Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 217 records · Page 12Linked to original sources

PubMed1996

The osteoblastic MC3T3-E1 cells synthesized C-terminal propeptide of type I collagen, which promoted cell-attachment of osteoblasts.

In this study, we purified C-terminal propeptide of type I collagen (PICP) from the conditioned medium of osteoblastic MC3T3-E1 cells by chromatographic and Agarose gel extraction procedures. PICP was confirmed to be present in bone by Western blotting using a specific antibody, and was proved to be synthesized by osteoblasts with metabolic labeling. PICP promoted cell-attachment of osteoblastic MC3T3-E1 cells. We conclude that PICP is synthesized by osteoblasts and stored in bone, and that it plays a role in the maintenance of bone cells on bone matrix.

Amino Acid Sequence↗

PubMed1996

Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure-activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds.

A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H-tetrazol-5- ylbiphenyl-4-yl)-methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.

Acetylation↗

PubMed1996

Neuro-otological findings after radiosurgery for acoustic neurinomas.

OBJECTIVE: To evaluate the neuro-otological complications in patients after radiosurgery for acoustic neurinomas. DESIGN: Inception cohort, retrospective study. SETTING: University hospital. PATIENTS: A consecutive sample of 46 patients with acoustic neurinomas who underwent unilateral gamma knife radiosurgery at the University of Tokyo, Japan, between June 1990 and June 1994 were followed up by otolaryngologists for more than 3 months. INTERVENTION: Gamma knife stereotactic radiosurgery. MAIN OUTCOME MEASURES: Neuro-otological examinations including pure tone audiometry, auditory brain stem response, and caloric test. RESULTS: Tumor growth occurred in 2 patients (4.3%). Seven (18%) of the 38 patients with preserved hearing of any extent became deaf within 1 year. In cases of gradual hearing loss, the average deterioration rate was approximately 8 dB per year. Abnormalities of auditory brain stem response preceded deafness in 2 patients. Caloric response, preserved before treatment in 13 patients, disappeared 4 to 13 months after treatment (median, 8 months) in 9 (69%) of them, whereas their hearing was preserved. Delayed facial palsy and persistent trigeminal neuropathy occurred in 10 (22%) and 7 (15%) of the 46 patients, respectively. Severe facial palsy tended to persist. CONCLUSIONS: The rates of neuro-otological complications of radiosurgery are almost comparable with those previously reported from other institutions. The deafness within 1 year after treatment might be attributed to a lesion in the cochlear nerve. Hearing loss did not parallel vestibular function loss. The persistent severe facial palsy contrasts with previously reported findings. Considering the serious facial nerve complications that occurred in some of our patients, further study to disclose the risk factors for neurological dysfunction would be needed for radiosurgery to become a true, safe alternative to microsurgery.

Adolescent↗

PubMed1996

Cytolysis of malignant glioma cells by lymphokine-activated killer cells combined with anti-CD3/antiglioma bifunctional antibody and tumor necrosis factor-alpha.

With the aim of developing an effective immunotherapy for malignant glioma, glioma cells were incubated with tumor necrosis factor-alpha (TNF-alpha) to increase their susceptibility to lysis by lymphokine-activated killer (LAK) cells. Treatment with exogenous TNF-alpha induced the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells. In addition, the cytolytic activity of LAK cells toward exogenous TNF-alpha treated glioma cells was significantly greater than LAK cell activity toward untreated glioma cells. This increase in cytolytic activity was blocked by anti-ICAM-1 monoclonal antibodies (MAb). Furthermore, co-treatment with a bifunctional antibody (BFA) composed of anti-CD3 (UCHT1) and antiglioma (G-22) antibodies synergistically increased the cytolytic activity of LAK cells towards TNF-alpha-treated glioma cells. These results indicate that a combination of exogenous TNF-alpha and anti-CD3/antiglioma BFA may provide an effective modified adoptive immunotherapy for patients with malignant glioma.

Antibodies, Bispecific↗

PubMed1996

An analysis of mutagens in the contents of the biliary tract in pancreaticobiliary maljunction.

A reflux of pancreatic juice into the biliary tract due to pancreaticobiliary malfunction has been considered to be an important factor in the development of biliary tract carcinogenesis. It is known that the contents of the biliary tract contain not only activated pancreatic enzymes but also certain mutagens. The purpose of this study was thus to isolate and identify such mutagenic substances. A 1:1 mixture of the control bile and pancreatic juice was mixed with bovine enterokinase (10 mg/ml), and the mixture was incubated at 37 degrees C for 12 h. The mixture was demonstrated to be reproducibly mutagenic by the Ames test. The mutagenic substances in these mixtures, which were separated using organic analysis, were found to be included in the water-soluble fraction and to contain amino acids. Mutagenic substances are thought to have a molecular weight of 1,500-3,500 and to be a complex of low-molecular-weight, stable, mutagenic substances including amino acids and peptides.

