Biomedical subjects
Publications and source records attributed to K Onoda.
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OBJECTIVES: Review three cases of unilateral gustatory disturbance due to central lesions caused by cerebrovascular disorders, describe clinical findings and the results of taste examinations, and discuss the central gustatory pathways in humans. STUDY DESIGN: Retrospective review of three gustatory disturbance cases due to cerebrovascular disorders. Additional review of 12 cases with central gustatory disturbance that have been reported. METHODS: Central lesions of three cases were examined by magnetic resonance imaging or computed tomography scan. Electrogustometry and a filter paper disk assay using taste solutions were performed in these cases for each of the bilateral gustatory nerves. RESULTS: In one case of pontine infarct, gustatory disturbance ipsilateral to the lesion was found, and in one case of thalamic infarct and one case of internal capsular infarct, gustatory disturbance contralateral to the lesion was observed. CONCLUSIONS: Fifteen cases of unilateral gustatory disturbance due to central lesions, including the present cases, have been reported to our knowledge. Examination of these cases strongly suggested that the central gustatory pathways in humans ascend ipsilaterally from the solitary nucleus of medulla oblongata to the pons, and from the pons, cross to a higher position in midbrain and reach the thalamus contralaterally.
Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.
BACKGROUND: To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion. METHODS: In protocol 1 isolated rat hearts were perfused at 37 degrees C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10 degrees C, hearts were reperfused at 37 degrees C with one of two buffers: group C, 60-minute reperfusion with KHB (K+, 5.9 mmol/L; Ca2+, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K+, 15 mmol/L; Ca2+, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37 degrees C with KHB containing colchicine (10(-5) mol/L) for 60 minutes. RESULTS: There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function. CONCLUSIONS: One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.
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Tenascin-C is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions during organogenesis and tissue remodelling. It has therefore been proposed as a stromal marker for epithelial malignancy. To test this hypothesis, 30 human lung cancers, presenting a variety of clinicopathological features, and six specimens of normal tissue were examined by Western and Northern blotting of tenascin-C protein and mRNA. The results obtained were: (1) elevated tenascin-C expression was detected in all 30 cases by Western blotting, with mRNA increase in 22 of them; (2) mRNA for a large isoform of tenascin-C, including an alternatively spliced sequence, was expressed in lung cancer tissues but not in normal lungs; and (3) metastasis to lymph nodes was frequently found in cases whose tenascin-C was degraded into small fragments. These results suggest that tenascin-C degradation can be used as a marker for metastatic potential of a tumour.
In cardiac reoperations, the less dissection needed, the less potential blood loss from divided epicardial adhesions and the less trauma to the heart. However, minimal cardiac dissection may result in inadequate topical cooling. Therefore the optimal delivery of cardiac solution has a great influence upon postoperative myocardial function in cardiac reoperations. We have examined the effect of the modified Buckberg's method compared to that of simple cold blood cardioplegia in valvular reoperations. In the cases of redo aortic valve procedures, antegrade-retrograde delivery of cardioplegic solution was done in the modified Buckberg's method. It was superior to simple cold blood cardioplegia in terms of the doses of dopamine needed when weaning from cardiopulmonary bypass and the ratio of spontaneous beating after aortic declamping. Nevertheless, myocardial protection measures for hypertrophied myocardium have not yet been established. In particular, reoperations for hypertrophied hearts pose many problems for cardiac surgeons. To achieve better cardiac function postoperatively, further investigations of hypertrophied myocardium are needed at the cellular or molecular level.
Alterations in platelet aggregability may play a role in the pathogenesis of qualitative platelet defects associated with cardiopulmonary bypass (CPB). We circulated fresh heparinized whole blood through tubing sets coated with heparin (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA), plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib expression were measured, before, during, and after this in vitro set up of circulation. In the two groups, the extent of hSIPA significantly decreased during circulation and was partially restored after circulation. Decreases in the extent of hSIPA were significantly less with use of heparin-coated circuits. There was an equivalent reduction in plasma vWF activity, in the two groups. Expression of platelet surface GP Ib decreased significantly during circulation and recovered after circulation. Reduction of surface GP Ib expression during circulation was significantly less in the C group than that in the N group. Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with the magnitude of hSIPA, in the two groups. The progressive removal of surface GP Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton into the cytoskeleton. Our observations suggest that use of heparin-coated circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of redistribution of GP Ib.
BACKGROUND: A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-microm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures. METHODS: Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator. RESULTS: Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O2 and CO2 transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability. CONCLUSIONS: This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.
