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Biomedical subjects

T Ishihara

Publications and source records attributed to T Ishihara.

At least 325 records · Page 18Linked to original sources

Intervertebral disc amyloidosis: histochemical, immunohistochemical and ultrastructural observations.

Intervertebral discs selected at random from autopsies and surgical operations on herniated discs were examined for evidence of amyloid deposition. Amyloid deposits were detected in 53 (81.5%) of 65 autopsy cases. Discs from subjects over 50 years of age revealed a significantly high incidence of amyloid deposition. Among herniated discs, amyloid deposits were documented in 49 (75.4%) of 65 surgical specimens. The incidence of amyloid deposition in intervertebral discs increased with advancing age. Intervertebral disc amyloidosis consisted of amyloid deposits of three morphological types: linear amyloid deposits around the degenerating chondrocytes (perichondrocyte type), and nodular or band-like deposits in the annulus fibrosus (annulus fibrosus type) and nucleus pulposus (nucleus pulposus type). We suspect that the precursor protein of perichondrocyte type amyloid is derived from chondrocytes, and those of annulus fibrosus type and nucleus pulposus types are derived from the blood. The amyloid deposits were resistant to treatment with potassium permanganate. Immunohistochemically, the amyloid deposits reacted with antibody against amyloid P-component, but not with antibodies against AA, A kappa, A lambda, transthyretin or beta 2-microglobulin. Ultrastructurally, the amyloid deposits were composed of 10 nm-wide nonbranching fibrils. The amyloid in herniated discs had the same biochemical and immunohistochemical properties as those found in autopsy cases. The immunohistochemical characteristics of the amyloid deposits suggest that it derives from an, as yet, unknown precursor protein.

Adolescent↗

Histochemical and ultrastructural studies of inclusion bodies found in tissues from three siblings with I-cell disease.

Tissues from three siblings with inclusion-cell (I-cell) disease (a 16 month old boy and two fetuses aborted at 20 and 18 weeks) were investigated histologically, histochemically and ultrastructurally. The lymphocytes, fibroblasts, endothelial cells, epithelial cells and histiocytes of various organs were affected. The cells had many intracytoplasmic vacuoles, which showed positive staining with colloidal iron, periodic acid-Schiff (PAS), alcian blue, and Sudan III and IV. Ultrastructurally, the cells contained various inclusion bodies, showing vesicles, granules, flocculent material, amorphous electron-dense globules and myelin structures. The amounts and ultrastructural features of the inclusion bodies differed among the various kinds of cells.

Abortion, Induced↗

Immunohistochemical classification of 140 autopsy cases with systemic amyloidosis.

One hundred and forty autopsy cases of systemic amyloidosis were examined using the potassium permanganate method for distinction of amyloid A protein from other amyloid proteins and an immunohistochemical technique. Of those cases, amyloid proteins were identified in 121 cases. There were 68 cases of amyloid A-related (AA) amyloidosis and these were the most common type among the cases (56.2%). There were 39 cases of immunoglobulin light chain-related (AL) amyloidosis (32.2%), six cases of beta 2-microglobulin-related (A beta 2M) amyloidosis (5%), and five cases of transthyretin-related (ATTR) amyloidosis (4.1%). Minute areas of amyloid deposits in four cases with AA were resistant to potassium permanganate pretreatment. In A beta 2M amyloidosis amyloid deposits were either resistant or sensitive to potassium permanganate pretreatment, from case to case. The coexistence of two different amyloid proteins was seen in three cases: one case had ATTR and A kappa types, and two cases had A beta 2M and AA types. Some discrepancies were seen between the immunohistochemical typing and clinical classification of amyloidosis referred to in the Annual of the Pathological Autopsy Cases in Japan, for example, one case of AA type in myeloma-associated amyloidosis and one case of AL type in secondary amyloidosis. From the present results, the importance of the immunohistochemical method in classifying amyloidosis is stressed.

Adult↗

Cellular distribution of polymer particles bearing various densities of carbohydrate ligands.

The density effect of carbohydrate-ligands on nanometer-order particles (nanoparticles) upon cellular binding and internalization was investigated. Poly(vinylbenzyl-beta-D-lactonamide) (PVLA), a beta-galactose-carrying styrene homopolymer, was employed as a model ligand for the asialoglycoprotein receptors on hepatocytes. In order to control the surface ligand densities on the particles, PVLA was mixed with poly(vinylbenzyl-D-gluconamide) (PVGA), a PVLA analog without beta-galactose, and their mixtures were used as surface coatings. The particles with low ligand densities associated more with hepatocytes than high ligand density particles. The surface density of the ligand considerably influenced the cellular distribution. Most of the particles bearing high densities of ligands were found inside the cells, whereas particles with low ligand densities were found on the plasma membrane surface of the hepatocytes. These results were indicative of high densities of ligands on the surface requiring hepatocytes to internalize the particles promptly by receptor-mediated endocytosis, while low densities of ligands on the surface was not sufficient to internalize, but allowed particles to bind on the cell surface. These findings enabled us to regulate cellular distributions of particles by controlling ligand density on the surface.

