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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 55 records · Page 3Linked to original sources

Detection of nocturnal wheezing in bronchial asthma using intermittent sleep tracheal sounds recording.

Common clinical features of bronchial asthma include bronchoconstriction during the night, particularly while asleep. Although bronchoconstriction reduces the quality of life and can cause life-threatening events, a clinical technique for evaluating bronchoconstriction during sleep has not been widely applied. In this study, we measured nocturnal wheezing by intermittent sleep tracheal sounds recording (ISTSR) to detect bronchoconstriction during the hours of sleep. Using ISTSR, we studied the number and duration of nocturnal wheezing episodes in 27 adult patients with bronchial asthma. Nocturnal wheezing was detected in 36 of 39 recordings. Although the pattern of hourly nocturnal wheezing count (hourly NWC pattern) varied among subjects, there appeared to be a reproducible pattern within individuals. When wheezing alternated between long and short duration, bronchoconstriction tended to be more severe. The NWC in 1 h (NWC/H) was positively correlated with subjective symptoms and inversely correlated with the morning per cent peak expiratory flow. The hourly NWC was significantly greater at 05:00 than that at midnight. Intermittent sleep tracheal sounds recording has potential to be a non-invasive clinical tool for detecting nocturnal bronchoconstriction during hours of sleep in patients with asthma.

Adolescent↗

Dynamic SPET parameters of 123I-MIBG cardiac imaging.

Early dynamic and late 123I-MIBG SPET studies were performed to investigate several parameters used to distinguish the characteristics of various cardiac disorders. Forty-six individuals (34 non-diabetic, 12 diabetic) with or without heart disease were included in the study. Early dynamic and late static SPET images were acquired using a triple-headed gamma camera. After selecting mid-sections from vertical (VLA) and horizontal (HLA) long-axis images, regions of interest were created over the apex, whole heart and anterior, inferior, septal and lateral walls of the heart. Various uptake ratios at 3, 11 and 19 min and 4 h after injection (HU3, HU11, HU19, DUP) and clearances (Kse: between HU3 and HU11; Ke: between HU11 and HU19; Kd: between HU19 and DUP) were calculated. There were significant differences among various cardiac pathologies on the delayed images. Cardiomyopathy patients showed the lowest uptake on the delayed images. When all segments in normal patients and all involved segments in myocardial infarcted patients were compared, there was significantly lower uptake of MIBG in infarcted segments at all time points. Kd showed the lowest value compared with Kse and Ke. In cardiomyopathy patients, Kse, Ke and Kd were significantly different from each other. Both Kse and Ke were significantly higher in cardiomyopathy patients than in normal patients. In conclusion, the results of this study are in line with published data and precise measurement of uptake and clearance was possible when excluding background and blood pool activity.

3-Iodobenzylguanidine↗

[Pulmonary infection caused by Mycobacterium gordonae].

A 57-year-old woman who had been operated on for colon cancer and given chemotherapy, presented in September 1995 with worsening cough and abnormalities on her chest X-ray film. Acid-fast bacilli were isolated from the sputum. The organism was classified as M. gordonae by biochemical tests and DNA/DNA hybridization. The patient was treated with rifampicin and clarithromycin. Subsequently, sputum cultures became negative and the chest x-ray film showed a decrease infiltration. The findings in the present case suggest that M. gordonae may cause pulmonary infection and should be considered as an opportunistic pathogen.

Female↗

[A trial for peripheral blood stem cell harvest by combination of G-CSF with ABVD regimen in the management of Hodgkin's disease].

We studied the possibility of performing peripheral blood stem cell (PBSC) harvests during the course of ABVD therapy by adding G-CSF to the treatment regimen. Six patients with high-risk Hodgkin's disease (HD) (5 untreated cases with bulky mass and 1 relapsed case) received G-CSF (5 micrograms/kg) subcutaneously from day 8 to day 13 of their first course of ABVD treatment; the numbers of CD34+ cells and CFU-GM were monitored. PBSC harvests were performed on day 12 and day 13 of subsequent ABVD plus G-CSF treatment courses. For all patients tested, we were able to harvest CFU-GM (3.78 +/- 1.19 x 10(5) colonies/kg) for peripheral blood stem cell transplants (PBSCT) by performing 2 to 4 cycles. of apheresis, without any modification to the original ABVD protocol. These findings suggest that ABVD plus G-CSF therapy is a strong candidate for the treatment of patients with high-risk HD who may undergo autologous PBSCT.

