Idiopathic thrombocytopenic purpura with X chromosome abnormality.
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Adult↗
Biomedical subjects
S Imoto
Publications and source records attributed to S Imoto.
Deregulated c-fos modulates B cell responses to switch mediators.
We examined effects of deregulated c-fos on the proliferation and differentiation of B cells in vitro, using splenic B cells from H2-c-fos transgenic mice. When these cells were cultured with lipopolysaccharide (LPS) plus recombinant interleukin 4 (rIL-4) (10(4) U/ml), the proliferative response of the B cells was augmented with any dose of LPS used. This augmented proliferation resulted in an increase in IgG1 production in the culture, at the lower concentrations of LPS (< 2.5 micrograms/ml). However, H2-c-fos B cells did not produce IgG1 in the culture at higher concentrations of LPS (> 5 micrograms/ml) probably due to the perturbation of B cell differentiation to antibody-forming cells. These results suggest that the deregulated expression of c-fos modulates the proliferation and differentiation of B cells stimulated with LPS plus rIL-4.
Animals↗
Role of I-A molecules in early stages of B cell maturation.
The role of the Ia molecule in the early phase of B cell development remains controversial. In contrast to previous studies, we have detected minute amounts of Ia (I-A) molecule on early B lineage (B220+IgM-) cells from normal bone marrow, using ELISA. The presence of the I-A molecule even on pro-B cells was deduced from experiments in which a monoclonal anti-I-A antibody completely blocked the generation of pre-B cells from B progenitor (B220-) cells in stromal cell-dependent B cell culture. Inasmuch as this antibody did not inhibit the maturation of pre-B cells to IgM+ B cells in culture, the I-A molecule on early B lineage cells probably plays a role in their maturation. We also examined the role of the I-A molecule in early B cell development, using transgenic mice harboring the antisense DNA to I-A beta-chain gene. The amount of I-A molecule on splenic B cells from the young transgenic mice decreased in the presence of abundant amounts of the antisense RNA. B cell development was perturbed in spleen from the transgenic mice. Stromal cell-dependent B cell cultures from these mice clearly showed that the maturation of B lineage cells was delayed at a very early stage of development (B220- to B220+). We propose that the I-A molecule on early B lineage cells may play an essential role in their maturation.
Animals↗
Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia with cyclosporin A.
Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a lymphoma-like disease. Although the histologic appearance of this disease is benign, it is clinically malignant, with chemotherapy being ineffective and the prognosis being poor. In this article, the authors report the results of treating two patients with AILD with cyclosporin A. One patient had cervical lymphadenopathy and fever, and AILD was refractory to both chemotherapy and alpha-interferon. However, treatment with cyclosporin A achieved complete remission. The other patient had generalized lymphadenopathy, and cyclosporin A was used as the treatment of first choice. Complete remission also was achieved in this patient, who still is in remission. These two cases demonstrate that cyclosporin A can be effective for treating AILD.
Cyclosporine↗
Multiple point mutation of N-ras and K-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia.
We analyzed activating mutations of N-ras and K-ras by the polymerase chain reaction and oligonucleotide hybridization in hematological disorders. Activating mutations of these codons were detected in 4 of 20 cases of myelodysplastic syndrome (MDS) and 15 of 77 cases of acute myelogenous leukemia (AML). Our of 19 cases of MDS and AML who carried active mutations, 7 cases were found to have two or more distinct mutations in activating codons of N-ras and K-ras. Ras mutation was found preferentially in progressive disease such as refractory anemia with excess of blasts (RAEB) of RAEB in transformation (RAEB-t). A relatively high incidence of ras mutation was found in M5 AML (40%). No ras mutations were found in other hematological disorders, such as acute lymphoblastic leukemia and chronic myelogenous-leukemia. The most frequent amino acid substitution was that of an aspartate for glycine at codon 12 of N-ras resulting from G to A mutation (11/35). The survival of AML patients who carried ras mutations showed no significant differences from those without ras mutations calculated by Kaplan-Meier. Seven cases of MDS and 7 cases of AML patients could be investigated at various points during their clinical course. Among these 14 cases, we found 2 interesting cases of MDS. The first case lost multiple clones carrying ras mutations during disease progression, the second case acquired mutation of the ras gene during disease progression. These results suggested that multiple point mutations of ras genes may not be initiating events but may contribute to a clonal evolution of MDS and AML.
