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Biomedical subjects

Y Morikawa

Publications and source records attributed to Y Morikawa.

At least 109 records · Page 6Linked to original sources

Effects of maternal bilateral ureteral ligation on formation of the glomerular basement membrane in fetal rat kidney.

BACKGROUND: The present study was designed to clarify development of filtration property of fetal renal glomerulus when maternal kidney is dysfunctional. MATERIALS AND METHODS: Maternal bilateral ureteral ligation was performed on days 17, 19, and 21 of pregnancy. One day after each operation, cationized ferritin (CF), native ferritin (NF), and horseradish peroxidase (HRP) were injected, respectively, in the fetuses. Distribution of the tracers in the fetal kidneys was investigated electron microscopically. RESULTS: On fetal day 20, clustered CF particles were present in the laminae rarae interna and externa of the glomerular basement membrane of the fetuses from ureter-ligated mothers, while the clusters were arrayed in three to four layers in that of the fetuses from sham-ligated ones. On fetal day 22, a relatively large amount of CF particles was present in the lamina rara externa in the fetuses from ureter-ligated mothers when compared to that in the age-matched control fetuses. On fetal days 20 and 22, the number of NF particles was decreased, and shortening of the time for filtration of HRP through the glomerular basement membrane was observed in the fetuses from the ligated mothers. CONCLUSIONS: These results suggest that dysfunction of maternal kidneys causes accelerated formation of fetal glomerular basement membrane and stimulates glomerular function in filtration in fetal rat kidney.

Animals↗

Triple primary cancers involving kidney, urinary bladder, and liver in a dye worker.

A case of triple primary cancers (renal cell carcinoma of the kidney, transitional cell carcinoma of the bladder, and hepatocellular carcinoma of the liver) was reported at autopsy. A 53-year-old man, who had a history of exposure to benzidine, underwent nephrectomy for a left renal cell carcinoma and 10 years later, transurethral resection of bladder tumor (TUR-Bt) for a transitional cell carcinoma of the bladder. At the age of 65, he was diagnosed as having multiple hepatic tumors. Histological examination of biopsy specimens showed these lesions to be undifferentiated carcinomas. Immunohistological examination of both biopsy and autopsy specimens revealed that multiple hepatic tumors were hepatocellular carcinomas, not metastatic tumors from kidney or urinary bladder: tumor cells of hepatic tumors were positive for alpha-fetoprotein, although renal cell carcinomas and transitional cell carcinomas of urinary bladder were positive for Ber-EP4 and keratin, respectively. These findings suggest not only that immunohistological examination is helpful for the diagnosis of multiple primary cancers but also that benzidine may be hepatocarcinogenic in addition to those cancers that are known to be associated with benzidine exposure, i.e., renal cell carcinomas and transitional cell carcinomas in urinary bladder.

Aged↗

Ten-year follow-up study on the relation between the development of non-insulin-dependent diabetes mellitus and occupation.

To investigate the relation between occupation and the development of non-insulin-dependent diabetes mellitus (NIDDM), we undertook a 10-year follow-up survey of male employees of a zipper and aluminum sash factory in Japan. Of 1,218 employees we followed 1,087 subjects. We classified the subjects into five occupations: managers, technical workers, clerical workers, workers in transport, and laborers. NIDDM incidence was 3.1% for 10 years. The age-adjusted incidence of the workers in transport was the highest and that in laborers was the lowest. We used a multiple logistic analysis for adjustment with baseline characteristics such as age, BMI, fasting plasma glucose, and family history of diabetes mellitus. Adjusted relative risk of the workers in transport compared with the laborers was significantly high (3.95). Our work suggests that occupation is related to the development of NIDDM.

Adult↗

Primary cardiac angiosarcoma: 53 months' survival after multidisciplinary therapy.

An 8-year-old girl underwent surgical excision of a tumor arising from the right atrium immediately after admission. Because histologic and immunohistochemical examination confirmed the diagnosis of angiosarcoma, adjunctive multidisciplinary therapy was administered for the following 2 years. She is leading a normal school life 53 months after the operation. Therapeutic strategy for this highly malignant cardiac tumor is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

In vitro activity of the hairpin ribozyme derived from the negative strand of arabis mosaic virus satellite RNA.