Animals↗

Spontaneous growth hormone (GH) secretion by unstimulated human lymphocytes and the effects of GH-releasing hormone and somatostatin.

We investigated in five normal subjects whether the secretion of GH from lymphocytes would occur spontaneously without mitogens and be regulated by GHRH and somatostatin as in the endocrine system. Peripheral blood mononuclear cells were isolated from heparinized blood by the standard Ficoll-Hypaque gradient centrifugation method, and incubated for up to 7 days with or without GHRH, somatostatin analog (SMS 201-995), cycloheximide, or actinomycin D. GH levels in the lyophilized samples were measured by a highly sensitive enzyme immunoassay. GH concentration in culture medium (5 x 10(5) cells/mL) time dependently increased in all subjects, reaching 0.47 +/- 0.18 ng/L at day 7. A protein synthesis inhibitor (cycloheximide) and RNA synthesis inhibitor (actinomycin D) completely blocked GH secretion from lymphocytes. Immunoreactive GH secreted by unstimulated human lymphocytes was similar to pituitary GH in terms of antigenicity and molecular weight. Physiological concentrations of GHRH (10(-10)-10(-8) mol/L) and SMS 201-995 (10(-8)-10(-6) mol/L) had no effects on the spontaneous secretion of GH from human lymphocytes. These results indicate that GH is spontaneously synthesized de novo and secreted from unstimulated human lymphocytes, and that the regulation of GH in the immune system differs from that in the endocrine system.

Adult↗

Effects of anti-prolactin autoantibodies on serum prolactin measurements.

The influence of anti-PRL autoantibodies on PRL measurements determined by immunoassays was investigated in 10 patients with anti-PRL autoantibodies. Four different immunoassay systems (two double-antibody radioimmunoassays (RIAs), a single-antibody RIA and an immunoradiometric assay (IRMA)) were examined. Total and free PRL were extracted from sera by precipitating gamma-globulin with polyethylene glycol with and without acidification, respectively. PRL values determined by direct measurement were compared with total PRL values. The proportion of free to total PRL levels determined by each immunoassay in sera with anti-PRL autoantibodies was significantly lower than in control sera. Values obtained by direct measurement of PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL autoantibodies the values varied from one immunoassay to the other. In sera with anti-PRL autoantibodies, double-antibody RIA 1, RIA 2 and single-antibody RIA 3 yielded values lower for PRL than for total PRL (52 +/- 15% in RIA 1, 40 +/- 8.8% in RIA 2, 40 +/- 14% in RIA 3), while PRL levels determined by IRMA were not significantly different (112 +/- 14%). Immunoglobulin G purified from serum with anti-PRL autoantibodies dose-dependently decreased the recovery of PRL assayed by the double-antibody technique, while it did not affect that by IRMA. These data suggest that the presence of anti-PRL autoantibodies gives variable results depending on the immunoassays used.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody.

Patients with anti-prolactin (PRL) autoantibody were surveyed among 208 patients with hyperprolactinemia (PRL > or = 30 micrograms/l) and 228 subjects with normal PRL levels, and the relationship of the antibody titers with serum PRL levels and their clinical course were studied. Diagnosis of possessing the anti-PRL autoantibody was based on the polyethylene glycol method, displacement of the binding of [125I]PRL with the serum by unlabeled PRL and the binding of PRL to protein G, the affinity gel for immunoglobulin G. Prolactin was measured by an immunoradiometric assay that we found was not affected by the anti-PRL autoantibody. A significantly high frequency of anti-PRL autoantibody in patients with idiopathic hyperprolactinemia (16%) and a positive correlation between titers of the autoantibody and serum PRL levels (r = 0.74, p < 0.01) may indicate that the anti-PRL autoantibody itself is another cause of hyperprolactinemia, probably owing to the delayed clearance of PRL. Most patients with anti-PRL autoantibody lacked the clinical symptoms of hyperprolactinemia, such as amenorrhea and galactorrhea, and spontaneous pregnancy occurred despite the marked hyperprolactinemic state, indicating that the biological activity of PRL was attenuated by the autoantibody. In addition, PRL levels and the titers of anti-PRL autoantibody were not changed significantly during the observation period of up to 5 years without any medical intervention. These results suggest that the anti-PRL autoantibody itself is one of the causes of hyperprolactinemia and that medical intervention is unnecessary for this type of hyperprolactinemia.

