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Biomedical subjects

M Tomonaga

Publications and source records attributed to M Tomonaga.

At least 91 records · Page 5Linked to original sources
PubMed1999

Poor outcome of autologous stem cell transplantation for adult T cell leukemia/lymphoma: a case report and review of the literature.

A limited number of patients with adult T cell leukemia/lymphoma (ATL) who received autologous stem cell transplantation (ASCT) have been reported. We report here a case of fatal systemic Candida krusei infection in a female patient with ATL undergoing ASCT. All of the eight patients (including seven patients in the literature) with ATL who received ASCT developed relapse of ATL or death due to ASCT complication, irrespective of subtype or remission state of ATL, source or selection of SCT or conditioning regimen. At present, ASCT appears to provide little benefit for ATL in contrast to that for other types of aggressive non-Hodgkin's lymphoma.

Adult↗
PubMed1999

Multi-clonal expansion of unique human T-lymphotropic virus type-I-infected T cells with high growth potential in response to interleukin-2 in prodromal phase of adult T cell leukemia.

We established a simple IL-2-dependent colony-forming assay for T cells infected with human T-lymphotropic virus type-I (HTLV-I). IL-2-dependent cell lines were subsequently established by expanding individual colonies in liquid cultures. Lymphocyte-rich fractions were prepared from 31 HTLV-I carriers, 12 patients with smoldering ATL, 11 chronic ATL, 12 crisis ATL and 10 acute ATL. Primary colonies of CD4+ p19+ T cells were formed in all cases of carriers, smoldering and chronic ATL, and in 10 of 12 crisis cases. In contrast, no colony was formed from cells of patients with acute ATL. The rate of establishment of cell lines in HTLV-I carriers was significantly lower than that in patients of prodromal phase ATL. Cell lines established from cells of three prodromal cases were clonally identical to the parent ATL cells, while others had clonally distinct cell lines. Our results indicated the presence of four components of HTLV-I-infected T cells: (1) normal carrier T cells capable of forming colonies but not cell lines; (2) pre-malignant T cells capable of forming colonies as well as cell lines; (3) malignant T cells capable of forming colonies as well as cell lines; (4) fully malignant T cells unresponsive to IL-2. Our results suggest the presence of a multiclonal expansion of unique T cells in the prodromal phase of ATL, which have a high growth potential in response to IL-2. The coexistence of multiclonality with a dominant ATL clone may be closely related to the underlying pathology in HTLV-I leukemogenesis.

Case-Control Studies↗
PubMed1999

The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes.

The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.

Adult↗
PubMed1999

New system for assessing the prognosis of refractory anemia patients.

Refractory anemia (RA) is a very heterogeneous disease regarding biological and clinical features. The International Prognostic Scoring System (IPSS) was useful for assessing the prognosis in the whole group of 219 myelodysplastic syndrome (MDS) patients. However, the IPSS was not sufficient in 132 RA patients. To predict survival and freedom from acute myeloid leukemia (AML) evolution, we investigated individual prognostic factors based on the clinical parameters (age, gender, morphologic features, cytopenias and cytogenetics) of 132 RA patients using univariate and multivariate analyses. Based on the results, we devised a new system for assessing the prognosis of RA patients. In our system, RA patients with pseudo-Pelger-Huët anomalies >/=3% were classified as high risk (12 patients); of patients without pseudo-Pelger-Huët anomalies >/=3%, those with intermediate/poor karyotype according to IPSS, Hb </=6 g/dl or mMgk >/=10% were classified as intermediate risk (57 patients); and those without high or intermediate risk were classified as low risk (67 patients). In our system, the analyses of both survival times and leukemia-free survival times revealed significant differences among the three groups (P < 0.0001).

Acute Disease↗
PubMed1999

Discrepant expression of membrane and soluble isoforms of Fas (CD95/APO-1) in adult T-cell leukaemia: soluble Fas isoform is an independent risk factor for prognosis.

