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Biomedical subjects

M Kawano

Publications and source records attributed to M Kawano.

At least 163 records · Page 9Linked to original sources

Cortical activation with sound stimulation in cochlear implant users demonstrated by positron emission tomography.

Six postlingually deaf patients using multi-channel cochlear implants were examined by positron emission tomography (PET) using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during different sound stimuli. The stimulation paradigms employed consisted of two sets of three different conditions; (1) no sound stimulation with the speech processor of the cochlear implant system switched off, (2) hearing white noise and (3) hearing sequential Japanese sentences. In the primary auditory area, the mean rCBF increase during noise stimulation was significantly greater on the side contralateral to the implant than on the ipsilateral side. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area (P < 0.01), the bilateral auditory association areas (P < 0.01), the posterior part of the bilateral inferior frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P < 0.05). Activation of cortices related to verbal and non-verbal sound recognition was clearly demonstrated in the current subjects probably because complete silence was attained in the control condition.

Acoustic Stimulation↗

Sequence analyses of human parainfluenza virus type 4A and type 4B fusion proteins.

cDNAs encoding human parainfluenza virus type 4A and type 4B (hPIV-4A and -4B) fusion (F) proteins were cloned and sequenced. The predicted amino acid sequences of the F proteins had similar characteristic traits to those reported for the F proteins of other paramyxoviruses. They were more closely related to the F proteins of simian virus 5 (SV5), mumps virus (MuV), hPIV-2 and Newcastle disease virus (NDV) than to the F proteins of hPIV-1, hPIV-3, Sendai virus (SV) and measles virus (MV). In addition, hPIV-4A, hPIV-4B, SV5 and MuV shared a common feature of genomic organization: there was a small ORF between the F and haemagglutinin-neuraminidase (HN)-coding sequences, implying a common ancestry.

Amino Acid Sequence↗

Identification of fusion regulatory protein (FRP)-1/4F2 related molecules: cytoskeletal proteins are associated with FRP-1 molecules that regulate multinucleated giant cell formation of monocytes and HIV-induced cell fusion.

Fusion regulatory proteins (FRPs) regulate virus-mediated cell fusion and multinucleated giant cell formation of monocytes. Anti-FRP-1 mAbs immunoprecipitated 80 kDa and 38 kDa proteins from HeLa cells. After long exposure other bands were detected, suggesting the presence of molecule(s) associated with FRP-1. To identify the molecule(s), we prepared monoclonal antibodies against immunoaffinity-purified FRP-1 complex derived from membrane fractions of HeLa cells. Immunofluorescence microscopy revealed that these monoclonal antibodies recognized the intracytoplasmic molecules in HeLa cells. Using immunoblotting, the antibodies reacted with 200 kDa, 70 kDa, 55 kDa and 35 kDa molecules, so we designated these molecules as FRP-related molecules (FRMs). Subsequently, we performed gene cloning from a HeLa lambda gt11 cDNA library using anti-FRM mAbs and immunoblotting analysis with either purified cytoskeletal proteins or specific antibodies against various cytoskeletal proteins. Three kinds of positive clone were obtained, which encoded partial sequences of vimentin, tropomyosin, and heat shock cognate protein 70 (hsc70). The 200 kDa molecule was expected to be a myosin heavy chain, judging from the immunoblotting pattern. Immunoblotting confirmed that these purified proteins were readily recognized by anti-FRM mAbs. Furthermore, anti-vimentin and anti-myosin mAbs reacted with the precipitates by anti-FRP-1 mAb, indicating a physical association between FRP-1 molecules and these cytoskeletal proteins. When anti-FRP-1 mAb was added to culture fluids of HeLa cells, the cell-shape and immunofluorescence-pattern stained with anti-FRM mAbs changed. Taken together, the fusion regulatory molecular complex is suggested to consist of at least FRP-1, hsc70, actomyosin and vimentin systems.

Antibodies, Monoclonal↗

Increased plasma levels of immunoreactive endothelin and von Willebrand factor in NIDDM patients.

OBJECTIVES: To elucidate the significance of plasma levels of endothelin (ET) and von Willebrand factor (vWF) as possible markers for endothelial dysfunction in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Plasma levels of ET and vWF were determined in 22 NIDDM patients with or without retinopathy and 10 normal control subjects. RESULTS: The plasma levels of immunoreactive endothelin (irET) and vWF in NIDDM patients were 0.78 +/- 0.06 pmol/l and 218.3 +/- 18.4%, respectively, which represented significant (P < 0.05, P < 0.01, respectively) differences from the values in the control group (0.50 +/- 0.06 pmol/l and 139.1 +/- 11.1%, respectively, n = 10). However, when the diabetic patients were divided into two groups according to the presence or absence of diabetic retinopathy, the plasma levels of irET and vWF in the NIDDM patients with retinopathy were significantly higher (1.01 +/- 0.07 pmol/l and 283.0 +/- 21.4%, respectively, n = 12) compared with the control group and NIDDM patients without retinopathy (0.59 +/- 0.06 pmol/l and 164.3 +/- 17.0%, respectively). Plasma levels of irET showed a significant (P < 0.01) positive correlation with the levels of vWF. CONCLUSIONS: These data strongly suggest that increased plasma irET reflects the endothelial cell damage in NIDDM.

