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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 289 records · Page 16Linked to original sources

[Hypothalamic and pituitary function in brain death].

Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.

Adolescent↗

[Experimental study on histological changes of articular cartilage of femoral head under nonweight-bearing conditions].

Histological changes of articular cartilage of the femoral head in the nonweight-bearing conditions were investigated using 10-week-old Wistar rats whose hind limbs had been unilaterally transected. At 2 weeks after limb transection, decreased DNA synthesis in chondrocytes and depletion of glycosaminoglycan in the cartilage matrix in the intermediate zone of the articular cartilage were observed. After 8 weeks, articular cartilage thickness decreased significantly, and at 16 weeks the number of chondrocytes diminished in comparison with those of a weight-bearing femoral head. At 20 weeks, chondrocyte death and reduced width of articular cartilage became evident. No osteoarthritic changes, however, were observed under nonweight-bearing conditions. These findings suggest that weight-bearing is very important in maintaining of both the structure and metabolism of the articular cartilage.

Animals↗

[Single lung allotransplantation of Japanese monkeys--an immunohistological appraisal of the acute rejection].

Eleven orthotopic single lung allotransplantations of Japanese monkeys (Macaca fuscata) were done without immunosuppression. In the 7 monkeys acute rejection was obvious on chest X-ray and hematoxyline-eosin (HE) staining of the biopsied specimen. On the chest X-ray film, progressive interstitial shadow of the grafts became apparent at the third postoperative day, and they turned out completely radiopaque at the 6th- or 7th postoperative day. The HE staining revealed prominent perivascular edema at the second postoperative day. Perivascular round cell infiltration appeared at the third day and the massive round cell infiltration was observed in the perivascular region, vascular wall and alveolar wall with the thickening of the alveolar wall. Immunostaining with human antilymphocyte monoclonal antibodies was also performed. CD8 positive cells (suppressor/cytotoxic T cell) were observed in the perivascular region at the second postoperative day, and CD8 positive cells and CD4 positive cells increased in number as the rejection progressed. Judging from the positive immunological cross reactivity between Japanese monkey and human, the early diagnosis of the acute rejection of the grafted lung may be possible by detecting the perivascular CD8 cells, even in the human-beings.

Animals↗

[Simple allergen skin test device Multi skit (tentative name)].

We have developed a device tentatively named Multi Skit (Mu), a simple allergen test device, in order to conduct the skin test safely, accurately and conveniently. The utility of this device was evaluated by determining how the results obtained by the intradermal test (In) and Mu were correlated with those obtained by IgE RAST (RA) in 65 AD patients. RA values concerning nine antigens were compared to results obtained by the In and Mu in terms of the positive and negative response coincidence rates, overall coincidence rates, and false-positive and false-negative response rates. The correlation between RA data obtained from the literature and the results of the scratch test (Sc) was also evaluated. The results of In and RAST values showed no correlation regardless of the food antigen used. Mu and RAST values showed correlation with respect to all 4 food antigens except soy-bean, resulting in overall coincidence rates of 66.2 to 87.7%, which were higher than those concerning the Sc. With respect to false-positive responses to environmental antigens, the rate obtained by Mu was higher than that by the Sc, but it was lower than that by the In. However, Mu was the most excellent test with respect to the other indices, i.e., positive and negative response coincidence rates, overall coincidence rates (73.9-89.2%) and false-negative responses. The mechanism of Mu makers it possible to minimize variations from one investigator to another, and the major drawback of all other skin tests. Mu is a safe and convenient screening skin test device which provides accurate and specific test results.

Adolescent↗

Effects of interleukin 4 on stromal cell-associated bone marrow culture.

We examined the effect of murine interleukin 4 (IL-4) on in vitro hemopoiesis associated with an endothelial-adipose cell line derived from a murine bone marrow stroma and termed 14F1.1. The addition of IL-4 to the co-culture led to the rapid disappearance of hemopoietic progenitors, and when greater than or equal to 20 U/ml IL-4 was added, this effect became remarkable. The stimulation of 14F1.1 cells by IL-4 before the start of co-culture accelerated the disappearance of hemopoietic progenitors, although continuous stimulation by IL-4 was needed. When IL-4 was added to the co-culture 2 weeks after initial incubation, the myeloid lineage progenitor cells disappeared within 1 week. When we examined whether the inhibitory activity on hemopoiesis was induced by 14F1.1 cells stimulated with IL-4, we found no distinct inhibitory activity in the 14F1.1-cell supernatant, but there was a slight increase in colony-stimulating activity. Colony formation of bone marrow cells seeded on top of 14F1.1 cells but separated by a thin 'empty' agar layer was enhanced by IL-4-treated 14F1.1 cells. We also noted the disappearance of the 'cobblestone' area, which had been the site of active hemopoiesis in this culture, together with the disappearance of any granulocyte-macrophage colony-forming units (CFU-GM), thereby implying that IL-4 alters the interaction between hemopoietic progenitors and stromal cells.

