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Biomedical subjects

H Tasaka

Publications and source records attributed to H Tasaka.

At least 19 recordsLinked to original sources

Growth retardation in childhood leukemia and lymphoma. Special reference to patients with CNS relapse.

We studied the growth of 89 patients who were long-term survivors of childhood leukemia and lymphoma. Eight patients with CNS relapse had a greater decrease in height standard deviation score (SDS) after the relapse than 81 patients without CNS relapse (p less than 0.0001). Two patients who received cranial irradiation when they were younger than 2 years of age demonstrated a marked decrease in height SDS more than 3.0 SD. Five patients appeared to have a decline in height SDS before their CNS relapse. There were no apparent changes in the weight of patients with or without CNS relapse. In endocrine studies, all eight patients with CNS relapse failed to show the normal growth hormone (GH) response to arginine, GH-releasing factor, and glucagon-propranolol tests, while spontaneous GH secretion during sleep was normal. Magnetic resonance imaging (MRI) revealed small pituitary glands in seven patients with CNS relapse. These findings suggest that in leukemia and lymphoma patients with CNS relapse, GH secretion is impaired at the hypothalamic level, resulting in a secondary atrophy of the pituitary gland. The MRI together with selected endocrinologic tests may help to clarify the mechanism of growth impairment in such patients. A decline in height SDS in each patient may be a useful marker for predicting a CNS relapse in a child with leukemia or lymphoma.

Adolescent

Modulation of expression of delayed hypersensitivity by mycobacterial antigen 85 fibronectin-binding proteins.

Although demonstration of delayed hypersensitivity to purified protein derivative of tuberculin (PPD) is an important element in the diagnosis of infection with Mycobacterium tuberculosis, many patients with tuberculosis are anergic. Several possible mechanisms for this specific lack of response have been described. We have now uncovered an additional one. T-cell fibronectin (FN), a lymphokine secreted by activated T cells, is closely associated with the initiation of delayed hypersensitivity reactions. Mycobacterial antigen 85 (Ag85) proteins have been shown to bind to plasma FN. The ability of Ag85 to bind to T-cell FN and modulate expression of delayed hypersensitivity was therefore studied. Purified Ag85 proteins from M. tuberculosis, Mycobacterium bovis BCG, or Mycobacterium kansasii bound to T-cell FN, fibroblast FN, and plasma FN in vitro. Purified 65-kDa heat shock protein (hsp65) from M. bovis BCG did not bind to any FN. Ag85, but not hsp65, inhibited the ability of T-cell FN to agglutinate monocytes in vitro in a dose-dependent manner. In vivo, mixtures of PPD or dinitrophenyl-ovalbumin and purified M. tuberculosis or M. bovis BCG Ag85 proteins elicited significantly smaller delayed hypersensitivity inflammatory reactions in sensitized guinea pigs than did PPD or dinitrophenyl-ovalbumin alone. Purified hsp65 did not inhibit expression of delayed hypersensitivity to PPD or dinitrophenyl-ovalbumin. We suggest that Ag85 proteins could inhibit in vivo expression of delayed hypersensitivity during mycobacterial infections because of their interaction with T-cell FN.

Agglutination

Abnormal development of cardiovascular systems in rat embryos treated with bisdiamine.

Administration of N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine, bisdiamine, in pregnant Donryu rats on day 10 of gestation induces a high incidence of cardiovascular anomalies in fetuses. Bisdiamine administration induced aplasia of the sixth aortic arch artery, with both the right and left primitive pulmonary arteries being directly linked to the truncus, and resulting in four types of malformation of pulmonary arteries (PAs). When two primitive PAs shared a single root, the consequence was either pulmonary trunk hypoplasia, as is seen in tetralogy of Fallot, or type I persistent truncus arteriosus (PTA) as classified by Collet and Edwards. When root portions of two PAs did not fuse, either type II or type III PTA resulted. In controls, the right dorsal aorta (DA) between the right seventh intersegmental artery (IA) and the site where both DAs fuse degenerated and the left aortic arch (AA) and the right subclavian artery (SA) were formed. Bisdiamine administration induced two additional types of vascular anomalies. In one of these, the right DA between the right 4AA and the right 7IA degenerated and a left AA accompanied by an aberrant right SA resulted. In the other type, the left DA between the left 4AA and the left 7IA degenerated and a right AA accompanied by an aberrant left SA resulted. These results indicate that administration of bisdiamine induces malformation in the great blood vessels by disturbing persistency and degeneration of aortic arch arteries and DAs.

