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Biomedical subjects

S Fukuta

Publications and source records attributed to S Fukuta.

At least 37 records · Page 2Linked to original sources

Effects of persistent perilymph fistula on the inner ear.

To study the effects of a persistent perilymph fistula on the cochlea, a small cannula was inserted into the scala tympani of the basal turn of cochlea in guinea pigs. A month later, cochlear morphology and blood flow were studied using either histological evaluation or the microsphere surface preparation technique. Some animals showed no cochlear morphologic changes or no cochlear blood-flow reduction, even if tubal patency was maintained and perilymph leakage lasted for 1 month. This suggests that a prolonged perilymph fistula, per se, causes no permanent cochlear damage. However, in some animals, hair cell damage and cochlear blood-flow disorders were observed. These observations and the causes of hearing loss in clinical cases of perilymph fistula were studied.

Animals↗

[Morphological study of cochlea in experimental chronic serum sickness].

Relationship of circulating immune complexes to some inner ear disorders has been suggested recently. Thus, bovine serum albumin (BSA) nephritis, a model of chronic serum sickness, was made and morphological, immunological studies of cochlea were performed using light microscopy, transmission electron microscopy and immunofluorescent antibody methods. Group 1 consisted of animal sensitized with daily BSA injections for 90 days; in group 2, BSA was administered for 70 days, daily, and after a three-weeks interval, injections were continued for another 21 days; group 3 consisted of animals sensitized with daily BSA injections for 100 days followed by BSA injection into the facial nerve via the stylo-mastoid foramen. The animals (group 3) were sacrificed on day 1 and 4 following facial nerve sensitization for examination of cochlear morphological changes. No morphological changes were observed (group 1). Protrusion of marginal cells into endolymphatic space was seen, because of swelling of endoplasmic reticulum of the cells of stria vascularis's (group 2). Slight hydrops was present mainly in the basal turn (group 3). No IgG deposits were found in all groups. It appears that the changes in group 2 were caused by rather chronic nephritis than immune reaction. We conclude that damage induced in the cochlea is negligible compared to the extensive lesions observed in the kidney in chronic serum sickness.

Animals↗

[Electron microscopic study on inner ear barotrauma: with emphasis on the cochlear damage].

In order to investigate inner ear barotrauma, guinea pigs were subjected to rapid decompression between 2 absolute pressure (ATA) and 1 ATA in a chamber. After pressure loading and observation for absence of Preyer's reflex, they were sacrificed immediately, 1 day, 1 week and 1 month later, respectively. Then, morphological changes of the organ of Corti and stria vascularis were studied under TEM and SEM. The immediate features noted were fracture of stereocilia with minimal intracellular changes. One day later, there was marked degeneration of outer hair cells and expansion of supporting cells. The damage to stereocilia clearly preceded morphological alterations within hair cell bodies and cannot be interpreted as arising secondary to hair cell degeneration. Most of outer hair cells eventually disappeared and were replaced by supporting cells. Inner hair cells degenerated slowly; 1 month later, some of them remained almost intact, despite disappearance of stereocilia. The continuity of reticular lamina was maintained not only immediately but also through the period of hair cell degeneration, thus preventing any leakage of endolymph into the organ of Corti. There was reversible dendritic swelling of inner hair cells immediately following the trauma. No changes of stria vascularis were observed over passage of time. The mechanism of hair cell damage due to inner ear barotrauma is presumed to be a deformity of the organ of Corti caused by pressure discrepancy between perilymph and endolymph resulting in an injury to stereocilia.

Animals↗

[A case of polyangiitis overlap syndrome].

A 25 year old man was admitted to our hospital on June 1, 1989 because of general fatigue and pleural effusion. He had noticed purpuras and nodules on his bilateral lower legs in July 1988. He was admitted to Nihon University Hospital and was diagnosed as allergic granulomatous angiitis. Methylprednisolone was administered. In March, 1989, a nodular shadow was detected in his lung CT films. From the findings of TBLB a granulomatous lesion was suspected. However, his clinical course was rather stable so he was discharged from the hospital. Two months later, he was suffered from fever and general fatigue. On his chest X ray film pleural effusion was detected in the lower part of his left lung. The nodular shadow was increasing gradually. Laboratory findings on his admission showed leukocytosis, thrombocytosis, elevated CRP and a high titer of RA factor. He was diagnosed as hypersensitivity angiitis in a broad sense based on his biopsy findings of the skin lesion. Furthermore, the diagnosis of an early stage of Wegener's granulomatosis (WG) or limited type of WG was also made from the clinical course of his lung lesion. The combination therapy with cyclophosphamide and methylprednisolone was started. It was so effective that the nodule of his left lung was almost disappeared. It seems that this case is one of the polyangiitis overlap syndrome proposed by Fauci.

