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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 649 records · Page 36Linked to original sources

Cervical discs are most susceptible to beta 2-microglobulin amyloid deposition in the vertebral column.

Intervertebral discs of 41 chronic renal failure autopsy cases were examined histologically and immunohistochemically to assess the distribution of beta 2-microglobulin-associated (beta 2m) amyloid in the vertebral column. The results demonstrated beta 2m amyloid to appear first in the cervical discs, then in the lumbar and upper thoracic discs, and finally in the middle and lower thoracic discs as the dialysis period is prolonged. The shortest dialysis period for which beta 2m amyloid was detected was one year and seven months. Deposition of beta 2m amyloid was most remarkable in the C4-5, 5-6, and 6-7 levels, which are known to sustain severe mechanical stress in daily life. Thus it is suggested that local mechanical stress accelerates beta 2m amyloidosis. A marked macrophage reaction was observed around the amyloid in cases of severe amyloidosis, the macrophages themselves being immunohistochemically positive for IL-1 beta and TNF-alpha. Amyloid deposition and reactive inflammation mediated by cytokines appear to be closely related to the pathogenesis of destructive spondyloarthropathy.

Adult↗

Congenital polyneuropathy in Walker-Warburg syndrome.

Polyneuropathy was found in a patient with the Walker-Warburg syndrome. The most dominant features were the presence of extremely and tortuously proliferated myelin sheaths, the most of which having no neurofilaments and neurotubules. The other peculiar findings were the presence of microfilaments in Schwann cell cytoplasms, which were very similar to neurofilaments, and the presence of partial and abrupt disappearance of myelin sheaths. The severity of neuropathy was variable among nerve bundles, and a few nerve bundles looked normal on light microscopy. The above-mentioned lesions did not suggest the degeneration and/or regeneration of normally developed nerve fibers. We could not conclude the pathogenesis of this neuropathy, however, it was logical to consider that they reflected dysplastic myelination due to Schwann cell dysmaturity as well as the cerebral dysplasia.

Axons↗

"Floating" labyrinth. Pathophysiology and treatment of perilymph fistula.

Collapse of the membranous labyrinth of the pars superior is a morphological change observed in 50% of animals with experimentally produced perilymph fistula, although the extent and degree of the collapse may vary greatly. The moderately collapsed membranous labyrinth may drift with CSF and/or perilymph pressure changes and this may stimulate sensory cells of the utricle and/or semicircular canals if the sensory cells are intact and the collapsed wall is in contact with the otolithic membrane and/or cupula. This condition is termed "floating" labyrinth. Caloric irregularity is often observed in electronystagmograms recorded from animals with experimental perilymph fistula. This is also observed in patients with perilymph fistula. Partial destruction of the vestibular organs using argon laser was performed in a patient with perilymph fistula who was incapacitated because of persistent positional vertigo after closure of the oval window fistula. Irradiation of the argon laser beam was directed to the macula utriculi, utriculoampullary nerve and singular nerve. The hearing of the patient was maintained, and vertigo disappeared after laser labyrinthectomy.

Audiometry, Pure-Tone↗

Treatment of vasospasm by balloon angioplasty: experimental studies and clinical experiences.

The vasodilation mode and degree of the invasion caused by balloon angioplasty were experimentally examined. Assessment by light microscopy and scanning electron microscopy demonstrated that the invasion to the implanted arterial wall, taken from a patient who died from vasospasm, was minimized by the use of the balloon under the condition at 1 atm, 10 times for 10 seconds. Furthermore, we applied angioplasty to eight patients who developed severe vasospasm after subarachnoid haemorrhage, and five showed improvement in neurophysiological (transcranial Doppler sonography), neuroradiological, and clinical examinations. In addition, blood vessels obtained from one patient who died 10 days after angioplasty, demonstrated similar findings to those of the experimental studies. It can be said that angioplasty will be one of the effective therapeutic methods to manage vasospasm when it is applied under the conditions mentioned above.

