Search PubMed⌕ Search

Biomedical subjects

M Yasunaga

Publications and source records attributed to M Yasunaga.

At least 55 records · Page 3Linked to original sources

Extramedullary tumor as presentation of leukemia: establishment of a new human GPIIb- and GPIIIa-positive leukemia cell line.

A 25-year-old man noted swelling of the right cervical lymph nodes in October 1983. Diagnosis of malignant lymphoma was made on the basis of pathological examination of biopsies. Despite both chemotherapy and irradiation treatment, blast cells appeared in the peripheral blood and bone marrow in April 1984. Immunophenotypic analysis demonstrated that the blasts in the patient's peripheral blood expressed CD13, CD33, CD41a, and no markers for T or B lymphocytes, suggesting that he had been suffering from megakaryocytic sarcoma. We established a new cell line derived from the blasts in the peripheral blood, designated KH184. KH184 cells expressed glycoprotein (GP) Ib (CD42b) and GPIIb/IIIa (CD41a), while platelet peroxidase (PPO) activity was negative in an ultrastructural study. Both Northern blot and flow cytometric analysis of surface antigens and DNA content revealed that treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) did not induce the maturation of these cells. Various cytokines such as interleukin 3 (IL-3), interleukin 6 (IL-6), and leukemia inhibitory factor (LIF) had no effect in promoting the growth of KH184 cells. KH184 cells expressing CD41a seem to possess unusual characteristics. KH184 cells, human GPIIb- and GPIIIa-positive leukemia cells, which lack response to TPA-induced differentiation, provide a new and unique model for the characterization of factors that are implicated in the terminal differentiation of megakaryocytes, and should aid in studies of the mechanism underlying the occurrence of megakaryocytic sarcoma.

Adult↗

Secretin prevents taurocholate-induced intrahepatic cholestasis in the rat.

Secretin is known to stimulate the flow of bicarbonate-rich bile from the bile-duct epithelium, but has no effect on hepatocytes. To investigate the effects of secretin on bile production during intrahepatic cholestasis, we infused secretin into rats with taurocholate-induced cholestasis. Secretin was given at 0.25 and 0.50 units.min-1.kg-1 to Wistar rats that simultaneously received a continuous infusion of taurocholic acid at above its maximum hepatic transport capacity to produce cholestasis. When taurocholic acid was infused at doses of 1.4 and 1.6 mumol.min-1.100 g b.w.-1, bile volume decreased in control rats. In contrast, the simultaneous infusion of secretin significantly increased bile flow and the biliary excretion of bile acids and bicarbonate. The serum taurocholic acid level at the end of the experiment was significantly lower in the secretin-treated groups than in the control group. These findings indicate that secretin prevents taurocholate-induced cholestasis and may enhance the biliary excretion of bile acids.

Animals↗

Endoscopic ligation of gastric varices using a detachable snare.

A new technique of endoscopic treatment for gastric varices is presented here, which was applied in 10 patients, either electively (n = 9) or as emergency therapy for bleeding (n = 9) or as emergency therapy for bleeding (n = 1). A detachable snare is placed endoscopically, tightened around the varix, and then detached using a similar principle to that of band ligation. Following one or two treatment sessions (one snare applied in seven cases, two snares applied in three cases), eradication of gastric varices was observed in all patients. No significant complications were encountered, and nine of 13 snares passed spontaneously, the remaining ones being removed when found during follow-up endoscopy. Short-term follow-up (4-12 months, mean: 7.2 months) did not show either reappearance of varices or rebleeding in any of the patients. Angiography and endoscopic ultrasonography performed in four patients before and after treatment showed regression or disappearance of intramural vessels. Further studies will show the relative value of this new technique compared to other treatment modalities such as banding or cyanoacrylate injection.

Aged↗

[IL-7].

