Search PubMed⌕ Search

Biomedical subjects

T Kyo

Publications and source records attributed to T Kyo.

At least 55 records · Page 3Linked to original sources
PubMed1994

Invasive oral aspergillosis in immunocompromised patients with leukemia.

The clinicopathologic characteristics of invasive oral aspergillosis in 16 immunocompromised patients who developed this infection during antileukemic chemotherapy are described. The primary site of the infection was the marginal gingiva, there was severe spontaneous pain, and the patients developed spiking fever and granulocytopenia. Necrotic ulceration of the gingiva rapidly extended to the contiguous mucosa, muscle, and bone. Microscopically, the necrotic tissue contained thrombotic vascular infarcts and there were hyphae that showed frequent transverse septa and dichotomous branching. The invasive organisms were not responsive to amphotericin B in the absence of remission of the leukemia and restoration of the depressed host defenses. In 15 patients who showed improvement of hematologic status, oral aspergillosis was controlled by the combination of antifungal chemotherapy and debridement of necrotic tissues.

Adult↗
PubMed1994

High frequency of RAS oncogene mutation in chronic myeloid leukemia patients with myeloblastoma.

To determine the role of the mutated RAS oncogene during development into the blast phase, we sequentially analysed RAS oncogene mutations in the bone marrow of 27 patients with chronic myeloid leukemia (CML). DNA from CML patients in chronic and blast phases and nude mouse tumor DNA formed by a tumorigenicity assay (in vivo selection assay) were subjected to the polymerase chain reaction (PCR) and oligonucleotide hybridization. In addition, one patient in the chronic phase and five in the blast phase were also analysed. PCR analysis of DNA from the leukemic patients revealed that 3.6% (1 of 28) and 15.6% (5 of 32) of the patients in the chronic and blast phases, respectively, had RAS mutations. N- or K-RAS oncogene mutations were found mostly in the blast phase (4 of the 5 patients with the RAS oncogene mutation). Of the 5 patients with the RAS oncogene mutation, three developed myeloblastoma, a myeloblast cell tumor, in the blast phase. None of the 28 patients without the RAS mutation developed myeloblastoma. These results suggest that the RAS oncogene mutation occurred in the late stage of the disease and contributed to transformation to the blast phase in some CML patients. The findings also indicate an association between the presence of the RAS mutation and the formation of myeloblastoma.

3T3 Cells↗
PubMed1994

[Characteristic clinical features and treatment of acute myelocytic leukemia with 8;21 translocation].

From 1981 to 1992 forty acute myelocytic leukemia patients with the 8;21 translocation [t (8;21) AML] were treated with intensive chemotherapy and radiotherapy. Their ages ranged from 12 to 81 years at the time of diagnosis. The 8;21 translocation occurred in 13.8% of all patients with AML. Of the 40 t (8;21) AML patients, 10 (25.0%) developed extramedullary tumors at sites such as mastoid, orbit and temporal region. This occurred more commonly among younger patients. Thirty-eight of the 40 patients (95.0%) achieved complete remission (CR). Of these 38 patients, 36 received post-remission chemotherapy. Since 1984, 29 consecutive patients have been given cranial irradiation, 24Gy, for prophylaxis and treatment of leukemic tumors. The twelve years remission and survival rate for this group are 68.3% and 62.1%, respectively. Of the 38 patients achieving CR, in those over 30 years of age at the time of diagnosis, 19 of 23 remain in first remission, whereas in the younger patients 5 of 13 have relapsed. The duration of CR of patients who developed extramedullary tumors was shorter than that of patients without such tumors. A second CR was achieved in 7 of 9 recurrent cases. Three remain in remission 21, 45, and 117 months after chemotherapy and allogeneic bone marrow transplantation. We attribute the very long duration of CR in our patients with t (8;21) AML to the intensive post remission therapy. Younger patients with t (8;21) AML and/or extramedullary tumors probably should receive early bone marrow transplantation.

Adolescent↗
PubMed1994

Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15;17 chromosomal translocation of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) has been characterized by 15;17 chromosomal translocation, which involves the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. The breakpoints have been mapped to three cluster regions in the PML gene, and to RARA gene intron 2. We have examined the distribution of breakpoints within RARA gene intron 2. An extremely restricted region (ERR) of 50 bp within RARA gene intron 2 was identified as the cluster region of breakpoints by polymerase chain reaction and sequence analysis of DNA from APL patients. To study experimentally the mechanism involved in the translocation, ERR was tested in NIH3T3 cells by in vitro transfection-recombination assay, in which target sequences were placed either downstream of the SV40 promoter or upstream of the neo gene. Cells were conferred resistance to G418 only when the promoter was fused to the neo gene by recombination of two target sequences during transfection. The molecular junctions were analysed in five clones, and all of them were shown to be confined within a 20 bp region in a 148 bp DNA fragment containing ERR. This suggests that ERR might be the illegitimate recombination hot spot in mammalian cells.

