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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 451 records · Page 25Linked to original sources

[Abnormalities in regulation system of granulopoiesis].

We studied the effects of several cytokines on the development of granulocyte-macrophage (GM) progenitors using the serum-deprived culture. SCF plays an important role in the GM-CSF- or IL-3-dependent production of neutrophils and macrophages. In vitro colony assay also suggests an increase in sensitivity of GM progenitors to cytokines (GM-CSF, IL-3, G-CSF and/or SCF) in a patient with juvenile chronic myelogenous leukemia. A high level of serum IFN-gamma was associated with leukopenia and thrombocytopenia in a patient with hemophagocytic syndrome. Based on the evidence that IFN-gamma significantly inhibited the proliferation of GM progenitors, IFN-gamma-mediated suppression was suggested as one of the mechanisms causing cytopenia. In patients with aplastic anemia and neutropenia, an increase of serum G-CSF levels was observed when neutrophils decreased remarkably in number. However, the serum SCF levels were constant in these patients. A failure of SCF to enhance colony growth in some patients with aplastic anemia implies qualitative abnormalities of hematopoietic progenitors.

Anemia, Aplastic↗

Possible role of stem cell factor as a serum factor: monoclonal anti-c-kit antibody abrogates interleukin-6-dependent colony growth in serum-containing culture.

The monoclonal rat anti-c-kit antibody (ACK2), which abrogates colony growth supported by stem cell factor (SCF), significantly inhibited the interleukin-6 (IL-6)-dependent growth of hematopoietic progenitors derived from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice and from bone marrow cells of normal mice in serum-containing culture. The numbers and types of colonies supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), however, were not influenced by the addition of ACK2 to the cultures of the bone marrow cells from normal mice. In replating experiments with pooled blast cells, ACK2 caused a partial, but significant, inhibition of GM colony growth supported by a combination of IL-6 and fetal bovine serum (FBS), which suggests that FBS is one source of the SCF activity. Conversely, the addition of SCF or FBS with IL-6 to a serum-free culture had significant synergistic effects on the total number of colonies derived from post-5-FU spleen cells and from pooled blast cells. The dose response study showed that the ability of 30% FBS to interact with IL-6 on the colony growth by post-5-FU spleen cells was equivalent to that of approximately 5 ng/mL SCF. These findings suggest that c-kit plays an important role in the growth of hematopoietic progenitors responding to IL-6, and that SCF in the serum affects the development of hematopoietic progenitors in serum-containing cultures.

Animals↗

Human monoclonal antibodies from a patient with primary biliary cirrhosis that recognize two distinct autoepitopes in the E2 component of the pyruvate dehydrogenase complex.

Peripheral B lymphocytes from a patient with primary biliary cirrhosis were infected with Epstein-Barr virus, and Epstein-Barr virus-transformed B lymphocytes producing large amounts of IgG antibodies to pyruvate dehydrogenase complex were selected, expanded and fused with the human-mouse heteromyeloma cell line F3B6. The resulting Epstein-Barr virus-transformed B-cell hybrids were repeatedly cloned by limiting dilution, and three stable hybridoma clones producing human monoclonal antibodies to pyruvate dehydrogenase complex were generated. These monoclonal antibodies, designated M18GP8, M37GP11 and M82GP8, specifically bound to pyruvate dehydrogenase complex, and their dissociation constant with pyruvate dehydrogenase complex was calculated to be 2.4 x 10(-11), 2.3 x 10(-10) and 2.6 x 10(-11) mol/L, respectively. These three monoclonal antibodies stained the mouse stomach/kidney cryostat sections in a typical immunofluorescence pattern of antimitochondrial antibody. Furthermore, the enzymatic activity of pyruvate dehydrogenase complex was almost completely inhibited by the three monoclonal antibodies. Western blotting analysis revealed that M18GP8 and M82GP8 reacted with only pyruvate dehydrogenase complex-E2 in contrast to M37GP11, which reacted with both pyruvate dehydrogenase complex-E2 and protein X. The binding of monoclonal antibody M37GP11 to solid-phase pyruvate dehydrogenase complex was partially inhibited by two different synthetic peptides corresponding to both the inner and outer lipoyl-binding domains of pyruvate dehydrogenase complex-E2. These monoclonal antibodies, which are the first human monoclonal antibodies to pyruvate dehydrogenase complex generated from a patient with primary biliary cirrhosis, will be a valuable tool for studying the B-cell autoepitopes in PDC and the mechanism of autoantibody production in primary biliary cirrhosis.

