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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 361 records · Page 20Linked to original sources

Immunogenicity and reactogenicity of the component acellular pertussis vaccine produced by a combination of column purified pertussis toxin and filamentous haemagglutinin.

This is the report on a prospective, single blind, comparative study of a component acellular pertussis vaccine produced by a combination of detoxified, column purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) combined with diphtheria and tetanus toxoids (DTcaP) and the traditional acellular pertussis vaccine produced with essentially the same method as described by Sato with DT (DTaP) of the same manufacturer. A total of 616 infants and children received DTcaP and a total of 289 received DTaP. In all age groups for both vaccines values of serum antibodies to PT and FHA after two doses of the vaccines were comparable to those of convalescent sera. Incidences of systemic and local reactions were, in general, not greatly different between DTcaP and DTaP recipients. In Japan the use of traditional acellular vaccines replaced whole cell vaccines in 1981. Protective antigens of Bordetella pertussis have now been specified and thus component vaccines have become theoretically possible. This is the first component vaccine which has been developed in Japan. Several other component vaccines are now under investigation in the world.

Antibodies, Bacterial↗

Interleukin-2 therapy of Langerhans cell histiocytosis.

A 20-month-old girl was diagnosed with Langerhans cell histiocytosis on the basis of a seborrheic skin rash, multiple punched out bony lesions, and skin biopsy findings. Combination therapy including alpha-interferon, vincristine, vindesine, cyclophosphamide, etoposide, cisplatin, betamethasone, THP-adriamycin, cytarabine and methotrexate was ineffective. Because cyclophosphamide enhanced lesion growth within the skull, we administered an intravenous infusion of interleukin-2 with remarkable efficacy. The reduction in lesion size with interleukin-2 treatment paralleled the increase in the percentage of CD16-positive natural killer cells in the peripheral blood.

Antineoplastic Combined Chemotherapy Protocols↗

New variant of congenital dyserythropoietic anemia with trilineage myelodysplasia.

We report the case of a male infant with a variant of congenital dyserythropoietic anemia (CDA), who developed severe hyperbilirubinemia on the day of birth, subsequent severe anemia, and hyperferritinemia. Bone marrow and laboratory examinations revealed features of CDA including trilineage myelodysplasia and erythroblasts with a binucleated nuclear morphology and ineffective erythropoiesis. The CDA in this patient was assumed to be a new variant type because of: the lack of internuclear chromatin bridges in the erythroblasts with abnormal nuclear morphology; a negative acid serum test; the presence of erythrocyte antigen I, and the effect of splenectomy. Trilineage myelodysplasia in CDA is not known. An abnormality in the stem cells was suggested to be the cause of CDA in this case.

Anemia, Neonatal↗

Primary intracranial epithelioid angiosarcoma--case report.

A 39-year-old male presented with an exceedingly rare primary intracranial epithelioid angiosarcoma in the right parietal lobe manifesting as weakness of the left hand. Neuroimaging revealed a well-defined intensely enhanced lesion in the right parietal lobe with peripheral cerebral edema. The tumor was grossly totally removed. Light microscopy of the surgical specimens revealed features typical of an epithelioid vascular tumor. The tumor cells showed intense positive immunohistochemical staining for cytokeratin and vimentin and focally positive staining for both Ulex europaeus agglutinin and anti-human endothelial cells, CD31. Tumor regrowth required two further operations. This progressive growth was consistent with an angiosarcoma. The tumor was diagnosed as an epithelioid angiosarcoma based on the histological and clinical characteristics. He became progressively obtunded and finally died. This is the first intracranial epithelioid angiosarcoma which expressed epithelial markers detectable by immunohistochemical methods.

Adult↗

[Surgical treatment of metastatic lung tumor from colorectal cancer].

