Biomedical subjects

H Hojo

Publications and source records attributed to H Hojo.

At least 55 records · Page 3Linked to original sources

PubMed1996

Differential production of interleukin-6 and its close relation to liver metastasis in clones from murine P815 mastocytoma.

Interleukin-6 (IL-6)-producing abilities of plastic-adherent and plastic-non-adherent P815 clones were investigated in connection with the liver metastasis. Most adherent clones produced IL-6 at high level (over 10 ng/10(5) cells per 48 h), and they coincided with highly liver-metastatic clones. The remaining adherent and all the non-adherent clones tested produced IL-6 at low level (under 1.5 ng/10(5) cells), and they coincided with the low or non-liver-metastatic clones. The IL-6 production was greatly enhanced by IL-1 alpha, but not by IL-6, tumor necrosis factor-alpha or interferon-gamma.

Animals↗

PubMed1996

Synergistic induction of metallothionein synthesis by interleukin-6, dexamethasone and zinc in the rat.

We investigated the reciprocal effects of interleukin-6 (IL-6), glucocorticoid and zinc (Zn) on metallothionein (MT) synthesis in rats. MT synthesis in the liver, which is a key responsible organ in acute phase responses, was induced by IL-6 or dexamethasone (Dex), and in an additive manner by a combination of IL-6 and Dex 18 h after injection. MT synthesis in the lung and heart was evaluated by immunoassay using a specific antibody to MT-1, because of its low concentration in these tissues. Heart concentrations of MT-1 were significantly increased by IL-6, and were further increased by the combination of IL-6 and Dex, although Dex by itself had no effect. This suggests a synergistic effect of IL-6 and Dex on MT-I synthesis in the heart. A similar synergism was observed in the lung. To study the effect of Zn on the induction of MT and acute phase proteins, Zn, IL-6 and Dex were administered in various concentrations. The increase in liver MT induced by the combination of IL-6 and Dex with Zn (130 micrograms MT/g of liver) was greater than the sum of the increases induced by (IL-6 + Zn) and by (Dex + Zn) (103 micrograms MT/g), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 and Dex depends on an adequate liver Zn content. Thus, the in vivo synergistic induction of acute phase proteins by IL-6, glucocorticoid and Zn may be required for the maximal and rapid response, not only in liver but also in other tissues including heart and lung. This suggests that the synergistic reaction may be important for an enhancement of the radical scavenging ability of tissues in acute phase responses.

Animals↗

PubMed1996

The relationship between the gene mutation of p53 and the protein expression of p53 and Ki-67 in non-Hodgkin's lymphomas.

The relationship between the mutation of the p53 gene and the expression of the p53 protein and the Ki-67 antigen has been investigated in 115 cases with non-Hodgkin's lymphoma, using the immunohistochemical double staining technique, single-strand conformational polymorphism and DNA sequencing methods. Eighteen cases showed more than 10% of p53+ cells and the others showed a few p53+ cells presented sporadically. Alterations in the p53 gene were detected in six cases with B cell type, consisting of five cases with point mutation and one case with point mutation and 15 base pairs deletion. These six cases showed a high percentage of p53+ cells and five cases revealed that the percentage of p53+ cells was higher than that of Ki-67+ cells (p53+ cells > Ki-67+ cells). Excluding the six cases with mutation of the p53 gene, all cases revealed that the percentage of p53+ cells was less than that of Ki-67+ cells (p53+ cells < Ki-67+ cells). Moreover, there was a positive correlation between expression of the p53 protein and of the Ki-67 antigen in histologic types of B cell lymphomas and of T cell lymphomas, respectively, except in small non-cleaved (Burkitt's) and lymphoblastic types. Therefore, sporadic cases showing p53+ cells > Ki-67+ cells revealed alteration of the p53 gene, and expressed abnormal p53 protein (mutant form). Most cases showing p53+ cells < Ki-67+ cells expressed normal p53 protein (wild type), and may reflect the rapid proliferation rate.

Base Sequence↗

PubMed1996

Expression of classical protein kinase C subspecies in non-neoplastic lymphocytes and non-Hodgkin's lymphomas: an immunohistochemical study.

