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Biomedical subjects

H Tasaka

Publications and source records attributed to H Tasaka.

At least 37 records · Page 2Linked to original sources

Acute promyelocytic leukaemia in a patient treated with etoposide for Langerhans cell histiocytosis.

We report a child with acute promyelocytic leukaemia (APL) who was treated with etoposide (VP16) for Langerhans cell histiocytosis (LCH). A 3-year-old Japanese girl was diagnosed as having LCH. She was treated with combination chemotherapy using VP16 and prednisolone. 56 months after beginning the chemotherapy she developed APL. Her bone marrow was occupied with atypical promyelocytes including giant granules and multiple Auer bodies. A cytogenetic analysis of the leukaemic cells showed 46,XX,11p-,14q+,t(15,17). The cumulative dose of the administered VP16 was 12,120 mg/m2, which suggested that VP16 may be responsible for the development of APL. The risk of developing secondary leukaemia after the administration of VP16 should therefore be considered when managing patients with LCH.

Child↗

[Bone marrow transplantation for a patient with ALL from her 75-year-old mother using cryopreserved bone marrow cells].

We report a 42-year-old woman with acute lymphoblastic leukemia who received allogeneic bone marrow transplantation (BMT) in the first remission from her 75-year-old, HLA-identical, MLC-non-reactive mother. Considering the difficulty to obtain a sufficient number of bone marrow cells from such an old donor, we harvested the cells (2.31 x 10(8)/kg) on day -37 and cryopreserved them until use. BMT was performed on June 3rd, 1993 after conditioning regimen with total body irradiation, high-dose AraC and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxisis was attempted by cyclosporin A and short-term methtrexate. Her hematopoietic recovery was favorable with no signs and symptoms of GVHD as far as day 218.

Adult↗

[Responsiveness of lymphocytes from patients with M. avium-intracellulare complex (MAC) infection to PPDs as measured by IFN-gamma production].

We investigated the responsiveness of peripheral blood lymphocytes (PBLs) from patients with M. avium-intracellulare complex (MAC) infection to the stimulation with PPDs by measuring their IFN-gamma producing ability. PBLs were obtained from MAC patients at active stage (culture-positive after three-month chemotherapy), those at inactive stage (culture-negative for three months after or during chemotherapy), and healthy donors. PPDs used were PPD-S prepared from M. tuberculosis, PPD-B from M. intracellulare, and PPD-Y from M. kansasii. PBLs from active MAC patients did not produce IFN-gamma to a significant extent by stimulation with any of three PPDs, while PBLs from inactive MAC patients showed higher responses to each PPD compared to those from active patients. In inactive MAC patients, the maximal response was observed to PPD-B among three PPDs. On the other hand, PBLs from healthy controls produced different levels of IFN-gamma in response to three different PPDs, and their response was most remarkable to PPD-S. These results indicated that the responsiveness of patients' PBLs to PPDs was impaired during active stage of MAC infection and restored on recovery from the disease.

Adult↗

Cloning, sequencing and expression of the gene for alpha antigen from Mycobacterium intracellulare and use of PCR for the rapid identification of Mycobacterium intracellulare.

The complete nucleotide sequence of alpha antigen secreted from Mycobacterium intracellulare (ATCC13950) was determined. The gene encoded 330 amino acids including 40 amino acids for signal peptide, followed by 290 amino acids for a mature protein with molecular mass 30,645 Da. The cloned gene was expressed in Escherichia coli by using an E. coli expression vector. Based on these results, the feasibility of rapid identification of M. intracellulare by two step polymerase chain reaction (PCR) was demonstrated.

Amino Acid Sequence↗

Identification of Mycobacterium avium complex strains belonging to serovars 21-28 by three commercial DNA probe tests.

