for postinfarction ventricular septal perforation].

The infarct exclusion technique with a xeno-pericardial patch which Komeda and associates firstly reported in 1990 is one of the best procedure to close ventricular septal perforation. A large patch can protect the perforation and the surrounding weak tissue from the internal left ventricular pressure. However, suturing this large patch to the left ventricular wall through the small incision is not technically easy because of the patch design in the ventricle. We modified the design of the patch. This round shaped bovine pericardial patch was sutured continuously to the left ventricular wall. Then, excessive part of the patch was trimmed to make a corn shape. Finally, the corn shaped patch fit the left ventricular wall naturally.

Aged↗
PubMed2005

[Delayed repair for blunt injury of the thoracic aorta complicated with the spinal cord injury; report of a case].

Blunt aortic injury is a major cause of death from blunt trauma and it generally accompanies with the other multiple serious injuries. A 67-year-old man sustained a blunt aortic injury and a fracture of 5th cervical vertebrae complicated with a spinal cord injury. A neurological examination showed a complete paralysis of the limbs. However, his respiratory status and circulatory status were stable. On admission, the paralysis improved resulting from high dose steroid injection and a cervical traction. An orthopedic operation was required before a cardiovascular operation even though computed tomography (CT) showed that a pseudo aortic aneurysm on the distal arch tended to enlarge in the short period. As a result, the aorta was repaired about 5 months after the injury. Delayed repair was performed in safe after careful and serial CT follow-up.

Accidents, Traffic↗
PubMed2005

Preoperative diagnosis of malignant transformation in mature cystic teratoma of the ovary.

OBJECTIVE: Malignant transformation of mature cystic teratomas (MCT) of the ovary is extremely rare. There are no established criteria of diagnosis before surgery for carcinoma arising from MCT of the ovary. Thus, we analyzed retrospectively tumor size and preoperative values of tumor markers in patients with MCT and investigated the possibility of preoperative diagnosis. METHODS: This was a retrospective case series of 278 patients with MCT of the ovary. Data were obtained from hospital charts and the pathology registry. Average tumor size (greatest diameter) was determined by the preoperative findings of both MRI and ultrasound examination. RESULTS: Malignant transformation was seen in five patients (11%) among those whose tumor was > or = 10 cm in diameter, four patients (23%) among those whose pretreatment serum SCC level was > or = 2.0 ng/ml, two patients (13%) among those over 60 years of age and five patients (2%) with a tumor on one side. Mean tumor size and serum SCC level were significantly higher than those of benign MCT. CONCLUSIONS: We conclude that patients over 60 years old who have unilateral MCT with SCC value of < or = 2.0 ng/ml and > or = 10 cm tumors may be a high-risk group for malignant transformation.

Adolescent↗
PubMed2005

[Off-pump coronary artery bypasssurgery in patients with mitral regurgitation].

Introduction of off-pump coronary artery bypass grafting (off-pump CABG : OPCAB) makes it possible to shorten the bypass time and cardiac arrest time in patients with both ischemic heart disease and valvular disease. This may be beneficial in patients with poor cardiac function and renal dysfunction. However, it is unclear whether such patients can tolerate the changes of hemodynamics during vertical displacement of the heart. In 3 patients who had ischemic heart disease with non-ischemic mitral regurgitation, we performed OPCAB prior to mitral valve plasty. The changes of mitral regurgitation observed by transesophageal echocardiography and several hemodynamic parameters were monitored as the heart was moved to various positions during OPCAB. When a heart positioner (Starfish) was used, hemodynamic deterioration was not observed, and there was also no aggravation of mitral regurgitation. Based on these results, we conclude that it may be possible to carry out OPCAB safely in patients with associated mitral regurgitation.

Adult↗
PubMed2004

Aberrant dynamics of histone deacetylation at the thyrotropin-releasing hormone gene in resistance to thyroid hormone.