The negative strand of the satellite RNA of tobacco ringspot virus [(-)sTRSV] is a self-cleaving RNA, of which self-cleaving domain is called the hairpin ribozyme. The negative strand of the satellite RNA of arabis mosaic virus [(-)sArMV] has been suggested to have a hairpin ribozyme-like secondary structure, and we have previously shown that this hairpin domain of (-)sArMV has ribozyme activity. Here we report characterization of the cleavage reaction of the (-)sArMV hairpin ribozyme. Mutagenesis analyses in a trans-acting system revealed, surprisingly, that the wild-type ribozyme was less active than almost all the other mutant ribozymes tested. In a cis-acting system (self-cleaving reaction), however, the reaction of the RNA containing the wild-type sequence proceeds highly efficiently. This result suggests that the inefficient cleavage of the wild-type substrate in trans-acting system may be due to low efficiency at the substrate-binding step but not at the chemical cleavage step in the reaction. We also constructed a chimeric ribozyme between the catalytic hairpin domain from (-)sArMV and the substrate-binding site from (-)sTRSV. This chimeric ribozyme had the highest activity among the trans-acting hairpin ribozymes tested.

Base Sequence↗

Purification and characterization of dipeptidyl aminopeptidase from Aureobacterium sp. WO26.

We isolated a bacterial strain with an enzyme which releases dipeptide from Gly-Arg-p-nitroanilide. The bacterium was tentatively identified as Aureobacterium sp. The enzyme, named AuDAP, was purified and characterized. It was homogenous by SDS-PAGE and IEF, and had a molecular mass of 90,000 Da by SDS-PAGE and 88,000 Da by gel filtration, so it may be a monomer. The isoelectric point was 3.8 and the optimum pH was 10.0. The purified enzyme hydrolyzed Gly-Arg-pNA, a model substrate for DAP I, and Arg-Arg-MNA, a model substrate for DAP III. However, this enzyme did not hydrolyze Gly-Phe pNA, also a model substrate for DAP I. These results suggested that this enzyme did not fall under the classification of mammalian DAPs and was similar to DAP BI from Pseudomonas sp. WO24 and dDAP from Dictyostelium discoideum, although several differences were observed between them. The N-terminal amino acid sequence of this enzyme showed no significant homology to any enzyme and protein, except only for DAP BI.

Dipeptidyl-Peptidases and Tripeptidyl-Peptidases↗

Purification and characterization of a dipeptidyl carboxypeptidase from Pseudomonas sp. WO24.

A dipeptidyl carboxypeptidase (DCP) activity was detected in cell-free extracts of Pseudomonas sp. WO24. After purification and characterization the enzyme was found to be homogeneous by SDS-PAGE, and had a molecular mass of 74,000 Da by SDS-PAGE and 72,000 Da by gel filtration, indicating that it is monomeric. The isoelectric point was 5.2 and optimum pH was 6.5-7.0. It showed a specific activity of 780 mumol/min/mg, which is the highest of the values shown by known enzymes. The enzyme hydrolyzed angiotensin I to angiotensin II and sequentially released Phe-Arg and Ser-Pro from the C-terminus bradykinin. The DCP could not cleave imido-bonds, Gly-Gly bonds, or tripeptides. The enzymatic activity was completely inhibited by 0.001 mM EDTA and 0.1 mM O-phenanthroline, but it was not affected by general serine and cysteine protease inhibitors. Addition of Zn2+ completely restored the original activity of the inactivated DCP treated with EDTA. These results suggest that this enzyme is a zinc metalloprotease. The characteristics of the purified enzyme are slightly different from those of the DCPs from Escherichia coli, Pseudomonas maltophilia, and Corynebacterium equi, and considerably from those of the DCP from Bacillus pumilus.

Amino Acid Sequence↗

A case of a pony with Cushing's disease.

The pars intermedia of the pituitary gland, and plasma ACTH and cortisol levels in the pony, which was first diagnosed in Japan as indicating equine Cushing's disease, were examined by immunohistochemistry and radioimmunoassay, respectively. The pars intermedia was greatly enlarged and most of its cells were immunoreactive for antisera to both adenocorticotropic hormone (ACTH) and beta-endorphin (beta-End). The plasma ACTH level was elevated when clinical symptoms appeared. The present results reveal that equine Cushing's disease in this pony was induced by the hypersecretion of ACTH and beta-End from the enlarged pars intermedia of the pituitary gland.

Adrenal Glands↗

[Thymic carcinoma associated with pulmonary sarcoidosis].

