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Biomedical subjects

Y Otsuka

Publications and source records attributed to Y Otsuka.

At least 91 records · Page 5Linked to original sources

Chronic effects of methylmercury in rats. II. Pathological aspects.

Chronic effects of methylmercury (MeHg) were examined pathologically in male Wistar rats fed on diet containing 0, 1 or 5 ppm Hg (as MeHg) for two years. Organs including the central nervous tissues were examined histopathologically using hematoxylin and eosin (H & E), Klüver-Barrera (KB), PAS or phenol-congo red stains. The peripheral nerve system tissues were also examined, using H & E and trichrome stains. Furthermore, immunoglobulins of renal specimens were demonstrated by direct immunofluorescence microscopy. Localization of mercury in the paraffin-embedded sections of the nervous tissue, kidney, liver, pancreas, spleen and testis was demonstrable by the photoemulsion histochemical method. In the 5 ppm group, mercury was readily detectable in tissues of the rats exposed for one year, one and half years, two years and two and half years. Mercury was detected in the cells of the brain such as neurons, neuroglial cells, and phagocytes, and also in most organs, particularly in the epithelium of renal tubules, liver cells, myocardium, in the macrophages of pancreas, spleen and testis. In the 1 ppm group, mercury was detectable in the epithelium of renal tubules and liver cells. Fibrosis of the glomeruli was found in the rat group given a high dose of methylmercury with all experimental methods. Granular IgG, IgM and C3 deposits were demonstrated in the glomeruli by direct immunofluorescence microscopy. The etiology of the pathological changes of glomeruli was suspected to be autoimmune glomerulopathy due to inorganic mercury filtration for a long time. It was difficult to determine the clinical signs and symptoms and pathological changes in the nervous system in spite of the deposition of mercury in the brain.

Administration, Oral↗

Mixed connective tissue disease associated with acute polyradiculoneuropathy.

A rare case of mixed connective tissue disease (MCTD) with acute polyradiculoneuropathy is reported. A 23-year-old woman presented with high body temperature, arthralgia and a headache, and developed gait disturbance two weeks later. She had many clinical features common to patients with MCTD. Her neurological manifestations were diagnosed as acute polyradiculoneuropathy based on the clinical picture, combined with supportive ancillary data, including cerebrospinal fluid (CSF) analysis, electrophysiological evaluation, sural nerve biopsy, peroneus brevis muscle biopsy, and magnetic resonance imaging (MRI). Her neurologic deficits, as well as associated laboratory findings, were improved by corticosteroid therapy.

Acute Disease↗

[The role of nitric oxide in two-kidney, one-clip renovascular hypertensive rats].

The relationship between blood pressure(BP) and nitric oxide(NO) in two-kidney, one-clip renovascular hypertensive rats (2K1C) was investigated. Although urinary NO2- + NO3-(NOx) excretion (UNOX V) increased 2 weeks after surgery (2W-2K1C), UNOX V decreased 4 weeks after surgery (4W-2K1C) compared with that of the control. UNOX V levels were restored 2 weeks after unclipping (U2K1C). BP and UNOX V did not change in 2K1C after treatment with L-arginine (Arg-2K1C). Aorta from 4W-2K1C and Arg-2K1C showed significantly decreased relaxation responses to acetylcholine(Ach), but Ach-induced relaxation of aorta in U2K1C returned to control-level responses. De-endothelialized aorta from 4W-2K1C, Arg-2K1C, and U2K1C had significantly decreased relaxation responses to lipopolysaccharide. These data suggest that: (1) transient increase of NO synthesis is accompanied by elevation of BP, but long-term elevation of BP decreases NO synthesis in endothelium and smooth muscle cells: (2) L-arginine supplement has no effect on the development of hypertension and on NO production by endothelium and smooth muscle cells in 2K1C.

Acetylcholine↗

Demonstration of the biological activity of peptide fragments related to human and rat hippocampal cholinergic neurostimulating peptide (HCNP).

Human and rat hippocampal cholinergic neurostimulating peptides (HCNPs) are 54.5% homologous; both stimulate acetylcholine synthesis in rat medial septal nuclei cultures. This in vitro system was used to test the bioactivity of short peptides containing human or rat HCNP sequences. Peptides with sequences corresponding to the N-termini and middle regions of both, and to the shared three C-terminal residues were not active. Tetrapeptides and hexapeptides whose C-terminus is this common sequence enhanced acetylcholine production, indicating that the minimum consensus sequence for HCNP activity is X-Gly-Pro-Leu.

