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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 145 records · Page 8Linked to original sources

[Interferon production in peripheral blood cells of patients with pulmonary mycobacterial disease].

Production of interferon (IFN)-alpha and IFN-gamma were examined in 31 patients with acute tuberculosis, 12 patients with atypical mycobacterial disease. IFN production was examined in cultures of unseparated fresh whole blood. Production of IFN-alpha was induced by hemagglutinating virus of Japan and production of IFN-gamma was induced by PHA. Patients with mycobacterial disease produced significantly less IFN-alpha than healthy subjects. In patients with acute tuberculosis, effective chemotherapy for 2 months restored IFN-alpha production. Patients produced less IFN-gamma than healthy subjects, but the difference was not significant. Patients with high serum CRP levels tended to produce little IFN-alpha. These results suggest that measurement of IFN production is useful for immunological evaluation of patients with mycobacterial disease.

Acute Disease

New aerodynamic aspects of nasal patency.

In considering possible aerodynamic indicators of subjective nasal stuffiness, we measured nasal resistance, acceleration change of nasal airflow, and alteration of differential pressure and compared those with the degree of severity of sensation of nasal obstruction in 75 patients. The acceleration change of airflow and alteration of differential pressure are presented as an equation: y = ax2 + bx + c, in which "a" represents the approximate shape of the curve. Nasal resistance, on either inspiration or expiration, and coefficient "a" of acceleration change the rapid phase from inspiration to expiration correlated well with subjective nasal patency, while coefficient "a" of acceleration change the rapid phase from expiration to inspiration and alteration of differential pressure either the rapid phase from inspiration to expiration or from expiration to inspiration did not correlate well with perception of nasal blockage. It seems that measurement of respiratory acceleration of airflow of quiet nasal breathing is a useful indicator of subjective nasal patency.

Acceleration

[Successful treatment of refractory anemia with excess of blasts in transformation with cytarabine ocfosfate].

A 58-year-old female was diagnosed as myelodysplastic syndrome (MDS) [refractory anemia with excess of blasts (RAEB)]. Although melphalan was administered, no response was obtained in the peripheral blood. Sixteen months after diagnosis, she developed RAEB in transformation (RAEB-t), and then overt leukemia. White blood cell (WBC) count elevated to 28,600/microliters with 34% of blasts. She was administered cytarabine ocfosfate (200 mg-->300 mg/day) orally, resulting in decrease of WBC count and blasts in peripheral blood. The drug has been given for 11 months, and her hematological data have now remained stable in RAEB. Cytarabine ocfosfate might be a useful drug for the treatment of high risk MDS such as RAEB and RAEB-t.

Acute Disease

[Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy].

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Aged

Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH.

Clinically relevant interassay precision profiles for thyrotropin (thyroid-stimulating hormone; TSH) were constructed with human serum pools measured over 4-8 weeks by six immunometric assays, in at least two different reagent lots. Functional sensitivities (the concentration at which the interassay CV is < or = 20%) were determined in four to eight clinical laboratories plus the respective manufacturer's laboratory. These studies revealed that the manufacturer's stated functional sensitivity limit is rarely duplicated in clinical practice. Loss of specificity (indicated by artifactually high values) was seen with some methods when used to measure certain unrefrigerated low-TSH sera. Measurement of TSH in four human serum pools (TSH < 0.05-0.25 mIU/L) by 16 different methods (each in at least eight UK or US laboratories) showed that some methods could not reliably distinguish subnormal from normal TSH values. Better pool rankings and fewer misclassifications of low-TSH sera as "normal" were seen with use of assays capable of "third-generation" functional sensitivity (0.01-0.02 mIU/L) than with assays with "second-generation" functional sensitivity (0.1-0.2 mIU/L). Because inter- and intramethod differences in functional sensitivity negatively impact the diagnostic accuracy and cost-effectiveness of a TSH-centered thyroid-testing strategy, laboratories should independently establish an assay's functional sensitivity by a clinically relevant protocol. Moreover, manufacturers should assess functional sensitivity more realistically and improve the robustness of assays to ensure that their performance potential is consistently met in clinical practice.

Drug Stability

Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats.