A 54-year-old man who worked as a farmer was admitted to the hospital in August 1989 because of bilateral hilar adenopathy that was detected during a mass screening. Laboratory examination showed a high serum lysozyme level and the PPD skin test was negative. Examination of a specimen obtained by transbronchial lung biopsy revealed non-caseous epithelioid cell granuloma. Sarcoidosis was diagnosed. The patient was not treated, and the bilateral hilar adenopathy had lessened by 1992. The patient was readmitted to our hospital because of right hilar and upper mediastinal enlargement seen on a chest radiograph in April 1994. Computed tomography and magnet resonance imaging disclosed an anterior mediastinal tumor in contact with the right upper lobe, the left inominate vein, and the pericardium. Bronchoscopy showed no abnormality in the right upper-lobe bronchus. Examination of a specimen obtained from the B3b bronchus showed no evidence of malignant cells. Examination of a tumor specimen obtained by transdermal biopsy showed squamous cell carcinoma. After the patient underwent combination chemotherapy, the tumor ws resected, along with the right upper lobe, the left inominate vein, and the pericardium, which were difficult to separate from the tumor. Postoperative pathological examination showed that squamous cell carcinoma was intermingled with normal thymus tissue. We believe that squamous cell carcinoma originated in the thymus. Non-caseous epithelioid cell granulomas were also found in the resected right upper lobe and in a mediastinal lymph node. The patient was discharged after post-operative irradiation of the mediastinum. Thymic carcinoma is rare, and sarcoidosis in a patient with thymic carcinoma is very rare. T lymphocytes are very important in the pathogenesis of sarcoidosis, and the thymus is involved in the growth and differentiation of T lymphocytes. The occurrence of these two diseases in one patient is interesting, but the relationship is not clear.

Carcinoma, Squamous Cell↗

Ischaemic heart disease deaths in a Japanese rural area evaluated by clinical records.

A community-based survey to examine the actual number of ischaemic heart disease (IHD) deaths was undertaken in the western area of Toyama, a rural area with a population of 209,000. IHD deaths (International Classification of Diseases [ICD], ninth revision, codes 410-414) and heart failure (HF) deaths (ICD code 428) according to the death certificate aged 15 to 74 in 1987 to 1990 were reevaluated from medical records using the criteria of the multinational monitoring of trends and determinants in cardiovascular disease (MONICA). Of 97 subjects with IHD and of 170 subjects with HF according to the death certificate, 85 cases (87.6%) and 143 cases (84.1%) could be examined, respectively. Using the MONICA criteria, of 85 subjects with IHD, 18 (21.2%) were reevaluated as "definite acute myocardial infarction (AMI)" and 30 (35.3%) as "possible AMI". On the other hand, of 143 subjects with HF, 1 (0.7%) were reevaluated as "definite AMI" and 12 (8.4%) as "possible AMI". From these results, the number of deaths as reevaluated IHD was estimated 104.5 in the study period, and it was 7.7% increase at least compared with the number of deaths judged from the death certificate.

Adolescent↗

Immunocytochemical localization of adrenocorticotropic hormone-immunoreactive cells of the pars intermedia in thoroughbreds.

OBJECTIVE: To analyze and characterize adenoma and hyperplasia of the pars intermedia (PI) of Thoroughbred mares. ANIMALS: 165 Thoroughbred mares, without clinical signs of hyperadrenocorticism that had been euthanatized or had died, of causes such as sudden death, colic, pneumonia, or trauma, and were necropsied. Five of those horses, 17 to 25 years old, had a large pituitary gland at necropsy. Eight mares, 5 to 15 years old with normal-size pituitary gland, were selected at random for comparison. PROCEDURE: A morphologic comparison of the pituitary gland between horses with and without tumors of the PI was conducted by use of immunocytochemistry and morphometry. RESULTS: In horses with normal pituitary gland, the PI was supplied by a vast capillary or sinusoidal plexus, which connected that in the pars distalis (PD) with that in the pars nervosa (PN). Cells of the PI stained slightly with ACTH antiserum, but some cells in the border region, which is contiguous to the PD, were strongly ACTH immunoreactive. At necrospy, horses with an enlarged pituitary gland also had adenoma of the pituitary gland involving the PI. Cells of the border region were hypertrophied and stained strongly with ACTH antiserum. The area and number of individual tumor cells of the border region of the PI of horses with adenoma were significantly increased, compared with those in horses with normal pituitary gland. CONCLUSIONS: Cells of the PI-PD border region may secrete substantial quantities of ACTH, owing to stimulation by corticotropin-releasing factor. Adenoma and hyperplasia of the PI in Thoroughbred mares may be associated with hyperadrenocorticism.

