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Biomedical subjects

M Tomonaga

Publications and source records attributed to M Tomonaga.

At least 217 records · Page 12Linked to original sources

Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia.

BACKGROUND: The authors conducted a survey of a large cohort of patients with adult T-cell leukemia (ATL) and a group of human T-cell leukemia virus type 1 (HTLV-1) carriers to elucidate whether measurements of soluble interleukin-2 receptor (sIL-2R) levels are indicative of ATL tumor burden and correlate with clinical progression. METHODS: Using a sandwich enzyme immunoassay, the authors determined sIL-2R in the serum of 135 patients with ATL diagnosed and subclassified according to the Japan Lymphoma Study Group criteria and in the serum of healthy HTLV-1 seropositive persons. Also included were patients in the preleukemic state of ATL (pre-ATL), which is characterized by only slight blood changes but does not fit the diagnostic criteria of ATL. In the five subjects who finally advanced to overt ATL, the authors prospectively performed serial measurements of the receptor. RESULTS: Serial measurements of sIL-2R levels taken until overt ATL developed showed that these levels in the initial samples were higher than those of control subjects, even when subjects were asymptomatic or in the pre-ATL state. The serial levels of the five subjects gradually increased despite being in a clinically stable condition, finally reaching markedly high levels at the time ATL became overt. The mean sIL-2R levels of the smoldering, chronic, acute, and lymphoma subtypes of ATL were 1680 U/ml, 6680 U/ml, 45,940 U/ml, and 34,620 U/ml, respectively (P < 0.01). The sIL-2R levels of each subtype at the time of diagnosis were more correlated with tumor burden, malignant behavior, and prognosis than lactate dehydrogenase (LDH) levels. In the low, moderate, and high sIL-2R subgroups, the median survival time and percent survival probability at 2 years was 30.2 months (46.0%), 16.5 months (25.0%), and 7.7 months (15.3%), respectively. CONCLUSIONS: Serial measurements of sIL-2R levels are of clinical importance because changes of the levels correlate with disease progression, especially in early phase of ATL. The data suggest that sIL-2R may be more useful than LDH. In addition, emphasis may be placed on sIL-2R as an indicator of ATL progression status and prognosis for survival. The value of this marker in clinical practice should be confirmed prospectively.

Carrier State↗

Primary central nervous system lymphomas. Immunophenotypic, virologic, and cytogenetic findings of three patients without immune defects.

BACKGROUND: Primary central nervous system (PCNS) lymphoma is a relatively rare disease, but an increasing incidence is reported. The Epstein-Barr virus (EBV), which is often found in lymphomas of immunocompromised patients, has been implicated in the development of lymphomas. Many cytogenetic analyses of nodal B cell lymphomas have been performed, but few studies on PCNS lymphomas have been reported. METHODS: The detection of EBV genome using the polymerase chain reaction (PCR) method and cytogenetic studies were performed, in addition to histopathologic and immunophenotypic approaches in biopsied tissue from three patients with PCNS lymphoma. Immunosuppressive states and exposure to mutagens were not clear in all patients. RESULTS: Histopathologic examination disclosed a diffuse type of malignant lymphoma in all patients. Immunophenotypic studies revealed B cell phenotype in all patients, two of whom showed positive reaction for CD5. The PCR method revealed no involvement of EBV genome in tumors in any patients. The cytogenetic study showed clonal chromosome abnormalities in all patients, and abnormalities of chromosome 1 (1q21), 6 (-6, 6q15 and 6q21), 7 (-7 and 7p15), and 14 (14q24 and 14q32) were prominent. The t(6;14)(q15;q32) observed in Patient 1 is the first case to be reported in human de novo lymphoma. CONCLUSIONS: These findings indicate that the causative role of EBV in PCNS lymphoma without immune defects is not clear. The cytogenetic findings were similar to those observed in nodal B-cell lymphoma, suggesting that the origin of PCNS lymphoma cells does not differ from nodal B cell lymphoma cells cytogenetically.

Aged↗

Endoneurosurgical treatment for hydrocephalus caused by intraventricular tumors.