Adult↗

Hydroxamamide as a chelating moiety for the preparation of 99Tcm radiopharmaceuticals (I).

Hydroxamamides contain a nitrogen and an oxygen as donor atoms, and can be synthesized by the simple reaction of nitriles with hydroxylamine. Benzohydroxamamide (BHam) was investigated as a new ligand for 99Tcm. The yield of the 99Tcm-BHam complex was determined by thin-layer chromatography using cellulose strips. A high yield of the complex was obtained at room temperature over a wide pH range, even at BHam concentrations as low as 5 x 10(-7) M. Cellulose acetate electrophoresis indicated that the complex was uncharged. When the 99Tcm-BHam complex was injected into mice, it was cleared gradually from the blood by means of the hepatobiliary system with low urinary excretion. Uptake by the stomach and the spleen was low. These results demonstrate the high affinity of BHam for 99Tcm and the high stability of the 99Tcm-BHam complex. The hydroxamamide group may be a promising chelating moiety for designing new 99Tcm radiopharmaceuticals.

Animals↗

Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression.

Introducing avidin-biotin complex ELISA for anti-DNA antibody, the mechanism of in vitro production of anti-ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL-6-IL-6R loop was studied in patients with systemic lupus erythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti-ssDNA antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density centrifugation responded to rIL-6 to produce IgG and IgG anti-ssDNA antibody. rIL-2 and rIL-4 had lesser effects on the differentiation of low density B cells. In fact, IL-6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti-IL-6R MoAb, MT18, which did not inhibit IL-6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL-6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL-6. Thus, endogenous IL-6 produced by high density B cells bound to the IL-6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti-IL-6 or anti-IL-6R MoAb (PM1), which inhibited IL-6 binding, both inhibited IgG anti-ssDNA antibody as well as total IgG production by SLE B cells in a dose-dependent manner. These results suggest that interruption of the autocrine IL-6 loop would be of therapeutic value in SLE.

Antibodies, Antinuclear↗

IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with rheumatoid arthritis.

There is evidence to suggest that CD5+ B cells may be associated with autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA). In this study, we found that the expression of CD5 on RA B cells increased spontaneously, following culture for up to 4 days in vitro in the absence of T cells, supporting the idea that the CD5+ B cell possesses distinctive features. The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4 (rIL-4). Other cytokines studied (rIL-1 alpha, rIL-2, rIL-5, rIL-6) did not alter CD5 expression. Studies of antibody production showed that rIL-4 could reduce spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a newly developed avidin-biotin complex ELISA, was also reduced by rIL-4. Furthermore, rIL-4 reduced the increase in IgM-RF production observed on stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). Thus, IL-4 might act as a regulator of the development of abnormal B cell differentiation in patients with RA.

Adult↗

The presence of immunoreactive parathyroid hormone-related protein in parathyroid adenoma cells.

Parathyroid hormone-related protein (PTHrP) was first identified in human malignant tumors associated with humoral hypercalcemia of malignancy. We immunohistochemically examined the distribution of PTHrP both in 7 normal parathyroid glands and in a 20 parathyroid adenomas. Sixty-five percent of parathyroid adenomas (13 cases) were positive for PTHrP, whereas only one normal parathyroid gland was positive for PTHrP in the area of transitional oxyphil cells. Many parathyroid adenomas (12 cases) were composed of both PTHrP-positive cells and--negative cells, and these two different type of cells showed a tendency to form nodules respectively in parathyroid adenoma. Although both chief cells and oxyphil or transitional oxyphil cells were positive for PTHrP in parathyroid adenoma, oxyphil or transitional oxyphil cells were more responsible for PTHrP production than chief cells. Chief cells are thought to produce parathyroid hormone mainly in parathyroid adenoma. On the other hand, little is known concerning the function and role of oxyphil or transitional oxyphil cells. Our results suggest that oxyphil or transitional oxyphil cells in parathyroid adenoma may have some functional roles different from those of chief cells through the production of PTHrP.

