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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 163 records · Page 9Linked to original sources
PubMed1996

Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study.

We conducted a prospective randomized study to compare granisetron, a 5-hydroxytryptamine-3 receptor antagonist with standard anti-emetics (control group) consisting mainly of metoclopramide, in the prophylaxis of emesis induced by conditioning prior to stem cell transplantation. Fifty-eight patients were evaluable for analysis. The number of emetic episodes expressed in terms of patient-days was significantly lower in the granisetron group than in the control group (P < 0.001). During the first 24 h of conditioning, 27 of the 31 patients (87.1%) in the granisetron group achieved control of emesis with less than three emetic episodes (major < or = ) a day compared with 37.0% in the control group (P < 0.001). The same degree of emesis control was maintained throughout the conditioning period in 51.% of patients in the granisetron group compared with 0% in the control group (P < 0.001). Adverse reactions were observed in 11.4% of patients in the granisetron group and in 25.9% in the control group. None of the events were serious. Based on these data, we conclude that granisetron is superior to standard antiemetics in protecting against the vomiting induced by conditioning for stem cell transplantation.

Adolescent↗
PubMed1996

[Subsets of lymphocytes in bronchoalveolar-lavage fluid from patients with idiopathic bronchiolitis obliterans organizing pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 5 patients with idiopathic bronchiolitis obliterans organizing pneumonia and from 7 control subjects. Lymphocytes were analyzed by two-flow cytometry. Differential cell counts showed that the percentage and the number of lymphocytes was higher in the patients (32.9 +/- 21.9%, 12.8 +/- 8.32 x 10(4) cells/ml) than in the controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4) cells/ml, p < 0.05). In particular, the patients had many more CD8+ S6F1+ lymphocytes (which are considered to be activated cytotoxic T lymphocytes; 32.2 +/- 11.8%, 42.0 +/- 26.5 x 10(3) cells/ml) than did the controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3) cells/ml, p < 0.01). These data indicate that activated cytotoxic T lymphocytes may be important in the pathogenesis of bronchiolitis obliterans organizing preumonia.

Aged↗
PubMed1996

Football injuries in a rural area.

This study was conducted to analyze the frequency and characteristics of football injuries in a rural hospital setting and compare it to the national data. More than 6,000 patients with a sport-related injury presenting to the emergency medicine department at the Marshfield Clinic between June 1, 1988 and June 1, 1994 were collected prospectively. Eight hundred forty-three (14% of total) patients sustained football-related injuries. A chart abstraction form was then used to retrospectively review football injuries documenting types, sites, and mechanism of injury, along with demographic aspects. The peak age sustaining football injuries was 17 years old (17.5%). Most of the football injuries occurred during school activities (73.7%). The most common site injured was the finger (16.5%), followed by the knee (15.7%). Sprains/strains were the most common diagnosis representing 40.2% of injuries overall. The most common mechanism resulting in a football-related injury was as a result of being blocked or tackled (52.7%). Surgery was required on 4.9% of individuals injured while playing football. Most patients (69.7%) were expected to recover from their injury within 14 days. There were more injured football players from our area in the age group 15 to 24 years as compared to the national data available. Diagnosis, site injured, and mechanism of injury from our study were comparable to other national publications. Prospective studies are needed to address the problem of football-related injuries. Such studies would require a multidiscipline team of experts.

Adolescent↗
PubMed1996

Uptake of technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 in tumor cell lines.

UNLABELLED: We investigated the kinetics, cellular uptake and intracellular distribution of 99mTc-tetrofosmin in tumor cell lines and compared them with those of 99mTc-MIBI and 201TI. METHODS: At specific intervals after incubation with radiotracers, cellular uptake was determined. Cells were also treated with nigericin, carbonyl cyanide m-chloro-phenylhydrazone (CCCP) and ouabain to determine their effects on the uptake of the tracers. RESULTS: Each tracer showed similar uptake kinetics in both cell lines, and a steady-state was maintained for at least 4 hr. Nigericin stimulated the uptake of both 99mTc-tetrofosmin and 99mTc-MIBI in HBL-2 cells, although it inhibited their uptake in SW-13 cells. Nigericin also inhibited 90% of 201TI uptake in both cell lines. Addition of CCCP caused 73%-97% release of accumulated 99mTc-MIBI from both cell lines with or without nigericin pretreatment, indicating that most of the accumulated 99mTc-MIBI was related to mitochondria. The effect of CCCP on accumulated 99mTc-tetrofosmin was less marked than that on 99mTc-MIBI in both cell lines, indicating that only a part of accumulated 99mTc-tetrofosmin, was related to mitochondria. Ouabain preincubation inhibited 74%-77% and 51%-53% of 201TI uptake in HBL-2 and SW-13 cells, respectively, as well as inhibited 22%-31% uptake of 99mTc-tetrofosmin in both HBL-2 and SW-13 cells. Uptake by the dead cells of either cell line was negligible for each tracer. CONCLUSION: Technetium-99m-tetrofosmin uptake depends on both cell membrane and mitochondrial potentials. Only a small fraction of 99mTc-tetrofosmin accumulates inside the mitochondria, while most 99mTc-MIBI accumulates inside the mitochondria. Thallium-201 uptake is partly independent of the Na+, K+ pump.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed1996

Will thallium-201 replace gallium-67 in salivary gland scintigraphy?