Animals↗

The effects of interleukin 6 and interleukin 3 on early hematopoietic events in long-term cultures of human marrow.

Interleukin (IL)-6 and IL-3, both alone and in combination, stimulate hematopoietic cells in short-term in vitro assays and in vivo. To study their ability to influence hematopoiesis in a system that mimics many features of the marrow microenvironment, long-term cultures (LTC) were produced by co-cultivating normal human marrow cells on feeder layers of murine marrow-derived stromal cells (M2-10B4 cells) genetically engineered to produce human IL-6 and/or IL-3. Feeders stably producing 20 ng/ml IL-6 slightly increased the output of clonogenic progenitors in these LTC but did not change the production of mature (total nonadherent) cells as compared to control cultures. Feeders producing 50 ng/ml IL-3 increased both clonogenic progenitor output (approximately threefold) and the output of mature cells (six-fold) as compared to controls. Feeders producing both factors also increased the output of both progenitors and mature cells. At the time of the weekly half-medium change when primitive clonogenic progenitors in the adherent layer are quiescent, such progenitors were actively cycling in all cultures with factor-producing feeders, as shown by [3H]thymidine suicide assays. Similarly, three sequential daily additions of 20 ng/ml of IL-6 also stimulated the quiescent progenitors to enter S-phase 2 days later, although single doses of recombinant IL-6 as high as 100 ng/ml failed to do so. The combined presence of IL-6- and IL-3-producing feeders, but neither alone, was also able to enhance more than twofold the maintenance and early differentiation of cells capable of generating clonogenic cells for at least a further 5 weeks in secondary LTC. Thus, the provision of a continuous source of IL-6 or IL-3 to primitive hematopoietic cells even in the LTC system can enhance late events in the hierarchy of hematopoietic cell differentiation, but a combination of the two factors is required to stimulate early multipotent progenitors.

Animals↗

[Immunotherapy using high concentration purified antigen showed remarkable effect in all cases].

Hoya (sea-squirt) asthma is a typical type I occupational asthma. A total of 22 females with this disease whose age ranged from 22 to 69 years were treated for two years with high concentration purified sea-squirt antigen named Ei-M having a molecular weight of 22,800. One case who developed ordinary bronchial asthma abandoned the immunotherapy during the early stage of the therapy, but in the remaining 21 cases remarkable effects were rapidly observed from the early stage of treatment. These cases did not develop asthmatic attacks even through they engaged in oyster shucking work and no symptomatic therapy was indicated. Serum anti-Ei-M IgG antibody was significantly elevated after the therapy. None of the treated cases developed any side effects.

Adult↗

Lack of evidence for abnormal autocrine or paracrine mechanisms underlying the uncontrolled proliferation of primitive chronic myeloid leukemia progenitor cells.

Previous studies have revealed a consistent defect in the cycling behavior of primitive neoplastic progenitor cells in patients with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML). This is manifested both in vivo and in long-term cultures of CML cells as an increased rate of turnover amongst Ph1-positive progenitor cell types whose counterparts in normal individuals are mainly quiescent. To determine whether this deregulated proliferative activity of primitive Ph1-positive cells might be explained by a perturbation in the production of growth factors that regulate the turnover of primitive normal cells, the possibility of either autocrine or paracrine mechanisms of Ph1-positive cell stimulation was investigated. Northern blot analysis of total cellular RNA extracted from various CML blood cell populations showed no evidence of increased expression of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL-6, or tumor necrosis factor-alpha (TNF-alpha) compared with analogous normal peripheral blood cell populations in which transcripts for most of these growth factors are not detectable. A similar analysis of RNA extracted from the adherent layer of 4-week-old long-term cultures established from CML marrow (in which the Ph1-positive cells typically disappear) or from CML blood seeded onto normal marrow adherent layers (in which Ph1-positive cells typically persist) also revealed no difference in growth factor production compared with analogous cultures established with exclusively normal cells. For some of the growth factors studied, the assessment of bioactivity detectable in the medium confirmed the RNA data. There was also no evidence of a decreased production of putative inhibitors of primitive hematopoietic cells, i.e. transforming growth factor-beta and macrophage inflammatory protein-1 alpha by CML versus normal cells or cultures. These results do not support the existence of BCR-ABL induced autocrine or paracrine mechanisms in CML and suggest that constitutive activation of events normally dependent on growth factor receptor stimulation is more likely to underlie the lack of proliferation control exhibited by primitive Ph1-positive cells.

Bone Marrow↗

[Long survival in a case of metastatic brain tumor].

