Search PubMedSearch

Biomedical subjects

S Imaizumi

Publications and source records attributed to S Imaizumi.

At least 19 recordsLinked to original sources

Effects of acute vs. chronic phorbol ester exposure on transepithelial permeability and epithelial morphology.

In previous experiments we have shown that acute (30 minutes) exposure to phorbol esters or other protein kinase C activators causes increased transepithelial permeability, specifically by the increased paracellular permeability through tight junctions. However, the role of protein kinase C activators in carcinogenesis is predicted upon a chronic exposure of an effective dose at frequent intervals for a prolonged period of time. We therefore sought to determine the effect of chronic phorbol ester exposure on transepithelial permeability by exposing cells of the polar renal epithelial cell line, LLC-PK1, to phorbol esters for time periods as long as 16 weeks. The following changes ensued: (1) after the initial drop in transepithelial resistance due to phorbol ester exposure, i.e., an increase in transepithelial permeability (in the acute phase of exposure), an adaptive response occurs as transepithelial resistances in chronically exposed cultures recover to approximately 50% of control values, (2) the cell sheets in chronically exposed cultures lose their acute responsiveness of transepithelial permeability to phorbol ester exposure, (3) cell sheet architecture changes as cells occasionally multilayer and actual polyp-like cell masses appear at high frequency, and (4) cytosolic protein kinase C activity decreases to 50% of control level with acute exposure and then is further decreased to less than 1% of control level in chronically treated cells; membrane-associated PKC activity is not as sharply decreased. The possible role of transepithelial permeability in carcinogenesis and the value of chronically treated epithelial cell cultures as a model for two-stage carcinogenesis are discussed.

Animals

[Effect of the rate of speech flow on speech intelligibility in normal and hearing-impaired subjects].

The relationship between the rate of speech flow and speech intelligibility was investigated in normal and hearing-impaired subjects. It is usually observed that a slowly and clearly delivered speech is easier for hearing-impaired patients to understand. The purpose of paper is to analyze this phenomenon clinically and to present useful data for developing new hearing aids. Four or 5 syllabic words lists were prepared for this experiment and speech stimuli were chosen from these lists. The subjects consisted of 15 normal subjects and 79 hearing-impaired patients (57 with inner ear hearing loss and 22 with retrocochlear hearing loss). Hearing tests were performed using a tape recorder with various speech control systems in a soundproof room. Speech samples were presented at three speaking rates, that is, a conversational speech rate, a rate one and a half times as fast as the conversational speech rate and a rate twice as fast as that rate. The results obtained in the normal subjects confirmed that the faster the speaking rate was, the more the word intelligibility was reduced. According to the results in the hearing-impaired subjects, both the correlation coefficient and regression parameter between the word intelligibility in this experiment and speech discrimination scores measured by 57S-monosyllabic lists were low at the conversational speaking rate, but the higher the speaking rate was, the closer the relation between the both factors was. It was estimated by analyzing the data of inner ear hearing loss and retrocochler hearing loss separately that the subjects with retrocochler hearing loss had more difficulty in speech-mediated communication than the subjects with inner ear hearing loss.

Hearing Loss

[A case of acute subdural hematoma in the posterior fossa with idiopathic thrombocytopenic purpura].

Intracranial bleeding is one of fatal complications in idiopathic thrombocytopenic purpura although its reported incidence is low. A case of spontaneous acute subdural hematoma complicated with idiopathic thrombocytopenic purpura was reported. He was hospitalized complaining of sudden onset of headache and nasal bleeding without neurological deficit. CT scan revealed subdural hematoma in the posterior fossa especially below the tentorium cerebelli. Further hematological examination proved very low platelet count (1,000/mm3) and antiplatelet antibody in confirmation of a diagnosis of idiopathic thrombocytopenic purpura. As his neurological status was good, he was treated medically. His symptoms and platelet count improved gradually with corticosteroid therapy. Reviewing the literature, acute subdural hematoma with idiopathic thrombocytopenic purpura was quite rare and only three cases reported.

Acute Disease

Mycolic acid-containing glycolipid as a possible virulence factor of Rhodococcus equi for mice.

By the use of various Rhodococcus equi strains differing in the length of carbon chains of glycolipid, we examined whether the glycolipid, glucose monomycolate, was contributing to the virulence of R. equi for mice. R. equi strains with longer carbon chain mycolic acid showed a higher virulence as determined by lethality and granuloma formation in mice than those with shorter ones. When purified glycolipid was injected into mice, granuloma formation and liver damage were most prominent with the glycolipid having longer carbon chain mycolic acid. Only a representative strain with longer carbon chain mycolic acid persisted in the spleen of mice after intravenous injection, while a strain with shorter carbon chain mycolic acid was readily eliminated. These results suggested that glycolipid was at least one of the virulence factors of R. equi and that the carbon chain length of mycolic acid might be critical in the expression of virulence.

