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Y Kohgo

Publications and source records attributed to Y Kohgo.

At least 145 records · Page 8Linked to original sources
PubMed1994

[Liver cirrhosis in primary hemochromatosis and Wilson's disease].

Iron is an essential element in all living cells because it serves machineries for biological oxidation including hemoglobin, cytochrome c oxidase, etc. Copper is also essential for mammalian life since copper is the prosthetic element of several life-essential enzymes. Although intracellular excessive iron and copper were usually sequestrated in ferritin and metallothionein molecules, accumulation of excess iron and copper may also cause severe tissue injury by including oxyradicals and lipid peroxidation and eventually bring about tissue fibrosis such as liver cirrhosis. Hemochromatosis and Wilson's disease are known as iron and copper accumulation disorders, respectively. In this chapter, we review the cirrhosis in hemochromatosis and Wilson's disease.

Hemochromatosis↗
PubMed1994

Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats.

To explore a mechanism of interleukin (IL)-6-induced hypoferremia in rats, iron metabolism was investigated both in vivo and in vitro. Recombinant IL-6 was intraperitoneally administered to male Wistar rats and the serial change of parameters related to iron metabolism was examined. After administration of IL-6, plasma IL-6 concentration increased rapidly, reached its maximum in 1 hr and thereafter decreased quickly. Plasma IL-6 3 hr after IL-6 injection (50 micrograms/kg) was 3 units/ml, which is a concentration capable of inducing hepatic 125I-labeled transferrin uptake in vitro using isolated hepatocytes. Plasma iron concentration and transferrin saturation had decreased to approximately one third of the initial level within 3 hr and then recovered. Total iron binding capacity remained unchanged for 6 hr, then began to decrease. Red blood cell count and hemoglobin concentration showed no remarkable changes during this period. By ferrokinetic study with plasma that contained iron 59-labeled transferrin, the plasma iron disappearance half time, calculated from the disappearance curve, was significantly shortened from 55 min to 22 min by IL-6 treatment (p < 0.01). The ferritin concentration in the liver was increased significantly after the administration of IL-6 (p < 0.001), but transiently decreased in the spleen. The plasma ferritin showed a gradual increase during the 6-hr period after IL-6 injection. The uptake of 125I-labeled diferric transferrin by isolated hepatocytes was increased by IL-6 treatment and this increment was inhibited by addition of 100-fold excess unlabeled transferrin. On the other hand, no significant increment of 125I-labeled diferric transferrin uptake was observed in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Point mutation of aldehyde dehydrogenase-2 gene in mutant strains of Long-Evans rats.

Long-Evans Cinnamon (LEC) and Long-Evans Agouti (LEA) rats are mutant strains established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma, but LEA rats do not develop liver diseases. We previously demonstrated that LEC rats had an impairment of liver aldehyde dehydrogenase (ALDH) activities, and all LEC rats which were fed with a liquid diet containing 5% ethanol died within 2 weeks. In the present study, we also found that LEA rats could not metabolize ethanol and died after being fed the same diet. Remarkably, in the liver of LEA rats, low Km ALDH activities were suppressed as much as in LEC rats. These results suggested that both LEC and LEA rats have hereditary deficiencies in ALDH. Nucleotide sequence analysis of ALDH2 genes in both LEC and LEA rats demonstrated that the point mutation of the codon for residue 67 encoding Gln to Asp was observed; this was not so in either Long-Evans rats or Wistar rats. This mutation in ALDH2 genes may cause inactivation of ALDR activity in LEC and LEA rats.

Aldehyde Dehydrogenase↗
PubMed1993

Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron.

In chronic inflammation it is reported that serum iron is depleted and hepatic iron is increased because of reticuloendothelial system iron blockade. However, recent studies indicate that hepatic parenchymal cells increase the uptake of transferrin-bound iron after in vivo stimulation with bacterial lipopolysaccharide, suggesting that endotoxemia itself or lipopolysaccharide-induced production of inflammation-related cytokines may also be responsible for this phenomenon. In this study the actions of inflammation-related cytokines on the synthesis of iron-binding proteins (transferrin and ferritin) and transferrin receptor and the uptake of transferrin-bound iron were investigated in a human hepatoblastoma cell line, HepG2, which is the most commonly used cell line for examining the regulation of hepatic protein synthesis by cytokines. The cells were exposed to interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha separately for 24 hr. In each cytokine treatment group, the level of transferrin, which is secreted into the conditioned medium, was found to be decreased compared with that of untreated cells. On the other hand, the biosynthesis of ferritin was markedly elevated after the same treatment. This increase in ferritin by cytokine treatment was diminished when deferoxamine was used concomitantly to deplete intracellular chelatable iron. After stimulation with interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha, 59Fe-labeled transferrin uptake into the cells was increased by 36%, 48%, or 18%, respectively, and this uptake was inhibited by the addition of excess unlabeled transferrin. A binding study with 125I-labeled diferric transferrin revealed that the three cytokines increased the number of transferrin receptors on the cell surface by 1.15-fold to 1.35-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
PubMed1993

Individual diversity of IL-6 generation by human monocytes with lentinan administration.

