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Biomedical subjects

M Kubota

Publications and source records attributed to M Kubota.

At least 19 recordsLinked to original sources

Effect of a 5-HT(1A) receptor agonist, flesinoxan, on the extracellular noradrenaline level in the hippocampus and on the locomotor activity of rats.

We have studied effects of 5-hydroxytryptamine 1A (5-HT(1A)) receptor-selective compounds on the extracellular noradrenaline (NA) level in the hippocampus of rats using microdialysis and on their locomotor activity. A selective 5-HT(1A) receptor agonist, flesinoxan (5 mg/kg, i.p.) increased the extracellular NA level in the hippocampus, and increased the locomotor activity. Both responses were blocked by pretreatment with a 5-HT(1A) receptor antagonist, WAY100635 (1 mg/kg, i.p.) and an alpha(2) adrenoceptor agonist, clonidine (50 microg/kg, i.p.). Bilateral intrahippocampal injection of flesinoxan (200 nmol in 2 microl, respectively) increased the locomotor activity of rats and the intrahippocampal perfusion of flesinoxan (1 mM, 2 microl/min) increased the extracellular NA level in the hippocampus. Bilateral intrahippocampal injections of a small amount of WAY100635 (0.1 nmol in 2 microl, respectively) blocked the flesinoxan (5 mg/kg, i.p.)-induced hyperactivity. Flesinoxan (5 mg/kg, i.p.) did not significantly influence the level of serotonin or its major metabolite in the hippocampus, or dopamine or its metabolites in the striatum. In conclusion, these behavioral as well as pharmacological results indicate that postsynaptic 5-HT(1A) receptor activation by flesinoxan increase the extracellular NA level in the hippocampus, which may be the cause of the increase of the locomotor activity.

Animals↗

Cloning and nucleotide sequence of a gene encoding a glycogen debranching enzyme in the trehalose operon from Arthrobacter sp. Q36.

A gene located just upstream of the treYZ operon was isolated from Arthrobacter sp. strain Q36. The gene, designated treX, encoded an 823-amino acid protein. The amino acid sequence of the protein had 50% identity with the TreX protein (isoamylase) from Sulfolobus acidocaldarius ATCC 33909 which has a treZXY operon on the genome. We suggest that Arthrobacter treX is an isoamylase gene, and that it is a component of a treXYZ operon.

Amino Acid Sequence↗

Important role of the hepatic vagus nerve in glucose uptake and production by the liver.

We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.

Animals↗

Zonisamide - induced urinary lithiasis in patients with intractable epilepsy.

We report here three patients with intractable epilepsy who developed urinary lithiasis during zonisamide (ZNS) treatment. Abdominal pain due to left-sided hydronephrosis was the initial symptom in the first patient, and it was resolved after the excretion of a stone. The second patient, who had no specific symptoms, was found to have a thick sludge of calcium phosphate in the bladder when he suffered from aspiration pneumonia and dehydration. The third patient, who had a history of recurrent urinary obstruction, was also found to have a thick sludge of calcium oxalate in the bladder. The urinalysis of the three patients revealed alkaline urine and hypercalciuria. Although their urinary lithiasis was resolved by discontinuation of ZNS and supportive therapy, routine examination of urine parameters such as pH and sediments, and daily urine-output checks are thought to be necessary during treatment with ZNS, especially for patients who are bedridden for a long time and receive multiple antiepileptic drugs.

Adolescent↗

New ocular movement detector system as a communication tool in ventilator-assisted Werdnig-Hoffmann disease.

A non-contact communication system was developed for a ventilator-assisted patient with Werdnig-Hoffmann disease who had lost all voluntary movements except for those of the eye. The system detects the extraocular movements and converts them to either a 'yes' signal (produced by one lateral eyeball movement) or a 'no' signal (produced by two successive lateral eyeball movements) using a video camera placed outside the patient's visual field. The patient is thus able to concentrate on performing a task without any intrusion from the detection system. Once the setting conditions of the device have been selected, there is no need for any resetting, as the patient is unable to move his body. In addition to playing television games, the child can use the device to select television channels, compose music, and learn written Japanese and Chinese characters. This seems to broaden the patient's daily world and promote mental development.