We have experienced thirty-one operations of metastatic lung tumors from colorectal cancer. Various factors affecting prognosis are studied based on 5-year survival in this report. Overall 5-year survival rate was 32%. Statistical significance was present in the relationship between the prognosis and both maximum diameter of lesions and the disease free intervals (DFI) after surgery for metastatic lesions. Though not significant, sex, stage of primary lesion, nodal involvement, surgical procedure, postoperative serum CEA were likely affecting factors on the prognosis. In contrast, there were no relationship between the prognosis and following factors: age, location of the metastatic lesion, DFI after the operation for primary lesion and chemotherapy. Although pulmonary metastasis is essentially an index of the advanced state of malignant diseases leading to poor prognosis, long-term survivors were encountered in our series of surgical treatments for pulmonary metastases from colorectal cancers. It was concluded to be important to make efforts to extend the indication for surgical treatment, since the appropriate selection of patients revealed to give excellent results from our experience of colorectal cancer. In order to improve the prognosis, early detection of pulmonary metastases is quite important, since the incidence of nodal involvement proved to be higher in lesions with larger diameter resulting in inferior survivals from the present study. In addition, low incidence of nodal involvement in small-sized lesion may support possible applicability of thoracoscopic surgery in the excision of metastatic tumors locating at peripheral lesion.

Adult↗

Different features of Ca2+ oscillations in differentiated and undifferentiated hepatocyte doublets.

Cytosolic free Ca2+ ([Ca2+]i) oscillations are postulated to play a critical role in cellular proliferation. By using doublets of normal rats (NR) and those 18 hours after two-thirds hepatectomy (PHR), we investigated cytosolic free Ca2+ ([Ca2+]i) responses in liver regeneration. Normal rat hepatocyte doublets that retain their bile canaliculi are polarized and well differentiated. PHR doublets, which also retain their bile canaliculi, were characterized as undifferentiated by (1) decreased canalicular secretion of fluorescein-isothiocyanate-labeled glycocholate; (2) increased labeling index of hepatocytes in BrdU staining (approximately 30%); and (3) impaired transfer of fluorescent dye injected into one cell of the pair to the other. Addition of phenylephrine to NR and PHR doublets in the presence of extracellular Ca2+ resulted in [Ca2+]i oscillations or a nonoscillatory-sustained increase in [Ca2+]i followed by a gradual return to the baseline. Extracellular Ca2+ was not required for [Ca2+]i oscillations but was necessary for a sustained increase in [Ca2+]i. Simultaneous addition of prazosin, alpha 1-receptor blocker, to doublets immediately abolished these [Ca2+]i responses. The [Ca2+]i level in each of the adjacent cells was synchronous in sustained increase in [Ca2+]i but asynchronous in [Ca2+]i oscillations. As the phenylephrine concentration was increased (1 to 100 mumol/L), oscillations were replaced by a sustained increase in [Ca2+]i in NR doublets. In contrast, in PHR doublets, oscillations remained, whereas the frequency of oscillations increased in a dose-dependent manner. These results indicate that the mechanisms of phenylephrine-evoked [Ca2+]i responses are different in differentiated and undifferentiated doublets and that the frequency modulation of [Ca2+]i oscillations may be involved in the intracellular signal transduction in the cellular proliferation process during liver regeneration.

Adrenergic alpha-Antagonists↗

[Clinical usefulness of urinary anti HIV antibody test--a large scale study from 11 institutes in Japan].