Effect of in vivo administration of lentinan on IL-6 generation by human peripheral blood monocytes was examined using 5 healthy volunteers. Monocytes isolated from them before and 3 days after intravenous administration of 2 mg lentinan per person were cultured for 2 days and then the levels of IL-6 in the supernatants of cultured monocytes were determined. In vivo lentinan administration elicited an increase in IL-6 generation by monocytes in 3 of 5 cases. Failure to increase IL-6 generation by monocytes in two cases is characteristic of lentinan, since these monocytes generated an apparent level of IL-6 in response to lipopolysaccharide, a potent monocyte activator. Thus, it was demonstrated that lentinan was capable of augmenting IL-6 generation by human monocytes and that there was individual difference in their responsiveness to lentinan.

Acute-Phase Proteins↗
PubMed1993

Production and characterization of specific asialoglycoprotein receptor antibodies.

Monoclonal antibodies (MoAbs) were produced by immunizing BALB/c mice with asialoglycoprotein receptor (AGPR) purified from human liver. The purity of AGPR was confirmed by SDS-polyacrylamide gel electrophoresis and by amino acid sequence. An enzyme-linked immunoassay revealed 24 monoclonal antibodies which reacted with human AGPR. By Western blot analysis, all antibodies recognized the 46 kDa human AGPR under the non-reduced conditions and four MoAbs recognized reduced protein. Two MoAbs reacted with AGPR derived from rat, rabbit and mouse liver under both non-reduced and reduced conditions, suggesting that we could obtain antibodies which reacted with AGPR epitopes shared by different species. In immunohistochemical studies, 30201-MoAb reacted with human liver tissue but not with other tissues. This antibody immunoprecipitated two major bands of 46 kDa and 39 kDa from [35S]-methionine metabolically labeled human hepatoma HepG2 cells. The determinant recognized by 30201-MoAb is a common epitope of AGPR which is present in different species and in both the precursor and maturation forms of the receptor.

Amino Acid Sequence↗
PubMed1993

Abnormal ethanol metabolism in Long-Evans Cinnamon rats, a mutant strain developing spontaneous hepatoma.

The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma (HCC). We first tried to examine effects of ethanol consumption on the development of HCC, and fed a Lieber's liquid diet containing 5% ethanol to LEC rats. However the rats died within 2 weeks because of acute alcohol intoxication. In LEC rats, the concentration of ethanol and acetaldehyde in blood was significantly higher, and liver alcohol dehydrogenase activity was slightly lower and acetaldehyde dehydrogenase activities were remarkably suppressed compared to those of Wistar rats. These results suggest that LEC rats have hereditary deficiencies of ethanol and acetaldehyde metabolizing enzymes.

Acetaldehyde↗
PubMed1993

Intracellular metabolism and cytotoxicity of transferrin-neocarzinostatin conjugates of differing molar ratios.

Transferrin-neocarzinostatin (NCS) conjugates with differing molar ratios of drug to protein were synthesized and their intracellular metabolism was investigated. The conjugate mixtures of transferrin-NCS were separated by DEAE-Sephacel column chromatography. The separated molecular species were examined with respect to binding affinity to transferrin receptor, cytotoxicity and intracellular metabolism using the human leukemia cell line, K562. Transferrin-NCS conjugate is capable of binding to transferrin receptors specifically and its reactivity became weaker as the ratio of bound NCS to transferrin was increased. Transferrin-6NCS did not bind measurably to the receptor. On the other hand, the cytotoxicity was augmented when the number of NCS molecules bound per molecule of transferrin was increased to 4NCS/transferrin, while transferrin-5NCS and transferrin-6NCS species exhibited low activity. Examination of the kinetics of metabolism by pulse chase study using 125I-labeled ligand indicated that unconjugated transferrin and transferrin-NCS conjugates were internalized in similar ways, although the degradation of internalized conjugate was more marked in the case of transferrin-4NCS than transferrin-1NCS. Thus, the molar ratio of transferrin-drug conjugate could be optimized with respect to both the binding activity to receptor and the intracellular metabolic pathway.

Animals↗
PubMed1993

Abnormal hepatic iron accumulation in LEC rats.