A 45-year-old man was admitted after resection of a metastatic brain tumor (papillary adenomatous adenocarcinoma, well differentiated) for both therapy and a search for the primary and any other metastatic lesions. An extensive general examination revealed no evidence of malignant lesion except for fibrous change in the right lung apex by roentgenography and CT scan. Histological examination of the right upper lobe and group II lymph nodes revealed a scar cancer presenting the same histology but no evidence of metastasis. The patient, who received CAP and FVM alternately, is currently healthy with no recurrence after 4 years.

Adenocarcinoma↗

Studies on antibacterial agents. III. Synthesis and antibacterial activities of substituted 1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acids.

A series of substituted 4-oxoquinoline-3-carboxylic acids having a methyl group at the 8-position was prepared and tested for their antibacterial activity. 7-(trans-3-Amino-4-methyl-1-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-6- fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid (21) exhibited highly potent antibacterial activity against both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa.

Acinetobacter↗

[Reproductive and developmental toxicity study of mofezolac (N-22) (3)--Teratogenicity study in rabbits by oral administration].

Mofezolac (N-22) is a new developed analgesic and anti-inflammatory agent. A teratogenicity study of N-22 was carried out in New Zealand White rabbits to examine the effect on the dams and the teratogenic potentiality. N-22 was administered orally at the dose levels of 12.5, 50 and 200 mg/kg during the organogenesis from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 28 of gestation and their fetuses were examined. There were no growth retardation and teratogenic effects on fetuses from the dams administered N-22, although the administration of 200 mg/kg produced a decrease in food consumption of the dams concomitant with the embryocidal effects as shown by an increase in the early resorption rate. Thus, non-toxic dose level of N-22 on the dams and fetuses was considered to be 50 mg/kg.

Abnormalities, Drug-Induced↗

Evoked potentials of self-interrupted Jacksonian epilepsy.

We describe a female case of Jacksonian epilepsy who can interrupt the spreading of her march by grasping her fingers firmly with her right hand. Neurophysiologically, Somatosensory evoked potential (SEP) was remarkably decreased in amplitude with pressure stimulation similar to her method. Such a change in SEP was observed also in a healthy subject. Accordingly, it is suggested that the stimulation only to the proprioceptor of fascia suppresses the activity in the cortex.

Aged↗

[Experimental study on maturational therapy of osteosarcoma cell].

We investigated the differentiation-inducing effects of dibutyryl cyclic AMP (dBc AMP) on several cultured osteosarcoma cell lines (DUNN, MOLONEY, OST, FBJ). 1. Cell growth rates of all the osteosarcoma cell lines were reduced by 3mM dBc AMP. 2. Both alkaline phosphatase activity and 45Ca2(+)-uptake were promoted by 3mM dBc AMP. 3. There was, in each cell line except for the OST cells, a marked enlargement of the cell processes under the light microscopic observation. At the electron microscopic level, there were also many findings indicating an increase in cell functions. These results suggest that the differentiation may be induced by cAMP in osteosarcoma cells, and that the differentiation therapy by cAMP-related drugs is promising for a clinical application.

Alkaline Phosphatase↗

[Effect of topical injections of native alpha-interferon (HLBI) in the treatment of skin lesions of adult T cell leukemia: report of a case].

A case of adult T cell leukemia associated with prominent skin infiltrations was treated with native alpha-interferon (Human lymphoblastoid interferon; HLBI). Although previous therapy with intramuscular injections of HLBI showed no effect on the skin lesions, this time topical injections of HLBI induced regression and disappearance of skin lesions within one month. Cellular immunity in this patient evaluated by PPD reaction and PHA blastoid transformation had been depressed at the time of systemic administrations of HLBI, but at the beginning of the topical injections of HLBI, they were within normal range. CD4/CD8 ratio reversed to 0.86 after topical injections of HLBI, suggesting the effect of HLBI on cytotoxic T lymphocyte activation. Thus, topical subcutaneous injections of HLBI may be an alternative form of therapy for ATL skin infiltrations when systemic HLBI administration is not effective, especially for the patient with normal cellular immunity.

Aged↗

Effect of granulocyte-macrophage colony-stimulating factor on chemiluminescence of human neutrophils.

We investigated the capacity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to enhance the function of neutrophils. Neutrophil function was measured in terms of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced luminol-dependent chemiluminescence (LDCL). LDCL of fMLP-stimulated neutrophils was enhanced up to 4.5 fold following preincubation with rhGM-CSF. This enhancement depended on the length of preincubation, reaching an optimal level at 120 min. The dose-response relationship for fMLP-induced LDCL of neutrophils preincubated with rhGM-CSF revealed that half-maximum enhancement was achieved at an approximately 20-fold higher concentration than that of colony-forming units in culture-derived colony formation. These results suggest that differences in dose dependency may be explained by differences in the distribution of receptor(s) for GM-CSF. This may also enable GM-CSF to affect the hematopoietic system, which contains cells at various levels of differentiation, thus mediating the host-defense mechanism.

Bone Marrow↗