An enzyme immuno assay kit has been developed to detect anti-HIV antibody in urine. In order to examine the clinical utility of the kit, 1333 urine samples were assayed. These samples consisted of 233 urine samples from HIV infected patients, 472 samples from HIV uninfected patients including 203 samples from patients with urogenital diseases, and 628 samples from normal subjects. Anti-HIV antibodies were detected in all the urine samples from HIV infected patients, and the diagnostic sensitivity for HIV infection was 100% with no false negative cases. A variety of anti-HIV antibody titers were found in the urine samples from HIV infected patients. However, no significant differences were found in the distribution patterns of urinary anti-HIV antibody titers among AC, ARC and AIDS patients. False positives were determined in only five samples in 628 healthy subjects (0.8%), one in 19 patients with hepatitis (5.3%), one in 45 patients with hemophilia (2.2%) and two in 105 pregnant women (1.9%). The antibody titers of all the false positive samples in these groups were less than the cut-off index multiplied by two. However, relatively high positive rates were demonstrated in the samples from urogenital diseases (11.8%), diabetes mellitus (20.0%) and auto-immune diseases (7.3%). False positive results were found to be directly correlated to the protein concentration of urinary protein, especially the immunoglobulin concentration in urine. The assay system was also evaluated by various reproducibility tests performed by different operators at different laboratories. The test results were satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

[Basic evaluation of nitric oxide inhalation therapy].

We studied the site of action of nitric oxide (NO) and the dose-response relationship between inhaled NO and PaO2. We also measured nitrosyl-hemoglobin (Hb-NO) levels in arterial and mixed venous blood and NO2 levels in our NO inhalation system to confirm the safety of NO inhalation. In an ovine model of ARDS induced by lung lavage, pressure-flow plots indicated that the site of action of inhaled NO was close to the alveoli. During hypoxia, pulmonary artery pressure decreased as the concentration of inhaled NO increased; PaO2 peaked at 10-20 ppm NO. The levels of Hb-NO in arterial and mixed venous blood during inhalation of 40-60 ppm NO under hypoxic conditions were greater than the levels under normoxic conditions, but Hb-NO still accounted for less than 0.1% of the total Hb. Less than 0.1 ppm on NO2 was generated during inhalation of 5 ppm NO. In conclusion, inhaled NO can dilate pulmonary vessels near alveoli without lowering the O2 carrying capacity of blood. In the present system, only a negligible amount of NO2 was produced.

Administration, Inhalation↗

A new model to study repair of gastric mucosa using primary cultured rabbit gastric epithelial cells.

The process of wound repair was investigated using primary cultured rabbit gastric mucosal cells. A confluent monolayer gastric mucosal cell sheet consisting mainly of mucous cells was wounded to make a cell-free area of constant size. The changes in the cell-free area were analyzed quantitatively by image analysis. The wound recovered in 36-48 h in controls; wound repair was accelerated by the addition of fetal calf serum (FCS) and hepatocyte growth factor (HGF) to the medium and was retarded by inhibitors of cytoskeletal proteins. In the process of normal wound repair, 5-bromodeoxyuridine (BrdU)-positive cells appeared around the wound in 24-36 h but disappeared after complete repair. In the FCS- and HGF-treated group, BrdU-positive cells were mainly detected 12-24 h after wounding. In this model the wound was repaired in two steps: an initial cell migration stage and a later proliferation stage. In conclusion, FCS and some growth factors accelerate wound repair with the induction of both epithelial cell migration and proliferation. The cytoskeletal system plays an important role in normal gastric restoration.

Animals↗

Enhancement of rat liver cell foci development by combined treatment with heterocyclic amines at low doses.

Potential synergism between 5 or 10 carcinogenic heterocyclic amines (Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, IQ, MeIQ, MeIQx, MeA alpha C, A alpha C and PhIP) acting at low doses was examined in a medium-term liver bioassay system for carcinogens. Immunohistochemically-demonstrated glutathione S-transferase placental form (GST-P) positive foci were assessed as the endpoint marker lesions. Male F344 rats were initially given diethylnitrosamine (DEN, 200mg/kg, ip) and beginning 2 weeks later received heterocyclic amines individually or in combination for 6 weeks. All animals were subjected to partial hepatectomy at week 3 and killed at week 8. A clear dose response relationship was observed for all heterocyclic amines, except for the nonhepatocarcinogen PhIP, with the dose used in earlier carcinogenicity assays and 1/5, 1/10, 1/25 and 1/100 of these levels. Carcinogenicity could be predicted for all compounds at the highest dose or lower dose levels except for PhIP. With combined administration of 5 or 10 chemicals, foci induction significantly exceeded the sums of 5 or 10 individual data for the 1/5, 1/10 and 1/25 dose levels, but not for the 1/100 case. The findings are of particular significance since several heterocyclic amines and other carcinogenic agents might be simultaneously generated during cooking, although each at very low concentration.

