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Biomedical subjects

K Tsunoda

Publications and source records attributed to K Tsunoda.

At least 19 recordsLinked to original sources

A high-efficiency cross-flow micronebulizer for inductively coupled plasma mass spectrometry.

A pneumatically driven, high-efficiency cross-flow micronebulizer (HECFMN) is introduced for inductively coupled plasma (ICP) spectrometries. The HECFMN uses a smaller nozzle orifice for nebulizer gas (75 microm in diameter) and a replaceable and adjustable fused-silica capillary for sample uptake. The HECFMN is optimally operated over a wide range of sample uptake rate (5-120 microL/min) at a rf power of 1100 W and nebulizer gas flow rates of 0.8-1.0 L/min when a 50 microm i.d. by 150 microm o.d. capillary is used. The aerosol quality is qualitatively examined in a simple manner, and the transport efficiencies are determined by direct filter collection. Compared with conventional cross-flow nebulizers (CFNs), the HECFMN produces much smaller and more uniform droplets and thus provides much higher analyte transport efficiencies (generally 24-95%) at the sample uptake rates of 5-100 microL/min. Several analytical performance indexes are acquired using an Ar ICPMS system. The sensitivities and detection limits measured with the HECFMN at 50 microL/min sample uptake rate are comparable to or improved over those obtained with a conventional CFN consuming 1 mL/min sample, and the precisions with the HECFMN (typically 1.1-1.7% RSDs) are slightly better than those with the CFN (1.6-2.3% RSDs). The ratios of refractory oxide ion-to-singly charged ion (CeO+/Ce+) are typically in the range from 0.7 to 3.3% for the sample uptake rates of 5-100 microL/min. The free aspiration rate of the HECFMN is 8.9 microL/min for distilled deionized water at the nebulizer gas flow rate of 1.0 L/min without any effect of pressure. The features of the HECFMN suggest good potential for HECFMN use in interfacing ICPMS with capillary electrophoresis and microcolumn high-performance liquid chromatography.

Journal Article↗

Complex objects are represented in macaque inferotemporal cortex by the combination of feature columns.

Intrinsic signal imaging from inferotemporal (IT) cortex, a visual area essential for object perception and recognition, revealed that visually presented objects activated patches in a distributed manner. When visual features of these objects were partially removed, the simplified stimuli activated only a subset of the patches elicited by the originals. This result, in conjunction with extracellular recording, suggests that an object is represented by a combination of cortical columns, each of which represents a visual feature (feature column). Simplification of an object occasionally caused the appearance of columns that were not active when viewing the more complex form. Thus, not all the columns related to a particular feature were necessarily activated by the original objects. Taken together, these results suggest that objects may be represented not only by simply combining feature columns but also by using a variety of combinations of active and inactive columns for individual features.

Action Potentials↗

Autologous transplantation of fascia into the vocal fold: long-term results of a new phonosurgical technique for glottal incompetence.

OBJECTIVES: To study the long-term results of autologous transplantation of fascia into the vocal fold, and to evaluate our use of autologous transplantation instead of bovine collagen injection in cases of glottal incompetence. STUDY DESIGN: Retrospective study of the patients who have undergone autologous fascia transplantation using our new technique. METHODS: Follow-up studies were performed for at least 1 year (up to 3 y) on 9 autologous fascia transplant patients (6 cases with type 1 procedures and 3 cases with type 2 procedures). Clinical observations, including laryngeal stroboscopy, and measurement of maximum phonation time (MPT) were carried out. RESULTS: During 3 months after autologous fascia transplantation, MPT gradually increased and stroboscopy showed improved glottal closure. These improvements continued beyond 1 year in all cases of type 1 surgery and 2 of 3 cases of type 2 surgery. CONCLUSIONS: Autologous transplantation of fascia into the vocal folds as a phonosurgical treatment for glottal incompetence yields excellent long-term results. Temporal fascia appears to be a highly suitable tissue for transplantation in Reinke's space. However, the fascia is less suitable for transplantation in the muscle. We speculate that transplantation of temporal fascia leads to regeneration of vocal fold tissue, perhaps using a mechanism similar to stem cell transplantation in other organs.

Adult↗

Sensorineural hearing loss as the initial manifestation of polyarteritis nodosa.