Actinomycetales Infections

Liposome-entrapped superoxide dismutase ameliorates infarct volume in focal cerebral ischaemia.

We studied the role of superoxide radicals in the pathogenesis of focal ischaemic brain injury using liposome-entrapped copper-zinc-superoxide dismutase which can penetrate the blood-brain barrier and cell membranes efficiently. Superoxide dismutase activities were significantly elevated in the blood and in the normal brain tissue 1, 2, 8, and 24 hours after a bolus intravenous administration of liposome-entrapped copper-zinc-superoxide dismutase. Copper-zinc-superoxide dismutase activities were also increased significantly in the ischaemic hemisphere and the contralateral cortex as well. The infarct sizes were reduced by 33%, 24% and 18%, respectively, for the anterior artery area, middle artery area, and posterior artery area by treatment at 24 hours following the injection of liposome-entrapped superoxide dismutase. These data demonstrate that superoxide radicals are important determinants of the size of an infarct following focal cerebral ischaemia, and that liposome-entrapped copper-zinc-superoxide dismutase may have pharmacological value for focal cerebral ischaemic injury.

Animals

Changes of polyphosphoinositides, lysophospholipid, and free fatty acids in transient cerebral ischemia of rat brain.

Phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4, 5-bisphosphate (PIP2), 1, 2-diglyceride (DG), lysophosphatidylcholine (LPC), and free fatty acids (FFA) contents, as well as their fatty acid composition, were measured in transient global cerebral ischemia. ATP and CTP were also studied. Male Wistar rats were subjected to 1, 5, and 30 min of ischemia and 10, 30, and 60 min of recirculation following 30 min of ischemia. In addition, for the quantification of PI, PIP, and PIP2, rats were also subjected to 30 and 60 min of recirculation following 5 min of ischemia. PIP2 and PIP decreased rapidly during 5 min of ischemia and recovered completely after recirculation. DG increased almost at the same rate during ischemia and returned to normal after recirculation. PI showed almost no changes throughout entire course. LPC increased during 5 min of ischemia and returned to normal after recirculation. Stearic acid and arachidonic acid contained in DG increased during 5 min of ischemia, whereas saturated fatty acids increased in LPC. Among the FFA accumulated during ischemia, stearic acid and arachidonic acid increased rapidly and were followed by increases of other FFA. From these results, the pathways for the increase of FFA during ischemia and the fate of FFA after recirculation are discussed. In addition, the importance of the changes of PIP, PIP2, and LPC is also discussed.

Adenosine Triphosphate

The effects of teleocidin and aplysiatoxin tumor promoters on epithelial tight junctions and transepithelial permeability: comparison to phorbol esters.

Control of transepithelial permeability by regulation of tight junctions is exerted by the non-phorbol ester tumor promoters, teleocidin and aplysiatoxin. Similar to the phorbol esters, tetradecanoylphorbol-13-acetate (TPA) and phorbol dibutyrate (PDBU), both teleocidin and aplysiatoxin cause a reversible decrease of transepithelial voltage and transepithelial resistance across LLC-PK1 renal epithelial cell sheets at concentrations as low as 10(-8) M. These compounds are effective from either side of these polar epithelial cells, i.e. apical or basolateral. The decreases in transepithelial gradients and resistance are paralleled by a rise in the transepithelial (paracellular) flux of D-mannitol between the cells (through the tight junctions). These four tumor promoters, TPA, PDBU, teleocidin and aplysiatoxin, are all known protein kinase C activators, and support the case for protein-kinase-C-mediated control of tight junctional permeability.

Carcinogens

Production of antikeratin autoantibodies by hybrid spleen cells of naive mice.

The mechanism of the occurrence of natural antikeratin antibodies in human sera was studied using hybrid spleen cells obtained from experimentally naive or from immunized mice. Antikeratin antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 5.9-9.5% of the culture supernatants of fused spleen cells taken from naive mice. When mice were immunized with keratins, the number of supernatants containing antikeratin antibodies was increased to eight out of 51 (15.7%). When immunized with non-keratin materials such as activated human T cells, adult T-cell leukaemia cell lysates, and human T-cell lymphotropic virus type-I (HTLV-I), 16.7-20.8% of the supernatants were found to contain antikeratin antibodies by ELISA. The antikeratin antibodies in the supernatants showed cytoplasmic staining of keratinocytes in human as well as mouse skin by indirect immunofluorescence. The antibodies reacted with extracted human epidermal keratins by dot-blot and Western blot analysis. Most antikeratin antibodies in the supernatants did not show cross-reactivity with exogenous antigens used for immunization and vimentin-type intermediate-sized filaments. These findings demonstrate that B cells producing antikeratin antibodies are common in naive mice, and produce various types of antikeratin antibodies following specific activation with epidermal keratins and non-specific immunological stimuli.