Activities of Daily Living↗

Comparative performance of magnetic resonance angiography and conventional angiography in moyamoya disease.

Patients with moyamoya disease verified by conventional cerebral angiography (CCA) were evaluated by means of magnetic resonance angiography (MRA), in order to clarify its advantages and limitations in comparison with CCA. This retrospective study was carried out in 13 hemispheres of seven patients with moyamoya disease (including one atypical patient). In MRA, magnetisation transfer contrast (MTC) and maximal intensity projection (MIP) techniques were used. A good correspondence between MRA and CCA was noted in 11 hemispheres (86.4%) on evaluating stenotic lesions and overestimation in the remaining 2. Underestimation of moyamoya vessels in MRA was noted in 3 hemispheres, since well developed moyamoya vessels were detectable, while poorly developed ones were not. No difference between MRA and CCA findings was found in 10 hemispheres (76.9%). MRA tends to overestimate the stenosis and underestimate moyamoya vessels. These characteristics may lead to wrong classification in the angiographic grade of patients with early and advanced stages and should be taken into consideration in interpreting MRA images of moyamoya disease (compatible rate of grade between MRA and CCA; 84.6%). In conclusion MRA with MTC and MIP techniques offers an acceptable quality of assessment of stenotic lesions and moyamoya vessels. MRA is a useful follow up method at present and in the near future it may replace CCA as the initial diagnostic tool.

Adult↗

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids.

To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.

Animals↗

Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis.

To compare the interleukin-6 (IL-6) gene expression in the peripheral blood mononuclear cells (PBMCs) and plasma IL-6 levels in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with those in patients undergoing hemodialysis. Eleven hemodialysis patients, 10 CAPD patients, 15 non-dialyzed patients with end-stage kidney disease (ESKD), and 7 healthy controls were included in this study. PBMCs were collected by differential centrifugation. Plasma IL-6 concentration was measured by enzyme immunoassay. Plasma IL-6 levels were significantly increased in the hemodialysis and CAPD patients as compared with non-dialyzed ESKD patients and normal subjects (p < 0.01). Following hemodialysis, plasma IL-6 levels exceeded those before hemodialysis. No significant difference was found in plasma IL-6 levels in CAPD patients and in hemodialysis patients when blood was drawn before hemodialysis. Low but steady-state levels of IL-6 mRNA expression were observed in the non-dialyzed ESKD patients. The expression of IL-6 mRNA in PBMCs was significantly increased in the patients undergoing hemodialysis or CAPD as compared with the non-dialyzed ESKD patients. The PBMC IL-6 mRNA was significantly lower in CAPD patients than in hemodialysis patients (p < 0.01). A significant correlation was found between the plasma concentration of IL-6 and the expression of IL-6 mRNA in PBMCs from patients undergoing hemodialysis or CAPD (p < 0.01). The hemodialysis or CAPD procedure contributed to the increase in PBMC IL-6 mRNA expression and plasma IL-6 concentration. CAPD treatment stimulated the production of IL-6 to a lesser extent than hemodialysis treatment.

Adult↗

An effective ultrasonic strain measurement-based shear modulus reconstruction technique for superficial tissues--demonstration on in vitro pork ribs and in vivo human breast tissues.

An effective shear modulus reconstruction technique is described which uses ultrasonic strain measurements for diagnosis of superficial tissues, i.e. our previously developed ultrasonic strain measurement and shear modulus reconstruction methods are combined and enhanced. The technique realizes very low computational load, yet yields fairly high quantitativeness, high stability and spatial resolution, and large dynamic range. The suitability of the method is demonstrated on in vitro pork ribs and in vivo human breast tissues (fibroadenoma and scirrhous carcinoma).

Adenocarcinoma, Scirrhous↗

Three cases of malignant lymphoma of the breast.

