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Biomedical subjects

S Hanada

Publications and source records attributed to S Hanada.

At least 73 records · Page 4Linked to original sources
PubMed1998

Granulocyte colony-stimulating factor in the combination chemotherapy for adult T-cell leukemia (ATL).

We evaluated the effect of granulocyte colony-stimulating factor (G-CSF) on the median survival of 17 patients with Adult T-cell leukemia (ATL). Standard-dose combination chemotherapy using the response-oriented cyclic multidrug (RCM) protocol with G-CSF (lenograstim 2 microg/kg/day or filgrastim 50 microg/m2/day) was administered between October 1990 and December 1994. Complete responses (CR) were achieved in 11 (64.7%) patients, and partial responses (PR) in 4 (23.5%) patients. The median duration of survival was 7.4 months, compared with 6.0 months in ATL patients treated with the RCM protocol alone (historical controls) (n.s.). Infectious complications were the cause of death in 4 (26.7%) of the 15 patients who died. The median duration of neutropenia (absolute neutrophil count < 1.0 x 10(9)/L) was 6 days. G-CSF, in the doses and schedules used here, may have shortened the duration of neutropenia and reduced the incidence of fatal infectious complications. However, concomitant use of G-CSF did not prolong the median duration of survival in patients with ATL treated according to the RCM protocol.

Adjuvants, Immunologic↗
PubMed1997

Treatment for adult T-cell leukemia.

The purpose of this study was to clarify the clinical efficacy of multidrug chemotherapy for aggressive adult T-cell leukemia (ATL). We report the therapeutic results of treatment of patients with aggressive ATL undertaken between 1986 and 1995. A total of 120 newly diagnosed patients with a performance status of 0-3 and aged < 70 years at diagnosis were entered into the study. Clinical features, including clinical subtypes, serum levels of lactate dehydrogenase and blood urea nitrogen, the response to chemotherapy, and doses of individual chemotherapeutic agents, were evaluated. Of the 120 patients enrolled, 97 had acute-type and 23 lymphoma-type ATL. The complete response rate and median survival of these patients were 25.3% and 9 months, respectively. The 2- and 5-year survival rates were 18.4% and 8%, respectively, and five patients have been alive for > 5 years and are disease-free. These long-term survivors had good prognostic factors at diagnosis. There was no correlation between the doses of the various chemotherapeutic agents and the survival duration. These results indicate that ordinary combined chemotherapy has limited ability to improve the prognosis of aggressive ATL. Our previous study indicated that expression of P-glycoprotein in ATL cells might be involved in resistance to chemotherapeutic agents, particularly doxorubicin, vincristine, and etoposide. Therefore, new therapeutic strategies will be necessary to improve the prognosis of ATL patients.

Adult↗
PubMed1997

Identification of interleukin-6 producing fibroblastoid cells in cerebrospinal fluid from patients with leukemic meningitis.

Cytokine producing native cells in cerebrospinal fluid (CSF) have not been identified. So, we investigated the cytokine producing ability of floating cells in CSF from patients with leukemic meningitis. Morphologic study revealed that established cell lines were polygonal or elongated in shape and had an abundant and irregular branched cytoplasm. Immunocytochemical analysis demonstrated positive reactivity with monoclonal anti-fibroblast antibody only. Interleukin-6 (IL-6) was constitutively produced in vitro by these cell lines; both interleukin-1 and lipopolysaccharides significantly increased its synthesis. These findings imply that these fibroblastoid cells are floating in CSF of patients with leukemic meningitis and produce IL-6 in response to various inflammatory stimulations in vivo.

Adult↗
PubMed1997

Porphyrobacter tepidarius sp. nov., a moderately thermophilic aerobic photosynthetic bacterium isolated from a hot spring.

A new thermophilic bacterium, strain OT3T (T = type strain), was isolated from a brackish hot spring. Strain OT3T is an obligate aerobe that synthesizes bacteriochlorophyll a and has a photosynthetic apparatus. This isolate is a thermophilic bacterium with an optimal growth temperature of 40 to 48 degrees C. The cells are nonmotile, ovoid to short rods. An analysis of 16S rRNA sequences revealed that the new strain forms a coherent cluster with members of the alpha-4 group of the alpha subclass of the Proteobacteria, which contains the genera Erythrobacter, Erythromicrobium, and Porphyrobacter. The closest relative is Porphyrobacter neustonensis, with a 16S rRNA sequence similarity of 96.8%. The in vivo absorption spectrum has maxima at 460, 494, 596, 800, and 870 nm. The main carotenoids are OH-beta-carotene sulfate derivatives, nostoxanthin, and bacteriorubixanthinal. Growth occurs with glucose, acetate, glutamate, butyrate, Casamino Acids, and yeast extract as sole energy sources. The pigment composition and nutritional profile of the new isolate are similar to the pigment composition and nutritional profile of P. neustonensis. Although there are marked differences in cell morphology between the new isolate and the budding bacterium P. neustonensis, the results of phenotypic and genetic comparisons suggest that the new isolate is closely related to P. neustonensis. Consequently, we assign the new isolate to the genus Porphyrobacter and propose the name Porphyrobacter tepidarius sp. nov. for it; the type strain of P. tepidarius is strain OT3 (= DSM 10595).

