11q23 abnormality and chronic myelomonocytic leukemia.
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Chromosome Deletion↗
Biomedical subjects
K Takatsuki
Publications and source records attributed to K Takatsuki.
A new form of alpha-chain disease with generalized lymph node involvement.
An autopsy case of alpha-chain disease (ACD) clinically manifesting generalized lymph node swelling, slight splenomegaly and long-standing ichthyosiform skin eruptions, was reported. Autopsy revealed systemic superficial and profound lymph node swelling and slight splenomegaly, but little or no tumorous lesion in any part of the alimentary tract or pulmonary tissue. The histologic picture of the lymph nodes showed a diffuse monomorphic plasmocytic lymphoma, and there was tumor cell infiltration in the spleen and bone marrow. Immunohistochemistry demonstrated that the tumor cells contained IgA devoid of light chains, i.e. ACD protein. Immunoelectron microscopy revealed that this abnormal immunoglobulin was localized in the rough endoplasmic reticulum and perinuclear space. Persistent chronic inflammation with infiltration mainly of helper-inducer T cells were found in the skin and dermatopathic lymphadenopathy was confirmed in the lymph node biopsies. From these peculiar clinicopathological features, this case is considered to be a previously unknown form of ACD.
Humans↗
Conserved immunogenic region of a major core protein (p24) of human and simian immunodeficiency viruses.
A murine monoclonal antibody (MoAb), VAK 4, has been known to specifically react with a major core protein (p24) as well as with its precursor (p55-57) and intermediate precursor (p40) of human immunodeficiency virus strain IIIB (HTLV-IIIB). Radioimmunoprecipitation assays revealed that VAK 4 MoAb precipitated a major core protein and its precursors from a variety of strains of HIV and also from simian immunodeficiency virus (SIV), although the molecular weights of the precursor proteins in each viral strain were slightly different. A protein synthesized by transfected Escherichia coli containing amino acid sequences corresponding to residues 121-436 of the HTLV-IIIB gag gene was reactive with VAK 4 MoAb, but the protein carrying only residues 121-309 was not reactive, suggesting that the epitope recognized by VAK 4 MoAb resides at the carboxyl terminus of p24 protein. A competitive enzyme-linked immunosorbent assay showed that patient sera containing anticore protein antibody inhibited the binding of VAK 4 to HTLV-IIIB. These findings suggested that VAK 4 MoAb recognized an immunogenic and conserved epitope belonging to a major core protein of HIV-related viruses.
Antigens, Viral↗
A gag-env hybrid protein of human T-cell leukemia virus type I and its application to serum diagnosis.
A fused gene of the gag and env sequences of human T-cell leukemia virus type I (HTLV-I), the causative agent of adult T-cell leukemia, was constructed in vitro and expressed in Escherichia coli. The gag-env hybrid protein accumulated as insoluble granules with a yield of approximately 12% of the total proteins. In an enzyme-linked immunosorbent assay done with the use of the gag-env hybrid protein, all 57 seropositive sera gave positive signals, and none of the sera from normal persons did. This system can produce large quantities of the gag-env hybrid protein, which can be used for mass screening of human sera for HTLV-I infection.
Epitopes↗
Histo- and immunopathological features of terminal AIDS. An autopsy case of a Japanese man with neurological signs as initial symptoms.
An autopsy case of a 37-year-old Japanese man, confirmed as an AIDS patient infected by an undetermined route of transmission, is presented. The initial symptoms of full-blown AIDS in this case were neurological, and the patient died of severe pneumonia 9 months after onset. The main histo- and immunopathological features were a marked depletion of helper-inducer T cells and dendritic reticulum cells in the lymphoid tissues, opportunistic infections, and some neuropathologic changes. Very few cells, possibly macrophages, immunoreactive with a monoclonal antibody (VAK-5) against HIV-gag protein P24 were found in the mediastinal lymph nodes. Numerous pathogens had induced opportunistic infections in many organs: severe and generalized cytomegalovirus infection, Pneumocystis carinii pneumonia, bronchopneumonia (possibly due to Pseudomonas aeruginosa), candidiasis in the tongue and oral cavity, and atypical mycobacteriosis in the pulmonic hilar lymph nodes. Vascular proliferation was found in the perinodal regions of some lymph nodes, but this was not neoplastic vascular proliferation compatible with that of localized Kaposi's sarcoma.
Acquired Immunodeficiency Syndrome↗
Exchange blood transfusion for acute hepatic failure: its limited availability depending on the type of injury in rats.