Amino Acids↗

PubMed1996

Bone chondroadherin promotes attachment of osteoblastic cells to solid-state substrates and shows affinity to collagen.

Chondroadherin, which is reported to be synthesized by chondrocytes and to promote their attachment, was purified from bovine bone. It was a minor component of bone organic matrix, and was present in the 4 M guanidine extract of demineralized bone. Chondroadherin promoted attachment of osteoblastic cells to solid-state substrates, and bound to collagen. Binding of chondroadherin to collagen was significantly higher than that of osteonectin or decorin. These findings imply that chondroadherin may play a role in maintaining bone cells on the collagen matrices of bone.

Amino Acid Sequence↗

PubMed1996

Pediatric brain stem gliomas with the predominant symptom of sleep apnea.

Two children complaining of sleep apnea presented with brain stem gliomas. In the early stage of their illness, neurological disorders were too subtle to be recognized as significant by the physicians or to be noted by the parents. Case 1 experienced an episode of unsteady gait and weakness in the bilateral arms, at the age of 5. When it recurred after 7 years of remission, the predominant symptom was sleep apnea. Case 2 exhibited nasality of speech as the earliest sign of this illness very early in his life, presumably 5 years before the diagnosis of brain stem glioma. A slight sleep apnea which developed afterwards did not draw attention of the physicians because no neurological signs other than paralyses of the bilateral soft palates were present. MRIs of the both cases revealed diffuse, infiltrating lesions in the pons, the medulla oblongata and the upper cervical spinal cord. Both cases shared some features: (1) diagnostic delay of several years from the first symptom; (2) the main lesion in the medulla oblongata, where important structures for respiratory control are identified; (3) infiltrative growth patterns in the MRI of the tumor, which might account for the uncommon clinical courses.

Blood Gas Analysis↗

PubMed1996

Progressive visual agnosia with posterior cortical atrophy.

A patient of posterior cortical atrophy characterized by early signs of progressive visual agnosia documented by repeated neuropsychological tests, is reported. SPECT and MRI findings showed left unilateral parieto-occipital involvement in the earlier stage. A PET study executed eight months later showed bilateral parieto-occipital hypometabolism, but predominantly in the left hemisphere. This suggests that the degeneration may have developed asymmetrically, progressing from left unilateral to bilateral.

Agnosia↗

PubMed1996

Side effects of high-dose interferon therapy for chronic hepatitis C.

BACKGROUND/AIMS: Various side effects have been reported in patients treated with alpha interferon, but their incidence and prognosis remain unknown. METHODS: Nine hundred and eighty-seven patients with chronic active hepatitis C received 6 to 10 MU of alpha interferon per day for 2 weeks and 3 times per week for 22 weeks. Autoantibodies, thyroid function tests, and fasting plasma glucose concentrations were evaluated prior to alpha interferon therapy. RESULTS: Of the 987 patients, 310 were required reduction in the dose of alpha interferon to 3 MU/day or cessation of alpha interferon therapy because of adverse reactions such as flu-like symptoms, leukopenia, and thrombocytopenia. Of the remaining 677, five developed diabetes mellitus, 12 had hyperthyroidism, and six acquired hypothyroidism. Of the 18 with thyroid disorders, five demonstrated antimicrosomal antibodies before therapy. Forty-four patients revealed high or low concentrations of thyroid stimulating hormone at the end of alpha interferon therapy. Three patients developed interstitial pneumonia, one acquired systemic lupus erythematosus-like syndrome, two had autoimmune hepatitis, two developed rheumatoid arthritis, and one developed autoimmune thrombocytopenic purpura. No patients had a history of an autoimmune disorder. One patient experienced sudden hearing impairment and one had retinal detachment. Melena was seen in three patients; two of these cases were compatible with ischemic colitis. Symptoms of depression were seen in 23 patients, and one patient manifested memory loss. CONCLUSION: High-dose alpha interferon therapy induces various adverse effects. Most of the side effects cannot be predicted, but are reversible.

Adult↗

PubMed1996

New approach for the treatment of medulloblastoma by transfection with glial fibrillary acidic protein gene.