Adult↗

Studies of currently used and experimental cochlear implants.

Since 1987 we have inserted multichannel cochlear implants in 60 patients with severe hearing impairment. The surgical procedures were not very difficult, and few postoperative complications were encountered. Postoperative speech recognition by every patients was satisfactory. Nevertheless, some patients complained about their hearing in a noisy environment, or while listening to either TV or music. Consequently, cochlear implants needs further improvement. To improve speech recognition ability, a newly developed experimental system was constructed. Judging from the electrode activation pattern, the new system extracted the features of consonants more successfully than the present system. However, when this new system was installed in cochlear implant patients, no significant improvement in consonant recognition was obtained.

Adult↗

Results with the currently used cochlear implant.

Over the past 7 years we have implanted the Nucleus multichannel cochlear implant in 60 patients with severe hearing impairment. The postoperative speech recognition of adult postlingually deaf patients was satisfactory. Adult prelingually deaf patients exhibited poorer speech perception than postlingually deaf patients. However, some patients showed better results than expected. The prelingually deaf patients needed a longer rehabilitation period than the postlingually deaf patients. There was considerable variation in performance among the prelingually deaf patients. As for juvenile deaf patients, some showed good speech perception ability, but postoperative rehabilitation took longer. The cooperation of doctors, audiologists, speech therapists, schoolteachers, and family members was essential, and the creation of a cochlear implant center for children is desirable to obtain better rehabilitation. On the questionnaire given to the cochlear implant patients, some complained about their hearing in a noisy environment or while listening to television or music. The present cochlear implant system obviously needs further improvement.

Adolescent↗

Cortical activation during sound stimulation in cochlear implant users demonstrated by positron emission tomography.

Three patients with prelingual deafness and six patients with postlingual deafness using multichannel cochlear implants were examined by positron emission tomography using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during three different sound stimuli: 1) with no sound stimulation, with the speech processor of the cochlear implant system switched off, 2) hearing white noise, and 3) hearing sequential Japanese sentences. In postlingually deaf patients, speech stimulation caused a significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area and the bilateral auditory association areas. In these patients, speech sound is thought to be processed by means of auditory cortices analogous to those in normal subjects. In contrast, in prelingually deaf patients, speech sound induced much less rCBF increase in auditory association cortices; this finding suggested underdevelopment of the neural network for complex sound analysis and speech sound recognition.

Acoustic Stimulation↗

[Pharmacokinetics of transbronchially injected flconazole in pulmonary aspergillosis].

A 68-year-old woman had a pulmonary aspergilloma in the left upper lobe, with old cavitary pulmonary tuberculosis. Surgery was not possible because of marginal ventilation, and the patient was treated by transbronchial injection of Fulconazole. After five injections of 50 mg of Fulconazole, the fungus ball had decreased in size. To study the pharmacokinetics of Fulconazole after transbronchial injection, its concentration in serum was measured. The values of serum Fulconazole concentration were 0.7 microgram/ml at 1 h, 0.8 microgram/ml at 4 h, 0.8 microgram/ml at 8 h, 0.7 microgram/ml at 12 h, 0.7 microgram/ml at 24 h, and 0 microgram/ml at 48 h after transbronchial injection. These results indicate that Fulconazole was absorbed well. Furthermore, these values are equal to those obtained after intravenous administration of 50 mg and are higher than those obtained after intravenous administration of 25 mg. Fulconazole may have been absorbed via the bronchial epithelium, because of destruction of alveoli, connective tissue proliferation in the cavitary wall and secondary bronchiectasis.

Aged↗

[Follow-up study of hepatic hemangiomas].

Hepatic hemangioma is the most common benign tumor of the liver, but there are a few reports on chronological changes in size of hepatic hemangioma. To elucidate natural history of hepatic hemangioma, we evaluated consecutive ultrasonograms of 27 hemangiomas in 23 patients. Underlying liver disease in these 23 patients included seven cases with chronic hepatitis, five cases with liver cirrhosis and three cases with fatty liver. The remaining eight cases showed no evidence of liver disease. Follow-up period ranged 12 to 114 months (average 44). During the follow-up, six (22.2%) hemangiomas changed in size on US, which included three lesions with increase in size, one lesion with decrease in size and two lesions with spontaneous regression. Of 12 patients with chronic liver disease, only one patient showed significant change in the hemangioma size, which regressed spontaneously. These results showed that there was no case showing increase in size of hemangioma in patients with chronic liver disease. Thus, if clinically diagnosed hemangioma which tends to increase in size is detected on US or other imaging modalities in patients with chronic liver disease, aimed aspiration biopsy should be preferably performed considering the possibility of hepatocellular carcinoma.