Adult↗

[Changes in right ventricular hemodynamic function by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test (UPAO) for the preoperative evaluation of lung function in patients undergoing lung resection. In this test, the main pulmonary artery of either side is occluded to simulate postoperative functional status. In order to evaluate the right ventricular hemodynamic function, we measured right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by thermodilution method. We investigated the relationships between changes in right ventricular hemodynamic function and postoperative complications related to cardiac functions, namely arrhythmias or heart failure. Thirty-four patients without heart disease prior to lung resection were examined by UPAO, and RVEF and RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by over 20% during UPAO. All of these patients had postoperative cardiac complications. The hypothetical ventricular function curves showed a large increase in RVEDVI relative to right ventricular stroke work index (RVSWI), suggesting a decrease in right ventricular function. In conclusion, these results suggest that changes in RVEDVI during UPAO may predict postoperative cardiac complications in patients undergoing pulmonary resection.

Adult↗

[Hemophagocytic syndrome with high level of interferon-gamma in the advanced stage].

Serum cytokines, lymphocyte subsets of peripheral blood and natural killer cell activity were serially assayed in a 3-year-old girl with hemophagocytic syndrome. Laboratory findings showed pancytopenia, increased levels of transaminases and hyperferritinemia and proliferation of histiocytes in bone marrow and pleural effusion. The administration of prednisolone resulted in a temporary improvement followed by a further exacerbation. The patient died in spite of the treatment with VP-16 and THP-adriamycin. Serum interferon-gamma (IFN-gamma) markedly increased in active phases. TNF-alpha, IL-1 beta and GM-CSF concentrations were normal or slightly elevated. The CD4/8 ratio of peripheral lymphocytes and natural killer cell activity also fluctuated according to clinical stage. These results suggested that IFN-gamma was the most important cytokine to activate histiocytes in this case.

Child, Preschool↗

[Thrombocytopenia in HIV-1 seropositive hemophiliacs].

When platelet counts were compared in 1986 and 1992 in 117 anti-HIV antibody positive and negative hemophilia patients, a clear decrease was found in the positive group. In 1992 platelet counts < 150 x 10(9) were present in 23.5% of the positive group in contrast to 5.8% of the negative group. Comparing platelet counts with other clinical parameters, a positive correlation was found with cholinesterase and a negative correlation with IgG in both the positive and negative groups, while negative correlations with beta 2-microglobulin and platelet-associated IgG were found in only the positive group. These findings implicate the chronic liver dysfunction present in hemophilia patients, apart from HIV infection, in the decrease in platelet counts, with immunodeficiency playing an additional role in the positive group. In the treatment of a hemophilia B patient showing decreased platelet counts, these counts increased consistent with the administration of Acyclovir and Zidovudine. It was demonstrated that HSV-1 and HIV-1 antigen are present on the soluble platelets of this patient and are recognized by antibodies in the patient's serum.

Adolescent↗

[Hydraulic conductivity of visceral pleura in dogs].

We measured the hydraulic conductivity of the visceral pleura in seven mongrel dogs in situ. The left chest was opened at the seventh intercostal space. A hemispherical capsule, filled with physiological saline, was attached to the visceral pleura of the left lower lobe by the negative pressure in the plate, using a vacuum pump. Transpleural fluid flow (V) was measured at different intracapsular pressures (delta P). The hydraulic conductivity was calculated from the relation between fluid flow and intracapsular pressure, i.e., the slope of the linear regression line. The hydraulic conductivity was 1.49 +/- 0.68 (mean +/- SD) nL.min-1 x cmH2O-2. Our values were smaller than those of former reports obtained in vivo. It is suggested that the dynamics mechanisms of plural effusion may be clarified by studies using our method.