Duloxetine is a dual inhibitor of norepinephrine and serotonin reuptake. Duloxetine (3.13-50 mg/kg p.o.) significantly prevented tetrabenazine (1 and 50 mg/kg s.c.)-induced ptosis in mice and rats. Moreover, duloxetine (1.56-12.5 mg/kg p.o.) also inhibited reserpine (1 mg/kg s.c.)-induced hypothermia in mice. When duloxetine (12.5-100 mg/kg p.o.) and 5-hydroxytryptophan (80 and 100 mg/kg i.p.), a precursor of serotonin, were administered simultaneously to mice and rats, head movement behavior and tremor were observed. In addition, duloxetine (25-100 mg/kg p.o.) significantly attenuated immobility in forced swimming in mice, as equally effective as commonly used antidepressant drugs. Duloxetine (12.5-25 mg/kg p.o.) significantly decreased rapid eye movement sleep and slow-wave deep sleep and increased the awake period, as shown in the rat EEG. However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a cholinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine-induced tremor in part. These results indicated that duloxetine produced behavioral and electroencephalographic responses resulting from the inhibition of norepinephrine and serotonin reuptake in vivo, and that it had a weak anticholinergic action. Therefore, duloxetine may be clinically useful as an antidepressant.

5-Hydroxytryptophan

[Early relapse after peripheral blood stem cell transplantation in acute myelogenous leukemia with t(8;21)].

We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very early after peripheral blood stem cell transplantation (PBSCT). He was admitted with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as having acute myelogenous leukemia with t(8;21). He achieved complete remission with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF was given from day 0 because of severe infection. WBC and platelete counts rapidly increased, however, from day 20 platelet count spontaneously decreased. Concomitantly bone marrow examination revealed the presence of blastic cells. RT-PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF receptors and increased 3H-thymidine uptake in the presence of G-CSF. These findings strongly suggest that the reinfusion of leukemic cells in PBSC and the administration of G-CSF after PBSCT might be relevant to early relapse in this patient.

Antineoplastic Combined Chemotherapy Protocols

[Comparative examinations of serum pepsinogen I, II and gastric area using computed radiography in the atrophic gastritis].

The relationship between serum PG I, PG II levels and extent of atrophic gastritis was examined. On 64 patients (male: 32, female: 32, 51.9 years old on average) with established diagnosis of either atrophic gastritis or normal. In the X-ray gastric examination, Fuji Computed Radiography (FCR) was used to obtain clear-cut images of the gastric area. Concerning the serum PG I level, patients in the group with atrophic gastritis showed lower levels than those of the people in the group with no atrophic change, but the variation was wide, and no definite tendency was seen in the relationship between the atrophic change and the serum PG I levels. Concerning the serum PG II level, as the atrophic change progresses, the serum PG II level tended to increase gradually. A significant reduction in the PG I/II ratio was seen in the group with atrophic changes (p < 0.01) in comparison with the group with no atrophic changes, and the PG I/II value tended to decrease. In conclusion, as a relationship between the atrophic change and the serum PG levels had a wide variation, we considered to be difficult by to measure the serum PG level to understand the presence and extent of the atrophic gastritis.

Disease Progression

Natural human interferon-alpha enhances the expression of intracellular adhesion molecule-1, integrin alpha 2 and beta 1 by a mucosal epithelial cell line.

We have found that pretreatment of a human oral mucosal epithelial cell line KB with natural human interferon-alpha (IFN-alpha) augments the expression of intercellular adhesion molecule-1 (ICAM-1), and the complex of CD29 and CD49b, which is known as very late antigen (VLA)-2, in a dose-dependent manner, whereas the expression of other adhesion molecules such as CD44 leukocyte function associated antigen-3 (LFA-3), VLA-4 and endothelial leukocyte adhesion molecule-1 (ELAM-1) did not show any significant changes under the same conditions. The pretreatment of KB cells with IFN-alpha also induces the adhesion of these cells to the human leukemia T cell line MOLT-16 and to peripheral T lymphocytes in a dose-dependent manner. However, the adhesion of the above-mentioned T cells to KB cells was not inhibited by specific antibodies against ICAM-1, CD29, and CD49b. The results thus show that adhesion molecules other than ICAM-1, CD29, AND CD49b are responsible for the induced adhesion between T cells and IFN-alpha-pretreated KB cells.

Antigens, CD

Lusitropic effects of a Ca2+ sensitization with a new cardiotonic agent, MCI-154, on diseased human hearts.