Adult↗

[Seminal plasma cytokines in nonbacterial prostatitis: changes following sparfloxacin treatment].

The detection of various cytokines; interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), was studied in patients with nonbacterial prostatitis (NBP), and the clinical efficacy of sparfloxacin was also reported. The seminal plasma of 11 normal men and 10 patients with NBP were examined for the cytokines. There was no IL-1 beta or IL-6 in the seminal plasma of normal men. TNF-alpha was detected in only one normal man. In the seminal plasma of the patients, IL-1 beta was detected in 2 out of 10, and IL-6 was also detected in 6. TNF-alpha was detected in 6 out of 10 patients with NBP. The rate of detection of IL-6 and TNF-alpha was significantly higher in the patients with NBP than in normal men. The average levels (range) of IL-1 beta, IL-6 and TNF-alpha were 28 pg/ml (27-29), 110 pg/ml (25-476) and 25 pg/ml (6-113), respectively. After treatment with sparfloxacin at a dose of 100 mg to 200 mg per day, their symptoms disappeared. The number of leukocytes in the seminal plasma decreased to the normal level and these cytokines were not detected. The favorable clinical effect was achieved in 13 of the 17 patients (76%). These findings suggested that the cytokines have an important role in the pathogenesis of prostatitis and that the level of the cytokines are useful indicators in patients with prostatitis, particularly with NBP.

Adult↗

Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes. Induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies.

Fusion regulatory proteins (FRPs) are newly defined cell surface molecules that enhance and/or induce virus-mediated cell fusion. Anti-FRP-1 Abs reacted with all of the established cells derived from humans and monkeys, whereas FRPs were found to be selectively expressed on a fraction of monocytes in human PBMCs. Granulocytes expressed no FRP-1 molecules, but approximately 18% of granulocytes expressed FRP-2 molecules. Alveolar macrophages also expressed FRP-1 molecules. FRP-1 expression was enhanced by culture of monocytes, but CD14 expression was not influenced by cultivation. Anti-FRP-1 Abs induced homotypic cell aggregation and multinucleated giant cell formation of monocytes. Anti-beta 2 integrin Ab blocked anti-FRP-1 Ab-induced cell aggregation, and anti-beta 1 integrin Ab and fibronectin inhibited anti-FRP-1 Ab-induced polykaryocyte formation. There was no competitive binding to monocytes between anti-FRP-1 Ab and anti-beta 1 or anti-beta 2 integrin Ab or fibronectin. Furthermore, there was no enhancement of beta 1 and beta 2 integrin expression by anti-FRP-1 Ab on monocytes. These findings suggest that anti-FRP-1 Ab activated integrin systems, and that the functions of anti-FRP-1 Ab were demonstrated through the activated integrin systems. Furthermore, it is inferred that integrin systems are involved in polykaryocyte formation of monocytes.

Amino Acid Sequence↗

Unique epitope of apolipoprotein A-I expressed in pre-beta-1 high-density lipoprotein and its role in the catalyzed efflux of cellular cholesterol.

The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to recognize pre-beta-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1 HDL, an HDL species of low molecular weight implicated in early cholesterol transport from cell membranes to plasma [Castro, G. R., & Fielding, C. J. (1988) Biochemistry 27, 25-29]. Incubation of plasma with this antibody significantly inhibited the efflux of labeled cholesterol from cultured fibroblast monolayers. A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre-beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad specificity for HDL (including pre-beta-1 HDL). This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species.

Amino Acid Sequence↗

Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system.

Anti-FRP mAbs induced polykaryocyte formation of U2ME-7 cells (CD4+U937 cells transfected with the HIV gp160 gene). Anti-FRP-1 mAb immunoprecipitated gp80-85, gp120 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the alpha 3 subunit of integrin. Both anti-FRP-1 and anti-FRP-2 mAb-induced cell fusion was blocked by anti-beta 1 integrin antibody, fibronectin or inhibiting anti-FRP-1 antibody. Therefore, anti-FRP mAbs were thought to induce the fusion via an integrin system(s). FRP-mediated fusion was temperature, cytoskeleton, energy and Ca2+ dependent. These experiments showed a possible regulatory function of cell fusion by an integrin system(s).

Amino Acid Sequence↗

The enucleation of thyroid tumors indeterminate before surgery as papillary thyroid carcinoma: should immediate reoperation be performed?