Histone acetylation status influences transcriptional activity, and the mechanism of negative gene regulation by thyroid hormone remains unclear, although its impairment by a mutant thyroid hormone receptor (TR) is critical for resistance to thyroid hormone (RTH). We found a novel RTH mutant, F455S, that exhibited impaired repression of the TRH gene and had a strong dominant-negative effect on the gene. F455S strongly interacted with nuclear receptor corepressor (NCoR) and was hard to dissociate from it. To analyze the dynamics of histone acetylation status in vivo, we established cell lines stably expressing the TRH promoter and wild-type or F455S TR. Treatment with a histone deacetylase (HDAC) inhibitor completely abolished the repression of the gene by T3. The histones H3 and H4 at the TRH promoter were acetylated, and addition of T3 caused recruitment of HDACs 2 and 3 within 15 min, resulting in a transient deacetylation of the histone tails. TR and NCoR were located on the promoter, and T3 caused NCoR dissociation and steroid receptor coactivator-1 recruitment. In the presence of F455S, the histones were hyperacetylated, and HDAC recruitment and histone deacetylation were significantly impaired. This is the first report demonstrating the direct involvement of aberrant dynamics of chromatin modification in RTH.

Acetylation↗
PubMed2004

Centripetal bias on preparation for smooth pursuit eye movements based on the anticipation.

It has been reported that a brief perturbation of a stationary target during fixation induces larger eye movement when monkeys anticipate future smooth pursuit than when they do not. Here, we recorded eye movements in human subjects after briefly perturbing a target and the eccentricity of its initial position was changed under three conditions: (1) subjects anticipated saccades for a target that appeared before; (2) they anticipated smooth pursuit for a target that appeared before; and (3) they anticipated smooth pursuit but did not know beforehand where the target started from. We found that in condition 2 substantial eye movements were induced by the perturbation started moving toward the center. However, weak responses were observed in conditions 1 and 3. These results indicate that ocular responses to brief perturbations of the target at eccentric positions are increased with centripetal bias when human subjects prepare for future smooth pursuit.

Adult↗
PubMed2004

Preoperative diagnosis of colouterine fistula secondary to diverticulitis by sonohysterography with contrast medium.

Colouterine fistulae secondary to sigmoid diverticulitis are unusual. Methods for diagnosis remain to be established. We report a case with a colouterine fistula in which sonohysterography detected the flow of ultrasound contrast medium between the uterine cavity and the sigmoid colon through the posterior uterine wall, thus confirming the diagnosis. The diagnosis was further substantiated by a charcoal challenge test. The patient underwent en bloc resection of the uterus, Fallopian tubes, ovaries and sigmoid colon, the organs involved with diverticulitis. This is the first report to describe a colouterine fistula successfully diagnosed by sonohysterography using ultrasound contrast medium.

Aged↗
PubMed2004

Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma.

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.

Adenoma↗
PubMed2004

In vitro digestion of sinigrin and glucotropaeolin by single strains of Bifidobacterium and identification of the digestive products.

Three strains of Bifidobacterium sp., B. pseudocatenulatum, B. adolescentis, and B. longum were studied for their ability to digest glucosinolates, sinigrin (SNG) and glucotropaeolin (GTL), in vitro. All strains digested both glucosinolates during 24-48 h cultivation, accompanied by a decline in the medium pH from 7.1 to 5.2. The digestion of glucosinolates by a cell-free extract prepared from sonicated cells of B. adolescentis, but not cultivated broth, increased in the presence of 0.5 mM l-ascorbic acid. Also, a time-dependent formation of allyl isothiocyanate (AITC) was observed when the cell-free extract was incubated with 0.25 mM SNG for 120 min at pH 7.0. These reaction features suggest that the digestive activity may have been due to an enzyme similar to myrosinase, an enzyme of plant origin. GC-MS analysis of the Bifidobacterial cultured broth showed that the major products were 3-butenenitrile (BCN) and phenylacetonitrile (PhACN), from SNG and GTL, respectively and nitriles, probably due to a decrease in the pH of the media. AITC and benzyl isothiocyanate (BzITC) were barely detectable in the broth. It was concluded that the three species of Bifidobacteria could be involved in digestive degradation of glucosinolates in the human intestinal tract.

