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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 271 records · Page 15Linked to original sources

[Magnetic resonance imaging in diffuse brain injury].

Forty cases diagnosed as diffuse brain injury (DBI) were studied by magnetic resonance imaging (MRI) performed within 3 days after injury. These cases were divided into two groups, which were the concussion group and diffuse axonal injury (DAI) group established by Gennarelli. There were no findings on computerized tomography (CT) in the concussion group except for two cases which had a brain edema or subarachnoid hemorrhage. But on MRI, high intensity areas on T2 weighted imaging were demonstrated in the cerebral white matter in this group. Many lesions in this group were thought to be edemas of the cerebral white matter, because of the fact that, on serial MRI, they were isointense. In mild types of DAI, the lesions on MRI were located only in the cerebral white matter, whereas, in the severe types of DAI, lesions were located in the basal ganglia, the corpus callosum, the dorsal part of the brain stem as well as in the cerebral white matter. As for CT findings, parenchymal lesions were not visualized especially in mild DAI. Our results suggested that the lesions in cerebral concussion were edemas in cerebral white matter. In mild DAI they were non-hemorrhagic contusion; and in severe DAI they were hemorrhagic contusions in the cerebral white matter, the basal ganglia, the corpus callosum or the dorsal part of the brain stem.

Adolescent↗

Synthesis of a 3-ether analogue of lipid A.

Lipid A 3-ether analogues were synthesized from allyl 2-deoxy-4,6-O-isopropylidene-2-trifluoroacetamido-alpha-D-glucopyr anoside and 3,4,6-tri-O-acetyl-2-trifluoroacetamido-alpha-D-glucopyranosyl bromide. The compound lost completely the endotoxic activity.

Animals↗

von Recklinghausen neurofibroma produces neuronal and glial growth-modulating factors.

Two kinds of novel neural trophic factors were currently detected in von Recklinghausen neurofibroma (NF1) extracts. One of the two was a growth factor, neuroblastoma growth factor (Mr less than 5 kDa), which promotes the proliferation of human neuroblastoma cell and survival and neurite-extension of rat cortical neurons, but differently from nerve growth factor (NGF) or NGF-like factors. The other one was a glial growth inhibitor (Mr = 100 kDa), which suppresses the growth of glioma cell lines, astrocytoma, glioblastoma, oligodendroglioma and Schwannoma. These factors do not appear to be previously identified cytokines or growth factors such as interleukins, granulocyte colony-stimulating factor, NGF and fibroblast growth factor. There was also detectable ciliary neurotrophic factor-like activity in the extracts. The primary cause of high contents of these factors in NF1 is not known, but may relate to fundamental mechanisms controlling growth and differentiation of neurons and glias during development of nervous system.

Animals↗

Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer.

Numerous factors that can influence the proliferation and differentiation in vitro of cells at various stages of hematopoiesis have been identified, but the mechanisms used by stromal cells to regulate the cycling status of the most primitive human hematopoietic cells are still poorly understood. Previous studies of long-term cultures (LTC) of human marrow have suggested that cytokine-induced variations in stromal cell production of one or more stimulators and inhibitors of hematopoiesis may be important. To identify the specific regulators involved, we performed Northern analyses on RNA extracted from human marrow LTC adherent layers, or stromal cell types derived from or related to those present in the adherent layer. These analyses showed marked increases in interleukin-1 beta (IL-1 beta), IL-6, and granulocyte colony-stimulating factor (G-CSF) mRNA levels within 8 hours after treatments that lead to the activation within 2 days of primitive hematopoietic progenitors in such cultures. Increases in granulocyte-macrophage (GM)-CSF and M-CSF mRNA were also sometimes seen. Bioassays using cell lines responsive to G-CSF, GM-CSF, and IL-6 showed significant elevation in growth factor levels 24 hours after IL-1 beta stimulation. Neither IL-3 nor IL-4 mRNA was detectable at any time. In contrast, transforming growth factor-beta (TGF-beta) mRNA and nanogram levels of TGF-beta bioactivity in the medium were detected at all times in established LTC, and these levels were not consistently altered by any of the manipulations that stimulated hematopoietic growth factor production and primitive progenitor cycling. We also found that addition of anti-TGF-beta antibody could prolong or reactivate primitive progenitor proliferation when added to previously stimulated or quiescent cultures, respectively. Together, these results indicate a dominant negative regulatory role of endogenously produced TGF-beta in unperturbed LTC, with activation of primitive hematopoietic cells being achieved by mechanisms that stimulate stromal cells to produce G-CSF, GM-CSF, and IL-6. Given the similarities between the LTC system and the marrow microenvironment, it seems likely that the control of human stem cell activation in vivo may involve similar variations in the production of these factors by stromal cells.