The efficacy of exchange blood transfusion for acute hepatic failure was evaluated using rats. Rats receiving a dose of carbon tetrachloride died later than 24 h after dosing. When their blood was replaced with blood from normal rats at 24 h, survival time was prolonged, and hepatic protein synthesis was enhanced at 36 h with improved prothrombin time (PT). Those rats surviving 120 h showed better histological grade of recovery from injury after treatment. In contrast, dimethylnitrosamine (DMN)-intoxicated rats showed no such improvement in survival time or PT. In rats given a nonfatal dose of carbon tetrachloride, serum glutamic-pyruvic transaminase values were five times higher than those in rats given DMN despite similar maximal PT. The benefit of exchange transfusion for acute hepatic failure may differ depending on the mechanism of development in rats. Enhanced hepatic protein synthesis may contribute to its effect.
Acute Disease↗
Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope.
A monoclonal antibody was produced to the exterior envelope glycoprotein (gp120) of the human T-cell lymphotropic virus (HTLV)-IIIB isolate of the human immunodeficiency virus (HIV). This antibody binds to gp120 of HTLV-IIIB and lymphadenopathy-associated virus type 1 (LAV-1) and to the surface of HTLV-IIIB- and LAV-1-infected cells, neutralizes infection by cell-free virus, and prevents fusion of virus-infected cells. In contrast, it does not bind, or weakly binds, the envelope of four heterologous HIV isolates and does not neutralize heterologous isolates HTLV-IIIRF and HTLV-IIIMN. The antibody-binding site was mapped to a 24-amino-acid segment, using recombinant and synthetic segments of HTLV-IIIB gp120. This site is within a segment of amino acid variability known to contain the major neutralizing epitopes (S. D. Putney, T. J. Matthews, W. G. Robey, D. L. Lynn, M. Robert-Guroff, W. T. Mueller, A. J. Langlois, J. Ghrayeb, S. R. Petteway, K. J. Weinhold, P. J. Fischinger, F. Wong-Staal, R. C. Gallo, and D. P. Bolognesi, Science 234:1392-1395, 1986). These results localize an epitope of HIV type-specific neutralization and suggest that neutralizing antibodies may be effective in controlling cell-associated, as well as cell-free, virus infection.
Amino Acid Sequence↗
Comparison of immunoperoxidase staining with indirect immunofluorescence, ELISA, and Western blotting assays for detecting anti-HTLV-I antibodies in systemic lupus erythematosus.
Serum antibodies against human T cell leukaemia virus type I (HTLV-I) were investigated in 12 patients by four methods: indirect immunoperoxidase staining, indirect immunofluorescence, enzyme linked immunosorbent assay (ELISA), and strip radioimmunoassay based on the Western blotting assay. Seven patients had systemic lupus erythematosus (SLE) and five various autoimmune diseases with one or more circulating autoantibodies. Serum samples from three patients were found to be HTLV-I-positive by the ELISA assay and sera from five patients showed a non-specific reaction by indirect immunofluorescence. These sera were negative when tested by indirect immunoperoxidase staining and Western blotting assay. All four methods gave positive results when tested with samples from 19 HTLV-I carriers and 16 patients with adult T cell leukaemia. Indirect immunoperoxidase staining and Western blotting assay are probably useful and more specific assays for the detection of anti-HTLV-I antibodies in samples from patients with autoimmune diseases.
Adult↗
Effect of the opioid kappa-receptor agonist U50488H on the secretion of arginine vasopressin. Study on the mechanism of U50488H-induced diuresis.
The effect of U50488H, a potent opioid kappa-receptor agonist, was investigated on the urine volume and on the secretion of arginine vasopressin (AVP) in response to dehydration or hyperosmolar or hypovolemic stimulation in conscious rats. This agonist markedly increased the urine volume in normally hydrated rats and suppressed plasma AVP in a dose-dependent manner in rats given hyperosmolar saline. This suppression of plasma AVP was completely reversed by concurrent injection of naloxone. U50488H also inhibited the release of AVP in dehydrated or hypovolemic rats. These findings indicate that the diuresis induced by U50488H is mainly caused by the suppression of plasma AVP. They also suggest that the kappa-opioid receptor plays an important role in regulating the secretion of AVP.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Clinical study on the serum levels of immunosuppressive acidic protein in patients with adult T-cell leukemia.
Serum levels of immunosuppressive acidic protein (IAP) were measured in patients with adult T-cell leukemia (ATL) in order to clarify its significance in this disease. The mean levels in patients with both acute (854 +/- 404 micrograms/ml) and chronic ATL (439 +/- 103 micrograms/ml) were significantly higher than in sera of healthy controls (367 +/- 104 micrograms/ml). However, mean levels in patients with smoldering ATL, healthy T-cell lymphotropic virus type 1 (HTLV-1) carriers and healthy controls showed no differences. Levels in crisis in chronic and smoldering ATL were similar to those in patients with acute ATL. Serial measurements of serum IAP in a number of patients revealed that the levels reflected each patient's clinical course, suggesting a potential for use in evaluating the effects of chemotherapy.
Deltaretrovirus Infections↗
Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.
One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.
Antineoplastic Combined Chemotherapy Protocols↗
Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.
Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.
