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Biomedical subjects

Y Tanabe

Publications and source records attributed to Y Tanabe.

At least 19 recordsLinked to original sources

Improved human islet isolation by a tube method for collagenase infusion.

BACKGROUND: Collagenase infusion into the pancreatic duct is an essential step in human islet isolation. We developed a new method for ductal canulation and collagenese infusion. METHODS: A total of 53 pancreata were divided into two groups: group 1 (n=23), the new tube method, and group 2 (n=30), the standard angiocatheter method. In group 1, a polyethylene tube was inserted into the duct and pushed to the tail. The tail was first expanded, followed by expansion of the body and then the head, by pulling out the tube. RESULTS: Total islet number and number/g pancreas (mean+/-SE) were significantly higher in group 1 (481,123+/-43,218 and 8,010+/-722) (mean+/-SE) than in group 2 (300,974+/-35,122 and 5,090+/-515, P<0.01). Total islet equivalent number and islet equivalent number per gram pancreas were also significantly higher in group 1 (319,176+/-39,354 and 5,455+/-652) than in group 2 (202,022+/-23,331 and 3,722+/-468, P<0.04). Islet purity and fragmentation showed no differences between the groups. CONCLUSIONS: The tube method improved islet yields. We recommended this method for human islet isolation.

Catheterization

Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation.

We describe an unique patient presenting with severe leukodystrophy compatible with Pelizaeus-Merzbacher disease and peripheral neuropathy consistent with Charcot-Marie-Tooth disease type 1 in addition to Waardenburg-Hirschsprung syndrome. A novel mutation was identified in her SOX10 gene, which encodes a transcription factor preferentially expressed in the late embryonic glial cell lineage and in mature myelin-forming cells of both the central nervous system and peripheral nervous system, as well as in the early neural crest cells. Heterozygous SOX10 loss-of-function mutations have been reported in patients with Waardenburg-Hirschsprung syndrome and its murine model, Dominant megacolon. However, neither Waardenburg-Hirschsprung syndrome patients nor Dominant megacolon mice have dysmyelinating features, suggesting the question of how SOX10 acts in the glial lineage in vivo. The novel mutation described herein does not disrupt the coding region but extends the peptide and hence is likely to act as a dominant-negative allele. Our findings indicate that dysfunction of SOX10 may lead to deficiency of myelination in the central nervous system and peripheral nervous system as well as hypopigmentation and enteric aganglionosis.

Alleles

Occurrence of ganglioside GD3 in neoplastic astrocytes. An immunocytochemical study in humans.

GD3 immunocytochemical analysis was performed in 25 human specimens obtained by autopsy and biopsy from patients with astrocytomas, anaplastic astrocytomas, cerebellar astrocytomas and glioblastoma multiforme (GM), using the ABC method. Extraction of the ganglioside fraction from GM was used for thin-layer chromatography (TLC) analysis to confirm the specificity of anti-GD3 monoclonal antibody (DSG-1). Normal astrocytes were not immunoreactive for GD3. Neoplastic astrocytes of low- to high-grade tumours were GD3 immunoreactive. In GM, the multinucleated giant cells were also immunoreactive. All immunoreactivity present was within the cytoplasm. In TLC analysis, enzyme immunostaining of gangliosides from GM with DSG-1 showed only one positive band, which had the same TLC migration rate as GD3, indicating that GD3 of the ganglioside fraction from GM is the antigen detected by DSG-1. The presence of GD3 within the cytoplasm of neoplastic astrocytes showing invasive and proliferative properties, is of considerable interest. The implications and possible significance of the presence of GD3 in the cytoplasm in glioma cells are discussed.

Adolescent

Demonstration of ganglioside GD3 in human reactive astrocytes.

Astrocytes are the cells that actively participate in the process of lesion repair in the central nervous system (CNS), and reactive astrocytosis of varying degrees becomes apparent with time in any pathological condition occurring in the normally developed postnatal CNS. Ganglioside GD3 (II3a(NeuAca2-8NeuAc)-LacCer, GD3) in reactive astrocytes from autopsied patients with Creutzfeldt-Jakob disease (CJD) and old cerebral infarction was investigated immunocytochemically, using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Reactive astrocytes in CJD and cerebral infarction demonstrated GD3-immunoreactivity within the cytoplasm. Normal astrocytes were negative. The present data raise the possibility that GD3 in reactive astrocytes has biological implications for the properties of the cells, such as cellular motility.