A 74-year-old male was referred for the sudden onset of bilateral sudden deafness. The patient had no history of any disease or trauma to the head. Pure tone audiometry revealed bilateral moderate, to severe, sensorineural hearing loss. Auditory brain stem responses (ABRs) showed normal peak and interpeak latencies. These audiological findings suggested that his hearing loss could be attributed to inner ear lesions. However, we felt an alternative explanation for this sudden deafness was likely to exist because the patient also had a month-long fever of unknown origin (FUO) and weight loss of 5 kg/month. Using the criteria of The American College of Rheumatology, we made the diagnosis of polyarteritis nodosa (PAN). Serum MPO-ANCA was positive (x 661). For treatment, the patient was begun on prednisolone and cyclophosphamide. Nine months later, fever, hypertension, nephritis, pneumonitis, and arthritis had completely resolved, the MPO-ANCA became negative (MPO-ANCA < x 10). Furthermore, his hearing improved.

Acute Disease↗

Immunohistochemical expression of Ets-1 transcription factor and the urokinase-type plasminogen activator is correlated with the malignant and invasive potential in meningiomas.

BACKGROUND: The Ets-1 transcription factor has been proposed to play an important role in the invasive process of tumor cells through the induction of urokinase-type plasminogen activator (u-PA). METHODS: Because meningiomas are potentially invasive tumors, irrespective of their malignancy grades, the authors immunohistochemically investigated Ets-1 and u-PA expression in tissues obtained from 50 benign (16 meningotheliomatous, 14 fibrous, 13 transitional, 6 angiomatous, and 1 microcystic), 4 atypical, and 6 anaplastic meningiomas and correlated their results with the malignancy and invasive potential. RESULTS: Ets-1 protein was expressed in 19 of the benign meningiomas (38%)whereas 31 (62%) were u-PA positive. The percentage of positive cells frequently was < 50%. In contrast, Ets-1 and u-PA expression was observed in all 4 atypical (100%) and all 6 anaplastic (100%) cases, respectively. The proportion of cells positive for Ets-1 and u-PA frequently were > or = 50%. A significant difference was observed between Ets-1 and u-PA expression in benign and high grade meningiomas (P < 0.0001). Moreover, Ets-1 expression was found to correlate significantly with u-PA positivity in meningiomas (P < 0.0001). Twenty-one of 60 meningioma cases (35%) showed infiltration either to the brain, dura mater, or bone. Eighteen of these 21 cases (85.7%) were positive for Ets-1 and u-PA. Ets-1 and u-PA positivity was found to correlate well with the invasive phenotype in meningiomas (P < 0.001). CONCLUSIONS: The findings of the current study support the possibility that the Ets-1 transcription factor, through u-PA induction, may be involved in the invasive process in meningiomas.

Blotting, Western↗

Effect of Zena F-III, a liquid nutritive and tonic drug, on the neurochemical changes elicited by physical fatigue in mice.

The effects of a liquid nutritive and tonic drug (NTD) on the neurochemical changes elicited by physical fatigue in mice were investigated in terms of the calcium-dependent dopamine synthesizing function of the brain. In this study, Zena F-III (Taisho Pharmaceutical Co., Ltd., Japan), one of the most popular NTDs in Japan, containing 15 crude drug extracts together with taurine, caffeine, and vitamins, and formulated based on the precepts of traditional Chinese medicine, was used. Male mice were forced to walk for 0-6 h at a speed of 3 m/min using a programmed motor-driven wheel cage. The serum and brain calcium levels in the mice were significantly increased following forced walking. The increase in brain calcium level began later and was more gradual than that in the serum calcium level, and reached its maximum value following forced walking for 3 h. The neostriatal dopamine level was also significantly increased, and locomotor activity significantly decreased following forced walking for 3 h. Prior oral administration of F-III (10 ml/kg) attenuated the increases in the serum and brain calcium levels, the increase in the brain dopamine levels, and the decrease in locomotor activity induced by forced walking. Taking into consideration these findings with our previous reports, it is suggested that physical fatigue leads to an increase in dopamine synthesis in the brain through a calcium/calmodulin-dependent system, thereby inducing behavioral changes, and that F-III inhibits this pathway and may alleviate overwork-induced physical fatigue.

Animals↗

Production of the entire extracellular domain of BP180 (type XVII collagen) by baculovirus expression.