Postoperative pulmonary hypertensive crisis is a major problem that may account for a substantial part of the postoperative mortality and morbidity. We, therefore, evaluated the effect of inhalation of low-dose nitric oxide (NO) on postoperative care in pediatric patients with pulmonary hypertension. We studied 10 infants and children ages 1-108 months (median age, 11 months) with congenital heart disease associated with pulmonary hypertension. The NO and N2 gas mixture was then mixed with varied quantities of air and oxygen and delivered into a respirator instead of an inspiratory tube. Patients were treated with inhaled NO for 38.6 +/- 19.6 h (range 1-200 h). All patients were eventually weaned from high level sedation and respirator. The NO concentration ranged from 2 to 5 parts per million. During NO inhalation patients demonstrated a statistically significant reduction in systolic pulmonary arterial pressure by approximately 26%; from 55 +/- 10 to 41 +/- 20 mm Hg. Inhalation of NO resulted in a significant increase of Pao2 from 110 +/- 16 to 149 +/- 29 mm Hg. A-aDo2 significantly decreased from 284 +/- 27 to 247 +/- 31 mm Hg. In conclusion, we have shown that a low-dose NO inhalation acted as pulmonary vasodilator in patients with preexisting pulmonary hypertension.
The aim of this study was to investigate how insulin secretion is controlled by phosphorylation of the myosin light chain (MLC). Ca2+-evoked insulin release from pancreatic islets permeabilized with streptolysin O was inhibited by different monoclonal antibodies against myosin light-chain kinase (MLCK) to an extent parallel to their inhibition of purified MLCK. Anti-MLCK antibody also inhibited insulin release caused by the stable GTP analog guanosine 5'-O-(3-thiodiphosphate), even at a substimulatory concentration (0.1 microM) of Ca2+. Free Ca2+ increased MLC peptide phosphorylation by beta-cell extracts in vitro. In contrast to the phosphorylation by purified MLCK or by calmodulin (CaM) kinase II, the activity partially remained with the beta-cell under nonstimulatory Ca2+ (0.1 microM) conditions. The MLCK inhibitor ML-9 inhibited the activity in the beta-cell with both substimulatory and stimulatory Ca2+, whereas KN-62, an inhibitor of CaM kinase II, only exerted an influence in the latter case. ML-9 decreased intracellular granule movement in MIN6 cells under basal and acetylcholine-stimulated conditions. We propose that MLC phosphorylation may modulate translocation of secretory granules, resulting in enhanced insulin secretion.
BACKGROUND AND PURPOSE: Although mice, rats, and other small animals are commonly used for molecular biology research, their use in the evaluation of cerebral vasospasm after subarachnoid hemorrhage is somewhat problematic because of the correspondingly small size of their cerebral vessels. We have already reported that the corrosion cast technique was useful for evaluating newly formed cerebral vessels in neural grafts in these small animals. In the present study we applied the corrosion cast technique to the evaluation of hemolysate-induced cerebral vasospasm in rats and performed three-dimensional analysis for comparison. The casting was done 10 minutes after the hemolysate injection, so that only acute "vasospasm" was assessed. METHODS: After withdrawal of 0.1 mL cerebrospinal fluid, 0.2 mL hemolysate (n = 9) or saline (n = 10) was injected into the cisterna magna of male Sprague-Dawley rats weighing between 300 and 350 g. Ten minutes later, perfusion of a semipolymerized casting medium was performed at an injection pressure of 100 to 120 mm Hg. The brains were immersed and corroded in 10% NaOH solution. After these procedures, the basilar artery as well as peripheral vessels was analyzed morphologically with scanning electron microscopy. Conventional histological analysis with the use of paraffin-embedded section with hematoxylin-eosin staining was also performed, and the results were compared with those for the corrosion cast methods. RESULTS: In the saline-injected group, SEM showed that the inner surface of the basilar artery was smooth and the form of the endothelial cell was printed on the surface of the cast. In the hemolysate-injected group, the basilar artery showed an apparent vasospasm over its entire length, and corrugation was observed on the inner surface of the basilar artery in a three-dimensional fashion. Higher magnification revealed that the nuclei of the endothelial cells were distorted. Local narrowing of the basilar artery and vasospasm in the arteries of the anterior circulation and in peripheral arteries were also observed. Measurement of the inner diameter of the basilar artery showed 37.8% contraction in the hemolysate-injected group compared with the saline-injected group by the corrosion cast method. This degree of vasospasm was similar to that observed by the conventional histological method. CONCLUSIONS: In this report we show that detailed three-dimensional observation in the rat can be performed qualitatively and quantitatively with the corrosion cast technique. We conclude that this method derives an accurate measurement of the diameter of rat major cerebral arteries and is more reliable for analyzing vasospasm in rats than angiography and other conventional procedures.