A flexible therapeutic ventriculoscope allowing for the use of a variety of different instruments has been developed. Endoneurosurgical instruments are composed of an endoscopic contact YAG laser endoprobe, grasping forceps and a punctured needle. Endoneurosurgical procedures include biopsies, III ventriculostomy, fenestration of the septum pellucidum, aspirations of cysts and excisions of tumors in the cerebrospinal fluid pathways. Our ventriculoscope allows the initial treatment for progressive hydrocephalus caused by intraventricular tumors to take the form of reducing ventricular size and decreasing intracranial pressure, and it can also be used to perform biopsy examinations, so that acceptable neurological outcomes and an accurate histological diagnosis can be obtained with fewer side effects. The subsequent therapies for hydrocephalus caused by intraventricular tumors include radical surgery for benign tumors, irradiation for radiosensitive tumors, and irradiation and/or chemotherapy for either malignant or disseminated tumors. We have tried to avoid the sequelae of shunt surgery and have achieved maximum effects with the minimum of procedures by using our ventriculoscope.

Adolescent↗

Ventriculoscope-guided ventriculoperitoneal shunt and shunt revision. Technical note.

A new small, flexible fiberoptic ventriculoscope for the accurate positioning of a ventricular catheter tip has been developed. The technique for ventriculoscope-guided ventriculoperitoneal shunt and shunt revision is described. The ventricular catheter can easily be positioned away from the choroid plexus. Choroid plexus adhering to the shunt tube can be coagulated during shunt revision. This procedure can thus prevent an obstruction of the ventricular catheter by an adherent choroid plexus.

Aged↗

Percutaneous flexible neuroendoscopic ventriculostomy in patients with shunt malfunction as an alternative procedure to shunt revision.

Three patients with shunt malfunction, who had previously undergone a shunting procedure for noncommunicating hydrocephalus of adolescent and adult onset, successfully underwent a percutaneous flexible neuroendoscopic ventriculostomy. This procedure was performed as an alternative treatment for shunt revision by the use of our newly developed flexible fiberoptic ventriculoscope. All patients were able to remain independent of the shunt system after the ventriculostomy. These results thus suggest that a percutaneous flexible neuroendoscopic ventriculostomy can be effective for the treatment of shunt-dependent patients with shunt malfunction in adolescents and adults.

Adolescent↗

DNA aneuploidy of adult T-cell leukemia cells.

To clarify the biological characteristics of adult T-cell leukemia (ATL), immunophenotyping and DNA aneuploid analysis were performed in 72 ATL cases, using flow cytometric techniques. DNA aneuploidy was found in 45 cases (62.5%); the DNA index ranged from 1.03 to 2.16 (mean: 1.24). The incidence of aneuploidy in smoldering, chronic, acute, and lymphoma ATL subtypes was 20.0%, 46.6%, 76.3%, and 77.8%, respectively. The aneuploid patients had a greater tumor burden (adenopathy, hepatosplenomegaly, and leukocytosis with ATL cells), a higher level of serum LDH, and a higher incidence of hypercalcemia, compared with the diploid group. Further, unusual aberrant immunophenotypes were identified predominantly in the aneuploid group. Patients with aneuploidy had a 7.6 month median survival time (MST) with a 2 year survival rate of 24.6%, significantly worse than in the patients with diploidy, whose MST was 25.4 months with a 2 year survival of 60.1%. In some aneuploid patients, the disease often progresses from a static to an aggressive form. Thus, the determination of aneuploidy and unusual immunophenotype should be useful for detecting clinical behavior and for monitoring ATL patients, particularly in regard to such progression.

Adult↗

Antitumor effect of exogenous/endogenous TNF (EET) therapy with cyclophosphamide on C6 glioma in rat.

We earlier reported that endogenous TNF could be induced in mice as well as in patients by successive administration of exogenous TNF as a primer and OK-432 as a trigger, and we termed this exogenous/endogenous TNF (EET) therapy. We studied the effect of EET therapy with cyclophosphamide (CY) on tumor-transplanted rats. In order to induce endogenous TNF, 5 x 10(5) U/kg of recombinant human TNF-S(AM2) (rTNF; 5.6x10(6) U/mg protein) was injected intravenously (iv) as a primer followed by injection of 25 KE/kg of OK-432 as a trigger. TNF activity induced in serum was about 500 U/ml. Only 1 U/g of TNF was detected in the brain. To evaluate the antitumor effect, C6 glioma cells (1.6 x 10(4) cell/5 microliters) was transplanted into the brain. On day 7 of the transplantation, the rats were administered iv with CY (75 mg/kg), treated with EET therapy 7 days thereafter, and survival days were checked. No clear difference in survival days was observed between the rats treated with the EET and the control group. Three rats out of 6 treated with CY survived for more than 40 days, and all the rats treated with the combination of CY and EET continued to survive. The histological examination on day 44 revealed necrotic changes at the tumor lesions in all of the surviving rats, and the animals were evaluated as completely cured. These results suggest that applied treatment based on the EET therapy will be also effective against malignant brain tumors.