3T3 Cells↗
PubMed1993

Detection of PML/retinoic acid receptor a gene rearrangements by polymerase chain reaction using genomic DNA in patients with acute promyelocytic leukemia.

Breakpoints of the 15;17 translocation in patients with acute promyelocytic leukemia (APL) have been identified within PML and retinoic acid receptor a (RARA) genes in chromosomes 15 and 17, respectively. A wide heterogeneity was observed in the breakpoints on the PML and RARA genes. Therefore, amplification of the breakpoints region by polymerase chain reaction (PCR) with genomic DNA has been considered to be difficult. In the present study, a method was developed to detect the 15;17 translocation with genomic DNA. Of 13 patients with APL, four were detected to have the rearrangement of genomic DNA. At present, reverse transcriptase-polymerase chain reaction analysis is one of the methods available for diagnosis and detection of the residual leukemic cells in APL. In this study, PCR analysis using genomic DNA of APL cells is proved to be useful for identifying the breakpoints of the PML and the RARA genes. Furthermore, this method is applicable to patients for whom RNA samples of the leukemic cells are not available.

Base Sequence↗
PubMed1993

Multi-institutional study of all-trans-retinoic acid as a differentiation therapy of refractory acute promyelocytic leukemia. Leukaemia Study Group of the Ministry of Health and Welfare.

We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 out of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.

Adolescent↗
PubMed1993

Femoral neck fracture. Factors related to ambulation and prognosis.

A total of 427 elderly patients with femoral neck fractures were studied retrospectively to identify factors that may be correlated with life expectancy and functional prognosis. Gender, age, prefracture activities of daily living (ADL), electrocardiogram ECG), electroencephalogram (EEG), cognitive function, hemoglobin level, total protein level, and type of fracture were evaluated to determine the correlation of each predictive factor with survival time after surgery and three-month postoperative walking recovery rate. The one-year survival rate was found to be 55.9%: 59.1% for women and 52.3% for men. The walking recovery rate was 55.8%. The most important factors affecting life expectancy were prefracture ADL, ECG, EEG, and cognitive function score (Hasegawa's score). Electroencephalogram and Hasegawa's score also were found to be important prognostic factors for postoperative ADL. Preoperative medical conditions are useful indicators for determination of functional prognosis and survival.

Activities of Daily Living↗
PubMed1992

The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy.

BACKGROUND: Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS: The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS: Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS: These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy.

Adolescent↗
PubMed1992

[Analysis of breakpoints on BCR gene in acute leukemia patients with Ph1 chromosome].

Eight cases with Ph1 positive acute leukemia (7 of acute lymphocytic leukemia: ALL, and one of acute myelocytic leukemia: AML) were studied molecular biologically to identify location of breakpoints on BCR gene in each patient. Six of the 8 patients (5 of ALL and 1 of AML) had rearrangements at bcr (M-BCR) region. Their locations of the breakpoint in M-BCR were similar to those of 59 chronic myelocytic leukemia patients. One of the remaining two patients had gene rearrangements at m-BCR-1 region in BCR intron 1, and the last patient did not have gene rearrangements at any site of m-BCR-1 and IgL C lambda region. Two cases had gene deletion at either 3' or 5' side of the bcr. A patient with bcr rearrangement was also analyzed by PCR method with reverse transcriptase (RT-PCR) and had simultaneous expressions of bcr3-abl and bcr2-abl chimeric mRNAs. These results indicate that Ph1 positive acute leukemia have heterogeneous characteristics in terms of the molecular biology. The molecular analysis will help for classifying the leukemic types and for elucidating the pathogenesis in Ph1 positive acute leukemia.

Acute Disease↗
PubMed1992

Cytogenetic 2; 18 and 18; 22 translocation in chronic lymphocytic leukemia with juxtaposition of bcl-2 and immunoglobulin light chain genes.

The majority of follicular lymphoma cells carry the typical chromosome translocation 14;18, which juxtaposes the bcl-2 gene to the immunoglobulin heavy-chain (IgH) gene. Variant translocations of the bcl-2 gene to the Ig lambda or Ig kappa gene have been found by molecular biological techniques in a significant fraction (approximately 10%) of chronic lymphocytic leukemia (CLL). However, there have been no reports describing the presence of cytogenetic 18;22 and 2;18 translocations in CLL, in spite of extensive karyotypic studies. We present here two cases of CLL, one with cytogenetically detected t(2;18)(p11;q21) and the other with the t(18;22)(q21;q11). The molecular analysis revealed that these translocations juxtaposed the bcl-2 and immunoglobulin light-chain (IgL) genes. The t(18;22) broke the 5' flanking region of the bcl-2 gene and juxtaposed to the immunoglobulin lambda light-chain (Ig lambda) gene in a head-to-head configuration, as in the cases previously described. In the case of the t(2;18), the bcl-2 gene and immunoglobulin kappa light-chain (Ig kappa) gene were juxtaposed in a head-to-tail configuration, which is opposite to that expected from the orientation of the genes on chromosomes. The breakpoint was located within the 5' untranslated region of the bcl-2 gene. The results presented here indicate that the bcl-2/immunoglobulin light-chain (IgL) gene juxtaposition seen in a fraction of CLL is the result of cytogenetically detectable reciprocal chromosome translocations 2;18 and 18;22.