Bacteria, Aerobic↗
PubMed1997

Gnathostomiasis in frog-eating snakes from Japan.

Gnathostoma doloresi parasitizes the gastric wall of wild (boars) and domestic (pigs) swine (Sus scrofa). Its larvae cause cutaneous larva migrans in humans. Amphibians, reptiles and a freshwater fish are infected with the advanced 3rd stage larvae. Prevalence of G. doloresi larvae were surveyed in several snakes, especially in a common frog-eating snake (Rhabdophis tigrinus). All species of snakes examined were infected with G. doloresi larvae suggesting that snakes are important reservoir hosts. Prevalence of G. doloresi larvae in frog-eating snakes was lower than that found in mammal-eating snakes. Thus, as a source of infection to snakes, small mammals may be more important than frogs in the natural life cycle of G. doloresi in Japan.

Animals↗
PubMed1996

Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers.

The serum levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were determined by radioimmunoassay in 38 patients with adult T-cell leukemia (ATL). Levels of serum DHEA and DHEA-S were also measured in 60 human T-lymphotropic virus type I (HTLV-I) carriers, and did not differ from those in 60 healthy control subjects. Serum levels in patients with ATL were lower than those in the age- and sex-matched healthy controls and in HTLV-I carriers with statistical significance. Serum DHEA and DHEA-S in male patients with acute and lymphoma-type ATL were 1.06 +/- 0.77 ng/ml and 245.8 +/- 192.9 ng/ml, respectively. Levels in male patients with chronic and smoldering-type ATL were 1.69 +/- 0.68 ng/ml and 477.6 +/- 251.5 ng/ml, respectively. Serum levels of DHEA and DHEA-S in patients with acute and lymphoma-type ATL were significantly lower than those in patients with chronic and smoldering-type ATL (P < 0.05). These data suggest that a decrease in serum levels of DHEA and DHEA-S may be associated with patients who have some clinical subtypes of ATL. Moreover, androgens may have a therapeutic role in patients with ATL, as administered in patients with hairy-cell leukemia. Because there is at present no curative chemotherapy for ATL, a trial combination of androgens and standard chemotherapy may be a reasonable therapeutic option in such patients.

Adrenal Cortex↗
PubMed1996

Laparoscopic-assisted creation of a vagina.

The applicability of laparoscopy for colpopiesis using pelvic peritoneum was examined in two women with the Mayer-Rokitansky-Kuster-Hauser syndrome. Using a modification of laparoscopic guidance proved advantageous for safe dissection of the vesicorectal space and accurate suturing of the pelvic peritoneum without laparotomy. A sufficient vaginal cavity was achieved in both patients. This modification of the original procedure, featuring introduction of a laparoscope, thus provides effective and safe conditions for creation of a new vagina.

Adult↗
PubMed1996

[Adult T-cell leukemia complicated with intestinal tuberculosis].

We report a patient with adult T-cell leukemia (ATL) complicated with intestinal tuberculosis. A 57-year old man was admitted to our hospital because of fever and dyspnea. He was diagnosed as ATL by leukocytosis [leukocyte count 18,200/microliters with 56% of abnormal lymphocytes which express CD4(+) and CD25(+)] and seropositive result of anti-HTLV-1 antibody. Combination chemotherapy for ATL improved his serum LDH level and peripheral lymph nodes, but fever was still persistent. He had an emergency operation because of perforation of the cecum during the chemotherapy. Histological examination of the resected cecum revealed caseous necrosis and numerous mycobacterium, which induced a diagnosis of intestinal tuberculosis. Although there have been several reports on pulmonary tuberculosis in patients with ATL, this is the first report of intestinal tuberculosis in ATL as far as we know. We conclude that if the patients with ATL have persistent fever of unknown origin, we should take account of intestinal tuberculosis as one of differential diagnosis.

Fever of Unknown Origin↗
PubMed1995

Acute hepatitis in rats expressing human hepatitis B virus transgenes.