Various reference strains of Mycobacterium avium complex (MAC) belonging to serovars 21-28 were identified by three DNA probe tests, i.e., Gen-Probe, AccuProbe and SNAP tests. All of these DNA probe tests were in agreement for strains identified as M. avium or M. intracellulare. The tested serovar strains involved M. avium, M. intracellulare, MAC reactive only with Probe X of SNAP test ('Probe X-reactive MAC'), M. scrofulaceum reactive with Probe X of SNAP test ('Probe X-reactive M. scrofulaceum'), and typical M. scrofulaceum which did not react with any of the probes. Both reference strains belonging to serovar 21 were M. avium, and none of the other serovars included this species. On the contrary, M. intracellulare was found in serovars 22, 25, 26, and 28. 'Probe X-reactive MAC' were also widely found in serovars 23, 24, 26, 27, and 28, while 'Probe X-reactive M. scrofulaceum' was seen only in serovar 22. These results confirm the usefulness of SNAP test to identify the MAC showing no reactivity to Gen-Probe and AccuProbe.

DNA Probes↗

Cloning and sequencing of the gene for alpha antigen from Mycobacterium avium and mapping of B-cell epitopes.

The complete nucleotide sequence of alpha antigen secreted from Mycobacterium avium (A-alpha) was determined. The gene encodes 330 amino acids, including 40 amino acids for the signal peptide, followed by 290 amino acids for the mature protein with a molecular mass of 30,811 Da. This is the first sequence of A-alpha. Comparisons between A-alpha and alpha antigens of Mycobacterium leprae, Mycobacterium bovis BCG, and Mycobacterium kansasii showed highly homologous regions which suggested a conserved functional domain and two less-homologous regions. Serological analysis of recombinant A-alpha, expressed by a series of deletion constructs, indicated the possibility that A-alpha carries at least six B-cell epitopes. The three antigenic determinants were common to Mycobacterium tuberculosis, M. kansasii, and M. avium. The results also suggested the possibility that there are three species-specific epitopes.

Amino Acid Sequence↗

[Tuberculin sensitivity to purified protein derivatives from Mycobacterium other than tuberculosis (PPD-B, PPD-Y, PPD-F and PPD-C) and PPDs among patients with mycobacteriosis--cooperative study of the Research Committee for the Mycobacteriosis in Japan].

Purified protein derivatives (PPDs) prepared from M. intracellulare (PPD-B), M. kansasii (PPD-Y), M. fortuitum (PPD-F), M. chelonei subsp. abscessus (PPD-C) and M. tuberculosis (PPDs) were simultaneously used in skin tests on patients diagnosed as having tuberculosis or atypical mycobacteriosis to reveal their specificity, clinical usefulness and immunological status of the patients. The mean diameter of reaction (redness) for patients with M. tuberculosis positive sputum (TB group, n = 71; age, 20-90 yrs) was PPDs, 20.4 mm; PPD-B, 7.9 mm; PPD-Y, 11.7 mm; PPD-F, 0.8 mm; and PPD-C, 0.3 mm. For M. avium complex positive patients (MAC group, n = 100; age, 31-89 yrs), the results were PPDs, 10.9; PPD-B, 16.9 mm; PPD-Y, 10.7 mm; PPD-F, 1.6 mm; and PPD-C, 0.3 mm. The M. kansasii positive patients (K group; n = 8) showed results of PPDs, 12.6 mm; PPD-B, 10.7 mm; PPD-Y, 20.8 mm; PPD-F, 0.5 mm; PPD-C, 0.0 mm. The M. fortuitum positive patients (F group; n = 5) had measurements of PPDs, 5.8 mm; PPD-B, 4.4 mm; PPD-Y, 9.8 mm; PPD-F, 17.8 mm; and PPD-C, 16.0 mm. The patients who were previously M. tbc. positive but presently negative patients (pre. TB group; n = 50) showed the following results: PPDs, 16.6 mm; PPD-B, 7.4 mm; and PPD-Y, 10.9 mm. For the patients who were previously M. avium complex positive (previous MAC group; n = 19), the results were PPDs, 10.4 mm; PPD-B, 9.9 mm; and PPD-Y, 7.7 mm. Also considering their frequency distribution curve, with exception of the previous MAC group, the patient groups showed specificity to the PPD of the bacilli detected. The previous MAC group recorded no significant difference in response to PPDs and PPD-B. Strong cross reactions were observed between PPD-F and PPD-C, and moderate reactions between PPDs, PPD-B and PPD-Y. Cross reactions were scarce between PPDs, PPD-B or PPD-Y and PPD-F or PPD-C. Though it is difficult to distinguish cross-reaction and multiple infections, majority of the patients (72-85%) showed greatest response to the PPD that corresponds with the species of bacilli detected. In conclusion, two or more PPDs applied simultaneously can be of aid in diagnosing mycobacteriosis especially in the early stages of the disease. Also, cross-reactions between atypical mycobacteria and PPDs should be taken into consideration when diagnosing infection caused by M. tuberculosis.