Adult↗
Renal lesions induced by ochratoxin A exposure in the F344 rat.
Groups of 80 male and female F344 rats were exposed by gavage to ochratoxin A, a naturally occurring mycotoxin, at levels of 21, 70, and 210 micrograms/kg body weight for up to 2 years. Ochratoxin A induced non-neoplastic renal tubular epithelial changes consisting of cytoplasmic alteration, karyomegaly, degeneration, and cysts. Exposure-related renal tubular proliferative lesions included focal hyperplasia, tubular cell adenoma, and tubular cell carcinoma. Renal tubular cell adenoma occurred as early as 9 months in 1 high-dose male rat, and both adenomas and carcinomas were seen in males by 15 months. At the terminal sacrifice, renal tubular cell tumors were found in both male and female rats, but the response was more pronounced in the males. The incidence of renal tumors in the high-dose rats was the highest of any National Toxicology Program (NTP) study completed to date. In the high-dose males approximately one-third of the renal carcinomas developed metastases. This study demonstrates that ochratoxin A is a potent renal carcinogen in the F344 rat and suggests that contamination of feedstuff by this mycotoxin may pose a potential hazard to domestic animals and man.
Adenoma↗
Mesenteric fibromatosis presenting as fever of unknown origin.
We report a case of fibromatosis, soft tissue tumors that are benign histologically, but exhibit behavior intermediate between benign and malignant diseases. Mesenteric fibromatosis grows vigorously without a general inflammatory reaction, and its symptoms are the result of obstruction and/or compression of the intestine. However, in our case, the general inflammatory reactions of fever and C-reactive protein (CRP) elevation was present at an early stage. Because this inflammatory reaction disappeared after surgical resection, it may have been induced by some inflammatory factors produced in the tumor, such as those produced in inflammatory fibrous histiocytoma. We found that computed tomography was useful in the detection of the cause of fever of unknown origin, and suggest that it should be recommended in cases of long-lasting unexplainable fever.
Adult↗
[Study for the nature of interfering substances responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125].
We studied the nature of IgM-like protein responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125. We isolated highly purified IgM-like protein from two patients with non-specifically high CA125 serum values in affinity high performance liquid chromatography (HPLC) using anti-human IgM antibody-TSKgel Tresy15PW column. The isolated IgM-like protein possessed CA125 activity determined in EIA method. SDS-PAGE profiles of this isolated IgM-like protein were compatible with that of normal human IgM, and were distinct from those of CA125 antigen. Moreover, we ruled out the possibility that the Fc region of anti-CA125 monoclonal antibody might be responsible for the non-specific reactive phenomena. Thus, the data obtained from the present study indicate that the IgM-like protein is an anti-idiotypic antibody against the anti-CA125 monoclonal antibody (OC125).
Antibodies, Anti-Idiotypic↗
[Percutaneous transhepatic intraportal administration of amphotericin B to a patient with multiple liver abscesses due to Candida albicans: with monitoring by fungal index as a parameter of Candida volume].
A 59-year-old female with acute promyelocytic leukemia in remission was admitted to our center because of an episode of incidental high fever with general fatigue. She was found to have hepatomegaly. Abdominal CT revealed multiple liver abscesses and a positive culture was obtained for candida albicans from an aspirated abscess. She was treated with percutaneous transhepatic intraportal administration of amphotericin B in addition to oral and intravenous administration. We confirmed the remission of these abscesses by means of the fungal index which is the difference between the values of the limulus test and endotoxin specific test. The fungal index appears to be useful for early diagnosis and treatment of fungal infection.
Amphotericin B↗
[Biological effect of estrogen metabolites in human breast cancer].