OBJECTIVES: Recognition of the problems of conventional cardiotonic agents has led to an interest in drugs that produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ (i.e., Ca2+ sensitizing agents). The importance of the effects of these compounds on left ventricular (LV) systolic function has been emphasized, whereas the effect of them on LV diastolic function is still problematic. To investigate the lusitropic action of a novel Ca2+ sensitizing agent, MCI-154, we compared the effects of MCI-154 on LV relaxation and filling dynamics with those of dobutamine in diseased human hearts. METHODS: We assessed the slope of the end-systolic pressure-volume relation (Emax), the time constant of LV pressure decay (Tw) and the maximum rate of LV early filling (dV/dtmax) before and after the infusion of dobutamine (n = 10) or MCI-154 (n = 9). LV volume and pressure were measured by a conductance catheter and a micro-tip catheter pressure transducer. RESULTS: When both agents increased Emax comparably, dobutamine decreased Tw from 51 to 37 ms and MCI-154 decreased Tw from 54 to 44 ms. The decrease of Tw with MCI-154 was less than that with dobutamine (17 vs. 29%, P < 0.05). At the same time, dobutamine increased dV/dtmax per end-diastolic volume (dV/dtmax/V) from 2.84 to 3.88 s-1, whereas MCI-154 did not. CONCLUSIONS: Diastolic properties were not compromised by MCI-154, though the alteration in them with MCI-154 was less than that with dobutamine when MCI-154 increased LV contractile state to the same extent as dobutamine. The present results suggest that MCI-154 would be an ideal Ca2+ sensitizing agent that enhances force during systole without impairing diastolic function.

Adult

Phylogenetic analysis of the genus Microbacterium based on 16S rRNA gene sequences.

16S rRNA gene (rDNA) studies of the six species of the genus Microbacterium, M. lacticum, M. laevaniformans, M. dextranolyticum, M. imperiale, M. arborescens and M. aurum, were performed and the primary structures were compared with those of 29 representative actinobacteria and related organisms. Phylogenetic analysis indicated that six species of the genus Microbacterium and representative four species of the genus Aureobacterium appear to be phylogenetically coherent as was suggested by Rainey et al., although the peptidoglycan types of these two genera are different (peptidoglycan type B1 or B2). Thus, the phylogenetical analyses revealed that members of actinobacteria with group B-peptidoglycan do not cluster according to their peptidoglycan types, but form compact cluster different from actinobacteria or actinomycetes with group A-peptidoglycan.

Amino Acid Sequence

Androgens directly stimulate mineralization and increase androgen receptors in human osteoblast-like osteosarcoma cells.

5 alpha-Dihydrotestosterone (DHT), an active form of testosterone, was shown to stimulate the mineralization of osteoblasts in a time- and dose-dependent manner in vitro in the presence of inorganic phosphate, as well as transforming growth factor beta and 1 alpha, 25 dihydroxyvitamin D3. However, DHT, stimulated the mineralization by a different mechanism from that of transforming growth factor beta and 1 alpha, 25 dihydroxyvitamin D3. We found that DHT increased the number of androgen receptors. These findings suggest that androgens directly stimulate mineralization in osteoblasts associated with an increase in the number of their receptors.

Alkaline Phosphatase

Fission yeast cut3 and cut14, members of a ubiquitous protein family, are required for chromosome condensation and segregation in mitosis.

Fission yeast temperature-sensitive mutants cut3-477 and cut14-208 fail to condense chromosomes but small portions of the chromosomes can separate along the spindle during mitosis, producing phi-shaped chromosomes. Septation and cell division occur in the absence of normal nuclear division, causing the cut phenotype. Fluorescence in situ hybridization demonstrated that the contraction of the chromosome arm during mitosis was defective. Mutant chromosomes are apparently not rigid enough to be transported poleward by the spindle. Loss of the cut3 protein by gene disruption fails to maintain the nuclear chromatin architecture even in interphase. Both cut3 and cut14 proteins contain a putative nucleoside triphosphate (NTP)-binding domain and belong to the same ubiquitous protein family which includes the budding yeast Smc1 protein. The cut3 mutant was suppressed by an increase in the cut14+ gene dosage. The cut3 protein, having the highest similarity to the mouse protein, is localized in the nucleus throughout the cell cycle. Plasmids carrying the DNA topoisomerase I gene partly suppressed the temperature sensitive phenotype of cut3-477, suggesting that the cut3 protein might be involved in chromosome DNA topology.

Amino Acid Sequence