The management of patients with thyroid nodules which are indeterminate as papillary thyroid carcinoma (PTC) before surgery but identified as such after surgery still poses great difficulty for the surgeon. Immediate reoperation is often not performed due to the indolent biological characteristics of this disease and the increased risk of associated surgical complications. We conducted a study to determine whether or not immediate reoperation should be performed. The prognosis of 91 patients with PTC who underwent enucleation only was compared with that of 321 control patients with non-advanced PTC who underwent radical surgery during the same period. There were no deaths due to PTC in either group. Distant metastasis was observed in 1.1% and 0.6% of the enucleation and control patients, respectively, while local recurrence was observed in 3.3% and 8.1%, respectively. These results suggest that immediate reoperation is not necessary for patients who have undergone enucleation only.

Adolescent↗

Hemiaplasia of the thyroid associated with Graves' disease: report of three cases and a review of the literature.

We recently treated three additional patients with hemiaplasia of the thyroid associated with Graves' disease, making a total of eight such cases. All eight of these patients were women and their chief complaints were goiter in five cases, whereas exophthalmos or palpebral edema were noted in six cases. All eight patients underwent surgery for Graves' disease. The left lobe was absent in six cases and the right lobe in two, whereas the isthmus was absent in six cases and the pyramidal lobe in four. A total of 102 cases of hemiaplasia of the thyroid, including our present three cases, have been reported in the world literature since 1970, with 32 of them consisting of hemiaplasia associated with hyperthyroidism. Of these, the cause of hyperthyroidism was Graves' disease in 22 cases, an autonomously functioning thyroid nodule in 7, and thyrotoxic multinodular goiter in 3. The left lobe was absent in 19 cases while the right lobe was missing in 12, and laterality was unknown in 1 case.

Adolescent↗

Fusion properties of cells constitutively expressing human parainfluenza virus type 4A haemagglutinin-neuraminidase and fusion glycoproteins.

We established HeLa cell lines that constitutively expressed the fusion (F) and/or haemagglutinin-neuraminidase (HN) glycoproteins of human parainfluenza virus type 4A (PIV-4A) and used them to analyse the roles of these glycoproteins in virus-induced cell fusion. No syncytium formation occurred, even in HeLa cells expressing both the F and HN proteins (HeLa-4aF+HN cells). Also no syncytium was found in a mixed culture of cells expressing the F protein (HeLa-4aF) and the HN protein (HeLa-4aHN). Syncytia were observed in HeLa-4aF cells transfected with the HN gene, but no syncytium formation was found in HeLa-4aHN cells transfected with the F gene. Co-cultivation of HeLa-4aF+HN cells with HeLa-4aF cells generated large polykaryocytes, whereas co-cultivation with HeLa-4aHN cells induced no cell fusion. Infection of HeLa-4aF cells with PIV-4A generated large syncytia and degenerated nuclei, whereas little or no polykaryocytes were found in HeLa-4aHN cells infected with PIV-4A. From the above findings, the following conclusions were drawn: (i) the expression of both the F and HN proteins in the same cell is necessary for cell fusion; (ii) the expression of the F protein alone enhances susceptibility to cell fusion; (iii) the constitutive expression of the HN protein promotes resistance to paramyxovirus-induced cell fusion.

Cell Fusion↗

HN proteins of human parainfluenza type 4A virus expressed in cell lines transfected with a cloned cDNA have an ability to induce interferon in mouse spleen cells.

Primary monkey kidney cells infected with human parainfluenza type 4A virus (HPIV-4A) were treated with various concentrations of formaldehyde. Formaldehyde (0.275%) treatment completely blocked virus production. However, when mouse spleen cells were cocultured with the fixed virus-infected cells, interferon was produced in the culture fluid. On the other hand, when mouse spleen cells were incubated with the fixed virus-infected cells in the presence of anti-HPIV-4A antiserum or a mixture of anti-HN protein monoclonal antibodies, interferon activity could scarcely be detected in the culture fluid. These findings indicated that the fixed virus-infected cells had an ability to induce interferon in mouse spleen cells and that the HN protein was related to interferon induction. Subsequently, a recombinant plasmid was constructed by inserting the cDNA of the HN gene of HPIV-4A into a pcDL-SR alpha expression vector. Mouse spleen cells produced interferon when cocultured with COS7 cells transfected with the recombinant plasmid, but did not when cocultured with COS7 cells transfected with the vector alone. Furthermore, we established HeLa cells constitutively expressing HPIV-4A HN (HeLa-4aHN cells) or F protein (HeLa-4aF cells). Type I (alpha/beta) interferon was detected in culture fluids of mouse spleen cells with HeLa-4aHN cells, but was not detected in those with HeLa-4aF cells. Therefore, it was concluded that the HN glycoproteins on the cell surface were sufficient for interferon induction to occur.

Animals↗

Solid cell nests of the thyroid in medullary thyroid carcinoma.

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Adolescent↗