In order to investigate the estrogen metabolism in human breast cancer, the estradiol 2- and 16 alpha-hydroxylase (2-, 16 alpha-OHase) activities were determined in the microsomal fractions of human breast tissues by using reverse-phase HPLC. The effects of estrogen metabolites on the cell proliferation were also examined by employing two human breast cancer cell lines. The 2-OHase activity was detected in most cancerous and noncancerous tissues, but the value in cancerous tissues was significantly lower than that in noncancerous tissues (p less than 0.05). Patients without lymph node metastases showed relatively higher activity than those with metastases (0.05 less than p less than 0.1). The 16 alpha-OHase activity was, however, found in only 23% of cancerous tissues. Among those, the activity was present in 52% of ER positive cancerous tissues, but almost absent in ER negative ones. The growth ER positive cell line, MCF-7, was suppressed with 2-hydroxyestrone and stimulated with 16 alpha-hydroxyestrone. The cell proliferation stimulated with 16 alpha-hydroxyestrone was not inhibited by the addition of tamoxifen, a strong antagonist of estradiol. Two metabolites had no effect on the growth of ER negative cell line, MDA-MB-231. These results suggest that estrogen metabolites influence the proliferation of human breast cancer cells as the endogenous regulatory factors and should be considered for the future endocrine therapy.
Adolescent↗
Loss of multiple point mutations of RAS genes associated with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome.
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Aged↗
Spontaneous remission in pure red cell aplasia associated with thymoma.
A 57-year-old woman with thymoma-associated pure red cell aplasia (PRCA) manifested spontaneous recovery of erythropoiesis. Anemia recurred before the surgical removal of her thymoma, however, and the second anemic remission following surgery did not occur promptly. In this report, we describe a rare occurrence of spontaneous remission in PRCA.
Erythropoiesis↗
[A remarkable effect of alpha-interferon in a case of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) refractory to steroids and combination chemotherapies].
We experienced a remarkable effect of recombinant interferon alpha 2a (alpha-IFN) in a case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which was refractory to steroids and combination chemotherapies. A 62 year-old woman was admitted because of high grade fever and extreme swelling of cervical lymph nodes. Poly-clonal hypergammaglobulinemia and plasma cell-like atypical lymphocytosis in the peripheral blood were demonstrated. Cervical lymph node biopsy disclosed histology of AILD. She initially responded well to prednisolone. Three months later, AILD relapsed in spite of prednisolone treatment. She received combination chemotherapies and responded well again. Seven months later, she became refractory to these combination chemotherapies. Consequently, we tried alpha-IFN (3 million units/day given intramuscularly). She became afebrile on the next day, and lymph nodes swelling gradually disappeared. She has been free from the disease for more than three months.
Antineoplastic Combined Chemotherapy Protocols↗
[Complete remission in erythroleukemia: induced with low dose Ara-C, consolidated with high dose Ara-C].
A 20-year-old man was admitted because of general fatigue. Peripheral blood examination revealed pancytopenia (WBC 1,700/microliters, RBC 210 x 10(4)/microliters, Plt 3.2 x 10(4)/microliters) with remarkable erythroblastosis. Bone marrow examination revealed erythroid hyperplasia and an increase of abnormal myeloblasts with Auer bodies (37% of non erythroid cells). A diagnosis of erythroleukemia (AML M6) was made. He received two courses of combination chemotherapy (BHAC-DMP and VAMA (VP-16, Ara-C, 6-MP, and doxorubicin (ADR)) but complete remission (CR) could not be achieved. Consequently, he was treated with LDAC. After two courses of LDAC. CR was obtained. Subsequently, he received two courses of HDAC as consolidation, and therapy has been off thereafter. He remains in CR state for more than 12 months.
Adult↗
[Study of non specific reactive phenomena in EIA method of CA 125].