The molecular mechanisms responsible for hepatocyte death and the events leading to viral clearance in hepatitis B virus (HBV) infections are not well understood. Elucidation of the mechanisms involved have been complicated by the difficulty of infecting human hepatocytes with HBV in vitro and the lack of an appropriate animal model. We report an animal model of human HBV infection by in vivo transfection. We have directly introduced a replication-competent, cloned HBV construct into rat liver by using a membrane fusion-promoting cationic lipid. HBV mRNA and 3.2-kb HBV DNA were expressed in the liver by this in vivo transfection method. In the majority of rats, HBV virions and hepatitis B e antigen were found in the blood 3-7 days after transfection, after which antibody to the e antigen appeared. Two to three weeks after the transfection, glutamic-pyruvic transaminase levels were elevated in serum, hepatocyte death and lymphocyte infiltration were observed in the vicinity of the portal vein of liver, and HBV virions were no longer detected in the serum. Thus, transfection of HBV into rats resulted in histological and serological changes comparable to HBV-induced acute hepatitis in humans. In contrast, no hepatocellular injury was observed in T-lymphocyte-deficient nude rats transfected with the same HBV construct, and viremia was substantially prolonged, providing direct evidence that T lymphocytes play an essential role in liver cell injury and in the clearance of HBV. This rat hepatitis model will be useful for studying pathogenesis of HBV infection.

Acute Disease↗
PubMed1995

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects.

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4-74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7-43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6-13.3% (mean 8.0%). In contrast to patients with acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the beta 7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced beta 7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.

Antigens, Neoplasm↗
PubMed1995

Chloroflexus aggregans sp. nov., a filamentous phototrophic bacterium which forms dense cell aggregates by active gliding movement.

Two strains of thermophilic photosynthetic bacteria, designated MD-66T (T = type strain) and YI-9, were isolated from bacterial mats in two separate hot springs in Japan. These new isolates were phenotypically similar to Chloroflexus aurantiacus in some respects. They were thermophilic filamentous photosynthetic bacteria that grew well at 55 degrees C either anaerobically as photoheterotrophs or aerobically as chemoheterotrophs. They exhibited gliding motility, produced bacteriochlorophylls a and c, contained chlorosomes, and required thiamine and folic acid as growth factors. However, isolates MD-66T and YI-9 had the ability to rapidly form mat-like dense aggregates of filaments, an ability which has not been observed in any C. aurantiacus strain. Carbon source utilization tests revealed that unlike C. aurantiacus, the new isolates did not utilize acetate, citrate, ethanol, or glycylglycine. An analysis of the carotenoid components revealed that isolates MD-66T and YI-9 contained mainly gamma-carotene and OH-gamma-carotene glucoside fatty acid esters. These isolates also contained only trace amounts of beta-carotene, which is a major carotenoid component (28.4% of the total carotenoids) in C. aurantiacus. The results of DNA hybridization studies suggested that the new strains were genetically distinct from C. aurantiacus (levels of similarity, 9 to 18%), and 16S rRNA sequence comparisons showed that strain MD-66T was related to C. aurantiacus at a similarity level of 92.8%. On the basis of our data, we propose that a new Chloroflexus species should be created for our new isolates; the name of this new species is Chloroflexus aggregans, and the type strain is strain MD-66 (= DSM 9485).

Bacteria↗
PubMed1995

Combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) for the acute or lymphoma type adult T-cell leukemia.

43 patients with the acute or lymphoma type ATL were treated with the new combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) between January 1989 and December 1991. Complete response (CR) and partial response (PR) were achieved in 20.9% and 65.1% of all treated patients respectively. The median duration of survival was 6.0 months. The survival duration of patients with a high serum lactate dehydrogenase (LDH) value (> or = 1,000 unit) and/or a poor performance status (PS) (PS 3 or 4) were also improved but not in patients with a severe leukocytosis (> or = 35,000/microliters). Toxicity was mild (grade 1 or 2) except hematologic toxicity in 4 patients (9.3%) and alopecia in one patient (2.3%). In spite of many patients with a poor PS (PS 3 or 4), our chemotherapeutic results are equal or superior to other previous reports. It seems that response-oriented chemotherapy is suitable for the ATL patients with poor prognostic factors. These results indicate that the RCM protocol is very useful as the first choice chemotherapy for the acute or lymphoma type ATL.

Adult↗
PubMed1995

Significance of elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukemia.