Aged

The hypotensive effect of docosahexaenoic acid is associated with the enhanced release of ATP from the caudal artery of aged rats.

Fish oils have been shown to lower blood pressure in hypertensive subjects. To determine the mechanism of this hypotensive effect, we examined the effects of docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP, AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats (100 wk) were fed a high cholesterol diet and were administered intragastrically ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA group) or vehicle alone (control group). Compared with the controls, rats supplemented with DHA had significantly greater (10.1%) DHA concentrations in the caudal arteries. This was associated with more total (n-3) arterial fatty acids, a greater unsaturation index of arterial fatty acids, 43.9% lower plasma noradrenaline levels and the repression of the elevation in blood pressure observed with advancing age. The amount of purines released, both spontaneously and in response to noradrenaline, from arterial segments of DHA-supplemented rats was significantly higher than that released from tissues of control rats. Regression analysis revealed significant negative relationships between the total amount of purines released from the artery and the systolic (SBP) and diastolic (DBP) blood pressures. These results suggest that in aged rats, supplementation with DHA alters the membrane fatty acid composition as well as the amount of ATP released from vascular endothelial cells and decreases plasma noradrenaline, and that these factors may ameliorate the rise in blood pressure normally associated with advancing age.

Adenosine Triphosphate

Absence of plasma protease-antiprotease imbalance in the formation of saccular cerebral aneurysms.

OBJECTIVE: We examined the hypothesis that a plasma protease-antiprotease imbalance contributes to the formation of saccular cerebral aneurysms and the suggestion that the assay of these enzymes might be a screening tool for people at higher risk for aneurysm formation. METHODS: From June 1997 through May 1998, the plasma leukocyte elastase, which is an important proteolytic enzyme, and alpha-antitrypsin and alpha2-macroglobulin, which are important antiproteolytic enzyme plasma proteins, were examined in 18 patients with ruptured aneurysms, 9 patients with unruptured aneurysms, and 22 controls. RESULTS: The elastase:alpha1-antitrypsin ratio and the elastase:alpha2-macroglobulin ratios were significantly higher in patients with ruptured aneurysms within 24 hours after subarachnoid hemorrhage (SAH) than in the controls. The protease-antiprotease imbalance depended on the elevation of the elastase level, which might be correlated with leukocytosis after SAH. The elastase level decreased to the control level 3 months after the onset of SAH. No significant difference in the elastase:alpha1-antitrypsin and elastase:alpha2-macroglobulin ratios was observed between the patients with unruptured aneurysms and the controls. CONCLUSION: These results do not support the hypothesis that a plasma protease-antiprotease imbalance is a potential marker to predict the formation of saccular cerebral aneurysms. The increase in plasma elastase levels in patients with ruptured aneurysms might be attributable to leukocytosis after SAH.

Adult

Cerebral blood flow in patients with normal pressure hydrocephalus.

Mean cerebral blood flow (CBF) of the whole brain was measured in 48 patients who underwent cerebrospinal fluid shunt surgery for normal pressure hydrocephalus (NPH) by performing first-pass radionuclide angiography using 99Tcm-hexamethylpropylene amine oxime. Patients were divided according to outcome into an 'excellent' improvement group, a 'good' improvement group, a 'fair' improvement group and a 'poor' improvement group. Patients with excellent and good improvement had a preoperative mean CBF of 40.4 +/- 3.9 ml.100 g-1.min-1 and 37.1 +/- 5.5 ml.100 g-1.min-1, respectively, both of which were significantly (P < 0.005) higher than that in 11 patients who showed fair improvement (30.8 +/- 3.2 ml.100 g-1.min-1) and six patients who showed poor improvement (31.8 +/- 2.5 ml.100 g-1.min-1). Patients with a clinical improvement after shunting had an increased postoperative mean CBF. We conclude that patients with a preoperative mean CBF of over 35 ml.100 g-1.min-1 can show favourable improvement after a shunting procedure, and that the preoperative mean CBF of 32 ml.100 g-1.min-1 can be considered the critical level for treatment.

