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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 199 records · Page 11Linked to original sources
PubMed1995

Late appearance of a Philadelphia translocation with minor-BCR/ABL transcript in a t(7;11)(p15;p15) acute myeloid leukemia.

We describe a patient with a t(7;11)(p15;p15) acute myeloid leukemia who was subsequently found to harbor the Philadelphia (Ph) translocation, in addition to the t(7;11), at the second relapse. A BCR/ABL transcript was detected at the second relapse by reverse transcription-polymerase chain reaction assay; the leukemic cells had a BCR/ABL fusion gene involving the minor breakpoint cluster region (minor-BCR; situated in intron 1 of the BCR gene). Although the Ph translocation is commonly detected in de novo acute leukemia and chronic myeloid leukemia as the primary leukemia-specific chromosomal translocation, our case suggests that this cytogenetic change might occur as an additional chromosomal change in neoplastic cells. Moreover, minor-BCR/ABL rearrangements may also occur as a late appearance of Ph translocation.

Base Sequence↗
PubMed1995

A modified landmark method for dealing with an event observed during a follow-up period.

Events observed during a follow-up period are generally more informative when predicting the prognosis of patients than the clinical data available at the start of follow-up. The present paper has aimed to introduce a modified landmark method for estimating a survival curve for patients in whom an event related to their survival had occurred at a given landmark time during the follow-up period. Survival curves were compared graphically by the conventional method, the Mantel-Byar method, the landmark method and the modified landmark method. The subjects were ninety-five patients with myelodysplastic syndrome who had been diagnosed between 1979 and 1992 at Tokyo Medical College Hospital, and followed-up until September, 1993. Disease evolution was used as the event. The survival curves for patients with and without the event, calculated by the conventional method, were biased and not applicable to the actual patients at the start of follow-up before the occurrence of the event. The curves obtained using the Mantel-Byar method were not biased but similarly not applicable to the actual patients. The landmark method gave unbiased curves applicable to patients with and without the event at a given landmark time, but the curve for those with the event included a lead time from the onset of the event to the landmark time. The modified method gave an unbiased estimation of survival for patients in whom the event had just occurred around a given landmark time.

Disease Progression↗
PubMed1995

[Cytofluorometric analysis of tumor cell size and follicle formation of B-cell lymphomas].

In order to investigate the size variation of neoplastic B cells (NBC) from lymph nodes of patients with B-cell lymphomas (BCL), we carried out two-dimensional analysis by flow cytometry (FCM) using the forward light scatter (FLS) and the fluorescence intensity (FI) of surface immunoglobulin light chain (sIgL). NBC were identified as having the homogeneous characteristics of both FLS and tumor-restricted sIgL (kappa or lambda). The FLS variation of NBC was then analyzed using CD3+ T-cells as a scale control. The results closely coincided with the cell types determined by the pathologic diagnosis. Secondly, we used FCM to investigate how strongly NBC express VLA-4 alpha and LFA-1 alpha, which seemed to play important roles in neoplastic follicle formation. The expression intensities of these molecules were classified into three grades (-, + & ++). The results were presented in the order of VLA-4 alpha and LFA-1 alpha; follicular 8/15 (++/++), 6/15 (++/+), 1/15 (+/++), partially follicular 3/5 (+/++), 2/5 (+/+), diffuse 2/16 (++/-), 6/16 (+/++), 8/16 (+/+), B-CLL 8/8 (-/+ or -). These findings suggest that follicular lymphomas are phenotypically distinguishable from diffuse lymphomas.

B-Lymphocytes↗
PubMed1995

Lack of effects of atomic bomb radiation on genetic instability of tandem-repetitive elements in human germ cells.