Adenoma↗

Different patterns of protein kinase C redistribution mediated by alpha 1-adrenoceptor stimulation and phorbol ester in rat isolated left ventricular papillary muscle.

1. In rat left ventricular papillary muscle, phenylephrine, an alpha 1-adrenoceptor agonist, had a staurosporine-sensitive positive inotropic effect and increased the particulate-associated protein kinase C (PKC) activity without significant changes in total PKC activity or in cytosolic Ca2+/phospholipid-independent kinase (PKI) activity. 2. A PKC stimulant, phorbol 12,13-dibutyrate (PDBu), decreased contractility and slightly increased PKC activity in the particulate fractions, with a marked decrease and increase in total PKC and PKI activities, respectively. 3. The PDBu-induced negative inotropic response was attenuated by two protease inhibitors, leupeptine and a microbial peptide isolated from Aspergillus japonicus (E-64), which are known to inhibit the conversion of particulate-associated PKC to PKI. 4. Such differences in the patterns of PKC redistribution, i.e. marked increases in particulate PKC and cytosolic PKI activities caused by phenylephrine and PDBu, respectively, may account for the opposite inotropic effects of PKC stimulation by an alpha 1-agonist and a phorbol ester.

Adrenergic alpha-Agonists↗

Drug resistant plasmid of Actinobacillus pleuropneumoniae isolated from swine pleuropneumonia in Thailand.

Actinobacillus pleuropneumoniae, isolated from the pneumonic lung tissue of pigs, was resistant to streptomycin, sulfadiazine and tetracycline. This isolate, TA5, possessed 2 plasmids (pTA51 = 3.7 Kb, pTA52 = 6.2 Kb); one of the plasmids (pTA52) was coded for resistance to SM and SA. Another isolate of A. pleuropneumoniae, TA8, also possessed 2 plasmids (pTA81 = 3.7 Kb, pTA82 = 4.4 Kb), with a plasmid (pTA82) coded for resistance to SM and SA. All 4 plasmids were not transmissible and small.

Actinobacillus Infections↗

[Studies on motile-Aeromonas infection 3). Phage typing of motile Aeromonas isolated from patients with diarrhea].

Phage types were determined for 102 strains of motile Aeromonas isolated from patients with diarrhea at four metropolitan hospitals in Tokyo. The following results were obtained. 1) Of the 102 strains examined, 52 (51.0%) were divided into 28 phage types. This rate was considerably higher, compared to our previous results, namely, 21.7% for strains isolated from natural environments and 25% for those isolated from meats. By bacterial species, phage types could be determined for 33 (52.4%) of 63 strains of A. hydrophila, for 16 (45.7%) of 35 strains of A. sobria, 2 (50.0%) of 4 strains of A. caviae and 1 (100%) strain of Aeromonas spp. 2) Of the 52 strains for which the phage types could be determined, the greatest number (16 strains, 30.8%) were identified as belonging to Type I group. These are followed by 5 strains (9.6%) which were identified as Type I/III group and 2 strains (3.4%) each identified as Type I/II, I/II/V, IV, V and VI groups. The remaining 21 strains were identified as belonging to one of the other phage type groups. Thirty-five (67.3%) of the strains for which the phage types were identified, were found to belong either to Type I group or to combinations with Type I. This demonstrated that 34.0% of the isolates from patients with diarrhea were related to Type I.

Aeromonas↗

Gastrointestinal examinations with digital radiography.

Basic imaging properties and clinical usefulness of an upgraded digital radiography system were evaluated. The system, which has 1,024 x 1,024 and 2,048 x 2,048 matrices, was upgraded with smaller focal spots (0.3 and 0.8 mm) and reduced thickness of the photoconductive layer of the video camera. Screen-film and digital images (with and without postprocessing) of the upper and lower gastrointestinal (GI) tract were used in the clinical evaluation. Overall modulation transfer functions of the upgraded digital system were comparable to those of the screen-film system, especially at the lower spatial frequency. Threshold contrasts of the two systems were similar despite a 50% reduction in incident exposure for the digital system. For the upper GI tract, digital images processed with unsharp masking techniques were comparable in quality to screen-film images before and after upgrade of the system. For the lower GI tract, screen-film images were better than digital images, except for those produced with a 2,048 x 2,048 matrix with unsharp masking. Further evaluation of the system for examination of other parts of the body seems warranted.