Adult

Induction of protective T cells against Listeria monocytogenes in mice by immunization with a listeriolysin O-negative avirulent strain of bacteria and liposome-encapsulated listeriolysin O.

Only listeriolysin O (LLO)-producing strains of Listeria monocytogenes generate protective immunity in mice. Based on the findings that endogenous gamma interferon (IFN-gamma) production was induced only by such strains and that purified LLO could induce IFN-gamma from NK cells, we have postulated that LLO may play a pivotal role in the induction of Th1-type protective T cells, which are highly dependent on IFN-gamma. In this study, mice were immunized with L. monocytogenes ATCC 15313, an LLO-nonproducing avirulent strain, along with LLO encapsulated in liposome (LLO-liposome). LLO-liposome was highly potent in the induction of various cytokines, including IFN-gamma. Immunization of mice with either LLO-liposome or the viable strain ATCC 15313 alone did not induce protection against challenge infection. In contrast, the combination of LLO-nonproducing bacteria plus LLO-liposome induced a significant level of protective immunity mediated mainly by Th1-type cells capable of producing a large amount of IFN-gamma in an antigen-specific manner. The protection afforded by the combination was not dependent on LLO-specific cytotoxic T cells. These results support the idea that the inability of an LLO-nonproducing avirulent strain or killed bacteria to induce the generation of protective T cells is due not to the lack of a central T-cell epitope(s) but to the lack of ability to induce the production of endogenous cytokine during the early stage of immunization; the results also suggest that an appropriate use of LLO at least in an animal model may be effective in the induction of antigen-specific Th1-dependent protective immunity to various kinds of intracellular parasitic bacteria.

Adoptive Transfer

Hypotension induced by exercise is associated with enhanced release of adenyl purines from aged rat artery.

To determine whether the antihypertensive effects of exercise are associated with release of ATP and its metabolites from arteries, we assayed blood pressure and the release of adenine nucleotides and nucleosides from the caudal arteries of exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill for 12 wk significantly decreased the rise in systolic and diastolic blood pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of oleic, linoleic, and linolenic acids in the caudal artery decreased significantly with exercise, demonstrating an association between exercise and the unsaturation index of caudal arterial fatty acids. The amounts of total adenyl purines released by the arterial segments from exercised rats, both spontaneously and in response to norepinephrine, were significantly greater by 80.0 and 60.7%, respectively, than those released by tissues from sedentary rats. These results suggest that exercise alters the membrane fatty acid composition in aged rats as well as the release of ATP from vascular endothelial cells and that these factors are associated with the regression of the rise in blood pressure normally observed with advanced age.

Adenine Nucleotides

A case of vasospastic angina presenting Brugada-type ECG abnormalities.

An electrophysiological study and a provocative test of coronary artery spasm was attempted in a 68-year-old man who was having syncopal attacks and chest pain. His electrocardiogram had the characteristics of Brugada syndrome and ventricular fibrillation (VF) was induced by programmed electrical stimulation. ST-segment elevation became exaggerated by procainamide, which could not prevent the induction of VF. Coronary angiography revealed no stenotic lesions, and spasm in the left coronary artery was induced by intracoronary administration of acetylcholine with similar chest pain to that experienced before. Under treatment with diltiazem and flecainide, which suppressed the induction of VF, the patient experienced no recurrence of symptoms despite persistent ST-segment elevation. No previous reports have described coronary spasm associated with Brugada-type ECG abnormalities, and patients with syncope should be evaluated carefully.

Acetylcholine

Exercise-induced rise in arterial potassium in patients with chronic heart failure.