It is generally accepted that phosphorylation plays a pivotal role in the cellular response of cell differentiation and proliferation. Immunohistochemical expression of classical protein kinase C (cPKC) subspecies (alpha, beta and gamma) in eight reactive lymphoid tissues, three normal spleens and 149 non-Hodgkin's lymphomas was examined. cPKC beta was observed primarily in the mantle zone B cells, but appeared as very faint staining in Ki-67 positive proliferated B cells in the germinal centers of secondary lymph follicles. In contrast to the reactive state, high levels of cPKC subspecies were recognized in the majority of 149 cases of non-Hodgkin's lymphoma, including those thought to have arisen from germinal center cells such as follicular lymphoma. The expression of cPKC alpha was found in higher frequency in T cell lymphomas than B cell lymphomas (P < 0.01) by the Chi-squared test. High levels of cPKC alpha were present only in high grade or highly aggressive lymphomas, showing the highest incidence in the small non-cleaved cell type, according to the International Working Formulation and National Cancer Institute (P < 0.01). cPKC gamma was not detected in normal lymphoid cells and was expressed in only four cases of non-Hodgkin's lymphomas. It is presumed that cPKC alpha and beta have a relationship to cell activation and proliferation of lymphoid cells of reactive and neoplastic states. It might be considered that the expression of cPKC alpha may have a relationship with aggressiveness in non-Hodgkin's lymphomas.

B-Lymphocytes↗

PubMed1996

The culture fluid of Isaira japonica yasuda augments anti-sheep red blood cell antibody response in mice.

Isaria japonica YASUDA was cultured in a liquid medium, and its culture fluid (IJCE) was tested for stimulatory activity to humoral antibody production. IJCE significantly enhanced the production of anti-sheep red blood cell (SRBC) plaque forming cells (PFC) by oral ingestions at 10 and 30 mg/kg/d for 4 consecutive days, either before or after SRBC challenge. It also recovered the reduction of anti-SRBC PFC response and number of spleen cells caused by treatment with 5-fluorouracil. It is suggested that IJCE is a promising source for an immunomodulating tool or medicine.

Adjuvants, Immunologic↗

PubMed1996

The relationship between adherence and liver metastatic ability in murine mastocytoma cell line.

P815 murine mastocytoma cells were separated to plastic-adherent and -nonadherent cell populations by repetitive in vitro selections. Their abilities of experimental and spontaneous metastases were investigated in the syngeneic DBA/2 mice. While the plastic-adherent populations were found to be liver-metastatic, the plastic-nonadherent populations were liver-nonmetastatic. The inability of plastic-nonadherent P815 cells to metastasize to the liver did not mean that these cells were not tumorigeneic because they could metastasize to tissues and/or organs other than the liver. Hence it could be looked as inability for liver specific metastasis resulted from, or related to, the loss of plastic adhesiveness. By limiting dilution of plastic-adherent and -nonadherent P815 cells, two series of well comparable P815 clones were established: (1) plastic-adherent, liver-metastatic clone and (2) plastic-nonadherent, liver-nonmetastatic one. Since these two series of P815 clone are originated from a common parent line, they might be valuable in the study of the molecular mechanisms of liver specific metastasis and of the relations between liver metastasis and cell adhesiveness.

Animals↗

PubMed1996

Effects of anti-intercellular adhesion molecule-1 and anti-lymphocyte-function-associated antigen-1 monoclonal antibodies on the metastasis of murine tumors.

Anti-intercellular adhesion molecule-1 (anti-ICAM-1) and anti-lymphocyte-function-associated antigen-1 (anti-LFA-1) monoclonal antibodies (mAbs) were injected into mice and their effects on tumor metastasis were investigated using two murine models. Depending on the dose, the anti-ICAM-1 mAb (KAT-1) expressed both inhibitory and promoting effects on liver metastases of ICAM-1 + LFA-1 + P815 mastocytoma cells, whereas it enhanced lung metastases of the ICAM-1-LFA-1-Meth-A fibrosarcoma cells at any doses. In contrast, anti-LFA-1 mAb (KBA) showed promoting effects only on the metastases of both tumor lines. Treatment of mice with either mAb enhanced metastases of P815 mastocytoma cells in the spleen.