Adolescent↗

A MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) mtDNA mutation that induces subacute dementia which mimicks Creutzfeldt-Jakob disease.

A 50-year-old woman with subacute dementia and brain atrophy on CT showed periodic synchronous discharge (PSD) on electroencephalogram (EEG) and myoclonus. She was initially suspected of suffering from Creutzfeldt-Jakob disease (CJD), but dramatically recovered over 5 months. Based on further investigations, the final diagnosis was mitochondrial encephalomyopathy with an A-to-G substitution at nucleotide position 3243 in mitochondrial DNA (mtDNA), commonly seen in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This case suggests that patients suspected of suffering from CJD should be evaluated for mitochondrial encephalomyopathy.

Creutzfeldt-Jakob Syndrome↗

Insulinoma with normal plasma insulin concentrations and insulin/glucose ratios during hypoglycemic episodes.

A patient with insulinoma had frequent hypoglycemic episodes with normal plasma insulin levels and insulin/glucose ratios. When immunoreactive insulin (IRI) concentrations in this patient were compared among plasma samples with the same C-peptide immunoreactivity (CPR) levels, the concentrations were significantly lower than in control patients with insulinoma and equal to or lower than those of normal subjects. In hepatic venous samples, CPR levels were significantly higher and the IRI/CPR molar ratios were lower than those in a control subject. These results may indicate that normoinsulinemia in this patient could be explained by increased hepatic extraction of insulin.

Adolescent↗

[Möbius syndrome with crossed total hemiatrophy--a case report].

The patient was a 26-year-old male who was noted to have asymmetry on the face, upper limbs, and trunk, and who showed no pursuit eye movements and no changes in the facial expression from birth. The patient developed transient global amnesia and was hospitalized. Neurological examination established atrophy of the right face, and left trunk involving the upper limb, and bilateral oculomotor and abducens nerve palsy. In auditory brainstem response, waves III to V were bilaterally obscured, and the blink reflex disclosed disturbances of peripheral facial nerve and the brainstem, suggesting developmental abnormalities of the facial motor nucleus. Contralateral R1 was also recorded in the blink reflex, and crossed trigeminofacial pathway was suspected. Möbius syndrome is associated with various muscle and skeletal abnormalities, but the coexistence of crossed total hemiatrophy has not been reported. We think that our case might be the first case of Möbius syndrome with total hemiatrophy.

Abnormalities, Multiple↗

[Pharmacokinetic and clinical evaluation of cefozopran in the pediatric field].

We conducted pharmacokinetic and clinical studies on cefozopran (CZOP, SCE-2787), an aminothiadiazolmethoxyiminoacetamido cephalosporin, and obtained the following results. 1. Concentrations in serum/excretion in urine We studied pharmacokinetic in children upon intravenous bolus injection and 30-minute intravenous drip infusion in single doses of 10 and 20 mg/kg. Upon intravenous bolus injection, mean serum concentrations 30 minutes after administration of 10 and 20 mg/kg were 27.8 and 52.3 micrograms/ml, respectively, and half-lives were 2.01 and 2.02 hours, respectively. Upon 30-minute intravenous drip infusion, mean serum concentrations on completion of the drip infusions of 10 and 20 mg/kg were 36.8 and 70.3 micrograms/ml, respectively, and half-lives were 1.74 and 4.11 hours, respectively. Their urinary recovery rates in the first 8 hours after administration were higher than 67.0% in the former regimen and between 23.2 to 98.0% in the latter. 2. Clinical results 54 patients were treated with CZOP for 32 cases of pneumonia, 11 cases of bronchitis, 3 cases of cervical lymphadenitis, 1 case of purulent tonsillitis, 2 cases of phlegmon, 2 cases of enterogastritis and 3 cases of urinary tract infections. CZOP gave "excellent" or "good" responses in 53 cases. 1 case of urinary tract infection showed fair response. Diarrhea was observed in 1 case. Abnormal laboratory test results were noted in 9 patients including elevations of eosinophils, GOT and GPT. In no cases the treatment had to be discontinued.