Animals↗

Acute myeloid leukaemia with t(9;11)(p22;q23) in a patient treated for adult T cell leukaemia.

A 37-year-old male patient with adult T cell leukaemia (ATL) began receiving chemotherapy in March 1992. He achieved complete remission in May 1992, but developed acute myeloid leukaemia (AML, FAB subtype M2) with t(9;11)(p22;q23) in May 1993. The presence of chromosome 11 abnormality at band 11q23 in this patient suggests that the AML was related to the chemotherapy with etoposide for ATL. Furthermore, the combination of etoposide with two cytostatic drugs, cyclophosphamide and carboplatin, possibly induced the leukaemia early (14 months) after the start of chemotherapy. To our knowledge, this is the first report of therapy-related AML after chemotherapy for ATL.

Adult↗

Poor response to intensive chemotherapy in de novo acute myeloid leukaemia with trilineage myelodysplasia. Japan Adult Leukaemia Study Group (JALSG).

The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Group AML-87 protocol. 40 (17%) patients had AML/TMDS. Platelet count was significantly higher (P = 0.006) and bone marrow blasts were fewer (P = 0.01) in the AML/TMDS group than in the AML without TMDS. Abnormal karyotype was shown in 12/30 patients (40%) analysed. The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63% v 81%) (P = 0.01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS (P = 0.0005). AML/TMDS also showed significantly worse disease-free survival (DFS) (P = 0.0001). Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR (P = 0.01) and a significant factor in predicting longer DFS (P = 0.04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML.

Adult↗

Prophylaxis of symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with all-trans retinoic acid.

A 61-year-old man with acute promyelocytic leukemia (APL) is described in whom some leukemic promyelocytes contained granules similar to those of basophils, and hyperhistaminemia developed after treatment with all-trans retinoic acid. The symptoms of hyperhistaminemia, mediated via H2 receptors, were prevented by the administration of an H2-blocker, famotidine, but wheezing due to bronchospasms, mediated via H1 receptors, developed and was improved by administration of chlorpheniramine. In APL, it is generally thought that the maturation of neutrophilic leukocytes is arrested at the level of abnormal promyelocytes. However, heterogeneity of leukemic promyelocytes has been described and in a few patients some leukemic promyelocytes have been known to show basophilic features. Marked basophilia and severe symptoms due to hyperhistaminemia have recently been reported after the treatment of APL with all-trans retinoic acid. Our case presented similar basophilic features, but indicated that the symptoms of hyperhistaminemia after administration of retinoic acid can be prevented with antihistaminic drugs and suggested that both H1- and H2-blockers should be administered to such APL patients with basophilia.

Basophils↗

Symptomatic Chiari malformation and associated pathophysiology in pediatric and adult patients without myelodysplasia.

The clinical characteristics of eight pediatric and five adult patients with Chiari malformation were evaluated. Six pediatric and five adult patients had associated syringomyelia. All patients initially underwent a suboccipital craniectomy with upper cervical (C-1 and/or C-2) laminectomy and duraplasty, and/or shunting procedures. The clinical characteristics of the pediatric and adult groups were compared. The mean interval between onset of symptoms and operation was shorter in the pediatric group (3 yrs 6 mos) than in the adult group (7 yrs 1 mo). Pediatric patients without syringomyelia had the shortest mean interval of 1 year 8 months. Preoperatively, the clinical features were more severe in the adult patients than in the pediatric patients. Postoperatively, seven of eight pediatric patients improved and one stabilized, while two of five adult patients improved, one stabilized, and in two the disease continued to progress despite multiple corrective procedures. Cine magnetic resonance imaging revealed correction of the abnormal cerebrospinal fluid (CSF) flow at the craniovertebral junction and decreased to-and-fro movement in the syrinx after posterior fossa decompression, which were closely correlated with the improvement of clinical features in pediatric patients. However, adult patients required further procedures because of the multifactorial nature of the disease. Evaluation of abnormal CSF pathways at the craniovertebral junction is important for investigating the pathogenesis of Chiari malformation and associated syringomyelia.