The LEC (Long-Evans cinnamon) rat is a mutant strain displaying hereditary hepatitis and spontaneous hepatocellular carcinoma, and shows abnormal hepatic copper accumulation similar to that occurring in Wilson's disease. We evaluated the iron metabolism of LEC rats compared to LEA (Long-Evans agouti) rats. Hepatic iron and ferritin concentrations were remarkably increased depending on age in LEC rats but not in LEA rats. Increased hepatic iron is normally associated with decreased serum transferrin and total iron binding capacity in hepatic iron overload. In LEC rats, however, both serum transferrin and total iron binding capacity increased with increasing hepatic iron. This increase of serum transferrin and hepatic iron may be an additional important factor contributing to liver injury in LEC rats.

Age Factors↗
PubMed1993

Cytokine mRNA expression of bone marrow stromal cells from patients with aplastic anaemia and myelodysplastic syndrome.

We studied mRNA expression of the cytokine granulocyte-colony stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), IL-6, IL-8 and stem cell factor of stromal cells derived from bone marrows of nine normal volunteers, eight patients with aplastic anaemia (AA) and seven patients with myelodysplastic syndrome (MDS). The proportion of endothelial cells, macrophages, fibroblast-like cells and adipocytes in stromal cells showed no differences between normal volunteers and the patients. Levels of cytokine mRNA expression were determined by reverse transcription-polymerase chain reaction. Spontaneous expression occurred and this was augmented by LPS stimulation in cells of all the normal volunteers and in most patients. When stimulated by LPS, the mean G-CSF and IL-1 beta mRNA expressions in patients with AA were significantly higher than normal volunteers, but there was one patient showing lower IL-1 beta, IL-6 and IL-8 expression with no response to LPS. LPS-induced IL-6 and IL-8 expression of two patients with MDS were significantly higher than normal. The spontaneous and LPS-induced protein concentration of G-CSF, IL-6 and IL-8 in culture supernatants from 15, 10 and four patients, correlated well with the mRNA expression. The correlation coefficients were 0 x 92, 0 x 78 and 0 x 91, respectively. In conclusion, there were a few patients whose aetiology appeared to be reduction of stromal cytokine expression in AA, but most patients with AA and MDS expressed normal or high levels of cytokine mRNA.

Adolescent↗
PubMed1993

Increased serum level of interleukin-5 in a patient with episodic angioedema and eosinophilia syndrome.

A case of episodic angioedema and eosinophilia syndrome is reported. An 18-year-old male suffered from monthly episodes of angioedema, pruritic papules, weight gain, and fever for twelve years. During the episodes, peripheral eosinophils and serum levels of interleukin (IL)-5, an eosinophil proliferating cytokine were elevated. Extensive evaluations disclosed neither visceral involvement nor evidence of parasitic infections, collagen diseases, or neoplastic disorders. Corticosteroid treatment brought about a dramatic clinical improvement concomitant with decrement of eosinophils and serum IL-5 was observed. These observations suggest that IL-5 may be a causative factor for this pathological state.

Adolescent↗
PubMed1993

Ectopic choroidal calcification of the eyes of a patient with parathyroid adenoma.

A 39-year-old man was admitted to our hospital complaining of general malaise, polyuria, disturbance of ocular movement and right cervical tumor. Blood examination revealed increased parathyroid hormone, hypercalcemia and hypophosphatemia, suggestive of hyperparathyroidism. Histology of the resected tumor revealed a benign parathyroid adenoma. Ectopic calcifications in the choroid and sclera were noted by computed tomography and further ophthalmological examination. Although ocular calcification in conjunctiva and cornea associated with hyperthyroidism is not unusual, sclerochoroidal calcification has not been reported previously in Japan. The possible cause of this unusual condition in this patient is discussed.

Adenoma↗
PubMed1993

Recombinant human granulocyte colony-stimulating factor can mobilize sufficient amounts of peripheral blood stem cells in healthy volunteers for allogeneic transplantation.

Peripheral blood stem cells (PBSC) are a good source for bone marrow reconstitution after intensive chemotherapy. The ability to transplant PBSC between allogeneic subjects would be a key step forward in the application of this procedure. For this purpose, we examined the mobilization and recovery of PBSC in healthy volunteers who were given recombinant human granulocyte colony-stimulating factor (G-CSF). Three informed healthy volunteers were injected with G-CSF subcutaneously at a dose of 2.5 micrograms/kg for 6 successive days and at 5.0 micrograms/kg for the following 4 days. The concentration of PBSC was assessed daily by CFU-GM and BFU-E assays, both of which peaked on the sixth to seventh day of G-CSF administration. Comparison between colony assays and hematological parameters revealed that flow cytometry analysis of CD34+ cells by mononuclear cell gating is a rapid and convenient method to quantify mobilized stem cells. The maximum numbers of CFU-GM were 432, 665, and 1386 colonies/ml blood. It is calculated that sufficient amounts of stem cells for transplantation (at least 1.0 x 10(5) CFU-GM/kg) could be obtained by leukapheresis of 5 to 201 blood when the peak was attained. This trial confirmed the feasibility of allogeneic transplantation using PBSC from healthy volunteers who have received G-CSF.