Animals↗

PubMed1995

Antioxidative roles of metallothionein and manganese superoxide dismutase induced by tumor necrosis factor-alpha and interleukin-6.

Antioxidative roles of metallothionein (MT) and manganese superoxide dismutase (Mn-SOD) induced by tumor necrosis factor (TNF) and interleukin 6 (IL-6) have been studied. Since pretreatment of rat with dexamethasone, an inhibitor of cytokine production, prevented MT synthesis induced by paraquat which is a typical superoxide generator, MT synthesis by oxidative stress may be, at least partly, mediated through cytokines. Pretreatment of rat with TNF or IL-6 prevented liver damage and lipid peroxidation caused by carbon tetrachloride. Administration of TNF increased activity of mitochondrial Mn-SOD and concentrations of cytoplasmic MT, but not activities of glutathione peroxidases and Cu,Zn-SOD in the liver. The increment of the Mn-SOD activity and MT was due to the de novo protein synthesis, because gene expression of mRNAs of Mn-SOD and MT in the liver was also induced by TNF and IL-6. These data strongly suggest that MT and Mn-SOD in the liver cooperatively play antioxidative roles. Pretreatment with TNF, however, did not affect the increased levels of plasma fibrinogen and liver MT induced by the following paraquat treatment, although it did prevent lipid peroxidation in the liver. The data suggest that MT is not directly induced by oxygen free radicals. Cytokines may be released by paraquat in tissues other than the liver and induce hepatic synthesis of acute phase proteins including fibrinogen, MT, and Mn-SOD. MT and Mn-SOD induced by cytokines in the liver exert an antioxidative role during acute phase response, therefore preventing tissues from injury by oxidative stress.

Acute-Phase Proteins↗

PubMed1995

Molecular genetic analysis of a female patient with pyruvate dehydrogenase deficiency: detection of a new mutation and differential expression of mutant gene product in cultured cells.

A new 18 bp insertion mutation in the gene for the alpha subunit of pyruvate dehydrogenase (E1 alpha) was found in a female patient with congenital lactic acidaemia. Cultured skin fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cells from this patient showed decreased and normal pyruvate dehydrogenase complex (PDHC) activity, respectively. This 18 bp insertion was a de novo mutation, because it was not present in her parents. Although this female patient was heterozygous for the normal and the mutant alleles, 97% of cultured skin fibroblasts expressed the mutant allele, while 100% of cultured lymphoblastoid cells, 94% of peripheral blood lymphocytes and 98% of IL-2-activated T-cells expressed the normal allele. These results suggest that in this patient the X chromosome containing the normal allele was predominantly inactivated in fibroblasts and the X chromosome containing the mutant allele was predominantly inactivated in lymphocytes. The diagnosis of E1 alpha deficiency is usually established by measurement of PDHC activity and the level of immunoreactive proteins. However, these methods are not sufficient to diagnose the disorder in female patients with E1 alpha deficiency due to differential inactivation of the X chromosome. Therefore, it is necessary to develop a new method to firmly establish the diagnosis of E1 alpha deficiency.

Alleles↗

PubMed1995

Spindle cell carcinoma of the parotid gland.

Spindle cell carcinomas of the salivary gland are extremely rare, with only a few cases having been previously reported. We present a 55-year-old man with a rapidly enlarging mass in the left parotid gland. Despite radical surgery, the tumour recurred, and led to death 11 months later. Histopathologically, the tumour was composed of two components, a squamous cell carcinoma component and a spindle cell sarcomatoid component. A diagnosis of primary spindle cell carcinoma of the parotid gland was made. Immunohistochemical studies revealed keratin positivity and vimentin negativity in the squamous cell carcinoma component: the spindle cell sarcomatoid component was positive for vimentin and negative for keratin, but showed focal positivity for epithelial membrane antigen. The origin of the sarcomatoid component and the differential diagnosis from malignant mixed tumours are discussed.

Carcinoma, Squamous Cell↗

PubMed1995

Comparison of the free and DNA-complexed forms of the DNA-binding domain from c-Myb.