Acylation↗

Distribution of hippocampal cholinergic neurostimulating peptide (HCNP) immunoreactivity in the central nervous system of the rat.

Hippocampal cholinergic neurostimulating peptide (HCNP), an undecapeptide isolated from the hippocampal tissue of young rats, enhances the cholinergic development in explant cultures of medial septal nuclei. This report concerns the distribution of HCNP immunoreactivity in the central nervous system (CNS) of 11- and 28-day-old Wistar rats; two affinity-purified anti HCNP antibodies were used. Immunoblot analyses of extracts of different regions of the brain revealed a single 23 kDa band that corresponded to the presumed HNCP precursor protein. Immunostaining of the various CNS structures of the 28-day-old rats was more intense than in those of 11-day-old animals. HCNP immunoreactivity was detected in neurons as well as in glia cells, particularly oligodendroglia. The perikarya of neurons in the cerebral cortex, hippocampus, limbic cortex, caudate, putamen, arcuate nucleus of hypothalamus, trigeminal subnuclei, rostroventrolateral reticular nucleus and dorsal horn of the spinal cord were positively stained. In addition, nerve fibers and terminals in the hypothalamic subnuclei, zona incerta, thalamic subnucleus, caudate, putamen, locus coeruleus, trigeminal subnuclei, dorsal motor nucleus of the vagus, dorsal horn of the spinal cord and intermediolateral column also displayed HCNP immunoreactivity. These observations would suggest that HCNP and its related molecules may have multifunctional roles in the CNS.

Animals↗

Vesnarinone-induced WBC disorders in Japan.

Vesnarinone is a new oral inotropic agent that augments myocardial contractility with little effect on heart rate or myocardial oxygen consumption. In Japan, vesnarinone was approved in June 1990 and first marketed in September 1990. Although the efficacy of vesnarinone has been confirmed, WBC disorders, which are principal adverse events associated with the use of vesnarinone, were found after marketing was begun in Japan. This survey was carried out to estimate the incidence of WBC disorders, the predominant periods in which these adverse events develop, and the effects of risk factors in the cohort of patients who have been administered vesnarinone since its market release in Japan. Data were available for 14,921 patients who took vesnarinone at least once during the period from 1 March 1991, through 28 February 1994. Vesnarinone-induced agranulocytosis, which is usually evidenced by a sharp decrease in granulocyte count, was seen in 0.25% of the patients. The cumulative incidence of agranulocytosis was 0.34% at 12 weeks. The predominant period of development was estimated to be the first 4 months after initiation of therapy, with the rate peaking in the second month. The risk of WBC disorders was higher among females.

Journal Article↗

Distribution of hippocampal cholinergic neurostimulating peptide (HCNP)-like immunoreactivity in organs and tissues of young Wistar rats.

This report concerns the distribution of the hippocampal cholinergic neurostimulating peptide (HCNP) in tissues and organs of 11-day-old Wistar rats. HCNP, originally isolated and purified from the hippocampus of young rats, is an undecapeptide (acetyl-Ala-Ala-Asp-Ile-Ser-Gln-Trp-Ala-Gly-Pro-Leu). HCNP distribution was investigated by using immunohistochemical techniques, employing an affinity-purified rabbit antibody that specifically recognizes HCNP and its 21-kDa precursor protein. Positively stained cells were detected in a variety of tissues and organs, including salivary gland, small intestine, colon, pancreas, bronchiole, adrenal gland, testis, as well as several others. The nerve fibres around blood vessels of almost all organs expressed HCNP. Our results suggest that HCNP or its precursor, or both, may have a specific function not only in the central nervous system, but also in the peripheral nervous system, and possibly in certain specialized duct and gland cells as well.

Amino Acid Sequence↗

Demonstration and characterization of hippocampal cholinergic neurostimulating peptide (HCNP) processing enzyme activity in rat hippocampus.