Adult↗
PubMed1993

[A case of advanced mediastinal choriocarcinoma showing complete remission for two years by high-dose chemotherapy with peripheral blood stem cell transplantation].

A twenty-six-year-old male patient with advanced choriocarcinoma originated from mediastinum was treated by high-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation. He had massive tumors in the cervical, mediastinal and bilateral lung fields. After 3 kur of PVeBV therapy (CDDP 60 mg x day 1-3, etoposide 160 mg x day 1-3, BLM 30 mg x day 1, VBL 12 mg x day 1), he obtained complete remission. PBSC was collected at the time of hematopoietic recovery and high-dose chemotherapy with PBSC transplantation was conducted because of the high possibility of recurrence. The hematopoietic recovery was rapid, and the patient remained well with no sign of recurrence for 24 months.

Adult↗
PubMed1993

Bone marrow transplantation for hematological diseases in Hokkaido--June 1985 to December 1991.

Bone marrow transplantation (BMT) was started in Hokkaido in 1985. In the present report we have reviewed the clinical outcome of patients treated with BMT for hematological diseases in Hokkaido. Fifty-eight allogeneic and 19 autologous transplants were registered by December 1991. The underlying diseases consisted of 47 leukemias, 14 lymphomas, 10 aplastic anemias and six myelodysplastic syndromes. Among the allogeneic BMT cases, 55 were human leucocyte antigen (HLA) identical and three were mismatched. Among the autologous BMT patients, two received their marrow purged with 4-hydroperoxycyclophosphamide and five, with monoclonal antibodies and complements. The conditioning regimens used for malignancies were chiefly cyclophosphamide (CY) plus total body irradiation, or busulfan plus CY. In many cases, cytokines were used for rapid recovery of decreased leukocytes. Engraftment was observed in 50 out of 52 evaluated allogeneic and 18 out of 19 autologous transplants. Ten allogeneic patients suffered from severe acute graft-versus-host diseases (GVHD), and extensive chronic GVHD appeared in 16 patients. Relapses were observed in four cases of allogeneic BMT and six of autologous BMT. The major complications were interstitial pneumonitis (IP) and severe infections. Long-term survival rates were almost 60% in both allogeneic and autologous transplants. Mild acute GVHD and limited chronic GVHD increased the survival rates. The results indicated that substantial problems such as GVHD, IP and relapses must be controlled in the near future for an improved outcome to be made possible.

Adolescent↗
PubMed1993

CD33, CD4-double positive blastic transformation in a patient with chronic myelogenous leukemia.

We report a 19-year-old female with blastic transformation of chronic myelogenous leukemia whose blasts had CD33 and CD4 phenotypes, although no significant characteristics were detected by morphological and histochemical analysis. In a colony assay with hematopoietic growth factors, the blasts proliferated and differentiated into myelo-monocytic lineage, particularly in the presence of GM-CSF or IL-3 + G-CSF. The blasts transformed from CML were assumed to be myelo-monocytic progenitor cells, corresponding to GM colonies. Blastic transformation expressing such a phenotype has not been reported previously.

Adolescent↗
PubMed1993

[Successful treatment with combination chemotherapy of BHAC-AMP in a case of acute myelofibrosis developed from myelodysplastic syndrome with multiple chromosomal aberrations].

A 62 year old male patient was previously admitted to another hospital in February 1989 because of palpitation. Peripheral blood examination revealed pancytopenia. Although the number of nucleated cells in the bone marrow aspirate was in the normal range. It contained 2.2% of blastic cells and dysplastic cells. He was diagnosed to be myelodysplastic syndrome with refractory anemia. He subsequently received repeated blood transfusions and other symptomatic treatments as an outpatient until 1990. When he was admitted to our hospital because of severe pancytopenia. The numbers of WBC, RBC, and platelets were 2,000/microliters, 134 x 10(4)/microliters, 2.9 x 10(4)/microliters respectively. Bone marrow aspiration resulted in dry tap, and biopsy at the iliac bone showed remarkable fibrosis with marked decrease of normal hematopoietic cells. Chromosome analysis revealed multiple aberrations such as 47XY, +8, 13q-, 14p+, 48XY, +8, +9, 13q+. The patient was treated with BHAC-AMP combination chemotherapy. After 3 cycles of the therapy, pancytopenia was improved and chromosomal aberration disappeared. This case was considered to be an acute myelofibrosis developed from myelodysplastic syndrome and worth to reporting with a review of literature, because drastic combination chemotherapy was extremely effective.

Aclarubicin↗