We report three cases of malignant lymphoma (ML) of the breast and discuss diagnosis and management. The first case is a 35-year-old woman who had a left breast tumor. Fine needle aspiration cytology (FNAC) showed ML. Mastectomy was performed without any adjuvant chemotherapy. Histology revealed diffuse large B-cell lymphoma of REAL classification. Seventy one months after surgery, lesions indicating relapse were detected in nodes of the right axilla, mediastinum and para-aorta. She underwent eight cycles of CHOP regimen, but 1 month after the chemotherapy a brain metastasis was detected. The patient then received a high-dose methotrexate regimen with whole-skull irradiation. The second case is a 47-year-old woman who had anterior neck swelling and bilateral breast tumors. Histology of the tumor revealed diffuse large B-cell lymphoma. The patient underwent eight cycles of CHOP regimen and high-dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT). Forty eight months after the PBSCT, there is no evidence of disease. The third case is a 38-year-old woman who had a right breast tumor. FNAC of the breast tumor showed ML and a CT scan of the chest revealed lymphadenopathy at the crus of the diaphragm. Histology of the tumor revealed low-grade B-cell lymphoma of MALT type. The patient underwent six cycles of CHOP regimen and HDC supported by PBSCT. Eighteen months after the PBSCT, relapse lesions were detected in nodes of the neck, mediastinum and renal hilum. The patient received nine cycles of a THP-COP regimen.

Adult↗

Magnetoencephalographic study of giant somatosensory evoked responses in patients with rolandic epilepsy.

We report five patients with rolandic epilepsy associated with giant somatosensory responses to median nerve stimulation, in whom we analyzed the pathophysiologic relationship between rolandic discharges and the somatosensory responses using magnetoencephalography. Four of the five patients showed giant P30m, the current source of which was localized in the primary somatosensory cortex, while the first cortical response, N20m, was not enhanced, except in one patient. The current source of the giant middle-latency component, N70m, was localized posterior to that of N20m, possibly in the posterior parietal cortex, in all patients. The initial positive peak and large negative peak of rolandic discharges were identical to P30m and N70m with respect to the current source localization, wave form, topographic pattern, and time relationship in the electroencephalogram and magnetoencephalogram, and somatosensory evoked magnetic field and somatosensory evoked potential records, respectively. In addition, the secondary sensory cortex was considered to be the generator of the middle-latency component in one patient. In one patient, the current intensity of the N70m was normalized along with clinical improvement and the disappearance of rolandic discharges, whereas those of other somatosensory evoked magnetic field components remained unchanged. Our data suggest that the rolandic discharge generator mechanism in these patients could be closely related to the developmental alteration of excitability in the primary somatosensory cortex, posterior parietal cortex, and secondary somatosensory cortex, which decreased with age, and it could share a common neuronal pathway, at least in part, with the giant P30m-N70m (N90m) in the somatosensory evoked magnetic field through the sequential and parallel processing of somatosensory information.

Case-Control Studies↗

Long-term outcome of endocrine function in patients with neurohypophyseal germinomas.