In a pilot study to detect the potential effects of atomic bomb radiation on germ-line instability, we screened 64 children from 50 exposed families and 60 from 50 control families for mutations at six minisatellite loci by using Southern blot analysis with Pc-1, lambda TM-18, ChdTC-15, p lambda 3, lambda MS-1, and CEB-1 probes. In the exposed families, one or both parents received a radiation dose > 0.01 Sv. Among the 64 children, only one child had parents who were both exposed. Thus, of a total of 128 gametes that produced the 64 children, 65 gametes were derived from exposed parents and 63 were from unexposed parents, the latter being included in a group of 183 unexposed gametes used for calculating mutation rates. The average parental gonadal dose for the 65 gametes was 1.9 Sv. We detected a total of 28 mutations at the p lambda g3, lambda MS-1, and CEB-1 loci, but no mutations at the Pc-1, lambda TM-18, and ChdTC-15 loci. We detected 6 mutations in 390 alleles of the 65 exposed gametes and 22 mutations in 1098 alleles of the 183 gametes from the unexposed parents. The mean mutation rate per locus per gamete in these six minisatellite loci was 1.5% in the exposed parents and 2.0% in the unexposed parents. We observed no significant difference in mutation rates in the children of the exposed and the unexposed parents (P = .37, Fisher's exact probability test).

Chromosome Mapping↗
PubMed1995

[Gamma delta T cells in peripheral blood and in bronchoalveolar lavage fluid from patients with sarcoidosis and idiopathic pulmonary fibrosis].

We measured levels of gamma delta T cells in peripheral blood and in bronchoalveolar lavage fluid from patients with sarcoidosis, from patients with pulmonary fibrosis, and from normal subjects. In blood from both groups of patients, the percentage of lymphocytes was significantly greater than normal. The number of CD3+ cells per cubic millimeter was significantly lower than normal in patients with sarcoidosis, and tendency to be lower than normal in patients with pulmonary fibrosis. The percentage of CD3+ cells tended to be low, but there was no significant difference. The percentage and number of gamma delta T cells in patients with sarcoidosis, and the number of gamma delta T cells in patients with pulmonary fibrosis tended to be high. In bronchoalveolar lavage fluid, the percentage of lymphocyte was significantly higher than normal, and the numbers of CD3+ cells and gamma delta T cells per cubic millimeter tended to be high. In both groups of patients, cell counts of lymphocytes were significantly higher than normal. Numbers of CD3+ cells and of gamma delta T cells were significantly higher than normal in patients with sarcoidosis, and tended to be higher than normal in those with pulmonary fibrosis. These findings indicate local activation of gamma delta T cell function, recruitment of these cells into the bronchoalveolar system, and augmentation of gamma delta T cell supply in the whole body, especially in patients with sarcoidosis. In patients with pulmonary fibrosis the results were inconclusive; they were not as striking as were the results in patients with sarcoidosis.

Adult↗
PubMed1995

[Chronic respiratory failure--survival for nine years with home mechanical ventilation].

We report the case of a woman, now 58 years old, with chronic respiratory failure due to spinal progressive muscular atrophy. She first noticed gradual progressive muscular weakness in her extremities in 1973. She started to complain of dyspnea on exertion in 1978. Chronic respiratory failure due to spinal progressive muscle atrophy was diagnosed in 1983. Home oxygen therapy was begun, but CO2 narcosis and exacerbation of chronic respiratory failure occurred at the end of that year. A tracheotomy was done and mechanical ventilation was begun. As her general condition improved and she could breathe without the ventilator for a few hours each day, home mechanical ventilation was begun. Seven years later, her general condition is still good and she can live without any life-threatening distress. There are few reports of patients in Japan who have survived for long periods of time with home mechanical ventilation. We believe that improvement in her respiratory care and in her social situation contributed to her long standing clinical course.

Chronic Disease↗
PubMed1995

Cytotoxic lymphocytes in the peripheral blood of patients with B cell lymphomas.

In order to analyze systemic immune surveillance in patients with B cell non-Hodgkin's lymphomas (B-NHL), we investigated circulating lymphocytes using two-color flow cytometry. The proportions of CD3-CD56+ natural killer (NK) cells and CD8++(bright) S6F1++ killer-effector T cells corresponding to activated cytotoxic T lymphocytes (aCTL) were studied in the peripheral blood of 26 patients with indolent lymphoma (IL) and 24 with aggressive lymphoma (AL). The AL patients with both limited disease and advanced disease had an increased proportion of NK cells. However, this feature was not evident in IL patients with either limited or advanced disease. In contrast, an increased proportion of aCTL was observed only in IL patients with advanced disease. These findings indicate that IL may differ from AL in terms of immune surveillance against neoplastic B cells.