Abnormalities, Drug-Induced

Virus-associated haemophagocytic syndrome with Epstein-Barr virus infection.

The clinical and histological findings of a 10-year-old girl with virus-associated haemophagocytic syndrome are presented. The serum levels of Epstein-Barr viral antigens were elevated. Epstein-Barr virus (EBV) genome was detected by polymerase chain reaction in bone marrow and lymph node specimens. Histologically, haemophagocytic histiocytes were present in bone marrow, and areas of non-suppurative necrosis were present in lymph nodes, where silver grain deposition of the EBV genome was demonstrated by in situ hybridization.

Antigens, Viral

Juvenile granulosa cell tumor in association with a high serum inhibin level.

Inhibin is a glycoprotein hormone produced mainly by ovarian granulosa cells. Recently measurement of serum inhibin levels was made possible by radioimmunoassay. We describe a patient with a juvenile granulosa cell tumor, a distinctive and rare form of granulosa cell tumor. This patient's serum inhibin level was extremely high preoperatively and returned to normal after the tumor was resected. This case suggests that serum inhibin level may be a useful marker of granulosa cell tumors.

Biomarkers, Tumor

Prognosis of children with virus-associated hemophagocytic syndrome and malignant histiocytosis: correlation with levels of serum interleukin-1 and tumor necrosis factor.

To clarify the correlation of cytokine level with the severity and prognosis of children with the hemophagocytic syndrome, we analyzed serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) levels in 26 children with either the virus-associated hemophagocytic syndrome (VAHS, n = 12) or malignant histiocytosis (MH, n = 14). When compared to healthy controls, 13 children had an elevated IL-1 (greater than or equal to 20 pg/ml) and 21 children had an elevated TNF (greater than or equal to 10 pg/ml) level at diagnosis. There was however, no significant difference in the frequency of these high levels between the patients with VAHS and MH. Neither IL-1 nor TNF levels correlated with other clinical or laboratory findings in either VAHS or MH. Two of the 12 patients with VAHS died of an intracranial hemorrhage and 7 of the 14 patients with MH died despite chemotherapy. The MH patients who had a high TNF level (greater than or equal to 50 pg/ml) had a poorer prognosis than those with a low TNF level (less than 50 pg/ml; p less than 0.01). In MH patients, other parameters, such as coagulopathy and lactic dehydrogenase, ferritin and IL-1 levels, did not correlate with prognosis. In 3 patients (2 with VAHS and 1 with MH) analyzed periodically, the change in TNF level was closely associated with the clinical progression or regression of the diseases. Serum cytokine levels may thus be monitored not only for predicting the severity and prognosis of VAHS or MH but also for determining the indications for or timing of chemotherapy. Moreover, TNF may play an important role in the progression of VAHS and MH.

Adolescent

[Identification of Mycobacterium avium and Mycobacterium intracellulare using three DNA probe tests, and their distributions in Japan].