Amines↗

Multiple effects of haemin binding on protease susceptibility of bovine serum albumin and a novel isolation procedure for its large fragment.

The effects of ligand binding on the proteolytic susceptibility of BSA were investigated. The rate for proteolytic digestion with either trypsin or chymotrypsin decreased in the presence of bilirubin and fatty acids, suggesting that overall albumin conformation is stabilized by these ligands. In contrast, haemin showed multiple effects on a proteolytic digestion pattern: the rate for the degradation of intact albumin greatly increased, but a large 45 kDa fragment accumulated during proteolytic digestion in the presence of this ligand. This unique fragmentation pattern allowed us to isolate the 45 kDa fragment at a high yield (about 30% on a molar basis) by one-step purification. Sequence analyses indicated that this fragment lies between residues Thr190 and Ala583, which constitutes domains II and III of the albumin molecule. Far-u.v. c.d. spectra strongly suggested that the secondary structure in the intact albumin is almost retained in the 45 kDa fragment. The isolated 45 kDa fragment showed haemin-binding ability, as evaluated by spectroscopic titration; upon re-digestion of the 45 kDa fragment, haemin showed strong protective effects. These results were consistent with the idea that haemin binding to BSA induces an increased protease susceptibility in the loop region between domains I and II, but in the overall conformation of domains II and III, a protease-resistant property.

Animals↗

Denatured state of ovalbumin in high concentrations of urea as evaluated by disulfide rearrangement analysis.

To investigate the highly denatured state of ovalbumin (molecular mass of 42.7 kDa, four cysteine sulfhydryls and one cystine disulfide) using the disulfide rearrangement approach, we established the peptide-mapping procedure using a cysteine-labeling technique with a fluorescent dye that allows the quantitative analyses for the disulfide-involved half-cystines. Ovalbumin denatured at a low protein concentration in 8-10 M urea, in which the protein showed complete unfolding as evaluated by far-UV CD spectra, was analyzed for the disulfide-involved half-cystines using the peptide-mapping procedure. Data clearly showed that the number of free sulfhydryls and intrachain disulfides were four and one, respectively, but that all six half-cystines are labeled with the dye. These results strongly suggested that 15 disulfide isomers that are theoretically possible for a molecule having one disulfide and four sulfhydryls are all generated during the denaturation. The quantitative data for the ratios of the observed labeling values for the six half-cystines, relative to the overall labeling values, were consistent with the view that the distribution of the 15 possible disulfide isomers at equilibrium depends on the number of amino acid residues separating the two half-cystines to the power of -1.9 to -2.0. Essentially, the same non-gaussian chain nature was also observed with kinetic data for sulfhydryl-disulfide exchanges after denaturation of native ovalbumin.

Amino Acid Sequence↗

Inhibition of mammary gland carcinogenesis by green tea catechins and other naturally occurring antioxidants in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz[alpha]anthracene.

Effects of the naturally occurring antioxidants on mammary gland carcinogenesis were examined in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz[alpha]anthracene (DMBA). Groups of 15-16 7-week-old rats received a 50 mg/kg body weight intra-gastric dose of DMBA, and starting one week thereafter placed on diet containing 0.4% catechol, 1.0% gamma-oryzanol, 2.0% phytic acid, 1.0% green tea catechins (GTC), 1.0% tannic acid or basal diet alone for 35 weeks. Although the final incidences and multiplicities of mammary tumors were not significantly different between DMBA-treated groups, the numbers of survivors in the antioxidant-treated groups at the end of the experiment at week 36 were significantly higher than in the basal diet group. In particular, the survival rate of the GTC group at 93.8% strongly contrasted with that of only 33.3% for rats on the basal diet. At the end of week 18, when all the animals were still alive, the average size of palpable mammary tumors was significantly smaller in the catechol, phytic acid and catechins groups. These results indicate that antioxidants, and GTC in particular, inhibit rat mammary gland carcinogenesis after DMBA initiation.