We studied the false positive phenomena in immunoassay of CA 125 using mouse monoclonal antibody, and studied the natures of interfering substances. The serum CA 125 level in 405 patients was determined simultaneously by using the EIA and RIA methods. The overall correlation was good between CA 125 levels of the EIA and RIA methods. However, CA 125 levels in 41 cases were remarkably higher in the EIA method as compared with the RIA method. None of these patients had any disease that was known to result in elevation of the serum CA 125 level. The CA 125 activity of sera from five patients with remarkably discrepant values was contained in the column fractions corresponding to a molecular weight of human IgM in gel chromatography of TSK gel G 4000 SWXL that was smaller than the molecular weight of CA 125. To further determine whether IgM was involved in the CA 125 activity, we investigated the effect of adding anti-human IgM serum to discrepant sera. CA 125 activity was markedly reduced by the antiserum, whereas CA 125 activity in non-discrepant sera were not effected by this antiserum. Thus, data obtained from this group of experiments indicate that the interfering material in discrepant serum is IgM.
Antibodies, Monoclonal↗
[Complete remission in multiple myeloma with natural interferon-alpha (HLBI) and melphalan/prednisolone intermittent therapy].
A 46-year-old man was admitted because of lumbago and numbness of the left leg. Pelvic X-ray showed a large defect in the left sacrum and CT revealed multiple punched-out lesions. Serum IgA was 1,740 mg/dl with a monoclonal component of IgA kappa by serum electroimmunofixation. Bence Jones protein of kappa type was detected in urine. Diagnosis of myeloma was made on the basis of histology of the biopsied sacral tumor. Repeated melphalan/prednisolone intermittent therapy (MP) was done with concomitant administration of natural interferon-alpha (IFN-alpha) 3 X 10(6) U intramuscularly for 67 days. Performance status including gait markedly improved. Normal bone marrow morphology and disappearance of M-protein by electroimmunofixation were achieved after 13 cycles of MP, when pelvic X-ray revealed prominent recalcification. No further treatment was instituted for subsequent 6 months, without any demonstrable M-protein. Complete remission of myeloma is rare with conventional therapies and thus new therapeutic modalities have been waited for. IFN-alpha may promise better responses if appropriately combined with other chemotherapies.
Antineoplastic Combined Chemotherapy Protocols↗
[Administration of haptoglobin in ABO incompatible bone marrow transplantation].
Haptoglobin was administered i.v. in 2 cases of ABO incompatible bone marrow transplantation for the prevention of hemoglobinuria due to acute hemolysis. The first case was a 25-year-old woman with severe aplastic anemia. The transplantation was both major and minor mismatch, where the donor was type A and the recipient was type B. The second case was a 31-year-old man with chronic phase of chronic myelogenous leukemia. The transplantation was major mismatch, where the donor was type B and the recipient was type O. After the administrations of haptoglobin 8,000 units we transfused bone marrow infusates from which incompatible erythrocytes were removed. Though prominent hemoglobinemia was observed in both cases, the serum haptoglobin values were not saturated and hemoglobinuria was not detectable. Haptoglobin appears to be useful for the prevention of acute renal failure associated with acute hemolysis in ABO incompatible bone marrow transplantation. Intravenous haptoglobin supplement therapy makes transplantation safer and may contribute to improve the recovery rate of total nucleated bone marrow cells after the erythrocyte depletion without worrying much about their contamination.
ABO Blood-Group System↗
[Successful treatment by a drainage of subdural hematoma in a case of intracranial hemorrhage due to DIC complicated with acute promyelocytic leukemia].
A 24 year-old female was admitted because of hypermenorrhea and petechiae. The peripheral blood tests on admission were consistent with acute promyelocytic leukemia complicated with DIC. BHAC-DMP therapy was started along with platelet transfusions and heparin administration. On the day 9 of admission, on the contrary to the improvement of hematological data, the patient suffered from severe headache and nausea. The neurological examination revealed anisocoria. Right side chronic subdural hematoma was a diagnosis made by emergency CT scan and was treated with drainage of the hematoma. Post-operatively, the patient did well, and achieved complete remission on the day 43 of admission. Since intracranial hemorrhages due to DIC complicated with leukemia are often fatal, those patients are usually treated conservatively. However, as shown in this case report, some cases might have an indication for the neurosurgical operation. It is important to check conditions carefully whether the patient has an indication for the operation.
Adult↗