Acetonitriles↗
PubMed2004

Relationship between bone resorption and adrenal sex steroids and their derivatives in oophorectomized women.

OBJECTIVE: To clarify the role of adrenal sex steroids and their derivatives on bone resorption in oophorectomized women. DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University. SUBJECT(S): Forty-eight women who were within one year of bilateral oophorectomy were recruited for this study. INTERVENTION(S): None of the subjects were treated with the drugs affecting bone metabolism. MAIN OUTCOME MEASURE(S): Urinary deoxypyridinoline (Dpyr) as marker of bone resorption and serum DHEAS, androstenedione (A-dione), testosterone (T) and estrone (E1) levels as adrenal sex steroids and their derivatives. RESULT(S): There was an inverse correlation between urinary Dpyr and serum concentrations of E1, DHEAS, or A-dione. There was no significant relationship between urinary Dpyr and T. CONCLUSION(S): These results suggest that adrenal steroids and their derivatives may influence the bone resorption in oophorectomized women.

Adult↗
PubMed2004

Role of the amygdalo-hippocampal transition area in the fear expression: evaluation by behavior and immediate early gene expression.

Using pre- and post-training lesions of the amygdalo-hippocampal transition area (AHi), the role of the AHi in the fear conditioning of rats was examined. Pretraining lesions by N-methyl-d-aspartate led to the enhancement of freezing behavior in auditory fear conditioning and contextual conditioning. However, the freezing of post-training-lesioned rats did not differ from that of the sham-lesioned rats. There were several regions of the brain observed in this study in which c-Fos and/or Egr-1 immunoreactive-positive cell expression changed in diverse manners after the test session. In the pretraining lesioned rats that were trained for auditory conditioning, the number of c-Fos and Egr-1 decreased in the infralimbic cortex (IL) and the number of Egr-1 increased in the basomedial amygdaloid nucleus (BM). In the pretraining AHi-lesioned rats that were trained for contextual conditioning, the number of c-Fos increased in the lateral periaqueductal gray (LPAG) and the number of Egr-1 increased in the BM. These results suggest that the AHi plays an important role in the acquisition of memory during conditioning alone, whereas it is improbable that the AHi had an effect on consolidation, retrieval, and expression in the case of either auditory or contextual fear conditioning. The findings also suggest that the freezing behavior was related to the changes in c-Fos and/or Egr-1 in the IL, BM, and LPAG. As in the case of the BM, the number of Egr-1 immunoreactive-positive cells was increased in both experiments, and it was possible that the activation of neurons with high basal levels of expression might be associated with memory retrieval or expression as a freezing behavior observed in the test session.

Acoustic Stimulation↗
PubMed2004

Insulin-like growth factor-I stimulates acromegaly-like specific mandibular enlargement in rats.

To help us investigate the time course of mandibular enlargement in acromegaly or acrogiantism to determine the most suitable period for occlusal treatment in this disease, our aim was to develop a rat model of acromegaly (acrogiantism). In this study, prominent mandibular enlargement was induced by continuous subcutaneous infusion of human recombinant insulin-like growth factor-I (IGF-I) (640 microg/day) in 10-week-old male rats for 4 weeks (n = 6); the control sham-operated group was injected with saline alone (n = 6). Circulating human IGF-I was clearly detectable in the IGF-I group during the four-week administration period, while endogenous rat IGF-I levels decreased. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. The length of every bone examined (mandible, maxilla, and femur) showed a significant increase compared to control rats, especially the mandible. Although the mandible did not continue to grow after discontinuation of IGF-I administration, it did not return to control size, unlike the maxilla and femur, and disharmonious jaw size (between maxilla and mandible) persisted even after circulating IGF-I levels normalized. These findings in our rat model suggest that mandibular occlusal treatment should only be considered for acromegalic (acrogiantic) patients after serum IGF-I levels have normalized and bone growth has ceased.