UNLABELLED: We investigated and compared findings on combined 99mTc pertechnetate-201Tl with those of [99mTc]pertechnetate-67Ga scintiscans to elucidate the advantages of 201Tl in detecting various salivary glands disorders. METHODS: We studied 23 patients: 6 had sialadenitis, 12 had benign tumors and 5 had malignant tumors. All but four patients had undergone [99mTc]pertechnetate (before and after lemon stimulation), 201Tl (early and delayed) and 67Ga imaging. RESULTS: Five of six sialadenitis patients showed various degrees of diffuse uptake of 99mTc. All six except one showed early uptake without retention of 201Tl on delayed imaging. The 67Ga scan showed uptake in all patients except one. Nine of 12 benign tumors showed a cold defect on 99mTc scans. Patients with Warthin's tumors and plasmacytoma showed increased 99mTc uptake at the tumor with retention. The 201Tl scan showed early uptake without retention in benign tumors except in three patients, two of whom had Warthin's tumor. Five of the benign tumors, however, were positive on 67Ga scan. None of the malignant tumors showed any uptake of 99mTc. The 201Tl scan showed uptake with tumor retention on delayed images in three patients; three other patients also had positive 67Ga scans. Overall, sensitivity and specificity of 201Tl in detecting malignant tumors were 60% and 73%, respectively, with a negative predictive value of 85%. Sensitivity and specificity for 67Ga were 60% and 47%, respectively, with a negative predictive value of 80%. CONCLUSION: In view of sensitivity, specificity and convenience of 201Tl as well as future prospects for dual-isotope acquisition, 67Ga may be replaced by 201Tl in detecting salivary gland disorder.

Adult↗
PubMed1996

[Bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation].

We report a patient who underwent allogeneic bone marrow transplantation for ALL. The patient presented low grade fever, cough and dyspnea at day 3 after after bone marrow transplantation. Imaging studies showed bilateral patchy infiltrates on chest X-ray and chest CT. Though treated by antibiotics, chest auscultation recognized marked bilateral inspiratory crackles. Transbronchial lung biopsy performed on day 34 showed bronchiolitis obliterans and an organizing interstitial pneumonia. The patient was treated with methylprednisolone and follow up computed tomography findings improved.

Administration, Oral↗
PubMed1996

[89Sr Therapy for pain relief in patients with bone metastases].

Radioactive strontium chloride (89Sr) was administered for pain relief in 6 patients with bone metastases (4 prostate cancer and 2 breast cancer patients). Out of 6 patients, 2 showed apparent relief of bone pain and improvement of QOL, and 3 showed slight relief of the pain with or without improvement of QOL; that is, 83% was effective. Side effects were seen in 2 patients; transient deterioration of bone pain in one patient and bone marrow suppression in the other patient. The patient who showed bone marrow suppression had rather more lesions of bone metastasis (diffuse metastasis) and least urinary excretion of the radioactivity. Urinary excretion for 2 days varied 5 to 40% of the administered dose and was less in the patients with more metastatic lesions.

Bone Marrow↗
PubMed1996

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

Adolescent↗
PubMed1996

Technical improvement in determining telomerase activity in hematologic neoplasias: a possibility of single cell determination of telomerase activity.

Chromosome termini, telomeres, provide important protective structure to avoid loss of master gene(s) that may present at subtelomeric regions. Since the telomere length might reflect the cell division, some biological aspects, including cellular senescence and cancer biology, of telomere length have been reported. To maintain a telomere length related to cell immortality, reactivation of telomerase in cancer cells is observed in approximately 85% of more than 1500 samples obtained from primary cancer tissues. Thus, telomerase is considered to be a new marker of neoplasias. In this paper, we present new techniques, including fluorescent TRAP that makes it possible to detect telomerase activity semi-quantitatively and in situ TRAP assay that allows us to determine the exact telomerase-positive cells.

Blood Cells↗
PubMed1996

A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions of SH2-containing signal transduction molecules.

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (ph1)-positive leukemia. We have previously shown SH2-containing phosphotyrosine phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL transformed cells (T., Tauchi, et al. J. Biol. Chem. 269, 15381, 1994). To elucidate the structural requirement of BCR-ABL for the interactions with SH2-containing signaling molecules, we examined a series of BCR-ABL mutants which include the Grb2 binding site deleted BCR-ABL (1-63 BCR/ABL), the tetramerization domain deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain deleted BCR-ABL (BCR/ABL delta SH2). These BCR-ABL mutants were previously shown to reduce the transforming activity in fibroblasts. We found that the tetramerization domain deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown the tetramerization domain deleted BCR-ABL mutant did not phosphorylate GST-SHP-2 in vitro. SHP-2 was co-immunoprecipitated with P13Kinase in BCR/ABL p210 transformed cells, however this interaction was not observed in the tetramerization domain deleted BCR-ABL mutant. Therefore the tetramerization domain of BCR-ABL is essential for interactions of these downstream molecules.