Digestive System↗

Delayed shortening and shrinkage of cochlear outer hair cells.

Slow shortening of cochlear outer hair cells has been speculated to modify cochlear sensitivity. Tetanic electrical field stimulation of isolated outer hair cells from guinea pigs shortened the cells for 2-3 min. Electrical stimulation reduced cell length and volume (-13.5 +/- 1.5 and -37.3 +/- 3.0% of initial values, respectively, n = 16) and decreased the intracellular Cl- concentration. Cytochalasin B (100 microM) inhibited electrical stimulation-induced shortening but not volume reduction. The following chemicals or manipulations inhibited the responses: 10 microM furosemide, 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 1 mM anthracene-9-carboxylic acid (AC9), 25 mM tetraethylammonium, 2.3 microM charybdotoxin (ChTX), 250 nM omega-conotoxin, and Ca(2+)-free medium. These findings suggest that both electrical stimulation-induced shortening and shrinkage of outer hair cells result not only from an actin-mediated contractile force, but also from Cl- efflux through furosemide-, DIDS-, and AC9-sensitive Cl- channels, and K+ efflux through ChTX-sensitive K+ channels.

Actins↗

Menkes' disease: report of a case and determination of eumelanin and pheomelanin in hypopigmented hair.

We report a male infant with Menkes' disease who showed, at the age of 3 months, slow growth, hair abnormalities such as pili torti and white hair, and low levels of serum copper and ceruloplasmin. The exceptionally bright portions of his hair contained eumelanin and pheomelanin at levels only half those of normal Japanese controls. After subcutaneous administration of copper-histidinate for 2 months, his scalp hair changed to dark brown.

Ceruloplasmin↗

Vestibular pathophysiologic changes in experimental perilymphatic fistula.

An animal model of experimental perilymphatic fistula (EPLF) was developed in the guinea pig in order to study vestibular pathophysiology. In experimental animals, 4 microL of perilymph was suctioned from one cochlea via the round window membrane. Changes in vestibular function were as follows. 1) During the acute stage (5 hours postoperatively), spontaneous nystagmus directed toward the normal side was noted in 57.4% of the EPLF animals. This lasted less than 24 hours. 2) One week postoperatively, direction-fixed positional nystagmus toward the lesioned ear was present in 22.7% of the EPLF animals, especially when the lesioned ear was positioned inferiorly. 3) With the ice water caloric test, no response was present in 58.1% of the EPLF animals and an irregular response was found in 22.6% of them, 1 week postoperatively. These results tend to indicate that tests of vestibular function may differentiate between patients with Meniere's disease and those with perilymphatic fistula. Histologic findings indicate that a floating labyrinth is the cause of positional nystagmus and caloric irregularity. The absence of caloric responses was associated with collapse of the vestibular labyrinth.

Animals↗

Increase in ubiquitin-immunoreactive nuclei in rat pituitary luteinizing hormone cells after castration.

Immunocytochemical detection of ubiquitin in the nucleus of rat LH cells and the effects of castration and testosterone replacement on the occurrence of immunoreactive ubiquitin in the nucleus were investigated. Immunoreactive ubiquitin occurred in certain nuclei, mostly belonging to identified LH cells. The concentration of testosterone in blood was altered by castration and implantation of testosterone into castrated rats, and the occurrence of ubiquitin was examined weekly for the following 4 weeks. In castrated rats, the proportion of LH cells with ubiquitin-immunoreactive nuclei was high throughout the experiment. In castrated rats implanted with testosterone, on the contrary, the proportion remained significantly lower. Ubiquitin may be involved in the cellular activity of LH cells in the rat pituitary.

Animals↗