Since neurohypophyseal germinomas occur at the pituitary and hypothalamic axis in children and adolescents, the endocrinopathy is one of the common and critical QOL determinants. We carried out a retrospective study on the outcome of endocrine function in patients with neurohypophyseal germinoma, in order to improve or preserve pituitary function after treatment. Sixteen patients (7 men and 9 women), aged 6 to 26 years were admitted and followed up for 95.3 (14-197) months. DI was noted in 12 patients in pretreatment and 16 in posttreatment regardless of tumor size. We carried out the replacement of GH in all 8 patients, presenting the symptoms under 15 years of age. Gonadal or gonadotropic, thyroid and adrenal hormones were replaced in 9, 12 and 15 patients, respectively. Patients with large tumor compressing chiasm or hypothalamus needed hormonal replacement such as gonadal or gonadotropic and thyroid hormones more frequently (<0.01) than those with small one. In addition, two patients with a small tumor at the pituitary stalk and the 3rd ventricle floor showed the improvement of secretion pattern in gonadotropins and ACTH after chemotherapy, although they later needed radiation therapy to control the tumor. Based on our study and review of literature, the endocrinological studies before and after treatment demonstrated that pituitary dysfunction present before treatment persisted or worsened even after tumor remission, except for patients with small and localized ones. The poor endocrine results is considered to be largely radiation-related. Chemotherapy alone seems to be insufficient to obtain complete response (CR). To avoid radiation related pituitary injury, combination of 24 Gy or less dosage of radiation and appropriate chemotherapy is essential. The earlier diagnosis by repeatedly using neuroimaging and serum and CSF tumor markers and earlier initiation of treatment, before irreversible pituitary-hypothalamic damage occurs, contributes to improvement of the outcome of pituitary functions in patients with neurohypophyseal germinomas.

Adolescent↗

Women's anxiety in old age and long-term care provision for the elderly.

The purpose of this study was to verify the differences in women's anxiety in old age, the expected long-term care provision, and the expected final location for terminal care for the women themselves and for their parents. In addition, we examined factors that related to their anxiety and needs. The subjects were 1,000 women of the Seikatsu Club customer cooperative association in Chiba; 539 responded to our survey. The subjects were more anxious for their parents than for themselves. They more strongly expected long-term care for their parents to be provided by their family than they expected the same for themselves. Although no differences were observed in the expected location for terminal care, most subjects expected their home to be the terminal location. Analysis by the multiple logistic regression model indicated that the following factors were significantly related to the anxiety in old age: age odds ratio [OR = 1.81], employment [OR = 2.25] for women, and planning to live with parents [OR = 2.42], housing conditions [OR = 0.56] for parents. The following factors were significantly related to the expected long-term care provision: age [OR = 2.22] for women, and age [OR = 2.15], living with parents [OR = 3.58], and employment [OR = 2.33] for parents. Age [OR = 2.14] for women, and planning to live with parents [OR = 2.09] for parents were significantly related to the expected final location of terminal care. This survey showed that women expected long-term care for their parents to be provided by their family, while many expected public long-term care services for themselves. This is the biggest difference in women's outlook on long-term care for their parents and for themselves. Multivariate analysis suggested that women aged 40 years or over, who will need long-term care in the future, tended to expect public home care services for themselves. It is virtually certain that the demand for public home care services will increase in the future.

Adult↗

Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of urinary uracil.

The importance of detecting heterozygosity for X-linked ornithine transcarbamylase deficiency is well known. Although the DNA analysis and the allopurinol loading tests are commonly used for this purpose, both methods require complicated procedures. In order to establish a simple test for detecting female heterozygotes, we examined the uracil and orotic acid in single-voided urine samples from 70 healthy women, and from 12 asymptomatic females with ornithine transcarbamylase deficiency. Based on the results of healthy women, we were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the sensitivity of OCT heterozygotes was 100%. We were also able to establish a second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic form) for diagnosis. Using this second cut-off line, the specificity of OCT heterozygotes was 100%. Our study has shown that the measurement of urinary uracil is a relatively simple and effective method for detecting female heterozygotes.

Female↗

Analysis of the prognostic factors relating to better clinical outcome in ganglioneuroblastoma.