Glial fibrillary acidic protein (GFAP) is one of the intermediate filaments found in mature normal astrocytes and differentiated glioma cells. It seems to be able to stabilize the cytoskeleton of the astrocyte and may play a role in maintaining astrocyte cell shape, in association with other cytoskeletal components such as microfilaments and microtubles. However, its tissue-specificity remains unclear. To clarify the effect of GFAP expression in brain tumour cells, transfer of the GFAP gene into the human medulloblastoma cell line, DAOY-1 (which does not express GFAP) was carried out using liposomes. Upon transfection, we observed the alterations in the characteristics of GFAP transfected cells. Cell growth, morphology and sensitivity to anticancer drugs were compared between GFAP gene transfected DAOY-1 and control DAOY-1 cells. Growth inhibition and increase of sensitivity to anticancer drugs were observed with GFAP expression in GFAP gene-transfected DAOY-1 cells. However, no morphological changes were noted.

Brain Neoplasms↗

PubMed1996

Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC).

The third component of complement (C3) is central to both the classical and alternative pathways in complement activation. In this study, involvement of C3 activation in the mucosal injury of UC was investigated. We examined the distribution of activated (C3b) and degraded fragments (iC3b/C3dg) of C3, terminal complement complex (TCC), and complement regulatory proteins in normal and diseased colonic mucosa including UC and other types of colitis using immunohistochemical techniques at the level of light and electron microscopy. While C3b and iC3b/C3dg staining was negligible in the normal mucosa, iC3b/C3dg and, to a lesser extent, C3b were deposited in UC mucosa along the epithelial basement membrane. The deposition was enhanced in relation to the severity of mucosal inflammation (C3b, P less than 0.05; iC3b/C3dg, P less than 0.01). Epithelial deposition of TCC was not observed in most UC mucosa. Immunoelectron microscopy showed that C3b and iC3b/C3dg were distributed mainly along the epithelial basement membrane and the underlying connective tissue in a granular, studded manner, and weakly present along the basolateral surface of epithelial cells. These C3 fragments were also deposited in inflammatory control mucosa such as ischaemic and infectious colitis. Our findings suggest that deposition of the C3 fragments occurs in inflamed colonic mucosa of diverse etiologies, including UC, but to define a role of the deposition in the development of mucosal injury in UC awaits direct study.

Adult↗

PubMed1996

Auditory findings after stereotactic radiosurgery in acoustic neurinoma.

Auditory function after gamma knife stereotactic radiosurgery (GK) was evaluated in 22 patients with newly diagnosed unilateral acoustic neurinoma who had had some measurable hearing preoperatively. No tumor growth was observed in any patients. The preservation rates for useful hearing (n = 13) and any measurable hearing (n = 22) were 62% and 86%, respectively, at 2 years after GK. Postoperative hearing dysfunction was attributed to progressive cochlear impairment in 13 patients and to progressive injury in the retrocochlear auditory pathway in 5 patients. Hearing tended to be well preserved when caloric response was unchanged postoperatively. Preservation of hearing was not associated with the initial tumor volume, decrease of tumor size, maximum tumor dose, or peripheral tumor dose.

Journal Article↗

PubMed1996

Gingko biloba extract EGb 761 is a suppresser of AP-1 transcription factor stimulated by phorbol 12-myristate 13-acetate.

Transcription factors are activated in response to a wide variety of extracellular stimuli. The present study investigated which step Gingko biloba extract (EGb 761), a flavonoid phytochemical rich preparation can affect signal transduction during AP-1 activation. Kinetic experiments with human Jurkat T-cell lines demonstrate that it takes 1 to 1.5 h to activate AP-1 DNA binding activity. These data indicate that c-fos mRNA is expressed and then AP-1 DNA binding activity is activated. Pretreatment of Jurkat T cells with 10 micrograms/ml EGb 761 suppresses AP-1 DNA activation and c-fos mRNA expression. These results suggest that the step in the signal transduction pathway for AP-1 activation that is inhibited by EGb 761 is upstream to c-fos mRNA expression.

Carcinogens↗

PubMed1996

Time-dependent expression of bone sialoprotein fragments in osteogenesis induced by bone morphogenetic protein.

Bone sialoprotein is unique to bone and dentin, but its precise role in these tissues is still unknown, although several hypotheses have been presented. We chose ectopic chondro- and osteogenesis induced by bone morphogenetic protein (BMP) as a model system to examine the role of this protein. Partially purified bovine BMP obtained by a three-step chromatographic procedure contained all the active BMPs (natural BMP cocktail). It was combined with insoluble bone matrix and subcutaneously implanted into rats. Expression of bone sialoprotein (BSP) in the implants was followed by using a monoclonal antibody as previously reported. Immunostaining studies showed BSP in the osteoblasts lining the new bone surface at 5 weeks. Western blotting showed 53 and 30 kDa bands, instead of the 57 kDa band normally found in rat femur. These two fragments were metabolically labeled with [3H]proline. The total amount of the fragments rapidly increased after 3 weeks, and at 5 weeks was 3 times as high as that at 2 weeks and still increasing. This time-dependent change was almost parallel to that of osteocalcin. The amount of bone estimated in terms of calcium content increased until 3 weeks and was remained at a plateau thereafter. Alkaline phosphatase activity was prominent only in the first 3 weeks. It was concluded that the 53 and 30 kDa BSP fragments might contribute to maintenance or remodeling in BMP-induced ectopic bone formation.