Antineoplastic Combined Chemotherapy Protocols↗
Influence of thyroid function on serum bone Gla protein.
The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.
Adolescent↗
Effect of parathyroid function on serum bone Gla protein.
The serum bone Gla protein (BGP) level was measured in patients with idiopathic hypoparathyroidism, and primary hyperparathyroidism, and normal volunteers. The mean serum BGP level was 4.5 +/- 0.20 micrograms/l in 40 normal volunteers. It was significantly lower in 12 patients with idiopathic hypoparathyroidism (1.6 +/- 0.21 micrograms/l, p less than 0.001) and significantly higher in 33 patients with primary hyperparathyroidism (13.0 +/- 1.3 micrograms/l, p less than 0.001). When a single intravenous injection of 30 micrograms of human PTH 1-34 was administered to the patients with idiopathic hypoparathyroidism, there was no significant change in serum BGP within the next 24 hours. Following a therapeutic oral dose of alfacalcidol, serum BGP was appreciably increased (p less than 0.001) from the preadministration value of 1.6 +/- 0.21 micrograms/l to 3.9 +/- 0.34 micrograms/l. In patients with primary hyperparathyroidism, the surgical excision of parathyroid adenoma led to a sharp decrease in serum PTH but a gradual decrease in serum BGP. The latter approximately paralleled the decline in serum alkaline phosphatase. Thus, serum BGP is a marker that reflects bone turnover status in parathyroid disease. It appears that the active form of vitamin D directly increases the secretion of BGP in existing osteoblasts and PTH mainly affects serum BGP to stimulate the bone remodeling cycles with its long term effect.
Adenoma↗
Studies of structure-function relationship of human parathyroid hormone using rat and human renal cortical cells in culture.
The structure-function relationship of human PTH was studied by testing the effects of its synthetic analogues on cAMP production in cultures of rat and human renal cortical cells. The human cell system was by two orders more sensitive to an agonist, hPTH1-34, than the rat cell system. In both culture systems, Tyr34hPTH3-34NH2, which by itself had no influence on adenylate cyclase, caused approximately 90% inhibition of the hPTH 1-34-induced cAMP production at a molar ratio of 1000:1. On the other hand, Tyr34hPTH5-34NH2, Tyr34hPTH7-34NH2, Tyr34hPTH8-34NH2 and Tyr34hPTH9-34NH2 had weak but distinct agonist activity. When these four analogues were tested in the presence of hPTH1-34, they acted as antagonists in the human cell system, whereas they still showed agonist activity in the rat cell system which was additive to that of hPTH1-34. These data indicate that the amino acids at positions 1 and 2 of hPTH are important for its biological activity and that those in the sequence 9-34 also participate in the activation of adenylate cyclase. The higher sensitivity to hPTH1-34 and the different response to some of the analogues of human renal cortical cells compared with rat renal cortical cells emphasize the importance of employing human cell systems in evaluating the structure-function relationship of hPTH.
Animals↗
Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese.
Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for BglII restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor beta-chain (TLR beta)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P less than .02) and 2.42 (P less than .01), respectively. Hybridization of digested DNA with the TLR beta probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P less than .05) higher than that in normal subjects (64%). When TLR beta-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P less than .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLR beta-region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLR beta loci, as has been demonstrated in Caucasians.
Adolescent↗
Glucagon and insulin for the treatment of hepatic failure in dimethylnitrosamine-intoxicated rats.
When rats received dimethylnitrosamine every 24 h until death, plus hormone treatment after the first 24 h, the survival was enhanced between 100 and 140 h compared with the control rats, with attenuated derangements of prothrombin time and serum albumin levels at 120 h. In rats given a single dose of dimethylnitrosamine, hepatic DNA synthesis peaked at 48 h. The synthesis was increased after hormone treatment when started immediately, but not when delayed for 24 h. Hormone treatment for 3 days starting 24 h after a single dose of dimethylnitrosamine produced a rapid normalization of decreased hepatic protein content on day 9, although hepatic DNA content was not affected. These results suggest that this treatment is effective for hepatic failure, and the promotion of restoration of liver function is a contributing factor to its effect, in addition to the stimulation of hepatocyte proliferation.
Animals↗
Establishment and characterization of an amylase-producing human myeloma cell line.
Two stable lines of IgA lambda-producing plasma cells (KHM-1A and KHM-1B) that were free of the Epstein-Barr virus were established from a patient with multiple myeloma complicated by hyperamylasemia. Surface marker studies of the two cell lines showed that the cells had no surface immunoglobulins but were positive for cytoplasmic immunoglobulins (IgA lambda) and for HLA-DR and PCA-1. Secretion of IgA monoclonal immunoglobulin by the two lines was detected by a plaque-forming cell assay and by an enzyme-linked immunosorbent assay of culture media. KHM-1B cells also secreted alpha-amylase, but no such activity was detected in the culture-conditioned supernatant fluid of KHM-1A.
Amylases↗