The Fas signalling system probably plays a critical role in the natural and chemotherapeutic cell death machinery, suggesting that aberrant Fas expression is involved in growth control of tumours. The membrane isoform (mFas) is a 45 kD cell surface protein containing a single transmembrane region, and induces apoptosis in normal or tumour cells, whereas the soluble isoform (sFas) lacks the transmembrane domain due to alternative splicing of the transcript and is thought to block Fas-mediated apoptosis. To clarify the clinical roles of expression of these two Fas isoforms in adult T-cell leukaemia (ATL), we investigated the levels of the Fas isoforms in 81 patients with ATL. The expression patterns of the Fas isoforms were heterogenous, and there was no significant correlation between mFas and sFas levels: 10/81 cases were negative for mFas and had high serum sFas levels, whereas the remaining 71 cases were positive for mFas and had various levels of expression of the two Fas isoforms. Irrespective of the status of mFas expression in leukaemic cells, the mRNAs encoding these isoforms were always detectable, indicating the potential for protein translation. Although mFas expressed on freshly isolated ATL cells could iduce apoptosis in vitro, positive versus negative mFas status was not associated with any clinical aspects of ATL, whereas the sFas level was strongly correlated with clinical parameters such as serum LDH activity, tumour burden, serum soluble IL-2R level, hypercalcaemia and prognosis. These results suggest that the ratio of Fas isoforms varies, and high expression of the sFas protein and message reflects the malignant behaviour of ATL and is an independent risk factor for the prognosis.

Female↗
PubMed1999

Experience with an ultrasonic aspirator in neuroendoscopy.

This report describes the clinical application of an ultrasonic aspirator for endoscopic neurosurgery. Eight patients with intraventricular hematoma with complete tamponade of the ventricular system and marked hydrocephalus were treated with the ultrasonic aspirator for endoscopic neurosurgery. Clinical evaluation and neuroimaging studies were obtained for one month. Removal of hematoma was confirmed on follow-up imaging. The ultrasonic aspirator is operated by electrostriction transducer on low generating power (15-30 watts). Its tube has an outer diameter of 1.8 mm. This aspirator is designed to fragment and aspirate the cattle-liver. On observing the adjacent neural and vascular structures with the neuroendoscope, the massive hematoma within the ventricles is removed with the use of this aspirator. Subtotal removal (> 90% of hematoma volume) was achieved in all patients. All patients tolerated the procedure well. However, postoperative re-rupture occurred in two patients prior to aneurysm clipping following an immediate interval. Three patients with hypertension, two patients with head trauma, and one patient after aneurysm clipping were discharged home within one month after treatment. Preliminary experience with this aspirator has demonstrated its feasibility and safety. Clinical application of this technique is expected in other fields of neurosurgery.

Adult↗
PubMed1999

Low prevalence of Helicobacter pylori in individuals with HTLV-I infection.

BACKGROUND: The prevalence of Helicobacter pylori in HIV-positive individuals is significantly lower than in HIV-negative controls. However, its prevalence in individuals infected with human T-cell leukaemia virus type I (HTLV-I), another important member of the human retrovirus family, has not been previously investigated. OBJECTIVE: To establish the prevalence of H. pylori in HTLV-I-positive individuals in the Nagasaki Prefecture, which is an area endemic for HTLV-I. METHODS: We examined sera from 146 HTLV-I-positive individuals with a mean age of 56.7 years, consisting of 45 adult T-cell leukaemia (ATL) patients, 13 HTLV-I-associated myelopathy (HAM) patients and 88 healthy carriers. Serum samples of 292 age- and sex-matched HTLV-I-negative controls were also examined. Serum anti-H. pylori immunoglobulin (Ig) G antibody was examined using an enzyme-linked immunosorbent assay kit. Twenty-eight HTLV-I-positive patients were examined endoscopically, assessed for H. pylori by culture, histology and CLO test using gastric biopsy specimens, and gastritis in these patients was also graded histologically. RESULTS: The seroprevalence of H. pylori was 48% in HTLV-I-positive individuals versus 64% in HTLV-I-negative controls (P < 0.01). In the three HTLV-I-positive groups, ATL patients and carriers had significantly lower seroprevalence of H. pylori than the HTLV-I-negative controls (P < 0.05). Assessment of H. pylori using gastric biopsy specimens also showed a significantly lower prevalence of H. pylori infection in HTLV-I-positive patients than controls (46% versus 70%, P < 0.05). Histological examination showed a significantly higher degree of activity, inflammation and glandular atrophy in the antrum and corpus in H. pylori-positive patients compared to H. pylori-negative patients. H. pylori-positive patients with HTLV-I infection had a more severe degree of glandular atrophy in the corpus than H. pylori-positive controls without HTLV-I infection. CONCLUSION: We have found a reduced prevalence of H. pylori in HTLV-I-positive individuals. Whatever the explanation, infection with HTLV-I does not predispose to the risk of H. pylori infection.