Hippocampal cholinergic neurostimulating peptide (HCNP) stimulates cholinergic activity of cultured medial septal nuclei explants. It consists of eleven amino acids that are located at the N-terminal region of its precursor protein. This report concerns the demonstration and characterization of an HCNP processing enzyme that cleaves the bioactive undecapeptide from the precursor. The enzyme was purified from the hippocampus of young Wistar rats. A synthetic deacetylated peptide (peptide(1-26)) consisting of the N-terminal 26 amino acids of the HCNP precursor protein served as substrate. The product of the enzyme reaction was identified and quantitated by HPLC using deacetylated HCNP as standard. The amount of undecapeptide generated was directly proportional to the time of incubation of the enzyme reaction mixture. From molecular sieving chromatography it was estimated that the molecular mass of the enzyme is close to 68 kDa. The HCNP processing enzyme has a pH optimum of 6.0 and a K m of 0.50 mM for peptide(1-26). Preincubation at 56 degrees C causes rapid inactivation of the HCNP processing activity. Enzyme activity is enhanced by EDTA and 1,4-dithiothreitol, and inhibited by antipain, chymostatin and E-64. These findings suggest that the enzyme probably has a thiol group in its active site. This novel enzyme of the hippocampus may represent a valuable tool for further studies on the general protein metabolism in the central nervous system, as well as for elucidating the neurochemical aspects of neurodegenerative disorders.

Amino Acid Sequence↗

Tenosynovial giant-cell tumor arising from the anterior cruciate ligament of the knee.

The localized form of tenosynovial giant-cell tumor is rarely located intraarticularly, especially in the large weight-bearing joints. We report the first case of localized, intraarticular tenosynovial giant-cell tumor arising from the anterior cruciate ligament of a knee in which locking and effusion had occurred. After arthroscopic removal of this tumor, the patient became asymptomatic.

Adult↗

Second case of zoonotic Onchocerca infection in a resident of Oita in Japan.

A non-gravid female Onchocerca was found in histopathological sections of a biopsy specimen taken from a painful nodule in the wrist of a 57-year old woman in Oita, in southern Japan. Six species of Onchocerca have been found in animals in Japan: two in wild bovids, one in equids, and three in domestic bovids of which one, Onchocerca sp., is only known by the microfilaria and infective stage. Distinctive morphological features of the worm, including a three-layered thick cuticle with prominent annular ridges at wide intervals, high somatic muscles and narrow lateral chords, resembled those of O. gutturosa, one of the three bovine Onchocerca species transmitted in the Oita region. However Onchocerca sp., which is also transmitted in this region, cannot be excluded. An ELISA test of the patient serum suggests that infections by Onchocerca spp. might be distinguished from those by Dirofilaria immitis, of which the number of human cases is increasing in Japan.

Animals↗

Stabilometric assessment in the anterior cruciate ligament-reconstructed knee.

OBJECTIVE: To examine the hypotheses that anterior cruciate ligament (ACL) reconstruction improves the proprioception of the knee beyond the level of ACL-deficient knees, and that proprioception of the knee correlates well with knee function after ACL reconstruction. PATIENTS: Fifty-three patients with ACL-reconstructed knees (22 men and 31 women), 30 physically active healthy volunteers with normal knees (15 men and 15 women), and 30 patients with chronic ACL-deficient knees (15 men and 15 women). MAIN OUTCOME MEASURES: A stabilometric assessment, which is considered to be a useful method for evaluating proprioception objectively, was used to compare the one-leg standing balance among three groups; and the relationship between subjective knee function, satisfaction, hop index, knee laxity, isokinetic thigh muscle strength, and one-leg standing balance in the ACL-reconstructed patients was also analyzed. RESULTS: The one-leg standing balance of the patients with ACL-reconstructed knees was still impaired compared with that of healthy volunteers (men, p < 0.05; women, p < 0.01), but significantly better than that of the patients with ACL-deficient knees (men, p < 0.001; women, p < 0.001). The one-leg standing balance of the patients with ACL-reconstructed knees correlated well with their functional outcomes such as subjective knee function (men, p < 0.001; women, p < 0.01), satisfaction (men, p < 0.01; women, p < 0.001), and hop index (men, p < 0.001; women, p < 0.001), whereas poor correlation was seen between functional outcomes and mechanical stability. CONCLUSIONS: The results suggest that knee function after ACL-reconstruction should be closely related with knee proprioception, and indicate that the usefulness of stabilometric assessment in the evaluation of the function of ACL-reconstructed knees.

Adolescent↗

Possible implication of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano body formation.