Animals↗

[Mechanism of hepatocarcinogenesis by hepatitis B virus].

The X gene product of hepatitis B virus (HBV) has a trans-activation function. The AP-1, AP-2, kappa B-like, and C/EBP-like sequences, and the 26-bp element in HBV enhancer were identified as X-responsive elements. Although the X protein possesses a transcriptional activation domain, it doesn't bind to the X-responsive elements. However, CREB/ATF-2 becomes able to bind to a CRE-related sequence in the 26-bp element once it complexes with X protein. In addition, X protein was shown to have amino acid sequences homologous to the essential domain of Kunitz-type serine protease inhibitors and directly interacted with the protease, tryptase TL2. Results suggest that X protein modulates the tryptase TL2 activity, which may be involved in the proteolytic cleavage of cellular transcription factors.

Amino Acid Sequence↗

[Transgenic mouse model for hepatocellular carcinoma in human hepatitis B virus infection].

The exact role of hepatitis B virus (HBV) in hepatocarcinogenesis is not known. We generated HBV x gene transgenic mice under the hypothesis that the viral transactivator may alter the host gene expression and lead to the development of hepatocellular carcinoma. The x gene under its own regulatory element caused progressive histopathological changes specifically in the transgenic mouse liver, beginning with multifocal foci of altered hepatocytes, followed by the appearance of neoplasia. This finding shows, for the first time, the direct involvement of HBV in the development of liver cancer. Analyses of events that follow the expression of the x gene suggest that the x gene acts at the early stage of carcinogenesis in the liver.

Animals↗

Intracellular mechanisms of pulmonary vasomotor dysfunction in acute lung injury caused by mesenteric ischemia-reperfusion.

BACKGROUND: A major hemodynamic feature of adult respiratory distress syndrome is pulmonary hypertension secondary to avid pulmonary vascular smooth muscle constriction. This study was undertaken to study the hypothesis that this pulmonary vasoconstriction may derive from pulmonary vasomotor dysfunction. METHODS: A rat model of acute lung injury was studied after 2 hours of superior mesenteric arterial occlusion followed by 4 hours reperfusion. Lung neutrophil accumulation was assessed by myeloperoxidase assay, and lung leak was assessed by iodine 125-labeled albumin lung/blood ratio. The following mechanisms of pulmonary vascular smooth muscle relaxation were studied in isolated pulmonary arterial rings: (1) endothelial-dependent cyclic guanosine monophosphate-mediated, (2) endothelial-independent cyclic guanosine monophosphate-mediated, (3) beta-adrenergic cyclic adenosine monophosphate-mediated. Control rats underwent sham laparotomy. Statistical analysis was done with unpaired Student t test. RESULTS: Lung myeloperoxidase increased from 6.2 +/- 2 to 42 +/- 5 units/gm (p < 0.05), and 125I-labeled albumin lung/blood ratio increased from 0.028 +/- 0.02 to 0.063 +/- 0.03 (p < 0.05) after mesenteric ischemia-reperfusion. beta-adrenergic cyclic adenosine monophosphate-mediated pulmonary vascular smooth muscle relaxation was dysfunctional in the lung-injured rats (62% +/- 5% relaxation versus 95% +/- 3% in controls) (p < 0.05). CONCLUSIONS: These data suggest a mechanistic imbalance of pulmonary vascular smooth muscle contraction and relaxation in acute lung injury. Such imbalance may contribute to the pulmonary hypertension found in adult respiratory distress syndrome.

Acute Disease↗

Gap junction of stratum granulosum cells of mouse follicles: immunohistochemistry and electron microscopy.