Bullous pemphigoid (BP) is an acquired autoimmune skin disease, and its target antigens are a 230 kDa plaque protein (BP230) and a 180 kDa transmembrane protein with interrupted collagenous domains (BP180, type XVII collagen), which localize at the hemidesmosome. In this study we have attempted to express the entire extracellular domain of BP180 (rBP180EC) as a secreted protein by baculovirus expression. Seventy out of 83 BP sera (84.4%) showed positive reactivity against rBP180EC by immunoblot analysis, and 56 out of 83 BP sera (67.5%) were positive against rBP180EC by ELISA. These figures were comparable with those when a bacterial recombinant protein encoding the NC16a domain of BP180 (rNC16a) was used as an antigen source. Reactivity of BP sera against rBP180EC by ELISA was completely abolished or significantly reduced by immunocompetition with rNC16a in 11 out of 14 BP sera tested, while the reactivity was not altered in the rest of the three sera. These findings indicate that the NC16a domain represents the major epitopes on the extracellular domain of BP180, although there are some other minor epitopes outside of NC16a which are uniquely expressed by rBP180EC. rBP180EC will be useful to develop a diagnostic tool for BP as well as to dissect a molecular role for BP180 in interactions of keratinocytes with epidermal basement membrane.

Autoantigens↗

Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism.

UNLABELLED: We evaluated the effects of fentanyl added to lidocaine for axillary brachial plexus block in 66 adult patients scheduled for elective hand and forearm surgery. In this double-blinded study, all patients received 40 mL of 1.5% lidocaine with 1:200,000 epinephrine, injected into the brachial plexus sheath using the axillary perivascular technique, and they were randomized into three groups. Group 1 was given lidocaine containing 2 mL of normal saline plus 2 mL of normal saline IV. Patients in Group 2 received lidocaine containing 100 microg fentanyl plus 2 mL of normal saline IV. Group 3 patients received lidocaine containing 2 mL of normal saline plus 100 microg fentanyl IV. Sensory and motor blockade were evaluated by using a pinprick technique and by measuring the gripping force, respectively. The success rate of sensory blockade for radial and musculocutaneous nerves and the duration of the sensory blockade significantly increased in Group 2 (323 +/- 96 min) as compared with Group 1 (250 +/- 79 min). However, onset time of analgesia was prolonged in every nerve distribution by adding fentanyl to brachial plexus block. IV fentanyl had no effect on the success rate, onset, or duration of blockade. We conclude that the addition of fentanyl to lidocaine causes an improved success rate of sensory blockade but a delayed onset of analgesia, although this may be accounted for by the decreased pH caused by the fentanyl. IMPLICATIONS: It is still unclear whether the addition of a peripheral opioid is useful for nerve blockade in humans. Peripheral application of fentanyl to lidocaine for axillary brachial plexus blockade in this study provided an improved success rate of sensory blockade and prolonged duration.

Analgesics, Opioid↗

Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus.

The development of experimental models of active autoimmune diseases can be difficult due to tolerance of autoantigens, but knockout mice, which fail to acquire tolerance to the defective gene product, provide a useful tool for this purpose. Using knockout mice lacking desmoglein 3 (Dsg3), the target antigen of pemphigus vulgaris (PV), we have generated an active disease model for this autoantibody-mediated disease. Dsg3(-/-) mice, but not Dsg3(+/-) littermates, produced anti-Dsg3 IgG that binds native Dsg3, when immunized with recombinant mouse Dsg3. Splenocytes from the immunized Dsg3(-/-) mice were then adoptively transferred into Rag-2(-/-) immunodeficient mice expressing Dsg3. Anti-Dsg3 IgG was stably produced in the recipient mice for more than 6 months without further boosting. This IgG bound to Dsg3 in vivo and disrupted the cell-cell adhesion of keratinocytes. Consequently, the recipient mice developed erosions in their oral mucous membranes with typical histologic findings of PV. In addition, the recipient mice showed telogen hair loss, as found in Dsg3(-/-) mice. Collectively, the recipient mice developed the phenotype of PV due to the pathogenic anti-Dsg3 IgG. This model will be valuable for developing novel therapeutic strategies. Furthermore, our approach can be applied broadly for the development of various autoimmune disease models.

Animals↗

Time course of left ventricular remodeling after myocardial infarction: a two-dimensional echocardiographic study.