Adult↗
PubMed1999

Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-1 genotype.

To investigate the diversity of morphology in adult T-cell leukaemia/lymphoma (ATL) and its possible association with the pathophysiology of ATL, we selected 36 acute cases and 14 chronic cases phenotypically confirmed to have >90% ATL cells in peripheral blood mononuclear cells. Prototype ATL cells were observed in all cases, although the percentage of all lymphoid cells varied considerably (48.9 +/- 23.8 in acute type, 29.6 +/- 18.9 in chronic type; P = 0.015). Chronic lymphocytic leukaemia (CLL)-like morphology with round nuclei was more frequent in chronic type than in acute type (52.0 +/- 24.9% v 16.6 +/- 13.1%; P < 0.0001). Unusual morphology (UM; lymphoblastic, vacuolated, granular pleomorphic or large cells) was more frequent in acute type than in chronic type (20.1 +/- 18.7% v 2.7 +/- 3.2%; P < 0.0001). Furthermore, there were significant negative and positive correlations of % CLL-like cells and % UM cells respectively, with serum LDH level, hypercalcaemia, performance status, and total number of involved lesions. Cases with aberrant immunophenotype (n = 6) or defective HTLV-1 integration (n = 22) showed lower % CLL-like cells and higher % UM cells than other cases, respectively. Cases with >50% CLL-like cells (n = 7; all chronic type) were younger (53.1 +/- 12.2 v 66.9 +/- 10.6 years; P = 0.038) and showed longer acute-crisis free survival (mean: 16.7 v 3. 0 years; P = 0.012) than chronic cases with <50% CLL-like cells. These results suggest that diversity in genotype, phenotype, morphology and behaviour of ATL are closely associated, and that CLL-like morphology is a good prognostic factor for chronic type.

Adult↗
PubMed1999

A case report of caudal regression syndrome associated with an intraspinal arachnoid cyst.

We report here a rare case of caudal regression syndrome associated with an intraspinal arachnoid cyst. The patient was a 6-month-old baby girl with multicomplex congenital abnormalities: sacrococcygeal dysgenesis and ventral curvature, large terminal cyst (myelocystocele), spinal arachnoid cyst, cerebellar hypertrophy (suspected), high imperforate anus, partial dysgenesis of the large intestine, omphalocele, atresia of the vagina, bilateral incomplete ureter duplication, incomplete pseudoduplicated bladder and bilateral talipes equinovarus. We performed plastic repair of the myelocystocele and perineal lesion for caudal regression syndrome and partial removal of the cyst wall for the intraspinal arachnoid cyst. She has been well for 3 years postoperatively, and her mental development is normal.

Abnormalities, Multiple↗
PubMed1999

Hemangioblastoma mimicking tentorial meningioma: preoperative embolization of the meningeal arterial blood supply--case report.

A 72-year-old male presented with a primary hemangioblastoma of the posterior fossa with unusual dural attachment and meningeal arterial blood supply from the external carotid artery and marginal tentorial artery. Preoperative embolization facilitated complete resection of the tumor with no resultant neurological deficit. Hemangioblastoma must be included in the differential diagnosis of tumors with dural involvement. Preoperative embolization is very useful in such tumors.

Aged↗
PubMed1999

Clonal analysis of B-cell leukemias and lymphomas using the polymerase chain reaction for the third complementarity determining region of the IgH gene: a study of 75 cases from Nagasaki Japan.