The gap junction (GJ) of stratum granulosum cells was investigated in growing and mature follicles of the mouse by means of light- and electron-microscopic immunohistochemistry, freeze-fracturing and deep-etching methods. GJ increased in number and size in concert with the progress of follicular maturation and decreased rapidly in the preovulatory mature follicle. GJ membrane showed invagination, most remarkably at 5 h after hCG injection, within the cytoplasm of the granulosum cell. Two types of internalization seemed possible, annular internalization and highly convoluted tubular invagination, both by an actin-mediated mechanism. At least, a part of the internalized GJ membrane seemed to be degraded by a certain lysosomal enzyme (s). Connexin43 (derived from rat cardiac muscle GJ) was indicated to be a constituent of GJ protein in the mouse stratum granulosum cell. There was no GJ particle coexisting with tight junctional strands; by contrast, a formation plaque appeared quite often on granulosum cells at various stages. Such a plaque is presumed to represent a precursor structure of the new GJ of these cells. So far examined, however, the formation plaque failed to show positive reaction against anti-Cx43 antibody.

Animals↗

Audiometric thresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads (Septopal).

Use of gentamicin-impregnated methylmethacrylate beads is a relatively new and effective method of treating osteomyelitis. Although previous studies have concluded that such therapy is associated with low systemic toxicity, no data are available relating the use of this treatment to ototoxicity and hearing loss. Audiometric thresholds from 28 cases of osteomyelitis treated by surgical debridement and long-term systemic antibiotics alone (14 subjects) or gentamicin-impregnated methylmethacrylate beads either alone or combined with systemic antibiotics (14 subjects) were analyzed. Results showed one permanent threshold shift in the gentamicin-impregnated methylmethacrylate beads group (8%) versus four permanent threshold shifts in the systemic antibiotics alone group (29%). Osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads are at no more risk and are probably at less risk of experiencing ototoxicity than patients treated with conventional long-term systemic antibiotics.

Adult↗

[New useful parameters or makers in diagnosis and condition. Analysis of disseminated intravascular coagulation--mainly molecular markers].

New assays for thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex, FDP-D-dimer, t-PA/PAI-1 complex and prothrombin fragment F1+2 are reviewed as molecular markers for disseminated intravascular coagulation (DIC). These are sensitive to early stage indication of DIC. Fluctuation of their levels was also relative to the state of DIC. It is therefore believed that they will play an important role in the diagnosis of DIC, as solid members of its parameter. On the other hand, t-PA/PAI-1 complex is suggested to be the complication marker of DIC, such as multiple organ failure (MOF), as its level was thought to reflect endothelial cell stimulation during DIC.

Antifibrinolytic Agents↗

[Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

Aged↗

[Estimation of filtration variables in isolated rat lungs for evaluation of pulmonary microvascular permeability].

In order to evaluate the microvascular permeability of donor lungs, we calculated the filtration variables; K (reflection coefficient), simultaneously. For the calculation of filtration variables, the isolated rat lungs were kept in zone three conditions (pulmonary arterial pressure > pulmonary venous pressure > alveolar pressure). We used Krebs-Henseleit solution (K-H) with 6% bovine serum albumin for the perfusate, and maintained perfusion using a constant pressure circuit system. The pulmonary venous and alveolar pressures were maintained at 2.5 and 2.0 cmH2O, respectively, and pulmonary arterial pressure was set so that change in lung weight occurred. We increased both pulmonary arterial and venous pressures by 3 cmH2O simultaneously, and obtained the initial filtration rate. Then we diluted the perfusate with K-H to about half concentration, and obtained the initial filtration rate. We obtained values of filtration variables of K=4.55 mg.min-1.cm H2O-1.g-1], Ppmv=0.59 cmH2O, and sigma =0.617. These values agree with values from previous reports. Since these three filtration variables are interrelated, this method for simultaneous measurement is more accurate than independent measurements. The chief advantages of this method are that it does not require direct measurement of interstitial pressure or collection of lymph fluid, and all variables are obtained simultaneously. Using this method, the vascular permeability of isolated rat lungs, can be estimated.