IL-7, a 25-kDa glycoprotein was cloned as a cytokine derived from bone marrow stromal cells, which induces proliferation of pre-B cells. IL-7 was found to be produced by the thymus, spleen, kidney and bone marrow stromal cells and induces proliferation of immature B and T cells. It has no effects on mature B cells but induce proliferation of mature T cells IL-7 R is expressed during the stages; B 220+ sIgM- of pre-B cells but not sIgM+ mature B cells, and also expressed CD4-8-, CD4+8- CD4-8+ T cells. It is shown that IL-7 can act only on these IL7R+ cells functionally in vitro and in vivo. We and other group demonstrated that IL-7, when used in combination with stromal cells or SCF can induce proliferation of pre-B cells. Recently we generated successfully SCF and IL-7 dependent pre-B cell lines, and now have used them for cell cycle analysis. To date, it was found that IL-7 is required for G1 to S transition. IL-7 also acts as a co-stimulus for the proliferation of antigen- or mitogen-activated T cells and can induce CTL response and LAK activity.

Animals↗

A multicenter study on the prognosis of fulminant viral hepatitis: early prediction for liver transplantation.

To determine the risk of death at an early stage of fulminant viral hepatitis, we created severity indexes drawn from clinical data on the day of development of encephalopathy in 128 patients with fulminant hepatitis B and 103 with fulminant hepatitis non-A, non-B. In fulminant hepatitis B, the risk score was 2.75 x BL + 2.75 x BR + 2.7 x AG + 2.3 x WB + 1.67 x CD + 1.56 x AL - 0.098 x PR - 0.88, where BL is 1 if total bilirubin is higher than 20 mg/dl, BR is 1 if the ratio of total to direct bilirubin exceeds 2.2, AG is 1 if age is above 40 yr, WB is 1 if white blood cell count is less than 4,000 cells/mm3 or more than 18,000 cells/mm3, CD is 1 if a hazardous disease coexists and AL is 1 if ALT is less than 100 times the upper limit of normal (otherwise all are 0), and PR is prothrombin time (percentage of normal value). Using a cutoff score of 0, we found the positive predictive value, negative predictive value and predictive accuracy to be 0.90, 0.86 and 0.89, respectively. Sensitivity and specificity were 0.94 and 0.77, respectively. In fulminant non-A, non-B hepatitis, the risk score was 2.66 x BR + 2.25 x BL + 2.24 x DI + 2.05 x AL +/- 1.38 x AG + 0.00021 x WB - 6.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protein-losing gastroenteropathy with facial anomaly and growth retardation: a mild case of Hennekam syndrome.

A 7-year-old boy with a peculiar face, protein-losing gastroenteropathy and growth retardation is reported. Although he has a face similar to those 5 cases reported previously by Hennekam et al. (Am J Med Genet 34:593-600, 1989) and Gabrielli et al. (Am J Med Genet 40:244-247, 1991), he is not mentally retarded nor does he have severe lymphedema. This patient seems to have a mild case of the Hennekam syndrome.

Albumins↗

IgG4 deficiency with Rothmund-Thomson syndrome: a case report.

We describe a patient with Rothmund-Thomson syndrome and IgG4 deficiency. In vitro examination of his peripheral mononuclear cells revealed impaired IgG4 synthesis. Susceptibility to sinus and pulmonary infections was cured by monthly immunoglobulin infusions.

Child, Preschool↗

Intrahepatic and extrahepatic biliary papillomatosis.

We report a case of biliary papillomatosis that occurred 8 years after resection of a bile duct tumor. In 1982, a 63-year-old man underwent a cholecystectomy because of cholelithiasis. At operation, a solitary tumor was found in the left intrahepatic bile duct, and a lateral hepatic segmentectomy was performed. The tumor was diagnosed as a benign papillary adenoma. In 1990, mild liver dysfunction was revealed in a routine medical examination. Ultrasonography and computed tomography showed a solid tumor measuring approximately 6 cm in diameter in the left hepatic duct. There was no appearance of jaundice during the course. In 1991, a partial hepatic resection and a bile duct resection were performed. At operation, two tumors were found and removed. These tumors were essentially the same as the bile duct tumor resected 8 years ago. They were diagnosed as biliary papillomatosis.