Using semi-nested polymerase chain reaction (PCR), we examined 75 Japanese cases of hematologic malignancies with B-cell antigens including 25 common acute lymphoblastic leukemia (ALL), 13 chronic lymphocytic leukemia (CLL), 28 B-cell malignant lymphoma (B-ML), 2 hairy cell leukemia (HCL), 7 acute myelogenous leukemia with B-cell antigens (AML-B), and 23 controls. When amplified products were analysed by a standard polyacrylamide gel electrophoresis, the sensitivity for detection of clonal IgH rearrangements in each group of ALL, CLL, B-ML, HCL, and AML-B was 88%, 92.3%, 71.4%, 100%, and 57.1%, respectively, with an overall sensitivity of 80.0%. There were no false positive results in any of the control samples. Single strand conformation polymorphism (SSCP) analysis of the amplified products gave rise to a much greater sensitivity, up to 84% overall. The false negative samples were mainly encountered in B-ML with SmIgG and non-Ig, suggesting miss-annealing between the primers used and the template DNA because of somatic hypermutation of IgH genes in such clones. This indicates that PCR analysis is very useful in detecting the clonal IgH rearrangements in B-cell malignancies, especially in ALL and CLL, but not in B-ML corresponding to neoplasms originating from pre-germinal center naive B-cells.

Clone Cells↗
PubMed1999

Neuroendoscopic approach to tectal tumors: a consecutive series.

OBJECT: The authors report a consecutive series of 10 patients who presented with signs and symptoms caused by tectal tumors. Clinical findings, radiographic features, neuroendoscopic management strategies, and histological findings are reported and discussed. METHODS: Since January 1990, 11 neuroendoscopic procedures were performed in 10 patients who harbored tectal tumors. The patients were followed for an average of 5 years (range 2 months-11 years), and a retrospective study was conducted in which case notes, radiological findings, operative notes, and histopathological findings were assessed. Magnetic resonance (MR) imaging was performed, and the images were used to classify patients into three groups: those with hypertrophy of the tectum in whom isointensity appeared on T1-weighted images (Group 1); those with a tectal tumor occupying the cerebral aqueduct in whom decreased signal intensity appeared on T1-weighted images, as well as no enhancement after gadolinium administration (Group 2); and those with a tectal tumor in whom mixed signal intensity and conspicuous evidence of contrast enhancement appeared on T1-weighted images (Group 3). The results of histological examination were consistent with MR imaging features: in Group 1, glial tissue or gliosis; in Group 2, benign astrocytoma; and in Group 3, malignant astrocytoma. Cerebrospinal fluid diversion was the only surgical treatment that provided relief from obstructive hydrocephalus. One patient in Group 3 underwent radiotherapy and subsequent partial tumor removal under neuroendoscopic guidance. Thereafter, the tumor remained in decline. All patients had normal intellectual status after undergoing surgery in which a neuroendoscope was used. CONCLUSIONS: Neuroendoscopic procedures can provide histological diagnosis, define the tumor-midbrain interrelationship, and be highly effective in treating obstructive hydrocephalus and in removing tectal tumors. This procedure may receive clinical application as a new management strategy for tectal glioma.

Adolescent↗
PubMed1999

[Phase I clinical study of SH L573 (fludarabine phosphate) in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma].

We have conducted a phase I clinical study of fludarabine phosphate, a new purine nucleoside derivative, in patients with chronic lymphocytic leukemia and adult T-cell leukemia/lymphoma. The patients were given intravenous administration at a dose of 15 mg/m2/day followed by 20 mg/m2/day and 25 mg/m2/day, each dose given consecutively for 5 days. The dose limiting factors were thrombocytopenia and neutropenia. The thrombocyte count and neutrocyte count dropped to their lowest value in week 1 to 2 after administration, but the changes were reversible, and these counts recovered in most patients. The maximum tolerated dose of the study drug was 25 mg/m2/day, and it was decided to administer 20 mg/m2/day as the recommended dose for the subsequent phase II clinical study.

Adult↗