Animals↗

Stem cell factor enhances proliferation, but not maturation, of murine megakaryocytic progenitors in serum-free culture.

The effects of recombinant rat stem cell factor (SCF/c-kit ligand) on murine megakaryocytopoiesis were studied using partially purified bone marrow cells derived from normal and 5-fluorouracil (5-FU)-treated mice in a serum-free culture system. SCF alone did not support the formation of megakaryocyte (M) and granulocyte-macrophage-megakaryocyte (GMM) colonies. However, the addition of SCF to cultures containing interleukin-3 (IL-3) resulted in a significant increase in the number of M and GMM colonies formed by bone marrow cells from normal mice, whereas IL-6 augmented only M colony growth. The stimulatory effect of SCF was approximately three to four times as high as that of IL-6 on the primitive progenitors capable of megakaryocytic-lineage expression derived from 5-FU-treated mice. In addition, SCF, but not IL-6, significantly increased the number of constituent cells in the individual M colonies supported by IL-3. On the other hand, SCF did not exert any effect on the size and DNA content of megakaryocytes in IL-3-dependent M and GMM colonies, whereas IL-6 enhanced the maturation of megakaryocytes. These results suggest that SCF stimulates the proliferative process in megakaryocytic progenitors and that the main activity of IL-6 is the promotion of megakaryocyte maturation.

Animals↗

Stimulation of mouse connective tissue-type mast cells by hemopoietic stem cell factor, a ligand for the c-kit receptor.

The proliferative capacity of mouse connective tissue-type mast cells (CTMC) was analyzed by using a newly discovered c-kit ligand, termed stem cell factor (SCF). More than 90% of CTMC in the peritoneal cavity responded to recombinant rat SCF (rrSCF) and were able to give rise to pure mast cell colonies in methylcellulose culture. Serial observation (mapping) of growth of individual CTMC in culture containing rrSCF confirmed their striking proliferative ability. No serum but accessory cells (non-CTMC cells) in the peritoneal population were required for the clonal growth of CTMC induced by rrSCF in our methylcellulose culture of whole peritoneal cells. The rrSCF-induced mast cell colony formation from peritoneal CTMC was completely inhibited by the addition of anti-c-kit antibody, which can block the binding of SCF to c-kit, to the culture. When IL-3 was combined with rrSCF, mast cell colonies dramatically increased in size. Mapping studies revealed that the combination of the two factors augmented the proliferative rate of CTMC. Approximately 60% of the constituent cells of the mast cell colonies which were formed from peritoneal CTMC in the culture containing rrSCF alone were stained with berberine sulfate, which is a characteristic of CTMC. However, most mast cells which were induced by rrSCF+IL-3 from peritoneal CTMC contained berberine(-)-safranin(-)-Alcian blue(+) granules. Although IL-4 exhibited little synergism with rrSCF in the induction of CTMC proliferation, the addition of IL-4 to the culture containing rrSCF+IL-3 resulted in an increase in mast cells which retained CTMC characteristics.

Animals↗

[Image-transmission using 64 kbps-ISDN (Integrated Services Digital Network) and mini-PACS].

We carried out the image-transmission using 64kbps-ISDN between two image workstations (IWS) of mini-PACS installed at the Department of Radiology, Osaka Teishin Hospital and the Kashiwa Works, Hitachi Medical Corporation. The distance between Osaka and Kashiwa is about 600 km. The subtraction of two images before and after transmission revealed no change of the data of the image during transmission. For 1/2 compression image, the times of image-transmission of 256 x 256, 320 x 320 and 512 x 512 matrix were 9, 17 and 33 second, respectively. The efficiency of image-transmission was about 80%. Using ISDN, we can make an accurate, rapid and cheap image-transmission.

Computer Communication Networks↗