Adult↗

[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases].

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

Adult↗

[Hypereosinophilic syndrome complicated by myelofibrosis].

Hypereosinophilic syndrome (HES) with myelofibrosis was diagnosed in a 36-year-old man on the basis of bone marrow biopsy findings and clinical features. Although the patient was treated with steroid (1 mg/kg), hydroxyurea, and immunosuppressive therapy, eosinophilia persisted. Patients with HES and myelofibrosis are usually unresponsive to antineoplastic agents and/or immunosuppressants. However, cyclosporin may be an effective alternative for such patients.

Adult↗

[A case of Fabry's disease with chronic renal failure].

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.

Adult↗

Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination.

The role of inhibitory Golgi cells in cerebellar function was investigated by selectively ablating Golgi cells expressing human interleukin-2 receptor alpha subunit in transgenic mice, using the immunotoxin-mediated cell targeting technique. Golgi cell disruption caused severe acute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and electrical recordings combined with immunocytological analysis indicated that elimination of Golgi cells not only reduces GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving both GABA inhibition and NMDA receptor activation is essential for compound motor coordination. Furthermore, this integration can adapt after Golgi cell elimination so as not to evoke overexcitation by the reduction of NMDA receptors.

Animals↗

Telomerase activity in lung cancer cells obtained from bronchial washings.

BACKGROUND: Telomerase, a ribonucleoprotein enzyme that functions in the maintenance of telomeres (specialized structures at the ends of chromosomes), has been reported to be a novel diagnostic marker for malignant diseases. We sought to determine whether measurement of telomerase activity in bronchial washings is of value in the diagnosis of lung cancer. METHODS: Extracts of cells in bronchial washings were analyzed for telomerase activity by use of a telomeric repeat amplification protocol (TRAP) assay. Telomerase activity inside cells was evaluated by use of an in situ TRAP assay. The results of both TRAP assays were compared with those obtained from cytologic examination, which employed standard Papanicolaou staining. RESULTS: When results from the two TRAP assays were combined, telomerase activity was detected in bronchial washings from 18 (82%; 95% confidence interval [CI] = 60%-95%) of 22 patients with lung cancer. In contrast, cancer cells were detected by cytologic examination in the bronchial washings of nine (41%; 95% CI = 21%-64%) of the same 22 patients, a statistically significant difference (two-sided P = .0061). In patients with lung cancer, telomerase-positive cells could be detected in bronchial washings irrespective of tumor location--11 of 14 (79%; 95% CI = 49%-95%) peripheral cancerous lesions and seven of eight (88%; 95% CI = 47%-100%) central cancerous lesions were detected by use of TRAP assays (for comparison, two-sided P = .5349). CONCLUSIONS: A high percentage of patients with lung cancers had detectable telomerase activity in bronchial washings. Thus, the use of a cell extract-based or an in situ TRAP assay in addition to cytologic examination may make the diagnosis of lung cancer more reliable.

Adult↗

Neuronal responsiveness to three-dimensional motion in cat posteromedial lateral suprasylvian cortex.

The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial lateral suprasylvian (PMLS) cortex was studied using a computer-controlled, stereoscopic 3D graphic display capable of reproducing the major visual cues for natural 3D motion, including motion disparity, size, texture, and shading changes. The animals were anesthetized with nitrous oxide supplemented with alphaxalone, and paralysis prevented eye movement. Systematic investigation of neuronal responsiveness to 3D motions in 26 different directions revealed that more than half of the PMLS cells were selectively responsive to approaching (AP cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or nonselectively responsive to motion in multiple directions (NS cells, 46 of 271). The dependency on these visual cues was investigated as a reduction in the response amplitude or the response selectivity for the removal of a single cue from the motion stimuli containing the full visual cues. The AP and RC cells showed a strong dependency on the motion disparity cue, moderate dependency on the size cue, and weak dependency on the texture and shading cues. The FP cells showed no dependency on those visual cues. The cue dependency analysis indicated the existence of nonlinear interactions between those visual cues. Comparison of the responses to a combination of the motion disparity and size cues with the summed responses to each of the individual cues revealed that the responses to the combined cues are roughly predicted as a linear sum between the preferred responses. This comparison also showed nonlinear summation between the nonpreferred responses, i.e., responses to the combined cues were smaller than the summed responses. A similar quasilinear summation of the preferred responses between the two eyes and a nonlinear summation of the nonpreferred responses were found in the AP and RC cells for the motion disparity stimulus. All of these observations indicate that quasilinear and nonlinear interactions of the responses to various stimulus elements underlie the 3D motion responsiveness of the PMLS cells.

