[Exacerbation of hypertriglyceridemia in two patients with chronic hepatitis C during interferon therapy].
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Biomedical subjects
Publications and source records attributed to K Okawa.
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To examine the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery after high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT), 20 patients with hematologic malignancies were divided into two groups. One group was given G-CSF at a daily dose of 50 micrograms/m2 subcutaneously, the other received no G-CSF. Neutrophil recovery was accelerated in the G-CSF treated patients and exceeded 0.5 x 10(9)/l at a median of 10 days post-PBPCT compared with 14 days in the control group (p < 0.01). This reduction led to a decrease in antibiotic use and a trend toward fewer febrile days in the G-CSF treated group.
Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and progenitor cells in the blood and bone marrow from 10 patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells, which were obtained before chemotherapy (BMMNCbefore) and after the stem cell collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The purified cells were stained with FITC-conjugated anti-CD34 antibody and one of the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19, CD33, CD38, CD45RO, CD56, and HLA-DR. CD34+ PBMNC harvested and the CD34+ BMMNCafter expressed CD13 and CD33 more frequently than CD34+ BMMNCbefore but expressed CD10 and CD19 less frequently than CD34+ BMMNCbefore. These data suggested that harvested PBMNC contain more myeloid lineage committed progenitors than BMMNCbefore, which might contribute to the rapid recovery of neutrophils after peripheral blood stem cell transplantation. No significant phenotypic differences of CD34+ cells between harvested PBMNC and BMMNCafter were observed except for the expression of CD11c. CD34+ PBMNC harvested coexpressed CD11c more frequently than both CD34+ BMMNCbefore and CD34+ BMMNCafter, which expression might be associated with commitment to the monocyte lineage.
In order to clarify the effects of longterm inhaled steroid therapy on bone metabolism, we examined 72 patients with bronchial asthma treated mainly with BDP (beclomethasone dipropionate). Multiple scanning X-ray photodensitometry was used to evaluate the degree of bone mineral loss. Osteocalcin, alkaline phosphatase (total and type III) was measured as a marker of bone synthesis and urinary pyridinoline, and deoxy-pyridinoline was measured as a marker of bone resorption. There was age related bone mineral loss. Urinary pyridinoline increased with aging. Treatment related bone mineral loss was not observed either in cases treated with BDP or in cases treated with continual oral steroids. Urinary pyridinoline and deoxy-pyridinoline decreased in patients treated with larger doses of for longer periods with BDP. Serum osteocalcin levels were lower in patients on continual oral corticosteroids. We conclude that inhaled steroid do not deteriorate bone metabolism in patients with bronchial asthma, when used appropriately.
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The reconstitution of lymphocyte subsets after high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) was studied using two-color flow cytometry in 14 patients with acute leukemia (four AML and two ALL) and malignant lymphoma (six NHL and two HD). The CD3+HLA-DR+ lymphocytes (activated T cells) and CD8+ lymphocytes increased markedly by 4 weeks after PBSCT. Most of the increased CD8+ lymphocytes were CD11b-, S6F1+ cells and CD8+CD11b+ cells remained low throughout the follow-up period. The CD4+ lymphocytes remained below the normal range up to 34 weeks after PBSCT. The ratio of CD4+ to CD8+ lymphocytes (CD4/CD8 ratio) transiently increased and then decreased below 1.0 at 2 weeks after PBSCT. The CD19+ lymphocytes and the CD3-CD16+CD56+ lymphocytes returned to normal levels in the early period. The CD4+CD45RA+ lymphocytes (suppressor-inducer) decreased to below the normal range, while the CD4+CD45RO+ lymphocytes (helper-inducer) increased more rapidly than the CD4+CD45RA+ lymphocytes. This study shows that an immunosuppressed state exists after PBSCT as is seen after bone marrow transplantation (BMT) and that B cell reconstitution is more rapid in PBSCT than in BMT.
A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.
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In this study the effect of K-76, a sesquiterpene compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochemical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotein concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.
We investigated the effects of long-term therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe aplastic anemia (SAA). The patient was too old to receive a bone marrow transplantation, and high-dose methylprednisolone and antilymphocyte globulin were ineffective. We administered rhG-CSF in combination with metenolone acetate. Trilineage blood cell components were recovered 6 months later. These findings suggest that long-term G-CSF therapy may be beneficial in patients with SAA who are not candidates for bone marrow transplantation.
A 56-year-old woman was admitted to our hospital in January, 1990 because of fever and petechiae. Leukocyte count of peripheral blood showed 41,000/microliters with 89% immature cells, and bone marrow was normocellular with 96.2% immature cells. They were medium to large in size, positive for peroxidase staining, CD-13 and CD-33. Half of them contained azurophilic granules. They showed metachromasia by toluidine blue, contained basophilic granules in electron microscopic examination and reacted to G-CSF, G-CSF and IL-3. She was diagnosed as acute basophilic leukemia and treated with BHAC-DMP and B triple-V regimen, but remission was not attained. She died of peritonitis due to gastrointestinal tract perforation and pneumonia in March, 1990. This is the fifteenth case of acute basophilic leukemia reported in Japan, and the hematological examinations performed in this patient were demonstrated.
A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.
Developing neurons transiently grow numerous spine- or filopodium-like dendritic protrusions (SLDPs). Electron microscopy on identified input and intracellular staining of postsynaptic cells were performed to gain insight into their significance. Newborn kitten-corticorubral axons, labelled with biocytin, commonly made synapses on SLDP, often multiply invaginated by the SLDPs. Correspondingly, intracellularly labelled kitten rubrospinal cells had numerous SLDPs. Taking into account that corticorubral synapses are largely formed on dendritic shafts in adult cats, it is likely that the SLDPs play some important role in the development of corticorubral synapses. We hypothesize that rubrospinal cells elongate SLDPs searching for corticorubral axons to form synapses.
The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease.
We developed an effective method for harvesting large numbers of peripheral blood stem cells (PBSC) for use in autotransplantation. Twenty patients with hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP-16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The optimal time for starting PBSC collection was determined by monitoring the CD34-positive stem cells in blood using immunomagnetic beads. PBSC were collected with a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was processed in each apheresis. Under these conditions, a total of 64 apheresis procedures was performed in the 20 patients. The mean numbers of mononuclear cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x 10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x 10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So far, 11 patients have been transplanted with PBSC and obtained rapid hematopoietic recovery. The median time to recover neutrophils more than 0.5 x 10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method for harvesting large numbers of PBSC allows safer autotransplantation in patients with chemoradiosensitive tumors, and is applicable to older patients.
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