The DNA-binding domain of c-Myb consists of three imperfect tandem repeats (R1, R2 and R3). The three repeats have similar overall architectures, each containing a helix-turn-helix variation motif. The three conserved tryptophans in each repeat participate in forming a hydrophobic core. Comparison of the three repeat structures indicated that cavities are found in the hydrophobic core of R2, which is thermally unstable. On complexation with DNA, the orientations of R2 and R3 are fixed by tight binding and their conformations are slightly changed. No significant changes occur in the chemical shifts of R1 consistent with its loose interaction with DNA.

Amino Acid Sequence↗

PubMed1995

Pseudosarcomatous myofibroblastic tumor of the urinary bladder in children: a study of 11 cases with review of the literature. An Intergroup Rhabdomyosarcoma Study.

Pseudosarcomatous myofibroblastic tumor (PMT) is the result of reactive proliferation of myofibroblasts. In children, PMT of the urinary bladder can be mistaken for embryonal rhabdomyosarcoma clinically, radiologically, and by light microscopy. We are reporting the clinical, histological, and immunohistological features of 11 patients with childhood PMT of urinary bladder that were diagnosed initially as a sarcoma, usually rhabdomyosarcoma. The morphologic spectrum of PMT is broad, with mixtures of myxoid, leiomyomatous, and sclerosing matrix patterns, the myxoid type being the most common. The proliferating cells consist of three forms of myofibroblastic cells: long spindle cells (type I), intermediate spindle cells (type II), and ganglion-like cells (type III), together with various types of inflammatory cells. The immunohistologic profile of the proliferating cells was characterized by positive reactions to vimentin, muscle-specific actin, alpha-smooth-muscle actin, polyclonal desmin, and keratin. Ultrastructural studies showed myofibroblastic differentiation of the tumor cells. No patients have had metastases or local recurrence. Histologic, immunohistochemical, and clinical data from 71 cases of PMT, including the 11 cases in this report, confirm the benign behavior of these lesions. The etiology of these lesions is unclear, including the absence of surgical or other trauma in all of the children.

Adolescent↗

PubMed1995

Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5'-terminal regulatory region of the human gene for thymidylate synthase.

Triple tandemly repeated sequences and the corresponding complementary sequence are known to exist in the 5'-terminal regulatory region of the human gene for thymidylate synthase (TS). To examine the function of these sequences, a set of deletion mutants was prepared and used in a transient expression assay. The results showed that at least one repeated sequence and its complementary sequence were necessary for the efficient expression of the gene. As another approach to understanding the function of this unique structure, DNA polymorphism in the same region was analyzed. In addition to the TS gene with the triple tandem repeat, the TS gene with a double tandem repeat was found in genomes of normal human subjects at an estimated frequency of 19% when genomes of 21 unrelated Japanese were analyzed. The expression activity of a reporter gene linked to the promoter region of the human TS genes with the two types of repeated sequence was examined and the result showed that the expression activity of the gene with the double repeat was lower than that of the gene with the triple repeat in the transient expression assay. Thus, it appears that the unique repeated sequences in the 5'-terminal region of the human TS gene are polymorphic and contribute to the efficiency of expression of the gene.

Base Sequence↗

PubMed1995

Ultrastructural and morphometrical analyses of Leydig and Sertoli cells in the testes of rats with hereditary polydactylism.

Rats of the polydactylous (PD) strain carry an autosomal recessive gene pd that causes polydactylism in homozygotes (pd/pd). Male homozygotes are sterile owing to an abnormality of spermatogenesis. In the present study, Leydig and Sertoli cells of 12-week-old pd/pd male rats were examined for ultrastructural alterations in an attempt to clarify the cause of the abnormal spermatogenesis. The relative volumes of the organelles were also determined with morphometry. Phenotypically normal pd/+ males served as controls. No morphological or morphometrical abnormalities were noted in the Leydig cells. However, two different types of Sertoli cell were evident: light cells and dark cells. The incidence of the dark Sertoli cells in pd/pd males was high (27%) compared with that in pd/+ males (6%). These dark cells contained quantities of lipid droplets in the cytoplasm and exhibited a significant increase in the relative volume of lipid droplets compared with the value for the light cells. The nuclei of the dark Sertoli cells were irregular in shape and were invaginated. These results suggest that dark Sertoli cells may have lower lipid metabolism, and in pd/pd males, the high number of these dark Sertoli cells may be related to abnormal spermatogenesis.