Base Sequence↗
PubMed1991

[Parallel loss of c-FMS and GM-CSF genes in myeloid leukemias with 5q-chromosome].

DNA contents of c-FMS and GM-CSF genes were analyzed by densitometer in nine patients with myelodysplastic syndrome or acute myeloid leukemia associated with abnormality of chromosome 5. Five patients with deletion in the long arm of chromosome 5 had loss of both c-FMS and GM-CSF genes. These findings suggest that c-FMS oncogene and GM-CSF gene locating in the critical region on chromosome 5 seem to have an important role in the process of leukemogenesis.

Aged↗
PubMed1989

9;22 translocation and bcr rearrangements in chronic myelocytic leukemia patients among atomic bomb survivors.

To elucidate the mechanism of leukemia induced by radiation, we studied both chromosome abnormalities and bcr rearrangements of seven CML patients with a history of atomic bomb exposure and 14 CML patients without the exposure. All patients, irrespective of radiation exposure, had 9;22 translocation and rearrangement of the bcr gene in the leukemic cells. Further analysis of breakpoints within the bcr gene demonstrated no distinct difference between the exposed and the non-exposed groups. The present study suggests that formation of the chimeric bcr-abl gene and its genetic products may play an important role in the development of leukemia in either radiation-induced or de novo CML.

Adult↗
PubMed1989

[Chemotherapy of adult ANLL].

One hundred ninety six previously untreated patients of adult acute nonlymphocytic leukemia (ANLL) were treated with B-DOMP therapy. 102 patients were treated in the conventional rooms and 94 patients were in the laminar airflow rooms. The complete remission (CR) rates were 78.4%, and 84.0% respectively. The CR rate of the groups whose age was 60 years or older was higher for the patients treated in the laminar airflow room than those is conventional rooms (75.8% versus 60.0%), and the fatality from fungal infection was substantially lower for the laminar air-flow room patients. Non cross resistant chemotherapy based on alternate administration of Daunorubicin (DNR) and Aclarubicin (ACR) was given to 54 patients with ANLL in remission. The median duration of remission was 48.0 months, with 38.4%, patients in remission at 8 years. A plateau phase indicating freedom from the risk of leukemic recurrence is not clearly apparent yet. The most serious toxicity was drug induced cardiotoxicity from increased total dose by long term maintenance therapy. Newly planned post remission chemotherapy that incorporated Etoposide and Mitoxantrone with ACR and DNR was given to 35 patients with ANLL in remission. Seventy nine percent (79%) of patients were remaining in remission at 2 years. Because many patients experienced significant side effects after each course of therapy, intensive post remission chemotherapy should be used in a setting where the physician is always attending and ready to serve the patients.

Aclarubicin↗
PubMed1989

[Progress in the treatment of acute myelogenous leukemia].

Results of treatment of AML have substantially progressed within the last decade. In almost all cases, the AML 3-year-survival rate did not exceed 1% in the 1960s. The 5-year disease-free survival rate now is ranges from 10% to 25% in adults and up to 45% in children. The 3-year survival at our hospital is 50%. Recent chemotherapy for acute leukemia is aimed at not only remission induction but also cure of the disease. Although some hematologists claim to stop chemotherapy as early as possible, there is considerable controversy regarding the total length of postremission treatment. Bone marrow transplantation is increasingly used to treat patients with acute leukemia in many facilities. Bone marrow transplantation assures a lower relapse rate than with chemotherapy alone. The limitations are the risk of transplant-related mortality, lack of a histo-compatible donor and advanced age. To achieve substantial improvement in results of AML treatment requires the development of new drugs, and the reduction of transplant-related death. An attempt to establish registries of HLA type for the transplantation from unrelated, HLA-identical donors is now under way.

Adult↗
PubMed1989

[Late appearance of Philadelphia chromosome with bcr gene rearrangement in an acute myelocytic leukemia patient].

A case of acute myelocytic leukemia (AML-M2) with a late appearance of Philadelphia chromosome (Ph1) is presented. Chromosome analysis revealed a normal karyotype at the time of diagnosis and for 23 months, when hematological relapse occurred, accompanied by abnormal clones, 46, XX, t(9;22) (q34;q11) (78%) and 45,XX, -16, t(9;22) (q34;q11), del (5) (q13q31) (22%). The patient died of GVHD after bone marrow transplantation. Molecular analysis confirmed bcr gene rearrangement in the cells with Ph1 chromosome. Acquisition of Ph1 chromosome during the course of hematological malignancies other than CML is extremely rare. This case is undoubtedly important for the understanding of leukemogenesis and the evolution of leukemia clones. The authors discussed possible mechanisms of Ph1 acquisition in the late stages of AML.

Adult↗