Adenoma↗

[Relationship between learning behavior and genetic factor on immobility shown during forced swimming test].

The relationship between learning and genetic factor on immobility in mice during a forced swimming test (FST) has been studied. The duration of immobility during the FST did not change significantly after the administration of either scopolamine (2.5 mg/kg, ip) or cyclohexamine (150 mg/kg, ip), although both drugs produced impairment in the learning task. This suggests that the increase in immobility observed during the second trial of the FST may not be related to learning which could occur during the first trial. Concerning the strain difference, first, the duration of immobility in C3H mice was shorter than that in ICR, ddY, C57BL and BALB mice. Second, after receiving shock stress in a box, ICR, ddY and C57BL mice, but not C3H mice showed a marked decrease in locomotor activity when placed in the box again without shock. Also during the FST, both C57BL and ddY mice, but not C3H mice showed prolongation of immobility and reduction in swimming after shock stress. The changes in locomotor activity, and immobility and swimming during the FST caused by shock stress in ddY mice recovered to normal levels after treatment with imipramine. From these results, it is suggested that the immobility shown during the FST, which may be independent of learning and dependent on some genetic factor, is a suitable model of depression in animals.

Animals↗

X-linked severe combined immunodeficiency with gamma delta T cells.

A patient with X-linked severe combined immunodeficiency (X-SCID) was found to have a deletion mutation of a four base pair in the transmembrane domain of the IL-2 receptor gamma chain gene, a subunit shared by the receptors for IL-4, IL-7, IL-9, and IL-15 (common gamma chain; gamma c). He had very few alpha beta T cells but had a considerable number of gamma delta T cells in his peripheral blood. Fluorescence in situ hybridization (FISH) analysis showed that the gamma delta T cells in his peripheral blood were not of maternal origin. He had received a Bacillus Calmette-Guerin (BCG) vaccination before recognition of the disease, and the BCG infection remained quiescent with no reaction for 19 months. After successful bone marrow transplantation, the site of the BCG vaccination showed a reaction, and live BCG were detected. It is useful to consider the relationship between the existence of gamma delta T cells and BCG in this case, and it is suggested that gamma delta T cells may be, in a given situation, less dependent on the gamma c chain than are alpha beta T cells.

Gene Deletion↗

Involvement of dopaminergic neurons in mouse-killing aggression in rats.

The sites associated with dopamine neurons which produce mouse-killing aggression (muricide) were examined in the rat brain. Muricide appeared in 60-80% of rats after being fed a thiamine-deficient diet for 28 days. Microinjection of dopamine (500 ng/rat) into the olfactory bulb (OB) significantly suppressed muricide, whereas injection into other brain areas failed to do so. The incidence of muricide after dopamine injection was 40% at 5 min and 20% at 15-30 min. When 6-hydroxydopamine (8 micrograms/0.5 microliter), following pretreatment with desmethylimipramine (25 mg/kg i.p.), was injected twice into the ventral tegmental area (VTA) or the olfactory bulb (OB) in nonkiller rats during thiamine-deficient feeding, the occurrence of muricide gradually increased over time. The present results suggest that degeneration of dopamine neurons projecting from the VTA to the OB may be related to mouse-killing aggression in rats.

Aggression↗

Expression of IL-3 receptor in testis.

Interleukin-3 (IL-3) is a potent growth factor for hematopoietic cells. IL-3 transmits its signal through a specific cell surface receptor which consists of a primary binding alpha subunit (IL-3R alpha) and a signaling beta subunit that is shared by the IL-5 and GM-CSF receptors. Here, we describe the expression of the alpha and beta subunit of the IL-3 receptor in mouse testis and testicular cell lines both at nucleic acid and protein levels. Our data indicate that IL-3R alpha is expressed on the cell surface of testicular Leydig cells and a Leydig cell tumor cell line I-10. Expression of the beta subunit mRNA was only faintly detected in testis, but not in I-10 cells. Immunoelectron microscopy has revealed that IL-3R alpha is present on cell membrane and microvilli.

Animals↗

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer.

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3-dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.

Animals↗

The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation.

Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.

Animals↗