Animals

Morphological and electrophysiological correlates of atrioventricular nodal response to increased vagal activity.

The mechanisms responsible for slowing cardiac impulse conduction through the atrioventricular (AV) node are not well understood but include anatomical architecture, presence of cells with diverse electrophysiological characteristics, and modulation by autonomic nervous system. The present study was designed to determine the site of vagally induced slowing of conduction through the AV node. We attempted to correlate the electrophysiological response of AV nodal cells to postganglionic vagal stimulation applied in different regions of the node with the morphological findings and patterns of acetylcholinesterase-positive staining of nodal tissue. This multifaceted approach revealed that vagal stimulation produced localized hyperpolarization of the cells from the N region of the AV node, which correlated with the strong acetylcholinesterase positive staining of the central nodal area. In contrast, the density of the acetylcholinesterase staining decreased toward both the AN and His bundle regions, whereas vagal stimulation had a negligible effect on the cells from these regions. These results suggest that vagal-induced depression of AV nodal conduction is produced by release of acetylcholine predominantly around the midnodal region and the depressive action of acetylcholine is concentrated on the cells occupying the same region (i.e., the N cells). Thus, there appears to be a close juxtaposition of nerve elements and effector cells in the midnodal region of the AV node. This unique combination of available neuromediator and responding cells with hyperpolarization and depressed action potential determines the midnodal region as the focus of vagal effect on AV nodal conduction.

Animals

Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats.

We studied the role of superoxide radicals in the pathogenesis of ischemic brain injury using a model of focal cerebral ischemia in 102 rats and liposome-entrapped CuZn-superoxide dismutase, which can penetrate the blood-brain barrier and cell membranes efficiently. The bolus intravenous administration of 25,000 units of liposome-entrapped CuZn-superoxide dismutase elevated superoxide dismutase activities in the blood and brain 1, 2, 8, and 24 hours later as well as in the ischemic hemisphere and contralateral cortex. Determined 24 hours after right middle cerebral and bilateral common carotid artery occlusion by the lack of staining for mitochondrial dehydrogenase activity with 2,3,5-triphenyltetrazolium chloride, infarct sizes were reduced by 33%, 25%, and 18% in the anterior, middle, and posterior brain slices, respectively, by treatment with liposome-entrapped CuZn-superoxide dismutase. Our data demonstrate that superoxide radicals are important determinants of infarct size following focal cerebral ischemia and that liposome-entrapped CuZn-superoxide dismutase may have pharmacologic value for the treatment of focal cerebral ischemic injury.

Animals

Phenytoin affects metabolism of free fatty acids and nucleotides in rat cerebral ischemia.

We investigated the effects of phenytoin on the rate of enzymatic release of free fatty acids and on the levels of energy metabolites and nucleoside phosphates in ischemic brain. Phenytoin (10 mg/kg i.v.) was administered 30 minutes before the onset of ischemia induced in 30 male Wistar rats by occluding the basilar and both common carotid arteries. The rats' brains were frozen in situ after 0, 5, or 30 minutes of ischemia or 10, 30, or 60 minutes of recirculation following 30 minutes of ischemia (n = 5 at each time). Nucleoside triphosphate levels were higher in the phenytoin-treated rats than in corresponding untreated rats at each time during and after ischemia. Phenytoin significantly attenuated the accumulation of lactate and free fatty acids (arachidonic acid and stearic acid) during ischemia and accelerated their recovery during recirculation. These results suggest that phenytoin has favorable protective effects on ischemic brain and that phenytoin may inhibit calcium-mediated phenomena, especially the inositol cycle, in cerebral ischemia.

Animals

[A follow-up survey for hearing aids evaluation using speech maps].

A new method for assessing the selected hearing aids was developed and applied 53 patients with hearing impairment. Our previous paper showed that the average confusion distance which was introduced in this method was useful for estimating the hearing aids. We carried out a follow-up survey in order to measure the usefulness of this method after 3 or 4 years practical hearing aid use. There were 34 patients out of 53 from whom we could obtain adequate information about their hearing aids. They were asked to rate their satisfaction with the recommended instrument in five degrees. Fifteen of the 34 patients who had purchased the recommended hearing aid rated it very satisfactory; four rated the aid satisfactory; eight rated the aid helpful; six rated the aid sometimes helpful; and one rated the aid unsatisfactory. The Spearman's rank correlation coefficient between the change in the speech discrimination score with and without a hearing aid and the user's evaluation was 0.34. The Spearman's rank correlation coefficient between the change in the average confusion distance and user's evaluation was 0.41. The value 0.34 is not significant, but the value 0.41 is significant at the 1% level of significance. Therefore, we think that the average confusion distance should be taken into consideration as well as the speech discrimination score at least for predicting successful hearing aid use. Finally we feel that there is need for the inclusive system which is able to estimate both the speech mediated communication ability and user's satisfaction.