Adult↗

Spectral analysis of airflow sounds in patent versus occluded tracheostomy tubes: a pilot study in tracheostomized adult patients.

Cannula occlusion is a life-threatening postoperative complication of tracheostomy. Current management largely relies on nursing care for prevention of fatalities because no proven mechanical, machine-based support monitoring exists. The objective of this paper was to address the problem of monitoring the state of cannula patency, based on analysis of airflow acoustic spectral patterns in tracheostomized adult patients in the patent and partially occluded cannula. Tracheal airflow sounds were picked up via a condenser microphone air-coupled to the skin just below the tracheal stoma. Signal output from Mic was amplified, high-pass filtered, digital tape-recorded, and analyzed on a mainframe computer. Although airflow frequencies for patient cannulae were predominantly low-pitched (0.1 to 0.3 kHz), occluded tubes had discrete high-pitched spectral peaks (1.3 to 1.6 kHz). These results suggest that frequency analysis of airflow sounds can identify a change in the status of cannula patency.

Adult↗

Hemodynamic benefits of long-term bunazosin (alpha-1 blocker) therapy in rats with myocardial infarction and heart failure.

To determine whether bunazosin (alpha 1-adrenoceptor blocking agent) can alter the hemodynamic profile of chronic heart failure secondary to myocardial infarction, the drug was administered to Wistar rats 4 weeks after coronary ligation, and continued for 4 weeks. In rats without bunazosin treatment, the left ventricular end-diastolic pressure (LVEDP) and the total vascular resistance index (TVRI) increased as a function of infarct size, while the cardiac index (CI) decreased. But in infarcted rats with bunazosin treatment, the mean aortic pressure and TVRI were reduced, the LVEDP was modestly lessened, and the CI was maintained. The greatest increase in CI after the treatment occurred in rats with infarcts of small and moderate size. Thus, long-term therapy with bunazosin improved LV dysfunction, relative to the size of infarction. This study suggests the beneficial effects of bunazosin therapy in patients with chronic heart failure.

Adrenergic alpha-Antagonists↗

Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTh-I, LT-IIa, and LT-IIb.

The heat-labile enterotoxins of Vibrio cholerae and Escherichia coli are related in structure and function. They are oligomers consisting of A and B polypeptide subunits. They bind to gangliosides, and they activate adenylate cyclase. The toxins form two antigenically distinct groups; members of each group cross-react but are not necessarily identical. Serogroup I includes cholera toxin (CT) and type I heat-labile enterotoxin (LT-I) of E. coli. LTh-I and LTp-I are antigenic variants of LT-I produced by strains of E. coli from humans and pigs, respectively. Serogroup II contains the type II heat-labile enterotoxin (LT-II) of E. coli. Two antigenic variants designated LT-IIa and LT-IIb have been described. The binding of CT, LTh-I, LT-IIa, and LT-IIb to gangliosides was analyzed by immunostaining thin-layer chromatograms and by solid-phase radioimmunoassay. The four toxins have different glycolipid-binding specificities. LTh-I and CT bind strongly to ganglioside GM1 and less strongly to ganglioside GD1b. However, LTh-I, unlike CT, also binds weakly to GM2 and asialo GM1. LTh-I, like CT, probably binds to the terminal sugar sequence Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal . . ., where GalNAc is N-acetylgalactosamine and NeuAc is N-acetylneuraminic acid. LT-IIa probably binds to the same sugar sequence to which CT and LTh-I bind, with the additional contribution to binding of a second NeuAc as in GD1b and GD2. Also, LT-IIa must bind the Gal beta 1-3GalNAc . . . sequence in such a way that its binding is relatively unaffected by attachment of NeuAc to the terminal galactose residue as in GD1a, GT1b, and GQ1b. LT-IIb probably binds to the terminal sugar sequence NeuAc alpha 2-3Gal beta 1-4GalNAc . . ., as it binds to gangliosides GD1a and GT1b but not to GM1.