Identification of Mycobacterium avium complex (MAC) was made using three DNA probe tests for MAC: Gen-Probe Rapid Diagnostic System for the MAC (Gen-Probe Inc., San Diego, U.S.A.), AccuProbe MAC Culture Identification or Confirmation Test (Gen-Probe Inc.); and SNAP Culture Identification Diagnostic Kit (MAC) (Syngene Inc., San Diego, U.S.A.). Various strains of MAC belonging to serovars 21 to 28 were identified by the DNA probe tests and showed the following. First, Serovar 21 and 25 belonged to M. avium and M. intracellulare, respectively. Each of them reacted with species-specific probes used in the three DNA probe tests [i.e., either M. avium-probe (in SNAP test; Probe A) or M. intracellulare-probe (in SNAP test; Probe I)]. Second, serovars 22-24 and 26-28 consisted of M. intracellulare, MAC strains that reacted with Probe X of SNAP test but lacked the reactivity with M. avium- and M. intracellulare probes of all the DNA probe tests, M. scrofulaceum that showed no reactivity with M. avium- or M. intracellulare-probe or Probe X, and M. scrofulaceum that had only the reactivity with Probe X. When the disease-associated MAC strains (35 strains), isolated in the Kanto to Kyushu areas in Japan, were identified using AccuProbe test, both the M. avium and M. intracellulare strains identified by the Gen-Probe test reacted with the MAC-probe but not with the M. tuberculosis complex (MTC)-probe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Study of detailed conditions in DNA probe test by use of Gen-Probe Rapid Diagnostic System for identification of Mycobacterium avium complex and Mycobacterium tuberculosis complex].

In order to improve feasibility of technical procedures in Gen Probe Rapid Diagnostic System (Gen Probe Inc., San Diego, CA, U.S.A.) for identification of Mycobacterium avium complex (MAC) and M. tuberculosis complex (MTC), we studied several test conditions in the DNA probe testing, such as stability of test bacterial suspension, optimal duration of bacterial cultivation, the number of organisms in test bacterial suspension required for accurate determination, and so on. With respect to concentration of organisms (MAC and MTC) in test bacterial suspension (0.1ml), we found that 5-fold dilution as well as 5-fold condensation of the standard bacterial suspension (McFarland No.1) gave substantially the same result as in the case where bacterial suspension at the standard concentration was used. This indicates that the test bacterial suspensions (0.1ml) containing either 1.5 X 10(7)-5 X 10(8) of MAC or 3 X 10(5)-8 X 10(6) of MTC are available for the DNA probe testing. Test bacterial suspension at McFarland No.1 prepared from fresh cultures (3-4 week-old) could be stored either at -80, -20 or 4 degrees C at least for 17 weeks without significant loss of reactivity to M. avium, M. intracellulare and MTC DNA probes. In this case, stability of DNA probe-reactivity was preserved in the following order: MTC, M. avium and M. intracellulare. Concerning the age of bacterial cultures, at least 16-week-old cultures of MAC and MTC after initial appearance of cell growth on 1% Ogawa's egg media were sufficiently reactive to either MAC or MTC DNA probe. In this case, MTC showed most stable reactivity during the course of long-term cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Probes

[Identification of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium tuberculosis complex by Gen-Probe Rapid Diagnostic System].

DNA probe testing for Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium tuberculosis complex (MTC) was performed using Gen-Probe Rapid Diagnostic System (Gen-Probe Inc., San Diego, Calif., U.S.A.). By DNA probe test carried out blindfold for 48 mycobacterial strains with code numbers obtained from Kyoto University (Prof. F. Kuze), 13, 7, and 5 strains were identified as to be M. avium, M. intracellulare, and MTC, respectively. The diagnostic specificity and sensitivity of this testing were 100%. In this experiment, % hybridization of M. avium complex (MAC) and MTC were 25-55% and 45-52%, respectively. DNA probe test for 54 MTC strains including M. tuberculosis, M. bovis, M. africanum and M. microti revealed that 53 strains, except for one strain donated as a niacin-negative M. tuberculosis, reacted with MTC probe but not with MAC-probes. The one exceptional strain reacted with both the MTC- and M. avium-probes. However, when ten colonies randomly isolated from this strain on 7H11 agar plate were subjected to the DNA probe test again, all of these colonies reacted with M. avium probe, but not with MTC probe. Moreover, one representative colony was found to have alpha-antigen specific for the MAC.