PURPOSE: To elucidate the precise reason for the better prognosis in ganglioneuroblastoma (GNB) than in neuroblastoma (NB), the prognostic factors (age at diagnosis, stage at diagnosis, primary site, N-myc amplification, Shimada classification, and ploidy) were analyzed. METHODS: A retrospective analysis of the 57 neuroblastoma cases (20 GNB cases and 37 NB cases), that had not been detected by mass screening over the past 19 years at the authors' institute, was carried out. RESULTS: A Kaplan-Meier analysis of the 5-year survival rates were 67.2% and 35.1% in cases of GNB and NB, respectively, and these rates were significantly higher in GNB (logrank test; P = .04631). No significant differences were seen between GNB and NB regarding the rate in patients 1 year of age or older (95.0% v 78.4%; P = .1005), the rate of advanced cases (60.0% v 78.4%, P = .1406), the rate of an unfavorable histology (Shimada classification, 54.5% v 68.4%, P = .4473), or the diploid pattern rate (75.0% v 76.9%, P = .9200). However, N-myc amplification was found exclusively in NB (amplified cases per examined cases; 15/31), and all cases with N-myc amplification died. When the 5-year survival rate was evaluated in the patient without N-myc amplification between GNB and NB, no significant difference was observed (logrank test; P = .8568). CONCLUSION: The better prognosis in patients with GNB was thus thought to be exclusively related to an absence of N-myc amplification.

Ganglioneuroblastoma↗

[Three pediatric cases of erythroleukemia: review of the literature on prognostic factors].

We encountered 3 patients with erythroleukemia who showed differing outcomes. The first patient was an 11-year-old girl who was treated with an ANLL 91 national protocol followed by bone marrow transplantation from an HLA-identical brother. She is still in complete remission after 6 years. The second patient was a 15-year-old girl. Treatment with low dose Ara-C was effective. She experienced a relapse once, but achieved her second remission with low dose-Ara-C plus vitamin D. Up to the present, she has maintained remission for 5 years. The third patient was a 1-month-old girl who initially presented with an increase of proerythroblasts with infiltration to the liver. Although her response to Ara-C and etoposide was favorable, she died of a generalized fungal infection in the leukopenic phase. Chromosomal analyses of bone marrow cells were normal for patients 1 and 2, but patient 3 had an abnormal complex karyotype. We think the prognosis for erythroleukemia in childhood is not necessarily poor in all cases. Appropriate treatment should be based on the patient's age, the proportion of proerythroblasts, and the presence of chromosomal abnormalities.

Adolescent↗

Gene structure of mouse BIT/SHPS-1.

BIT/SHPS-1/SIRPalpha/P84 is a unique molecule with a high degree of homology with immune antigen recognition molecules (immunoglobulin, T-cell receptor and MHC), and is highly expressed in the brain. The extracellular region contains three immunoglobulin-like domains (V-type, C1-type and C1-type), and the intracellular region contains two signalling motifs that interact with SHP-2 protein tyrosine phosphatase. BIT-coated plates support cell-substrate adhesion and neurite extension of neurons, and BIT participates in neuronal signal transduction. Diversity of the V-type domain sequences of human BIT has been reported. In the present study we analysed the structure of the mouse BIT gene (Bit). The protein coding region consists of eight exons corresponding to a signal peptide, a V-type domain, a C1-type domain, a C1-type domain, a transmembrane region and three parts of one cytoplasmic region. The two signalling motifs are encoded in one exon. Four splicing forms of mouse BIT were revealed. We also found the sequence diversity in three mouse strains, namely BALB/c, 129/Sv and C57BL/6. The substitution patterns of amino acids and nucleotides indicate positive pressure to alter the amino acids in the V-type domain in evolution. Immunoblot analyses showed that mouse BIT and human BITalpha are predominantly expressed in the brain. On the bases of these findings we discuss the possibility that BIT contributes to the genetic individuality and diversity of the brain.

Alternative Splicing↗

Layer-specific horizontal propagation of excitation in the auditory cortex.

Optical imaging was conducted in rat auditory cortex slice preparations to study how horizontal excitation propagates in the cerebral cortex. When a horizontal cut was made between supragranular and infragranular layers, electrical stimulation of layer II/III elicited horizontally propagating excitation in supragranular layers with the same propagating velocities as those seen before a cut was made. Electrical stimulation of layer VI or the border between the white matter and layer VI also elicited horizontally propagating excitation in infragranular layers with the same propagating velocities as those seen before a cut was made. These results suggest that the horizontal propagation of excitation in supragranular and infragranular layers can occur independently in the auditory cortex.

Animals↗