Adult↗

[Skin reaction test using PPD-B].

Inapparent infection caused by Mycobacterium avium-M. intracellulare complex was examined in healthy persons by skin reaction tests using purified protein derivatives of M. intracellulare ATCC 19530 (PPD-B). Skin reaction to PPD-B was evaluated as positive, as it was for PPDs, when the diameter of the reaction (redness) was 10 mm or more, and it was evaluated as significantly positive when the reaction was the same or larger than that to PPDs. Examination of 379 volunteers (ages 18-53, one female only) from the Kaitaichi Station, Ground Self-Defence Force gave the following positive and significantly positive rates by age respectively: 12.8% and 10.3% for ages 18-19, 25.8% and 9.0% for ages 20-29, 39.7% and 12.8% for ages 30-39, and 51.2% and 15.5% for ages 40-53, and the rates were 32.7% and 11.1% for all ages combined. The positive rates to PPDs, on the other hand, were 33.3% for ages 18-19, 65.7% for ages 20-29, 91.0% for ages 30-39, and 95.2% for ages 40-53, and the rate was 74.1% for all ages combined. The PPD-B positive rate increased with age from 12.8% at 18-19 years of age to 51.2%, but the significantly positive rate showed no significant increase. Evaluation to PPD-B and PPDs were both positive, because of the difficulty of determining clearly whether the cause was M. tuberculosis and M. avium complex infection or cross reaction of skin reaction to PPDs and PPD-B.

Adolescent↗

[Tuberculin sensitivity to purified protein derivatives (PPD) from M. intracellulare (PPD-B), M. kansasii (PPD-Y), M. fortuitum (PPD-Y) and M. tuberculosis (PPDs) among healthy volunteers].

To reveal the epidemiology of mycobacteria other than Mycobacterium tuberculosis in Japan, we tested 379 healthy volunteers from Self Defence Force Army stationed in Hiroshima Prefecture with 0.05mcg of PPDs, 0.1mcg of PPD-B, PPD-Y and PPD-F. Majority of the volunteers had been immunized with BCG by thirteen years old. Rate of positive reaction (diameter of redness > or = 10mm) in each PPD in each age group were; PPDs [18-19yr (n = 39); 30.8%, 20-29yr (n = 178); 63.5%, 30-39yr (n = 78); 91.0%, 40-53yr (n = 84); 92.9%], PPD-B [12.8%, 24.7%, 38.5%, 48.8%], PPD-Y [5.1%, 14.6%, 26.9%, 26.2%], PPD-F [0%, 10.1%, 12.8%, 10.7%]. Frequency distribution curve of PPDs in age groups above 20 years old had a peak at about 14mm of diameter, while low-responder were dominant in age 18 to 19. In PPD-B, there were two peaks, one in less than 5mm and the other between 10 to 15mm which was considered as the group sensitized by M. avium complex and became larger in older age group. In PPD-Y and in PPD-F, the frequency distribution showed an exponential curve with a little shift to right in older group in PPD-Y. As there was a considerable degree of cross-sensitivity, we provisionally regarded the maximum reaction of four PPD (larger than 5mm) or the reaction which is 75 per cent or more of each person's maximum reaction as specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