Acromegaly↗
PubMed2004

Altered expression of p53 mRNA in the brain and pituitary during repeated immobilization stress: negative correlation with glucocorticoid receptor mRNA levels.

In our previous study, apparent reduction of glucocorticoid receptor (GR) mRNA was seen in the hippocampus and the hypothalamic paraventricular nucleus (PVN) during repeated immobilization (IMO) stress, but not following starvation. Our laboratory has also shown that the sp1 activates, whereas tumour suppressor p53 represses the promoter activity of GR gene. In an attempt to reveal the possibility that transcription factors such as sp1 and/or p53 are involved in the regulation of GR mRNA expression in the hippocampus and in the PVN in vivo, we examined the expression of GR mRNA, p53 mRNA, and sp1 mRNA in the hippocampus and in the PVN during repeated IMO and following starvation. In addition, the expression of these mRNAs was examined in the anterior pituitary, another GR-rich area. GR mRNA in all subfields of the hippocampus was robustly decreased, while GR mRNA in the anterior pituitary was increased, 24 h following 4 x IMO (2 h daily, for 4 consecutive days) and immediately after 5 x IMO. GR mRNA in the PVN was significantly decreased immediately after 5 x IMO, but not at 24 h after 4 x IMO. Conversely, p53 mRNA in the PVN and hippocampus was increased, whereas p53 mRNA in the anterior pituitary was decreased, 24 h following 4 x IMO and immediately after 5 x IMO. Sp1 mRNA was unchanged in all areas examined following repeated IMO. Following 4 days of starvation, neither GR mRNA, p53 mRNA nor sp1 mRNA showed any changes in the PVN and the hippocampus, except there was a minor decrease in GR mRNA in CA1-2. In the anterior pituitary, 4 days of starvation induced a minor, but significant increase in GR mRNA, whereas it decreased p53 mRNA. Overall, regression analyses revealed a negative correlation between GR mRNA levels and p53 mRNA levels in CA1-2 and dentate gyrus of the hippocampus and in the anterior pituitary. GR mRNA in the PVN also showed a tendency towards the negative correlation with p53 mRNA levels. The results raise the possibility that p53 negatively regulates GR mRNA expression in the PVN, the hippocampus and the anterior pituitary during repeated immobilization stress.

Animals↗
PubMed2004

Strong association of C-reactive protein with body mass index and 2-h post-challenge glucose in non-diabetic, non-smoker subjects without hypertension.

AIMS: Increases in C-reactive protein (CRP) levels have been shown to be associated with cardiovascular diseases as well as asymptomatic atherosclerosis and to be closely related to traditional cardiovascular risk factors. The aim of this study was to determine the clinical and biochemical characteristics associated with CRP in non-diabetic, non-smoker subjects without hypertension. METHODS: A 75-g oral glucose tolerance test was performed on 305 Japanese subjects aged 40-70 years who were undergoing health examinations. We recruited non-diabetic, non-smoker subjects without hypertension. Subjects with known cardiovascular diseases, chronic or acute inflammation, malignant diseases, or autoimmune disorders were excluded. Plasma high-sensitivity CRP was measured in 125 subjects who satisfied the admission criteria. RESULTS: Plasma CRP levels were significantly higher in the 28 subjects with impaired glucose tolerance (IGT) than that in the 97 subjects with normal glucose tolerance (NGT) (median 0.53, range 0.18-1.10 mg/l vs. median 0.32, range 0.17-0.49 mg/l; P = 0.032). There was a positive correlation of CRP with body mass index (BMI), triglycerides, uric acid, fasting glucose, oral glucose tolerance test (OGTT) 1-h glucose, OGTT 2-h glucose, and a negative correlation with HDL cholesterol. Multivariate regression analysis identified BMI (F = 8.57, P = 0.004) and OGTT 2-h glucose (F = 5.96, P = 0.016) as independent predictors for CRP. CONCLUSIONS: BMI and OGTT 2-h glucose are the most important predictors for plasma CRP in non-diabetic, non-smoker subjects without hypertension.

Adult↗