Adult↗
PubMed1995

[Aplastic anemia associated with ovarian bleeding].

A 22-year-old female was admitted on June 19, 1993 with pancytopenia. Aplastic anemia was diagnosed and she was treated with anti-thymocyte globulin. After one month, she started to feel abdominal pain. Her platelet count was 1.3 x 10(4)/microliters at that time. Computed tomography revealed vast accumulation of blood in the abdomen and pelvis. A total of 1,000 ml blood was obtained from the right ovarium and she underwent right partial oophorectomy. Although ovarian bleeding is rarely reported in aplastic anemia, we should always keep in mind this possibility when abdominal pain occurs in a female patient.

Adult↗
PubMed1995

[Frequency analysis of crackles recorded with a stethoscope-equipped recorder].

Crackles were recorded with one of two systems in a total of 58 cases and compared. In one system a stethoscope was attached to a microphone; in the other system no stethoscope was used (see reference 9). Coarse crackles were recorded with the stethoscope system in 11 patients, and with the microphone-only system in 12 patients. Most patients with coarse crackles had bronchiectasis. Fine crackles were recorded with the stethoscope system in 13 patients, and with the microphone-only system in 22 patients. Most patients with fine crackles had idiopathic pulmonary fibrosis. Each record was examined visually, and all crackles recorded during one inspiration were selected. Power spectra were estimated with the maximum entropy method and peak frequencies were determined with the damped least-squares method. Type-I crackles were defined as those with all peak frequencies below 800 Hz; these low-pitched sounds may correspond to coarse crackles. Type-II crackles were defined as those with peak frequencies over 800 Hz regardless of the existence of peaks below 800 Hz; these high-pitched sound may correspond to fine crackles. The "%Type II" was defined as the percentage of the total crackles that were Type-II crackles. The %Type II value among coarse crackles was 10 +/- 16% with the stethoscope and 3 +/- 7% with the microphone. Among fine crackles, the values were 65 +/- 22% with the stethoscope and 79 +/- 23% with the microphone. For both kinds of equipment, the %Type II differed significantly between coarse and fine crackles (p < 0.01). The stethoscope-transmitted sound had components that could be used to differentiate fine crackles from coarse crackles. For clinical purposes, crackles recorded with a stethoscope are as useful as those recorded with a microphone only.

Auscultation↗
PubMed1994

[Evaluation of malignancy and viability of brain tumors by 201Tl SPECT: the correlation between 201Tl SPECT and pathology, clinical progress and the intensity of enhancement on CT images].

Thallium-201 (201Tl) SPECT was performed 48 times in 26 patients to clarify its usefulness in the evaluation of malignancy and viability of brain tumors. The early counts ratio (ER) and delayed counts ratio (DR) of a lesion compared with normal brain were obtained 10-15 minutes and 3 hours, respectively, after intravenous administration of 185 MBq of 201Tl chloride. Untreated high grade malignant tumors and recurrent tumors did not always show high ER and DR, and they were widely distributed. High grade malignant tumors that showed low ER and DR were not well enhanced on CT or MRI. In low grade malignant tumors, such as pituitary adenoma which was well enhanced on CT, ER and DR were as high as in high grade malignant tumor. Whether a tumor recurred within three months after radiotherapy or not was retrospectively predicted at accuracy rates of 93.8% and 87.5% with cut-off points of 4.0 for ER and 3.5 for DR. Cerebral radiation necrosis showed ring-like increased uptake of 201Tl in proportion to the progress of necrosis and intensity of enhancement on MRI. In conclusion 201Tl SPECT is considered to be less useful for lesions that are well enhanced on CT, because they show high uptake of 201Tl regardless of their malignancy and viability. On the other hand, in tumors that are not well enhanced on CT. 201Tl shows good accumulation in viable and high grade malignant lesions. 201Tl SPECT should be performed in such cases.

Adult↗
PubMed1994

Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes.