DNA Probes

[Reactivities of various mycobacteria species against DNA probes (Gen-Probe Rapid Diagnostic System) specific to Mycobacterium tuberculosis complex, Mycobacterium avium and Mycobacterium intracellulare].

Various mycobacterial species (22 species, 178 strains) were studied for their reactivity to DNA probe specific for Mycobacterium tuberculosis complex (MTC), M. avium or M. intracellulare, using Gen-Probe Rapid Diagnostic System (Gen-Probe Inc., San Diego, Calif., U.S.A.). All the MTC strains, including M. tuberculosis, M. africanum, M. bovis and M. microti reacted with MTC-DNA probe at the % hybridization value of 42.8-51.9% (values higher than 10% are regarded as positive), but their reactivity to MAC-DNA probes (0.8-2.5%) was under the cut off value (10%). The test strains (28 strains) of M. avium complex (MAC) segregated into two groups on the basis of reactivity to DNA probes specific for M. avium and M. intracellulare, that is, one group (16 strains) positively reacted with M. avium-probe but not with M. intracellulare-probe, and the other group (12 strains) showed the converse reactivity. The two groups did not show a reactivity with MTC-probe higher than the cut off value. Nontuberculous mycobacteria other than MAC, including M. kansasii, M. marinum, M. simiae, M. asiaticum, M. scrofulaceum, M. gordonae, M. szulgai, M. malmoense, M. xenopi, M. gastri, M. nonchromogenicum, M. terrae, M. triviale, M. fortuitum, and M. chelonae (subsp. abscessus and chelonae) reacted with neither MTC- nor MAC-probe and values for % hybridization (0.6-3.6%) were lower than the cut off value. These findings indicate extremely superior specificity of the DNA probes (Gen-Probe) for MTC, M. avium and M. intracellulare, thereby indicating the usefulness of Gen-Probe Rapid Diagnostic System for the MTC and MAC in clinical use.

Animals

[Study on recombinant BCG].

For the purpose to establish the system to express foreign antigen from Mycobacterium bovis BCG. We have cloned, sequenced and expressed genes for secreting proteins, alpha antigen, MPB64, MPB57 and MPB70 from M. bovis BCG. The upstreams and structural genes were characterized. The gene for alpha antigen of Mycobacterium kansasii was also characterized. The gene for alpha antigen of M. kansasii (k-alpha) was chosen for the further study at first. This gene was fused with shuttle plasmid PIJ666-PAL5000 obtained from T. Kisser and transfected to M. bovis BCG (Tokyo). Transformant was obtained by a selection with kanamycin. It was able to secrete k-alpha antigen. DNA-containing a B-cell epitope (Glu-12-Leu-Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 P17 gag was fused to this vector at C terminal of k-alpha. Using this vector, we have succeeded to express foreign antigen in M. bovis BCG. The products were analyzed in one or two dimensional electro-phoresis. The results thus obtained will be reported elsewhere.

Amino Acid Sequence

Acute leukemia with normal platelet count at diagnosis.

Thirty-six (17.8%) of 202 children with acute lymphoblastic leukemia (ALL) and 2 (3.7%) of 54 children with acute nonlymphoblastic leukemia (ANLL) had a platelet count over 150 x 10(9)/l at diagnosis. Children with ALL and a platelet count over 150 x 10(9)/l were analysed in detail. The ALL patients without thrombocytopenia tended to be male predominant and had less frequent bleeding manifestations (p less than 0.01). These patients without thrombocytopenia had also significantly less marked leukocytosis (p less than 0.01), less severe anemia (p less than 0.05) and lower percentages of bone marrow blasts (p less than 0.05) than those with thrombocytopenia. In addition, ALL patients without thrombocytopenia had a significantly higher probability of continuous complete remission than those with thrombocytopenia (p less than 0.01).