Bile Duct Neoplasms↗

Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation.

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.

Adenosine Triphosphate↗

Effects of secretin on bile production in two kinds of cholestatic models by choledocho-caval fistula and bile duct ligation in rats.

Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24-hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance.

Animals↗

Detection of proliferating hepatocytes by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in patients with acute hepatic failure.

This study evaluated whether liver regeneration could take place after massive or submassive necrosis of liver cells in 25 patients with several kinds of hepatic failure by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). PCNA positivity was significantly higher (P less than 0.01) in the patients who survived than in the patients who died. Furthermore, PCNA-positive hepatocytes were recognized diffusely in the lobule of the liver in survivors. There was positive correlation between PCNA positivity and plasma concentration of AFP (alpha-fetoprotein), (r = 0.77, P less than 0.01). These results show that liver regeneration could take place after massive necrosis of liver cells in survivors from acute hepatic failure and that immunohistochemical staining for PCNA is useful for prognostic evaluation.

Antibodies, Monoclonal↗

Analysis of lymphoid follicles in liver of patients with chronic hepatitis C.

Using immunohistological methods, we studied the lymphoid follicles in liver biopsy specimens obtained from patients with chronic hepatitis C(CH-C) to determine whether they represented an autoimmune manifestation. In 84 specimens obtained by liver biopsy from 76 patients positive for C-100 antibody, we assessed the presence or absence of lymphoid follicles within the portal areas, and then compared the clinical and immunohistological profiles of the two groups defined on this basis. There were no significant differences in the serological and clinical profiles of the two groups, but the T4:T8 cell ratio within the portal areas differed significantly. A T4:T8 cell ratio > 1.0 was more common in the specimens containing lymphoid follicles. This finding resembled the distribution of T cell subpopulations in the portal areas of patients with autoimmune hepatitis, and suggested that lymphoid follicles may be worth investigating to elucidate the relationship between chronic hepatitis C and autoimmune hepatitis.

Autoimmune Diseases↗

Ultrastructural studies of the bile duct in alcoholic liver disease.

The fine structural characteristics of the bile duct in patients with alcoholic disease are described. Dark cell metamorphosis, edematous microvilli, and increased number of pinocytotic vesicles on the basal wall surface of the duct epithelium were observed. These alterations may be interpreted as evidence of disordered water metabolism, probably reflecting secretion and reabsorption hyperfunction in the duct epithelium. In addition, widened intercellular spaces in the basal half of the epithelium suggested retention of fluid following reverse pinocytosis along the lateral cell surface. Although no alterations of the duct epithelium distinct from those in patients with other liver diseases were apparent in patients with alcoholic liver disease, the basement membrane of the bile duct exhibited unusual duplication with multiple layers and occasional loop-formation in lacunae on the basal surface.

Adult↗

Incidence of hepatitis D virus infection in Japanese patients with hepatocellular carcinoma--immunohistochemical investigation of the delta antigen.

In order to clarify the incidence of the delta agent among hepatocellular carcinomas (HCCs) in Kurume, where the hepatitis B infection and its related HCC are most prevalent in Japan, liver tissues from sero hepatitis B surface antigen-positive autopsy cases, with or without HCC, were immunohistochemically investigated for detection of the delta antigen. Only one patient (1.7%) among 58 patients with HCC was found to have delta-antigen in the nuclei in the hepatocytes, which were diffusely distributed throughout the non-cancerous liver. None of 26 patients with liver cirrhosis showed delta-antigen in the liver tissue. The incidence is so low that the delta agent is unlikely to have a role in the development of HCC in our areas.

Antigens, Viral↗

Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction.