We identified the telomere length at different hematological phases in 16 patients with myelodysplastic syndromes (MDS), showing disease evolution with a conventional Southern blot hybridization using the (TTAGGG)4 probe. The MDS patients studied were classified into three groups according to the pattern of telomere length reduction. The first group had telomere shortening at the time of disease diagnosis. In four of the six MDS patients in this group, the disease progressed within 6 months postdiagnosis and each of them survived for less than 1 year. Moreover, in this group four patients showed a 5q anomaly with or without additional changes, and 50% of patients in this group had complex chromosome abnormalities. The patients in the second group showed reductions in telomere length after disease progression; two of these three patients showed gradual disease progression and had one or two chromosome abnormalities. The third group comprised the remaining seven MDS patients; they showed no telomere reduction by disease evolution. Two patients in this group experienced rapid disease progression. These results may indicate that telomere reduction is linked to disease evolution in some MDS patients, perhaps as a result of genomic instability because patients with complex chromosome abnormalities were clustered in the first group. However, because some MDS patients show disease progression without telomere reduction, genetic changes, including point mutations of certain gene(s), may also contribute to disease progression. We further noted that telomere shortening at the time of MDS diagnosis might indicate a poor MDS prognosis.

Acute Disease↗
PubMed1994

Combinations of stem cell factor with other hematopoietic growth factors enhance growth and sensitivity to cytosine arabinoside of blast progenitors in acute myelogenous leukemia.

The blast progenitors in acute myelogenous leukemia grow in response to hematopoietic growth factors (HGFs), and their sensitivity to antileukemic drugs is influenced by HGFs. We report the effects of stem cell factor (SCF) on the growth and sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) of blast progenitors in acute myelogenous leukemia. SCF stimulated both colony formation and self-renewal of blast progenitors and, when used in combination with other HGFs, synergistic enhancement of colony formation was noted in 8 of the 15 patients examined. Cell fractionation studies demonstrated no unique growth dependency on SCF in either CD34+ or CD34- populations. Blast cells of patients that displayed synergistic growth enhancement with SCF displayed the highest Ara-C sensitivity when HGFs were used in combination with SCF. The tritiated thymidine suicide test (20-min exposure) revealed that the proportion of blast progenitors in the S phase of the cell cycle was highest when SCF and another HGF were simultaneously present, although 24-h exposure killed most or all of the blast progenitors. These data indicate that SCF enhances growth and sensitivity to Ara-C of acute myelogenous leukemia blast progenitors in a closely correlated fashion and that the cell cycle changes as well as other mechanisms are involved in the Ara-C sensitivity modulation by SCF.

Adolescent↗
PubMed1994

Ligand-dependent polyubiquitination of c-kit gene product: a possible mechanism of receptor down modulation in M07e cells.

Quantities of proteins in cells are balanced by protein synthesis and degradation. Protein ubiquitination is an important adenosine-triphosphate dependent proteolytic pathway for "short-lived" proteins. We show that soluble steel-factor (SLF) stimulation at 37 degrees C rapidly induced polyubiquitination of c-kit protein in growth-factor-dependent human-myeloid cell line M07e, resulting in smeared, retarded migration of c-kit protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the molecular weight region of 145 kD. Receptor ubiquitination was almost completely absent when cells were treated with SLF at 4 degrees C or at 37 degrees C in the presence of 0.2% sodium azide, or when the cells were pretreated with anti-c-kit monoclonal antibody or genistein, a tyrosine-kinase inhibitor. This suggested that c-kit ubiquitination was ligand dependent and appeared to require intrinsic tyrosine-kinase activation of the c-kit protein. Flow-cytometric analysis of c-kit expression on the cell surface of M07e cells showed down modulation of c-kit within 5 minutes after soluble-SLF treatment at 37 degrees C. However, rapid receptor down modulation was almost completely suppressed when cells were treated with SLF at 4 degrees C or at 37 degrees C in the presence of 0.2% sodium azide, conditions that concomitantly suppressed polyubiquitination of c-kit protein. In addition, these conditions almost completely suppressed radiolabeled SLF (125I-SLF) internalization after ligand-receptor interaction. Pulse-chase studies of 35S-methionine-labeled c-kit protein showed that SLF stimulation at 37 degrees C strikingly enhanced c-kit degradation (T1/2; approximately 20 minutes) compared with that in cells stimulated with SLF at 4 degrees C or at 37 degrees C with 0.2% sodium azide. However, in the presence of chloroquine, which blocks lysosomal degradation, this ligand-induced c-kit degradation at 37 degrees C was only suppressed in part. These data suggest that SLF-induced polyubiquitination of the c-kit receptor protein may play a role in regulation of c-kit-encoded protein-receptor expression in M07e cells.