OBJECTIVES: In patients with chronic heart failure (CHF), exercise is frequently associated with skeletal muscle fatigue and breathlessness due to heightened ventilatory response. The exercise-induced rise in potassium, which is released from the exercising skeletal muscle, has been implicated in ventilatory control during exercise. The aim of the present study was to determine whether the exercise-induced rise in arterial potassium is altered in patients with CHF and to examine the relationship between increased exercise ventilation and exercise-induced hyperkalemia in patients with CHF. METHODS AND RESULTS: We evaluated 88 patients with CHF (25 patients were in class I, 35 in class II, and 28 in class III according to the New York Heart Association functional classification) and 14 normal subjects. Subjects performed symptom-limited ergometer exercise while expired gas, arterial blood gas, and arterial potassium were analyzed. The increases in ventilation (deltaV(E)), effective alveolar ventilation (deltaVA), and carbon dioxide output (deltaV(CO2)) from rest to peak exercise decreased as the severity of CHF advanced. The ratio of deltaV(E) to deltaV(CO2) was significantly elevated in class III patients, although there was no difference in the ratio of deltaVA to deltaV(CO2) among the four groups. Rest and exercise arterial P(CO2) did not differ among the four groups and was controlled within the normal range. The increase in arterial potassium (deltaK+) from rest to peak exercise was markedly reduced as the severity of CHF advanced: (mean +/- SD) 1.70+/-0.32 mmol/L in normal subjects; 1.46+/-0.27 mmol/L in class I patients; 1.15+/-0.24 mmol/L in class II patients; and 0.78+/-0.24 mmol/L in class III patients. The ratios of deltaVA or deltaV(CO2) to deltaK+ were not different among the four groups. The ratio of deltaV(E) to deltaK+, however, was significantly greater in patients in class III than in normal subjects or patients in class I or II. CONCLUSIONS: The deltaK+ from rest to peak exercise was markedly reduced as the severity of CHF advanced. The increased exercise ventilation due to increased physiologic dead space in severe CHF was not accompanied by the corresponding augmentation of exercise-induced hyperkalemia. Exercise-induced hyperkalemia does not contribute to the increased ventilatory drive to keep normal arterial P(CO2) during exercise in the presence of increased physiologic dead space in severe CHF.

Exercise

[Effect of vasodilators on femoral-to-radial arterial pressure gradient after cardiopulmonary bypass].

In 57 adult patients undergoing valve replacement surgery or valve plastic surgery, pressure gradient between the femoral and radial artery was evaluated after cardiopulmonary bypass (CPB). During CPB, the rectal temperature was kept at mild or moderate hypothermia. Nitrates and prostaglandin E1 were administered in all patients during operation. Patients were divided into two groups; Group A of 31 patients who had history of hypertension and received some vasodilators up to the operation, and Group B of 27 patients who had no history of such medication. There was no difference in patient's characteristics, anesthetic time, CPB time and aortic cross clamping time between the two groups. There was a significant difference between the pre-CPB and post-CPB in hematocrit data. Systemic vascular resistance (SVR) decreased significantly from the pre-CPB level to the post-CPB level. There was no significant difference between Group A and Group B in SVR, but a higher femoral-to-radial artery pressure gradient was observed in Group A until the end of operation. Hypertension and the use of vasodilator change the tone of peripheral blood vessels and intensify femoral-to-radial artery pressure gradient after CPB.

Aged

[Effect of preoperative chemotherapy for bulky N2 non-small-cell lung cancer].

The effect of chemotherapy as the adjuvant therapy to bulky N2 disease (stage IIIA) non-small-cell lung cancer was examined. From January 1992 to December 1996, 464 patients with non-small-cell lung cancer underwent surgery. Seven patients (1.5%) with N2 disease (stage IIIA) received two cycles of preresectional cisplatin and vindesin chemotherapy, followed by standardized surgical resection (Group A). 46 patients (9.9%) had pathological N2 disease (T1-3, M0) after surgery (Group B). In Group A a complete resection was accomplished in two patients (28.6%), and five patients had incomplete resection with a deseased margin, followed thoracic irradiation 60 to 75 Gy. In three patients in Group A the N2 disease was pathologically downstaged to N1 or N0 disease. Overall survival at five years in Group A and in Group B was 48% and 39%, and median survival time was 49 months and 38 months. Although complete resection rate was lower in Group A (28.6%) than in Group B (78.2%), there was no significant difference between five year survival and median survival time in Group A and Group B. These data may be thought to suggest that induction chemotherapy in Group A was effective on occult micrometastatic disease.