Animals↗

Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals.

The telomerase activity and length of telomeres of peripheral blood mononuclear cells obtained from 124 healthy individuals aged 4-95 years was measured. Telomerase activity level was semiquantitatively assessed by a fluorescent-telomeric repeat amplification protocol (fluorescent-TRAP) using an internal telomerase assay standard, fluorescent primers and an automated laser fluorescent DNA sequencer. Telomeric length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age-related progressive reduction of size was observed. TRF length in peripheral blood mononuclear cells obtained from normal individuals (aged 4-39 years) decreased by approximately 84 bp per year, while in individuals aged > or = 40 years it decreased by 41 bp per year. In contrast, telomerase activity showed an apparent biphasic pattern with aging. Individuals aged 4-39 years showed a progressive decrease in telomerase activity, whereas 65% of those aged > or = 40 years showed relatively stable but very low telomerase activity, and the remaining individuals aged > or = 40 years had no detectable telomerase activity. These data obtained from normal individuals might in the future be of value to help risk stratify and manage the care of patients with leukemia.

Adolescent↗

A sole del(15q) anomaly in post-myelodysplasia acute myeloid leukemia.

We report the second case of post-myelodysplasia acute myeloid leukemia (post-MDS AML) with a sole chromosome change del(15q). This anomaly is rarely seen. To our knowledge, only seven cases so far have been reported in human neoplasias, including one case each of acute myeloid leukemia (AML), acute lymphoid leukemia, post myelodysplasia AML, myelodysplastic syndrome, myelofibrosis, macroglobulinemia, Hodgkin's lymphoma and uterine leiomyoma. This case suggests that del(15q) is related to lympho-myeloproliferative disorders. Moreover, we speculate that certain oncogene(s) located on 15q might have some role in the progression of the disease, since the del(15q) anomaly appeared only in the AML phase in this case.

Acute Disease↗

Pregnancy among long-term survivors of acute leukemia. A second nationwide survey.

A second nationwide survey was conducted to determine the outcome of pregnancy in long-term survivors of acute leukemia and to clarify the influence of treatment on the offspring of long-term survivors. In July 1996, 336 survey responses were received from the 498 Japanese institutions surveyed. A total of 89 cases (39 spouses of male patients and 50 female patients) who had babies during their first remission were analyzed, including 43 patients from the first survey in 1991. Median age at the birth of first baby was 30.7 years for male patients and 28.6 years for female patients. A total of 109 of the 117 pregnancies resulted in live births and eight resulted in abortions. A total of 58 cases had single children and 23 cases had two or more, generally from separate pregnancies, but including two pairs of twins. The infant was male in 59 cases, female in 37 and gender was not reported in 13 cases. Ages of children ranged from 2 months to 20 years at the time of this study and all children were in good health. There were two minor anomalies, both of which were surgically corrected. Of the 81 parents bearing live infants, 75 remained in complete remission. Five fathers died (four of relapse and one of another disease). In conclusion, there was no apparent increase in pregnancy complications or congenital anomalies in the children of long-term survivors with acute leukemia.

Acute Disease↗

Homeobox genes in hematopoiesis and leukemogenesis.

Homeobox genes have a strikingly conserved 61-amino acid sequence, encoding DNA-binding domain. Some homeobox genes, located in four clusters are designated HOX A through D, while others are known as divergent homeobox genes. Many researchers have demonstrated that hematopoietic cells express many homeobox genes. Induced over- and under-expression of these genes has been used to demonstrate their affect on some aspects of hematopoiesis and leukemogenesis. Recently, knock-out mice of homeobox genes by targeted disruption have also been used to examine their hematological effect. There are examples of the aberrant expression of a homeobox gene causing leukemias in humans. In pre-B acute lymphoblastic leukemia (ALL) with t(1;19) translocation, a fusion protein is created between E2A and a homeobox gene PBX. In T-cell ALL with t(10;14) translocation, the HOX 11 gene is deregulated. In acute myeloid leukemia (AML) with t(7;11) translocation, the HOX A9 gene is rearranged. In this review article, many functions of homeobox genes both at the early stem cell level as well as at the later stages of hematopoietic differentiation, and the leukemogenic effect of altered homeobox genes are discussed.

3T3 Cells↗