Child

Establishment of a foreign antigen secretion system in mycobacteria.

In order to develop recombinant Mycobacterium bovis BCG into a useful multivaccine vehicle, we established a foreign antigen secretion system in mycobacteria in which an extracellular alpha antigen of Mycobacterium kansasii was utilized as a carrier. By using this system, a B-cell epitope (Glu-12-Leu-Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 p17gag, which was identified by a fusion protein-based method, has been successfully obtained from BCG along with the alpha antigen. This is the first report of expression and secretion of a foreign viral antigen from BCG. It is possible that the system can become a universal vaccination vehicle applicable to protection against various infectious diseases.

Amino Acid Sequence

Cloning and expression of the gene for the cross-reactive alpha antigen of Mycobacterium kansasii.

The gene for the extracellular alpha antigen of Mycobacterium kansasii was cloned by using the alpha-antigen gene fragments of M. bovis BCG as probes. Gene analysis revealed that this gene encodes 325 amino acid residues, including 40 amino acids for the signal peptide, followed by 285 amino acids for the mature protein. A comparison of the nucleotide sequences of the genes isolated from these two mycobacterial species showed that the levels of DNA and amino acid homology were 84.8 and 89.1%, respectively. The hydropathy profiles were also compared, and two highly changed hydrophilic regions were observed, which might account for the antigenic diversity of this antigen or its acquirement of antigenic specificity.

Amino Acid Sequence

Identification of various serovar strains of Mycobacterium avium complex by using DNA probes specific for Mycobacterium avium and Mycobacterium intracellulare.

Reference strains of the Mycobacterium avium complex (MAC) belonging to serovars 1 to 28 were examined with DNA probes (Gen Probe Rapid Diagnostic System for the MAC; Gen Probe Inc., San Diego, Calif.) specific for either M. avium or Mycobacterium intracellulare. This study revealed that the earlier designations of the MAC serovars, in which serovars 1 to 3 and 4 to 28 were regarded as M. avium and M. intracellular, respectively, should be revised as follows. First M. avium includes serovars, 1 to 6, 8 to 11, and 21. Second, M. intracellulare includes serovars 7, 12 to 20, and 25. However, other serovars, such as serovars 22 to 24 and 26 to 28, involve M. intracellulare, Mycobacterium scrofulaceum, and MAC that are lacking in the reactivity with either DNA probe and that are too disordered to enable a conclusive description here, particularly concerning their taxonomic positions in the MAC.

Antigens, Bacterial

[Prognosis of childhood mediastinal lymphoma].

Between 1973 and 1989, 16 children with non-Hodgkins lymphoma (NHL) with a mediastinal mass (MM) were treated at our institution with multi-agent chemotherapy and radiotherapy. They also received central nervous system (CNS) prophylaxis including intrathecal methotrexate administration (14 cases) and cranial irradiation (7 cases). Twelve were boys and 4 girls. Median age was 11 +/- 3. One patient died of air way obstruction one day after admission. Fourteen of 15 patients entered into complete remission (CR) and one patient partial remission. Five remains in CR 7 to 175 months after diagnosis (median 76 months). Nine patients relapsed in the bone marrow (3 cases), CNS (3), testicles (1), neck lymph node (1) and bones plus kidneys (1). Of these, 7 patients died within 13 months after initial relapse. The disease free survival (DFS) and overall survival of all patients were 27% and 33%, respectively. Analysis of the prognostic factors among patients with MM+ -NHL revealed that the serum LDH level below 1,000IU/l was a good prognostic sign. Other factors such as age, stage, initial WBC count, size of MM and response of the MM to the initial treatment did not correlate with DFS. Because of its rarity and the poor treatment result, we need more aggressive treatment program by a multiinstitutional study for MM+ -NHL.

Adolescent

[Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team].

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.

Adolescent