Adolescent↗

Morphological and immunophenotypical characterization of Japanese B-cell lymphocytic leukemia.

We have analyzed the clinical and laboratory features of 42 patients with B-cell leukemia. Based on the FAB criteria, the cases were classified in 3 groups: I) typical CLL 15, II) atypical CLL 9 which included 6 cases with large cells, and III) B-cell lymphoma in leukemic phase 18. Cases diagnosed as typical CLL (group I) had similar features to those seen in CLL patients from Western countries. The morphology and markers in cases from group III corresponded to B-cell lymphoma in leukemic phase. On the other hand, group II included 3 cases classified as atypical CLL according to FAB criteria. 1 CLL/PL and 2 mixed CLL and 6 cases with rather distinct features, namely: 1) lymphocytosis (42 +/- 41 x 10(9)/l in average) with large mature-looking lymphocytes with abundant cytoplasm: 2) an immunological profile consistent with CLL but, in addition with the consistent expression of CD38; 3) absence of a monoclonal band in the serum and 4) a clinical course and prognosis similar to CLL. Our findings suggest the existence of a B-cell disorder in Japan very close to CLL but distinct from typical and atypical CLL as seen in Western countries. Further studies would clarify whether such an entity is exclusively confined to Japan having a distinct natural history.

Adult↗

Obstruction of the superior sagittal sinus caused by parasagittal meningiomas: the role of collateral venous pathways.

The authors present studies of eight patients who had obstruction of the superior sagittal sinus caused by parasagittal meningioma. The results indicate that meningeal veins and end-to-end anastomoses of the superficial veins of the cerebrum play important roles as collateral venous pathways. This assessment suggests that, in patients with obstruction of the superior sagittal sinus, venous phase angiography should be carefully interpreted before surgery is attempted for parasagittal meningiomas.

Cerebral Angiography↗

Human T-lymphotropic virus type-I influence on hepatotropic virus infections and the subsequent development of hepatocellular carcinoma.

We studied the serologic status, with respect to hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus type-I (HTLV-I) of blood donors in an area endemic for adult T-cell leukemia (ATL). Similarly, we studied the serologic status of hepatocellular carcinoma (HCC) patients from the same district. In the donors, the incidence of serological positivity for these viruses was 0.95, 1.23, and 3.75%, respectively. There was a positive correlation between the presence of anti-HCV and serological HTLV-I positive status in these subjects (1.9 vs. 1.1%) for those with HTLV-I negative status, implying high susceptibility for HCV infection among HTLV-I carriers. Fifty-nine percent of HCC patients were positive for anti-HCV and twenty-six percent of those were simultaneously positive for the antibody to HTLV-I. HCC patients infected with HTLV-I were younger than patients not so infected (61.5 +/- 8.8 vs. 64.8 +/- 8.4 years, p < 0.05). These observations suggest the possibility that HTLV-I could be one of the factors that promote the development of HCC caused by hepatotropic viruses.

Adolescent↗

[Localization of platelet-derived endothelial cell growth factor in human glioblastoma and meningioma].

Localization of platelet-derived endothelial cell growth factor (PD-ECGF) in the surgical specimens of 11 human glioblastomas and 12 meningiomas was immunohistochemically examined with a polyclonal anti-PD-ECGF rabbit IgG. PD-ECGF was mainly localized in macrophages distributing around blood vessels at the peripheries of tumor tissue, especially of glioblastoma. PD-ECGF-positive macrophages were frequently accumulated in the vascular-rich stroma of glioblastoma, where occasionally expressed proliferating cell nuclear antigen-positive endothelial cells. However, few macrophages expressing PD-ECGF were scatteringly seen in meningioma. These findings suggest that PD-ECGF plays an important role in the growth of glioblastoma by affecting the stromal angiogenesis.

Brain Neoplasms↗