Animals↗

PubMed1994

Protection by sinomenine against endotoxin-induced fulminant hepatitis in galactosamine-sensitized mice.

Sinomenine, an epimorphinan alkaloid, was tested for protecting hepatitis induced by lipopolysaccharide (LPS) in galactosamine (GalN)-sensitized mice. Sinomenine protected against the hepatic injuries in the dose range of 10-100 mg/kg in a dose-dependent manner and suppressed the production of tumor necrosis factor (TNF), which appeared in serum earlier than aminotransferases in GalN/LPS-treated mice. Sinomenine significantly suppressed the in vitro production of superoxide anion and hydrogen peroxide in the macrophage cultures stimulated with phorbol 12-myristate acetate. It is discussed that sinomenine prevents GalN/LPS-treated hepatic failure by suppressing TNF production and/or reactive oxygen generation.

Analgesics↗

PubMed1994

Pathogenetic changes in the lung bud of mutant rats with heritable pulmonary lobation anomalies.

The present study aimed at investigating pathogenesis of pulmonary lobation anomalies in fpl/fpl mutant rats. Day 12-15 embryos were first examined for pulmonary lobation. Lung serial sections were then made and examined for bronchial branching and distribution of extracellular matrices (ECMs). The lung buds of both fpl/fpl embryos and their phenotypically normal fpl/+ littermates were formed as bilateral protrusion of the foregut on gestation day 12. In fpl/+ embryos, three processes appeared on the right lung bud on day 13, and fissures were completely formed by day 14. In fpl/fpl embryos, the right lung bud had no clear process on gestation day 13, and fissures were not formed on day 14 and thereafter, with the exception of incomplete separation between the cranial and middle lobes. Histological observation revealed that the right main bronchial bud of fpl/+ embryos ramified all lobar bronchial buds by gestation day 13. ECMs, a borderline between endodermal bronchial buds and surrounding mesenchyme, disappeared at the distal end of each lobar bronchial bud. By contrast, in fpl/fpl embryos, the right main bronchial bud did not ramify the middle and intermediate lobar bronchial buds at its lateral and ventral portions, but swelled on gestation day 13. It was covered with ECMs at the lateral side but not at the ventral region, from which the middle and intermediate lobar bronchial buds arose on gestation day 14. These observations suggest that altered distribution of ECMs causes branching abnormalities of the lobar bronchial buds and subsequent lobation anomalies in fpl/fpl embryos.

Animals↗

PubMed1994

Gaucher's disease, type I (adult type), with massive involvement of the kidneys and lungs.

A 33-year-old Japanese male, first diagnosed as having Gaucher's disease at the age of 3 years, died of renal and pulmonary failure. Autopsy findings disclosed the proliferation of Gaucher's cells in the liver, bone marrow, lymph nodes, kidneys and lungs. Electron-microscopical findings suggested that the Gaucher's cells observed in the renal glomeruli might be derived from circulating macrophages.

Adult↗

PubMed1994

Characterization of a cytotoxic factor produced by rat bladder cancer cell line: its identity to TNF alpha.

Clone C19 derived from a rat bladder cancer cell line BC31ad constitutively released cytotoxic factor RCF. The serum-free C19-conditioned medium was partially purified by DEAE-Sephacel, Sephacryl S-200 and MonoQ-FPLC chromatographies to the specific activity of 6.4 x 10(6) U/mg protein (LM assay). RCF was a 17-kDa protein with pI 4.6-5.0. Anti-RCF serum neutralized the cytotoxic activity of rat and mouse, but not human, tumor necrosis factor-alpha (TNF alpha) as well as RCF. The partial amino acid sequence of RCF was homologous with the sequence 43-58 of rat TNF alpha. RCF and rat TNF alpha showed a similar cytotoxic spectrum against several tumor cells. Furthermore, they induced a marked proliferation of mouse T cells in combination with a suboptimal dose of ConA or anti-CD3 antibody, however, human TNF alpha almost not. Taken together, RCF was substantially regarded as rat TNF alpha.

Amino Acid Sequence↗