Fusion Proteins, bcr-abl↗
PubMed1996

Replication errors in hematological neoplasias: genomic instability in progression of disease is different among different types of leukemia.

Genetic alteration, including genomic instability, is an ultimate step toward the malignant process. One approach to delineating replication errors in cancer cells is to determine the alterations of microsatellites, which are short, repeated nucleotide sequences existing throughout the genomes. We used a fluorescent system to assess microsatellite changes in seven loci (D2S123, D3S643, D5S107, LPL, D17S261, TP53, and D18S34) of 73 consecutive patients with various hematological neoplasias. De novo acute leukemia patients had a low frequency (<1%) of microsatellite alterations at each locus, and none of them demonstrated multiple microsatellite changes. In chronic myeloid leukemia patients, no microsatellite instability was detected in the chronic phase, whereas a relatively high frequency (25%) of multiple microsatellite changes was evident in the blastic phase, and half of these patients had multiple microsatellite changes. About 50% of the patients with myelodysplastic syndrome (MDS) and post-MDS acute myeloid leukemia (post-MDS AML) had microsatellite alterations. We next compared microsatellite alterations in two different hematological phases (MDS and post-MDS AML phases); 5 of 11 patients with post-MDS AML had de novo appearance of microsatellite instability during disease progression. This indicates that genomic instability at multiple microsatellite loci could occur either before or after leukemic transformation in MDS patients. We concluded that genomic instability in chronic myeloid leukemia might be linked to blastic transformation in combination with cytogenetic changes. In contrast, MDS patients had replication errors as a relatively early genetic event as well as a late genetic event. These results suggest that the involvement of genomic instability in the progression of disease is different among various types of leukemia.

DNA Replication↗
PubMed1995

The expression pattern of erythrocyte/megakaryocyte-related transcription factors GATA-1 and the stem cell leukemia gene correlates with hematopoietic differentiation and is associated with outcome of acute myeloid leukemia.

To understand the clinical implications of transcription factors and their biologic roles during cellular differentiation in the hematopoietic system, we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in human leukemia cell lines and various leukemia patients using the reverse transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected; GATA-1 expression in HL-60 cells was downregulated during the process of monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1 expression and was preferentially detected in patients with leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients with monocytic leukemia were clustered in the group with no detectable GATA-1 expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De novo AML patients with SCL gene expression had a lower complete remission (CR) rate and had a significantly poorer prognosis. Among the patients with AML not expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that the expression pattern of transcription factors reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene expression may have prognostic value for the outcome of patients with AML.

Acute Disease↗
PubMed1995

The MEF2B homologue differentially expressed in mouse embryonal carcinoma cells.

The MEF2 gene family encodes a MADS-box transcription factor which regulates expression of many muscle-specific genes. We examined the expression of the MEF2 genes in mouse embryonal carcinoma P19 cells before and after in vitro muscle differentiation induced by dimethyl sulfoxide (DMSO). At least three different MADS/MEF2 domains (MEF2A, 2B and 2D) were isolated from P19 cells with the MOPAC technique (mixed oligonucleotides primed amplification of cDNA). Although two of the MADS/MEF2 domain sequences were identical to those of human MEF2A and MEF2D, another domain sequence was similar but not identical to that of human MEF2B. While the transcription of MEF2A and MEF2D was up-regulated during differentiation of P19 cells, the MEF2B homologue was abundantly transcribed in undifferentiated P19, F9 and ES cells and down-regulated in adult heart, skeletal muscle or brain, suggesting that the murine MEF2B homologue might have a function distinct from other members of the MEF2 gene family in embryogenesis and development.

Amino Acid Sequence↗
PubMed1995

Repulsive and attractive mechanisms for the formation of corticofugal projections.

Neocortical neurones project axons to subcortical and cortical structures according to their laminar location. The axon-target interactions which produce lamina-specific efferent connections were studied in an organotypic coculture of rat visual cortex with either superior colliculus (SC) or heat-treated SC. Morphological studies with fluorescent dye demonstrated that axons from upper layer neurones did not invade living SC, which receives axonal projections from layer 5, but did extend into denatured SC. In addition, the treatment considerably reduced the number of layer 5 neurones which project to the SC. These results suggest that SC contains a repulsive factor for axonal extension from the upper cortical layer as well as an attractive factor for axonal growth from layer 5 neurones.

Animals↗
PubMed1995

Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression.

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.

Adult↗
PubMed1995

Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form.

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4-h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4-h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a "turn-off switch" for activated c-kit kinase.

Alternative Splicing↗