Adrenal Glands↗

Monoclonal antibody CC3C195, which detects cancer-associated antigens in serum, binds to the human Lea blood group antigen and to its sialylated derivative.

Mouse monoclonal antibody CC3C195, which detects elevated levels of its antigen in sera from many patients with colon and pancreatic cancer, binds with high affinity to the sialylated human Lea blood group antigen NeuAc alpha 2-3Gal beta 1-3 [Fuc alpha 1-4]GlcNac . . . and with lower affinity to the Lea blood group antigen itself.

Animals↗

Monoclonal antibody Leo Mel 3, which inhibits killing of human melanoma cells by anomalous killer cells, binds to a sugar sequence in GD2 (II3(NeuAc)2-GgOse3Cer) and several other gangliosides.

Human anomalous killer (AK) cells lyse freshly isolated human melanoma cells which are insensitive to human natural killer cell-mediated lysis. Monoclonal antibody Leo Mel 3, an IgM (k), produced by a hybridoma obtained from a mouse immunized with human melanoma cells, binds to melanoma cells and inhibits their conjugate formation with AK cells as well as their AK cell-mediated lysis. Other IgM antibodies from the same fusion that bind melanoma cells do not inhibit (Werkmeister, J. A., Triglia, T., Andrews, P., and Burns, G. F. (1985) J. Immunol. 135, 689-695). Leo Mel 3 binds several different gangliosides from melanoma cells, as determined by immunostaining thin layer chromatograms. Binding is abolished by treatment of the gangliosides with neuraminidase. In solid-phase radioimmunoassay, Leo Mel 3 binds strongly to ganglioside GD2 and less strongly to gangliosides GT3, GD3, and GQ1b. It does not bind to other gangliosides including GM1, GM2, GM3, GD1a, GD1b, and GT1b. Thus, the epitope recognized by antibody Leo Mel 3 is found in the sugar sequence of ganglioside GD2, GalNAc beta 1-4[NeuAc alpha 2-8NeuAc alpha 2-3]Gal beta 1-4Glc beta 1 .... This sequence may contain a target in melanoma cells recognized by AK cells.

Antibodies, Monoclonal↗

Study of immunological mechanism in dilated cardiomyopathy.

To determine the immune disturbances involved in the pathogenesis of dilated cardiomyopathy (DCM), the conditions in humoral and cellular immunity of DCM patients were studied. To examine the status in humoral immunity in DCM patients, circulating anti-heart antibodies (AHAbs) were analyzed. Circulating-AHAbs were classified into 4 types "heterophile-like", "intracellular", "intercalated disc" and "nuclear" patterns by indirect immunofluorescence technique, and a high rate of heterophile-like antibody was found in DCM. The cytotoxicity of this antibody was examined in cultured myocardial cells using the two-step method of the complement dependent cytotoxic test. The mean cytotoxic index (CI) value of the heterophile-like antibody positive sera was 22.3, which showed an apparent cytotoxicity against the cultured cells and it may be complement dependent. In addition, the frequency of lymphocyte subsets using monoclonal antibodies (OKT4, OKT8, Leu7, Leu11) and natural killer (NK) activity were evaluated to determine whether DCM patients had an imbalance in cellular immune reactions, which support the hypothesis of an immune disturbance as the pathological mechanism of DCM. The peripheral lymphocyte counts were significantly lower in patients with DCM (1737 +/- 874/mm3) than in normal controls (NC, 2088 +/- 556/mm3) and in patients with ischemic heart diseases (IHD, 2395 +/- 469/mm3, both p less than 0.01). The percentage of T, B, OKT4 and OKT8 positive cells was not statistically different among DCM, IHD, and NC groups, whereas the percentage of T gamma cells was significantly reduced in DCM patients (6.5 +/- 5.0%, p less than 0.05). NK functional activity as tested in DCM patients was frequently deficient (24.1 +/- 16.7% in DCM, 36.7 +/- 12.2% in NC). After 4-hr incubation with recombinant interleukin2 (rIL2), rIL2 induced the enhancement of NK activity in 3 out of 4 DCM patients with low NK activity, although, there was a non-responder to rIL2 in this group. These results suggested that DCM patients have a low IL2 production and/or less numbers of mature cells with NK cell function. Therefore, an imbalance in humoral and cellular immune reactions may cause insidious myocardial damage and subsequently lead to development of DCM.

Angina Pectoris↗

Study on lymphocyte subsets and NK cell function in patients with dilated cardiomyopathy.