Amino Acid Sequence↗
PubMed1994

Stimulatory effect of human insulin on erythroid progenitors (CFU-E and BFU-E) in human CD34+ separated bone marrow cells and the relationship between insulin and erythropoietin.

Erythropoietin is known to be effective for the treatment of anemia in chronic renal failure, but the efficacy of erythropoietin for anemia in other diseases is not so great. Insulin exerts a growth promoting activity in various kinds of cells. In the present study, the effects of insulin on erythroid progenitors (colony forming units-erythroid, CFU-E; and burst forming units-erythroid, BFU-E) in human bone marrow were examined at various concentrations of recombinant human erythropoietin (rh-Epo) to clarify the relationship between erythropoietin and insulin. Human insulin stimulated the formation of CFU-E and BFU-E in the presence of three concentrations (0.25, 5, and 100 U/ml) of rh-Epo. Stimulatory effects of human insulin on CFU-E and BFU-E were also observed in the nonphagocytic and nonadherent bone marrow fraction (NP-NA fraction) and in the NP-NA and T cell-depleted fraction at each concentration of rh-Epo. Human insulin further stimulated the CFU-E and BFU-E growth in CD34+ separated bone marrow cells. These results indicate that the enhancing effect of human insulin on erythroid progenitors is not mediated through monocytes and macrophages or T cells, suggesting a direct action on erythroid progenitors.

Animals↗
PubMed1994

Neuronal responsiveness in areas 19 and 21a, and the posteromedial lateral suprasylvian cortex of the cat.

Responsiveness to slits and pattern stimuli was quantified in a total of 68 cells sampled in the posterior extreme of the lateral suprasylvian (PS) cortex as response indices. The cells were studied in relationship to their locations in several subareas of the PS cortex, including areas 19 (n = 15) and 21a (n = 32) and the posteromedial lateral suprasylvian cortex (PMLS; n = 21). These subareas were identified based on retrograde labelling from area 17 and also supplemented with photic responsiveness. This analysis revealed that each cortical area contains cells expressing different combinations of stimulus features. Area 19 contained two major groups of cells: (1) those with strong end-stop selectivity combined with moderate orientation or direction selectivity, and (2) those with weak end-stop selectivity combined with strong orientation selectivity. The groups of cells with strong or moderate orientation selectivity showed a strong preference for stripe over visual noise patterns and relatively large modulatory responses to motion of individual stripes. The PMLS contained one major group of cells with strong end-stop and direction selectivities and with poor orientation selectivity. They also showed stronger preference for visual noise than cells in the other cortical areas and rather weak modulatory responses. Area 21a contained only one group of cells with strong orientation selectivity and length summation property rather than end-stop selectivity, and they also lacked direction selectivity. These cells exhibited a strong preference for stripe patterns and moderate or weak modulatory responses. Altogether, these findings indicate that each cortical area is specialized in expressing different stimulus features. The two groups of cells in area 19 may encode the position and motion of discontinuous visual elements such as corners and line ends and continuous elements such as lines and edges. PMLS cells may encode the motion of single elements or associated motion of multiple discontinuous elements such as textures and backgrounds. Area 21a cells may specifically encode the orientation of long, continuous elements such as lines and edges. In support of this view, two types of statistical analyses demonstrated that the combinations of the response properties expressed in individual PS cells are highly correlated with their locations in cortical areas and that the anatomical locations of individual PS cells are reliably predicted from the sets of response indices expressed in these cells.

Analysis of Variance↗