Aged

Effect of percutaneous transvenous mitral commissurotomy on postexercise breathlessness as determined by ventilation during recovery from constant workload exercise.

We evaluated the effect of percutaneous transvenous mitral commissurotomy (PTMC) on ventilatory variables and dyspnea during recovery from a 6-minute submaximal constant workload exercise, and showed that the decrease in postexercise ventilation after PTMC was closely related to improvement in postexercise dyspnea after PTMC. Ventilation during recovery from submaximal constant workload exercise is related to postexercise breathlessness and can be used to assess the effectiveness of therapeutic interventions.

Adult

Specification of motor neuron identity by the MNR2 homeodomain protein.

Sonic hedgehog signaling controls the differentiation of motor neurons in the ventral neural tube, but the intervening steps are poorly understood. A differential screen of a cDNA library derived from a single Shh-induced motor neuron has identified a novel homeobox gene, MNR2, expressed by motor neuron progenitors and transiently by postmitotic motor neurons. The ectopic expression of MNR2 in neural cells initiates a program of somatic motor neuron differentiation characterized by the expression of homeodomain proteins, by neurotransmitter phenotype, and by axonal trajectory. Our results suggest that the Shh-mediated induction of a single transcription factor, MNR2, is sufficient to direct somatic motor neuron differentiation.

Animals

Involvement of 26-kDa membrane-bound tumour necrosis factor precursor in bidirectional feedback regulation on 17-kDa tumour necrosis factor production after stimulation by lipopolysaccharide.

The authors have previously shown that 26-kDa membrane-bound tumour necrosis factor precursor (proTNF) on the cell-surface of primed human monocytic cell line THP-1 is involved in positive feedback regulation of lipopolysaccharide (LPS)-dependent TNF-production. Here, we provide direct evidence for modulation of responsiveness of the THP-1 cells against LPS by membrane-bound pro-TNF. When THP-1 cells were cocultivated with a heterogeneous cell line (proTNF/3T3 cells) which constitutively expressed membrane-bound proTNF, LPS-dependent TNF-production by THP-1 cells was significantly suppressed and the normal level was restored by the presence of anti-TNF antibody during cocultivation. The proTNF-3T3-induced decline of TNF-production of THP-1 was observed primarily at the mRNA level, although no difference was observed in the mRNA level of interleukin 1 beta, another LPS-inducible cytokine. These results suggest that proTNF could also be involved in the negative feedback regulation of LPS-dependent TNF-production through cell-to-cell contact. The augmentation of LPS-dependent TNF-production accompanied by the production of endogenous proTNF induced by exogenous agent was inhibited by protein kinase C inhibitor, whereas proTNF/3T3-induced suppression of TNF-production could not be restored to the normal level. It thus seems possible that proTNF might act on macrophages as a bidirectional regulator of its production by THP-1 cells depending on co-induced signals.

3T3 Cells

Analysis of exploratory eye movement in a patient with lupus psychosis.

The psychiatric and cognitive condition of a patient with lupus psychosis was evaluated. Using a device that detects the corneal reflection of infrared light, the patterns of eye tracking movements were recorded before the onset of lupus psychosis, after remission, and again 1 year later. Electroencephalographic findings and cerebrospinal fluid levels of both interferon alpha and interleukin-6 were also obtained longitudinally. Electroencephalographic findings and clinical signs were correlated to the levels of interferon alpha in cerebrospinal fluid. Analysis of exploratory eye movements revealed marked decreases in the number of eye fixation, mean eye-scanning length and total eye-scanning length. Even though the lupus psychosis resolved and the electroencephalographic findings became normal, the eye movement patterns showed remaining deterioration. It was concluded that analysis of exploratory eye movements in patients with systemic lupus erythematosus may be useful in diagnosing lupus psychosis, and may also present a diagnostic clue to subclinical lupus psychosis.

Adult