Aging↗

PubMed1996

Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the Bacillus subtilis genome containing the skin element and many sporulation genes.

As part of the Bacillus subtilis genome sequencing project, we have determined a 283 kb contiguous sequence from 210 degrees to 232 degrees of the B. subtilis genome. This region contains the 48 kb skin element which is excised during sporulation by a site-specific recombinase. In this region, 310 complete ORFs and one tRNA gene were identified: 66 ORFs have been sequenced and characterized previously by other workers, e.g. acc, ans, bfm, blt, bmr, comE, comG, dnaK, rpoD and sin operons; cwiA, gpr and lysA genes; many sporulation genes and operons, spo0A, spoIIA, spoIIM, spoiiP, spoIIIA, spoIIIC, spoIVB, spoIVCA, spoIVCB and spoVA, etc. The products of 84 ORFs were found to display significant similarity to proteins with known function in data banks, e.g., proteins involved in nucleotide metabolism, lipid biosynthesis, amino acid transport (ABC transporter), phosphate-specific transport, the glycine cleavage system, the two-component regulatory system, cell wall autolysis, ferric uptake and sporulation. However, the functions of more than half of the ORFs (52%, 160 ORFs) are still unknown. In the skin element containing 60 ORFs, 32 ORFs (53%) encode proteins which have significant homology to gene products of the B. subtilis temperate phage phi 105 and/or the defective phage PBSX.

Bacillus subtilis↗

PubMed1996

A Bacillus subtilis gene cluster similar to the Escherichia coli phosphate-specific transport (pst) operon: evidence for a tandemly arranged pstB gene.

We have determined the complete nucleotide sequence of the Bacillus subtilis homologues of the Escherichia coli phosphate-specific transport (pst) genes in the framework of the international B. subtilis genome sequencing project. The pst genes in E. coli form an operon arranged in the order pstS, pstC, pstA, pstB and phoU. In the case of B. subtilis, there are also five ORFs presumably forming an operon. The deduced amino acid sequences of the products of these ORFs show striking similarities to their E. coli counterparts. Comparison of the organization of the pst operon of B. subtilis with that of E. coli revealed that the gene corresponding to phoU is missing, while there are two genes homologous to pstB in B. subtilis. The pst operon is located at 222 degrees on the B. subtilis chromosome.

Amino Acid Sequence↗

PubMed1996

Tumor necrosis factor-alpha gene transfer augments anti-Fas antibody-mediated apoptosis in human glioma cells.

To effectively induce apoptosis in human glioma cells, we tried to transfer the tumor necrosis factor (TNF)-alpha gene into glioma cells to produce TNF-alpha locally in these cells. The stable transfectants of three glioma cells (U251-SP, U251-MG, and T98G) were resistant to exogenous TNF-alpha, but their cell surface expression of the Fas antigen was dramatically enhanced by about 10 to 100-fold as compared with untransfected glioma cells exposed to exogenous TNF-alpha. The Fas antigen is a transmembrane cytokine receptor protein of the nerve growth factor/TNF receptor superfamily. Although the untransfected glioma cells tested were resistant to anti-Fas antibody-mediated apoptosis, the TNF-alpha gene-transfected glioma cells exhibited high susceptibility to anti-Fas antibody-mediated apoptosis. Thus, TNF-alpha gene transfer combined with anti-Fas antibodies may be useful for the treatment of malignant glioma.

Antibodies↗

PubMed1996

Epithelial cell proliferation during colonic chemical carcinogenesis in the rat.

To define the significance of alterations in epithelial cell proliferation as a marker of high risk mucosa for colorectal cancer, we examined cell proliferative events in the colonic mucosa during chemical carcinogenesis using in vitro bromodeoxyuridine labelling and by analysing serial colonoscopic biopsy specimens from dimethylhydrazine (DMH)-treated rats. In both the rectum and flexure of the colon, an increased labelling index of colonic epithelial cells, an upward extension of the proliferating zone and an upward shift of the major area of DNA synthesis of epithelial cells were observed during DMH-induced colonic carcinogenesis in rats. These changes preceded the development of the colonic tumour and were observed in endoscopically normal rectal mucosa where the tumour was absent. We confirmed the altered cell proliferative events preceding the development of the tumour by examining serial colonoscopic biopsies. The results suggest that these alterations are features that identify premalignant colonic mucosa in DMH-treated rats.

Animals↗