Adolescent↗

[Pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Pharmacokinetic and clinical studies on biapenem (L-627), a newly developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of biapenem was studied in 14 children at doses of 6 mg/kg and 12 mg/kg administered through 30 minutes-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 22.5, 29.9 micrograms/ml, and 0.84, 0.85 hours, respectively. Their urinary recovery rates were 54.5 to 76.1% and 37.3 to 59.5%, respectively. Cerebrospinal fluid levels of biapenem in two patients with purulent meningitis were 0.88 and 2.72 micrograms/ml, and the penetration rates were 3.7 to 8.3%. 2. Clinical study: Forty-nine patients were treated with biapenem at doses exceeding 90 to 100 mg/kg/day for purulent meningitis and at doses between 15.0 and 36.0 mg/kg/day for other infections. Biapenem gave "Excellent" or "Good" responses in 48 cases, hence an efficacy rate of 98.0% was obtained. Only one patient with pneumonia showed a fair response. No adverse reactions were observed. Abnormal laboratory test results were noted in 7 patients including elevation of GOT, GPT, and eosinophils. In no cases the treatment had to be discontinued.

Absorption↗

[A case of Fisher's syndrome with upbeat nystagmus].

We reported a case of Fisher's syndrome with upbeat nystagmus. The syndrome manifested itself with the appearance of diplopia and ataxic gait preceded by cold-like symptoms. Although slight blephaloptosis, marked bilateral upward gaze palsy, and restricted abduction of the right eye were observed, light reflexes and Bell's phenomenon were normal. A slight decrease in the muscular power of the distal extremities, bilateral fingertip dysesthesia, and diminished sensation of vibration were observed. All muscle stretch reflexes were absent, and no pathologic reflexes were noted. Truncal ataxia and incoordination were observed. The cerebrospinal fluid showed albumino-cytologic dissociation. Upbeat nystagmus in five directions of gaze was recorded on the EOG, the smooth pursuit eye movement showed a staircase pattern, and dysmetria was present in the saccadic eye movement. The caloric test elicited a satisfactory response, but the visual suppression test produced poor suppression. Taken altogether, the test results suggest that the responsible lesions in this case were not only peripheral but also central, extending from the midbrain to the tegmentum pontis and the vestibulocerebellum.

Adolescent↗

[A case of polymyositis with ventricular tachycardia].

We reported a case of polymyositis with ventricular tachycardia. She had been suffering from proximal dominant muscle weakness and palpitation for 11 months. Holter EKG demonstrated 23 beats ventricular tachycardia. The noninvasive cardiac examination (Thalium cardiac scintigraphy, echocardiography, radionuclide ventriculography) demonstrated no abnormal findings. After initiation of steroid therapy, muscle strength and CK improved and ventricular tachycardia disappeared. Ventricular tachycardia is one of the important complications of polymyositis.

Adult↗

Immunohistochemical and pathological characteristics of dystrophic amyloid in surgically excised cardiac valves.

One hundred and thirty-six cardiac valves obtained surgically from 124 patients (aged 15-77 years) were examined. Microdeposition of amyloid was present in sclerotic or sclerocalcific lesions of aortic valves in 38 out of 75 (51%) and mitral valves in 21 out of 61 (34%). Amyloid deposition was not significantly related to the age of the patients. An antiserum raised against a low molecular weight protein extracted from amyloid-laden valvular tissues (about 20 g) reacted positively to amyloid in the cardiac valves. It did not react to amyloid deposition containing fibril proteins including light chain related amyloidosis, reactive amyloidosis, systemic senile amyloidosis, isolated atrial amyloidosis, beta-2-microglobulin related amyloidosis and beta protein related amyloidosis. Further, amyloid in the cardiac valves failed to react immunohistochemically to anti-AA, anti-AL, anti-TTR, anti-ANF, anti-beta 2M and anti-beta protein antibodies. These findings suggest that an unknown amyloid protein is involved in the damaged valves.

Adolescent↗

[An ontogenic study of behavioral sensitization to cocaine in the rat].

The present study examined ontogeny of behavioral effect of acute cocaine administration and behavioral sensitization to a challenge dose of cocaine in rats previously treated with chronic cocaine. Acute stimulating effects of cocaine in behaviors were observed in as early as 7-postnatal-day (PND) rat. However, they needed higher dose of cocaine than adult rats. Adult pattern of response to acute doses of cocaine was seen in stereotypy and locomotion at 21 PND, and in rearing at 28 PND. Rats at ages of 7, 14, 21 or 28 PNDs received repeated injections of either saline or cocaine 15 mg/kg twice a day for five consecutive days. After an abstinent period of three weeks, sensitization to a challenge dose of cocaine (15 mg/kg) was assessed. Cocaine-induced stereotyped behaviors were significantly enhanced only when cocaine-pretreatment was initiated at PND 21 and 28, but not at the earlier ages of PND 7 or 14. These results suggest that cocaine-induced behavioral sensitization occurs only when subchronic cocaine administration was commenced after PND 21.

Animals↗