In order to forecast the clinical course of acute myocardial infarction (MI), the time course of the functional changes of the left ventricular myocardium that result in remodeling was evaluated with two-dimensional echocardiography (2DE). The study group comprised 45 patients with anterior MI treated with successful percutaneous transluminal coronary angioplasty. 2DE studies were performed on days 1, 3, 7 and 14; months 1 and 3 and 1 year after MI, and the following parameters were recorded: (1) infarcted wall thickness, (2) traced length of the endocardium and of the epicardium on end-diastolic apical long axis images, and (3) wall motion score (total of asynergy scores of 16 segments of left ventricle (LV); normal: 0, hypokinesis: 1, akinesis: 2, dyskinesis: 3). According to the peak creatine kinase (CK) level, patients were classified into L group (CK > or =8000 U/L, n=16), M group (8000> CK > or =4000, n=13) and S group (CK <4000, n=16). The following results were obtained. (1) There was progressive thinning of the infarcted myocardium up to 1 month after (1 day: 9.3+/-1.7, 14 days: 6.3+/-1.7 vs 1 month: 5.9+/-1.8 mm, p<0.05; vs 1 year: 5.9+/-1.9 mm, NS). (2) Dilatation of the LV cavity occurred shortly after MI and continued up to 14 days (endocardium at 14 days: 176.8+/-13.6 vs 1 day: 164.1+/-11.4 mm, p<0.01; vs 1 year: 176.3+/-12.7 mm, NS). (3) The wall motion score improved rapidly by 14 days, and continued to improve gradually to 1 year (1 day: 12.2+/-3.4, 14 days: 6.8+/-4.0, 1 year: 4.6+/-3.1). (4) The expansion ratio (endocardial length at 14 days/1 day) was significantly greater in the L group than in the S group (p<0.05). Comparing the groups, the LV cavity of the L group remained dilated up to 14 days, whereas that of the S and M groups was dilated up to 7 days (L group 14 days: 179.3+/-11.9 vs 1 day: 156.9+/-9.2mm, p<0.01; vs 1 year: 180.0+/-14.1 mm, NS) (S group 7 days: 171.7+/-13.6 vs 1 day: 161.5+/-7.2 mm, p<0.01; vs 1 year: 172.7+/-14.4 mm, NS) (M group 7 days: 170.5+/-10.5 vs 1 day: 157.7+/-14.5 mm, p<0.05; vs 1 year: 177.08+/-9.6 mm, NS). Serial 2DE on days 1 and 14 after MI were useful for evaluating the course of LV remodeling and to forecast cardiac function in the chronic phase of MI. Determining the length of hospital stay on the basis of infarction size is justified.

Aged↗

Hoarse voice resulting from premature ageing in Werner's syndrome.

Werner's syndrome is characterized by clinical signs of premature ageing. A 42-year-old man presented with three-year history of hoarseness. Also noted were skin atrophy of the face and hands, ulcerations around the ankles, and a history of cataracts. A clinical diagnosis of Werner's syndrome was made. Laryngoscopy revealed bowed vocal folds resulting in a spindle-shaped defect with glottal incompetence during phonation. Examination also revealed decreased maximum phonation time and vocal fatigue. At surgery, atrophy of the vocalis muscle was noted. Furthermore, degeneration of muscle fibres was noted in the temporalis muscle. The atrophic changes in the vocal folds that occur with ageing and result in an increased fundamental frequency were seen in this patient. The characteristic hoarseness of Werner's syndrome appears to be the result of premature ageing of the vocal-folds.

Adult↗

Nonsense mutation of islet-1 gene (Q310X) found in a type 2 diabetic patient with a strong family history.

Islet-1 (Isl-1) is one of the transcription factors that play an important role for the formation of the islet cells. We scanned the Isl-1 gene in 77 Japanese type 2 diabetic patients with a family history and found a heterozygous nonsense mutation (Q310X) in 1 diabetic patient. The mutation was not found in 180 nondiabetic subjects. This mutation is located in the putative transactivation domain and deletes 40 amino acids of the COOH-terminal lesion. The Q310X mutant exhibited a 50% reduction in activity compared with the wild-type when tested for stimulation of transcription of a human amylin promoter-linked luciferase reporter gene in betaTC3 cells. The patient was a 49-year-old nonobese man who was diagnosed as having type 2 diabetes at 32 years of age and has been treated with sulfonylureas. The mutation was found in his mother, who has type 2 diabetes, and in his 14-year-old daughter, who has normal glucose tolerance but a relatively low insulin response. This is the first reported finding of Isl-1 gene mutation in type 2 diabetes. Although Isl-1 is not a common predisposing gene for Japanese type 2 diabetes, the mutation in this gene may be a rare cause of diabetes in isolated families.

Adolescent↗