The short segments of cDNA encoding glycoprotein (GP)Ib alpha, GPIIb, GPIIIa and platelet factor (PF) 4 were amplified using reverse transcriptase-polymerase chain reaction (RT-PCR) in order to characterize various types of megakaryoblasts. Cell lines with megakaryocytic features (K562, CMK and HEL) were tested. GPIb alpha, GPIIb and GPIIIa mRNAs were found to be present in K562, CMK and HEL cells, while only HEL cells expressed PF4 or mRNA. These results suggested that megakaryoblastic cell lines could be categorized into two groups, one with the PF4 transcript and the other without it. PF4 mRNA was present in the cells obtained from one Down's syndrome patient with transient myeloproliferative disorder and in one patient with primary myelofibrosis and megakaryoblastosis. On the other hand, one patient with acute megakaryoblastic leukemia transformed from refractory anemia had a poor prognosis with megakaryoblastic leukemia cells which expressed no PF4 mRNA. These observations suggested that the expression of PF4 mRNA in peripheral blood megakaryoblasts may indicate the absence of a true leukemic process.

Aged↗

Megakaryocytic leukemia and platelet factor 4.

The de novo megakaryocytic leukemia fulfilling the FAB criteria is still an uncommonly recognized variant of acute leukemia. Many studies have shown that the megakaryocytic leukemic events may occur at a pluripotent stem cell level and clinical observations reveal that the megakaryocytic leukemias are diverse entities. The immunophenotyping using monoclonal antibodies against platelet specific surface antigens and the ultrastructural detection of platelet peroxidase reaction do not provide sufficiently useful information to determine whether a megakaryocytic leukemia is chronic, acute, therapy-responsive or therapy-unresponsive. More sophisticated techniques are required to further characterize megakaryocytic leukemic cells. In this review, we emphasize that megakaryocytic leukemic cells can be categorized into two groups; one with the PF4 mRNA, and the other without it, and that the expression of PF4 mRNA in the blasts could be a useful marker for the identification of mature megakaryoblasts. It seems that the patients with blasts expressing PF4 mRNA will have a longer survival and a better response to chemotherapy than those without PF4. We further discuss the fact that the detection of mRNAs of the IL-6 receptor, PDGF A- and B-chains, and TGF beta 1 in megakaryocytic leukemic cells will be useful to clarify the mechanisms involved in the proliferation of megakaryocytic leukemic cells and fibroblasts in the bone marrow. Furthermore, we reviewed data showing that megakaryocytic erythroid, and mast cell lineages share the nuclear transcription factor known as GF-1 (NF-E1 or Erf-1). We suggest that characterization of megakaryocytic leukemia should be performed using monoclonal antibodies against erythroid, megakaryocytic and mast cell lineages.

Base Sequence↗

Modulation of GM-CSF receptor beta-subunit and interleukin-6 receptor mRNA expression in a human megakaryocytic leukemia cell line.

Our present study was designed to clarify the mechanism by which the same megakaryocyte progenitor cells respond to various cytokines at different stages of megakaryocyte development. We examined the changes in mRNA expression of granulocyte macrophage colony-stimulating factor receptor beta-subunit (GM-CSFR beta-subunit), which was a common subunit of a high-affinity interleukin-3 receptor (IL-3R) and a high-affinity GM-CSFR, and interleukin-6 receptor (IL-6R) during megakaryocyte development in a human megakaryocytic leukemia cell line (CMK) which could proliferate and/or differentiate in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, GM-CSF, and IL-6. We found that GM-CSFR beta-subunit mRNA was expressed constitutively in CMK cells and was transiently down-regulated by TPA and IL-6, while the expression of IL-6R mRNA was increased by TPA in association with the differentiation of megakaryocytes. Furthermore, the TPA-induced down-regulation of GM-CSFR beta-subunit mRNA expression and its recovery were blocked by cycloheximide (CHX), a protein synthesis inhibitor, suggesting that these modulations required de novo protein synthesis. These findings imply that multi-lineage cytokines such as GM-CSF and IL-3 may contribute preferentially to the regulation of the earlier development of megakaryocyte progenitor cells with high densities of multi-lineage cytokine receptors, while IL-6 may be limited in its action to supporting the maturation of more differentiated megakaryocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