Evaluation Studies as Topic

[A study of voice mutation and physical growth--a longitudinal observation].

Past studies on the relationship between mutational voice change and body growth were generally made on grouped subjects and no exact longitudinal observation was performed. In the present report, a longitudinal study was made on 100 young male students in their puberty, in which voice recordings and measurements of physical parameters including body height and weight were performed twice for each subject with yearly interval. Information on subjective evaluation of voice abnormality was also obtained from each subject. The recorded voice samples were subjected to subsequent analysis for obtaining fundamental frequency (F0) and formant values. The following results were obtained. 1. A negative correlation in the rate of change was observed between F0 and physical parameters such as body height and weight, and sitting height. 2. It was suggested that the mutational period consisted of the rapid and slow phases. The rate of growth in body height and sitting height was more significant in the rapid phase. 3. Subjective voice abnormality and physical growths such as the development of the laryngeal prominence were often noted even before the rapid phase. After the rapid phase was over, all the cases showed secondary sexual characteristics including the laryngeal prominence. 4. Before and during the rapid phase, there was a tendency for the values of F1 and F2 to increase, while that of F3 to decrease. After the rapid phases was over, there was a trend that F1 and F2 increased, while F3 remained unchanged.

Adolescent

[Relapsed stage I neuroblastoma successfully treated by allogeneic bone marrow transplantation in second remission: case report of a 7-year-old girl].

Stage I neuroblastoma in a seven-year-girl have had local recurrence with bone metastasis. Second surgery was performed after the aggressive chemotherapy including cisplatin, VP16, cyclophosphamide, vincristine and doxorubicin. She underwent allogeneic bone marrow transplantation from her HLA identical brother, following the preparative regimen consisting of high-dose melphalan and total body irradiation (12 Gy). Clinical course after the transplantation was uneventful. She is still alive with no evidence of disease for twenty-eight months after the transplantation. It is suggested that bone marrow transplantation is an effective way of therapy even in a patient with relapsed neuroblastoma.

Adrenal Gland Neoplasms

In vivo binding site of pemphigus vulgaris antibodies and their fate during acantholysis.

Ultrastructural localization of pemphigus vulgaris antigen-antibody complexes and their fate during acantholysis were studied in epidermal sheets obtained from the area surrounding the bullae and in acantholytic cells in blister fluid. The distribution of pemphigus vulgaris antibodies already bound to the keratinocytes in early acantholytic lesions was detected with ferritin-conjugated goat antihuman IgG. Ferritin particles were observed on the surface of keratinocytes with particular affinity for desmosomal structures. The acantholytic cells in the blister fluid bound only a small number of ferritin particles on their surface. During incubation at 37 degrees C, pemphigus vulgaris antigen-antibody complexes on the surface of separated desmosomes were internalized and recognized in cytoplasmic vesicles. Endocytosis of separated desmosomes also was observed in vivo when freshly obtained epidermal sheets were immediately processed for routine electron microscopic study. These findings suggest that pemphigus vulgaris antibodies are densely located on desmosomes and that the antigen-antibody complexes, together with other serum proteins on the keratinocyte surface, are internalized by a process of endocytosis.

Acantholysis

Congenital cutis laxa.

We have encountered 2 cases (mother and son) with an autosomal dominant form of cutis laxa, which is clinically characterized by inelastic, loose, and pendulous skin without systemic organ involvement. The histopathological findings disclosed that the elastic fibers were decreased in number and had abnormalities in shape. Furthermore, electron microscopic observations showed some variations in structural abnormalities of the elastic fibers between the 2 cases. These findings may suggest that the elastic fibers seen in congenital cutis laxa give various features for elastogenesis and elastolysis in the individual cases, perhaps due to aging.

Adult

Hearing aid evaluation using psychoacoustical proximity between Japanese monosyllables.

To facilitate hearing aid selection, a new method was developed to assess the qualitative changes in speech perception with and without a hearing aid. This method utilizes maps of the Japanese monosyllables where the degrees of confusion are represented by distances between the monosyllables. On these maps, perceptual failures of the monosyllables can be simply analyzed by connecting confused stimuli and the corresponding wrong responses. The qualitative characteristics of monosyllable confusion for 53 patients with hearing impairment were comparatively analyzed with and without hearing aids. Results show that this method is useful for describing the qualitative effects of hearing aids on speech perception, and that it thus provides important information for hearing aid selection.

Adolescent