We have previously demonstrated that hippocampal cholinergic neurostimulating peptide (HCNP)-related components accumulate in almost all Hirano bodies in Sommer's sector of the hippocampus of elderly individuals, and that the number of HCNP-positive Hirano bodies is greater in patients with Alzheimer's disease. Although Hirano bodies occur preferentially in the neuronal processes of the stratum pyramidale of the hippocampus, they can be seen occasionally as small inclusions, intermingled with neurofibrillary tangles and in association with senile plaques. Here we show that the small inclusions are also recognized by an anti-HCNP antibody, and by using immunoelectron microscopy demonstrate that these HCNP-positive inclusions, intermingled with tau protein-positive neurofibrillary tangles and beta-amyloid-positive senile plaques are indeed Hirano bodies. These findings strongly suggest that HCNP-related components may be involved in Hirano body formation.

Aged↗

[A case of lung metastasis from breast cancer successfully treated by FLEP (5-FU leucovorin, etoposide CDDP) combined arterial infusion chemotherapy].

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Adult↗

Demonstration of deacetylated hippocampal cholinergic neurostimulating peptide and its precursor protein in rat tissues.

This report concerns the demonstration of hippocampal cholinergic neurostimulating peptide (HCNP), its deacetylated analogue (free HCNP) and HCNP precursor protein in rat tissues. To avoid possible enzymatic degradation during sample manipulation, tissue extracts were prepared under acidic conditions using trifluoroacetic acid. The tissue contents of free HCNP and of precursor protein were determined by radioimmuno-assay (RIA) using two antibodies with different specificities, and by a combination of HPLC and RIA. Free HCNP was detected in neuronal and renal tissues, but not in liver. All tissues examined had measurable amounts of HCNP precursor protein. The concentrations of free HCNP and precursor in neuronal tissues were inversely related to the age. These results suggest that the deacetylated analogue of HCNP and its precursor protein may have significant physiological functions, especially in the central nervous system of young animals.

Aging↗

Accumulation of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano bodies.

We have previously isolated from the hippocampus of young rats a novel peptide termed 'hippocampal cholinergic neurostimulating peptide' (HCNP) which specifically enhances the cholinergic activity of the septohippocampal system in vitro. Cloning and base sequence analysis of HCNP-specific cDNA from rat and human cDNA libraries revealed that the 1.1 kDa peptide aligns at the N-terminal region of its 21 kDa precursor protein. An affinity-purified rabbit antibody to rat HCNP prepared by us recognizes the C-terminal domain of the peptide, while an antibody against human HCNP binds to a large portion of the peptide. In this report we show that both antibodies react with HCNP-related components present in the soluble cytosol fraction of human brain tissue. Immunohistochemical examination of human nervous system tissues from elderly individuals revealed that Hirano bodies in Sommer's sector of the hippocampus were specifically stained by anti-HCNP antibodies. The number of HCNP-positive Hirano bodies was greater in patients with Alzheimer's disease than in normal, age-matched individuals. The immunohistochemical results were substantiated by immunoelectron microscopy. The present findings indicate that HCNP-related components accumulate in Hirano bodies, suggesting that patients who bear these inclusions may have a disturbance of the septo-hippocampal cholinergic system, considered to be of importance for learning and memory formation.

Aged↗

Helicobacter pylori colonization in children with peptic ulcer disease. III. Diagnostic value of the 13C-urea breath test to detect gastric H. pylori colonization.

The efficiency of the 13C-Urea Breath Test (13C-UBT) for the detection of Helicobacter pylori colonization in gastric mucosa was evaluated. The 13C-UBT was performed in five pediatric and six adult subjects who had had upper gastrointestinal endoscopy within 2 weeks. H. pylori colonization was confirmed in two pediatric and three adult subjects with peptic ulcer combined with antral gastritis, by histological examination of antral biopsy specimens. When an individual with H. pylori colonization ingested a solution containing 13C-urea, a significant amount of 13CO2 appeared in the respiratory CO2 within 10 min. The mean cumulative percentage dose of 13C recovered in the breath over 30 min in the cases with H. pylori colonization was significantly higher than that in those who were not colonized (4.91 vs 0.41, P < 0.001). In addition, the effect of antibiotic on the eradication of H. pylori from gastric mucosa was monitored by 13C-UBT in two cases. The values of cumulative percentage dose of 13C over 30 min fell to the same levels as those observed in H. pylori negative subjects after just 2 weeks treatment with amoxicillin; however, positive results were obtained again 1 month after the withdrawal of amoxicillin. In summary, 13C-UBT is a simple, reliable, non-invasive method in the diagnosis of gastric H. pylori colonization especially for pediatric patients.

Adolescent↗