We assessed the clinical efficacy and determined the effective dose of erythropoietin (EPO) in 48 children scheduled for open heart surgery without blood transfusion. The children were divided into three groups: group 1 (n=21) was treated with 300 U/kg of EPO; group 2 (n=11) was treated with 150 U/kg of EPO; and group 3 (n=16) was not treated with EPO. EPO was administered on the day of hospital admission (6 to 7 days prior to surgery), on the following day, immediately after surgery, and on the following day. Immediately after surgery, the hemoglobin concentration in groups 1 and 2 was significantly higher than that in group 3. The reticulocyte count in groups 1 and 2 was significantly higher than that in group 3. Open heart surgery was completed without transfusion in all 21 patients in group 1 (100%), 10 of 11 in group 2 (90.9%), and 11 of 16 in group 3 (68.8%). EPO caused no adverse reactions. In conclusion, EPO was effective as an adjuvant therapy for open heart surgery without blood transfusion in children. Administration of a relatively high dose of EPO (300 U/kg) seems to be effective for pediatric patients.
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Myasthenia gravis developed in a 35-year-old man after removal of an encapsulated anterior mediastinal tumor that was preoperatively diagnosed as a teratoma based on a computed tomographic image. Postoperative pathologic diagnosis of the excised tumor was thymoma. The patient was in crisis after the initiation of immunosuppressive treatment. The therapy was changed to immunoadsorbent perfusion therapy because of concurrent severe pneumonia and an extremely high serum concentration of anti-acetylcholine receptor antibodies. Respiratory support was necessary for 2 months after reoperation.
The possible involvement of depression on cellular immunity in reactivation of varicella-zoster virus (VZV) in herpes zoster oticus was investigated. The subjects comprised 59 cases of herpes zoster oticus, 33 cases of herpes zoster sine herpete (ZSH) with facial paralysis, and 205 cases of Bell's palsy. The transformation rate of lymphocytes to phytohaemagglutinin in herpes zoster oticus tended to be lower than that in Bell's palsy. In skin tests with purified protein derivatives of tuberculin, the positivity rate in herpes zoster oticus was significantly lower than that in Bell's palsy (p < 0.015). In skin tests using VZV antigen the positivity rate in herpes zoster oticus and ZSH were significantly lower than that of Bell's palsy (p < 0.001 and p < 0.015, respectively). Thus, it was noted that cellular immunity, especially specific cellular immunity against VZV, was significantly depressed in herpes zoster oticus and ZSH. We consider that depression of specific cellular immunity plays an important role in triggering reactivation of VZV and onset of these diseases.
This study was undertaken to clarify the beliefs and attitudes of Japanese businesses towards AIDS. Questionnaires were mailed to 1,655 Japanese companies listed on the Tokyo Stock Exchange in June 1993, and the response rate was 38% (n = 620). About 60% of the responding companies had already implemented or were developing AIDS measures. Only 7% of the companies had an AIDS policy, and 5% of the companies were developing one. Eighty-five per cent of the companies perceived AIDS education as necessary, while 53% of the companies replied that HIV testing was unnecessary. As reasons for providing AIDS education, avoiding discrimination and anxiety in the workplace were frequently cited. Ninety-five per cent of the companies wanted guidelines or manuals for AIDS to be developed by the Ministry of Labour, or to have training courses for personnel in charge of education or counselling provided by the Ministry. Although AIDS measures are currently unsatisfactory in Japanese businesses, they are expected to develop effective measures, considering their high recognition of the need for AIDS education.
BACKGROUND AND PURPOSE: Although it has been suggested that collagen plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no constructive research to prove it directly. In this study we stopped the transcription of the procollagen type I gene by introducing antisense oligonucleotides for its mRNA in a rat femoral artery model of vasospasm induced by blood and assayed the changes in the vasoconstrictive activity of the vessel and expression of the procollagen mRNA. METHODS: We applied antisense, sense, or missense oligonucleotides, located at the carboxyl propeptide region for alpha 1(I) procollagen mRNA, onto the femoral artery in a rat femoral artery model of vasospasm. The diameter of the artery was measured by angiography. The transcription level of the procollagen gene in the arterial tissue was assayed by use of reverse transcription-polymerase chain reaction. Morphological change in the artery was observed with aldehyde-fuchsin-Masson-Goldner staining. RESULTS: In the model, when the artery was exposed to antisense oligonucleotides in pluronic gel for 5 days to prevent arterial contraction, the contraction was inhibited at a significant level (76.0% +/- 5.6) when compared with that in control experiments using sense oligonucleotides (64.0% +/- 2.4), missense oligonucleotides (63.5% +/- 3.5), or gel alone (62.1% +/- 5.8). The application of antisense oligonucleotide resulted in a marked decrease in alpha 1(I) procollagen mRNA expression as determined by polymerase chain reaction, indicating that the collagen reduction by antisense oligonucleotides occurred at the transcription level. Histological staining suggested that collagen accumulation at the site in the artery where antisense oligonucleotide had been administered was indeed less than that in the control artery. CONCLUSIONS: The results indicate that the induction of procollagen type 1 could cause pathogenesis of the arterial contraction induced by blood in a rat femoral vasospasm model.