Although it has been recognized previously that several markers are present in the cerebrospinal fluid (CSF), their clinical usefulness of these markers in the diagnosis of malignant lymphoma infiltrating to the CNS has not yet been established. In order to determine their diagnostic usefulness as markers of meningeal infiltration by lymphoma cells in patients with adult T-cell leukemia (ATL), we measured some soluble factors in the CSF of patients with ATL and non-ATL patients. Soluble CD4 (sCD4) was highly elevated in all patients with ATL and meningeal infiltration. The CSF level of the soluble interleukin-2 receptor (sIL-2R; sCD25) was markedly elevated in 13 (72.2%) of 18 patients with ATL and meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of patients with ATL and meningeal infiltration were significantly higher than in non-ATL patients (p < .01 and p < .001, respectively). These findings indicate that levels of sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration by leukemia cells expressing CD4 and CD25 on surface membranes. CSF levels of sCD4 in 14 (60.9%) of 23 ATL patients and sCD25 in 13 (72.2%) of 18 ATL patients without meningeal infiltration were moderately elevated. These findings suggest that a small number of leukemic cells which were not detected by conventional CSF examination may have infiltrated the meninges in these patients. Sequential measurements of sCD4 and sCD25 in CSF obtained from patients with meningeal infiltration by leukemic cells showed that sCD4 and sCD25 levels reflected the activity of leukemic meningitis and correlated with the number of cells in CSF. However, the levels of sCD4 in CSF did not fall below the limit of detection even when the number of cells in CSF became normal. It is thought that the level of sCD4 in CSF is a more sensitive marker for detecting the infiltration of leukemic cells in CSF than the number of cells present in the CSF considering the clinical course of two patients with acute type ATL. Therefore, ATL patients with meningeal infiltration should receive treatments until sCD4 levels become normal and not just until the number of cells become normal. Our results also suggest that measurement of CSF levels of sCD4 and sCD25 is useful for the differential diagnosis of aseptic meningitis and meningeal infiltration by leukemic cells in patients with smoldering ATL. We conclude that measurement of soluble factors in CSF plays an important role in diagnosis, prophylaxis and treatment of meningitis in patients with ATL.

Biomarkers, Tumor↗
PubMed1994

Cytotoxicity of recombinant Fab and Fv immunotoxins on adult T-cell leukemia lymph node and blood cells in the presence of soluble interleukin-2 receptor.

Single-chain immunotoxins anti-Tac(Fv)-PE40 and anti-Tac(Fv)-PE40KDEL, composed of variable domains of the anti-Tac monoclonal antibody and truncated forms of Pseudomonas exotoxin, have shown potent cytotoxic activity against malignant peripheral blood mononuclear cells (PBMCs) from adult T-cell leukemia (ATL) patients originating from the Caribbean. However, several clinically important issues have not previously been addressed. These include the potential of soluble interleukin 2 receptor in ATL patients to block immunotoxin effectiveness, the relative sensitivity of malignant lymph node cells (LNCs) versus PBMCs, the effect of an immunotoxin with a prolonged half-life, and finally whether ATL cells from patients in Japan have toxin sensitivity equal to those of the Caribbean patients. To resolve these questions, we studied 32 malignant PBMC and LNC samples from 30 ATL patients from Japan. PBMCs from 27 of 27 patients were very sensitive with 50% inhibition of protein synthesis achieved with 0.02-0.85 ng/ml (0.3-13 pM) of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fv)-PE40. LNCs had sensitivity very similar to that of PBMCs in the five patients tested. The fully recombinant immunotoxin, anti-Tac(Fab)-PE40, which has 8-10 times the t1/2 alpha and beta compared to the Fv-immunotoxins, was also very cytotoxic toward cells from 27 of 27 patients tested with 50% inhibition of protein synthesis of 0.08-25 ng/ml. It was found that purified soluble interleukin 2 receptor added to the cytotoxicity assay decreased the cytotoxic activity of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fab)-PE40, but that 1 x 10(4) units/ml or less had minimal competitive effects. It was found that ATL patients who have responded even incompletely to conventional chemotherapy have soluble interleukin 2 receptor levels lower than this at posttreatment. We conclude that recombinant immunotoxins containing anti-Tac(Fv) are effective against Japanese ATL PBMCs or LNCs and might be most effective if used in vivo after conventional chemotherapy. If it is found in humans that the effectiveness of single-chain recombinant toxins is limited by short half-life, anti-Tac(Fab)-PE40 should be considered as an alternative agent.

ADP Ribose Transferases↗
PubMed1994

Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T-cell leukemia.

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T-cell leukemia (ATL) and other malignant and non-malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 +/- 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 +/- 9.2 U/ml). Non-ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 +/- 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 +/- 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL.

CD4 Antigens↗