9,10-Dimethyl-1,2-benzanthracene↗

Role of extracellular matrix in wound repair by cultured gastric mucosal cells.

Effects of extracellular matrix on wound repair of cultured gastric epithelial cells were assessed. Artificial wounds were made by mechanical cell denudation in confluent rabbit gastric epithelial cell sheets which were formed on different types of extracellular matrix (e.g., collagen type I and type IV, laminin, fibronectin and Matrigel). Changes in wound size were analyzed quantitatively. Cell migration and proliferation were observed in stages of the wound repair process. The speed of wound repair was different with each extracellular matrix studied and was fastest on Matrigel. The type of extracellular matrix used in this study modulated both cell migration and proliferation. Therefore, it is concluded that extracellular matrix plays an important role in rates of gastric mucosal wound healing.

Animals↗

Hepatocyte growth factor accelerates the wound repair of cultured gastric mucosal cells.

Effects of hepatocyte growth factor (HGF) on gastric wound repair were assessed. Artificial wounds of uniform size were made by mechanical cell denudation in confluent rabbit gastric mucosal cell sheets. The changes in wound size were analyzed quantitatively. The wound repair process contained an initial migration stage and a later proliferation stage. The wound was completely repaired in 36 h in controls; this repair was accelerated by HGF with the induction of cell migration followed by proliferation and was retarded by tyrosine protein kinase inhibitor genistein. HGF might play some roles in gastric ulcer healing.

Animals↗

Effect of myosin light chain kinase inhibitor wortmannin on the wound repair of cultured gastric mucosal cells.

The effects of myosin light chain kinase inhibitor wortmannin on wound restoration were investigated using a culture cell model. Rabbit gastric mucosal cells formed confluent monolayer cell sheets within 48h. Cell sheets were wounded to create wounds of uniform size. The restoration was monitored by a time-lapse video disc recorder and was analyzed. The wound was completely restored with early cell migration and late proliferation in controls. Wortmannin inhibited cell migration, thus inhibiting proliferation. Results indicate that the cytoskeleton plays a key role in the restoration of gastric mucosa.

Androstadienes↗

Crucial role of intralobe peptide-peptide interactions in the uptake and release of iron by ovotransferrin.

The mechanism for reversible iron binding in the N-terminal lobe of ovotransferrin was investigated by a protein fragmentation approach. The iron-saturated N-terminal half-molecule of ovotransferrin was proteolyzed into large 30-kDa (1-279) and small 6-kDa (280-332) fragments by a single cleavage with Achromobacter protease I, producing a stable nicked form. For the separation of the two fragments, denaturing conditions were required. The isolated large fragment contained all four iron-coordinating ligands and the anion-binding ligand, and according to spectroscopic titration analysis, it showed iron binding capacity. The iron-bound large fragment, however, showed a blue-shifted visible absorption spectrum and a much decreased iron stability compared with those of the intact half-molecule. Analyses by ion-exchange chromatography revealed that the large fragment reassociates with the small fragment. In order for reassociation to occur, iron must be bound to the large fragment; upon reassociation, the large fragment regained its stable iron binding capacity as well as a visible absorption spectrum almost indistinguishable from those of the intact half-molecule. These data are consistent with a two-step sequential pathway for reversible iron binding in the N-terminal lobe of ovotransferrin that includes an initial iron binding intermediate having a perturbed metal environment and its transformation into the stable iron-bound holoform by peptide-peptide interactions between the large coordinating and small noncoordinating segments.

Alcaligenes↗