An acquired defect or damage of a subpopulation of suppressor T lymphocytes is reported in connection with autoimmune diseases. In the present study, the role of immunity was examined in 7 patients with dilated cardiomyopathy (DCM). The frequency of lymphocyte subsets using monoclonal antibodies and natural killer (NK) cell activity was evaluated to determine whether DCM patients had lymphocyte abnormalities that would support the hypothesis that the pathological mechanism of DCM is an immune disturbance. The peripheral lymphocyte counts were significantly lower in patients with DCM and higher in patients with ischemic heart disease (IHD) than in normal controls (NC) (p less than 0.01). The percentage of T cells, B cells, OKT4 and OKT8 positive cells was not statistically different among the three groups studied here, whereas the percentage of T gamma cells was significantly reduced in DCM patients (p less than 0.05). NK cell functional activity as tested in DCM and IHD patients was frequently deficient (22.1 +/- 19.3% in DCM, 13.8 +/- 3.0% in IHD, 37.4 +/- 12.7% in NC). Our results suggest that an imbalance in cellular immune reactions partly explain the pathogenesis of DCM.

Adult↗

Immunological study of heart diseases with special reference to the cytotoxicity of the heterophile antibody against cultured myocardial cells.

In our previous study, a high rate of "heterophile antibody" was found in idiopathic cardiomyopathy. In the present investigation the cytotoxic activity of this antibody was examined in cultured myocardial cells. Trypsin treated cells cultured for 3 days were used in the two-step method of the complement dependent cytotoxicity test. The trypan blue dye-exclusion method was utilized to determine the percentage of surviving cells, and the cytotoxic effect was expressed by the cytotoxic index (CI). With fresh rabbit serum as complement, the mean CI value of the heterophile antibody positive sera was 20.7, which was in contrast to the value of anti-heart antibodies negative sera (p less than 0.01). As the cytotoxic effect to the heterophile antibody was absent without the complement, it may be complement dependent. Thus, our results suggest that the heterophile antibody may play a role in the pathogenesis or be an incremental factor of idiopathic cardiomyopathy.

Animals↗

Circulating anti-heart antibodies in heart diseases detected using an immunofluorescent technique.

Circulating anti-heart antibodies (C-AHAb) were examined in the sera of 132 patients with heart diseases and of 65 normal healthy controls using an indirect immunofluorescent technique. The patient groups consisted of 31 with dilated cardiomyopathy, 22 with hypertrophic cardiomyopathy, 38 with myocardial infarction, 15 with angina pectoris and 26 with rheumatic valvular disease. The indirect immunofluorescent staining patterns were classified into 4 types: "heterophile", "intracellular", "intercalated disc" and "nuclear" patterns. The positive incidence of C-AHAb was 81% in dilated cardiomyopathy, 77% in hypertrophic cardiomyopathy, 65% in rheumatic valvular disease, 58% in myocardial infarction, 40% in angina pectoris and 39% in normal healthy controls. A high rate of "heterophile" antibodies was found in the idiopathic cardiomyopathy group: 65% in dilated cardiomyopathy and 55% in hypertrophic cardiomyopathy. The intracellular staining pattern was present in 42% of rheumatic valvular disease. These findings suggest that positive C-AHAb and staining patterns may be useful in the assessment of the pathogenesis of certain types of heart diseases.

Adult↗

Experimental myocarditis. II. Cardiac lesions in rats induced by immunization with heterologous heart extracts.

The production of myocardial lesions and circulating anti-heart antibodies has been studied in the present experiment. Twenty-one of Wistar rats were divided into 3 groups: 9 rats immunized with heterologous heart extracts, Freund's complete adjuvant and diphtheria-tetanus-pertussis (DTP) vaccine, 8 rats injected phosphate buffered saline adjuvant mixture with DTP vaccine and 4 rats untreated as control. Injection of heterologous heart extracts emulsified with Freund's complete adjuvant and DTP vaccine developed focal myocardial lesions in all of the subjected rats. The lesions were characterized by focal and diffuse interstitial cellular infiltration with myocardial necrosis. The circulating antibodies reacted to rat heart extracts were detected in 77.8% of the subjects. The antigen, reacted with the antibodies, located intracellular spaces in myocardium. The severity of cardiac lesions were not functional to the titer of circulating anti-heart antibodies may play little role in the pathogenesis of myocardial damage at least in this experimental myocarditis.

Animals↗