Blotting, Northern↗

Continuous activation of primitive hematopoietic cells in long-term human marrow cultures containing irradiated tumor cells.

Human hematopoietic cells can be maintained in vitro for many weeks in the absence of exogenously provided hematopoietic growth factors if an adequate stromal cell containing adherent layer is present. We have now extended the use of this type of long-term culture (LTC) system to create a model of perturbed hematopoiesis in which human tumor cells that constitutively produce a variety of factors are co-cultured together with normal human marrow cells. In the present study, we used the human bladder carcinoma cell line (5637) because these cells were known to produce not only a variety of factors active directly on hematopoietic cells but also factors that can stimulate hematopoietic growth factor production by human marrow stromal cells. Analysis of mRNA extracted from the adherent layer and measurement of growth factor bioactivity in the medium of established LTC of human marrow containing irradiated 5637 cells, showed increased levels of interleukin-1 and -6, as well as granulocyte and granulocyte-macrophage colony-stimulating factor production by comparison to control cultures. As in normal cultures, high proliferative potential clonogenic hematopoietic cells were found almost exclusively in the adherent layer of these co-cultures, but these primitive cells were maintained in a state of continuous turnover, in contrast to control cultures where the same cell types showed the expected oscillation between a quiescent and a proliferating state following each weekly change of the medium. A similar perturbation of primitive progenitor cycling was achieved by adding medium conditioned by 5637 cells twice a week to otherwise normal LTC. The presence of irradiated 5637 cells in the LTC or the addition of 5637 conditioned medium also resulted in modest (2- to 3-fold) but sustained increases in the total hematopoietic progenitor population, as well as in the final output of terminally differentiated granulocytes and macrophages. These findings indicate that primitive hematopoietic cells in LTC can be kept in a state of continuous activation for many weeks by appropriate endogenous or exogenous hematopoietic growth factor provision and that this does not necessarily lead either to their rapid exhaustion or to a large amplification in output of mature progeny.

Blotting, Northern↗

Functional variations in parenchymal microvascular systems within the brain.

Variations in microvascular system functions were observed among a number of brain areas. The rates of local blood flow varied 18-fold among areas and were extremely high in neuroendocrine structures. Marked differences in blood flow were also found within some brain structures. The volume of radiolabeled blood in perfused parenchymal microvessels ranged from 5 to 70 microliters/g and correlated closely with local cerebral blood flow. The hematocrits within parenchymal microvessels were 45-75% of the arterial hematocrit, which indicates that red cells more rapidly traverse brain microvessels than do plasma proteins. The mean transit times of blood through parenchymal microvessels were extremely short and ranged from 0.3 to 0.6 s.

Animals↗

An anomaly of the radial artery--relevance for the forearm flap.

The radial artery runs between the Flexor Carpi Radialis tendon and the Brachioradialis tendon in the distal one-third of the forearm. Here it is covered only by the superficial fascia, subcutaneous tissue and skin, so that it is easy to palpate. However, the case reported here describes a rare anomaly of the radial artery which has relevance to use of the forearm flap.

Arteries↗

Emergency center ultrasonography in the evaluation of hemoperitoneum: a prospective study.

The reliability of ultrasonographic detection (US) of hemoperitoneum in blunt abdominal trauma was evaluated in a prospective study of 72 patients. Independent of the examiner, sensitivity, specificity, and accuracy were, respectively, 86.7%, 100%, and 97.2%. Laparotomy was indicated in 76.9% of US hemoperitoneum-positive cases. No negative laparotomies were performed in this study group. If hemoperitoneum is revealed in US and vital signs are unstable, we think laparotomy is indicated. We believe that US in an emergency center is a quick, safe screening method in the evaluation of blunt abdominal trauma. US might take over a great part of the role of diagnostic peritoneal lavage.

Abdominal Injuries↗

Significance of magnetic resonance imaging in acute head injury.

One hundred seventy-seven patients who had incurred head trauma were studied with magnetic resonance imaging (MRI). Patients varied from those with mild injury without any focal neurological deficit to those with severe injury with post-traumatic coma. Altogether, 177 lesions were demonstrated by MRI in 123 of 177 patients within 3 days of injury using T2-weighted (SE2000/40,2000/111) and T1-weighted (IR1500/500/40) multislice sequences. In contrast, computerized tomography (CT) demonstrated 103 lesions in 90 patients. MRI was superior to CT in the diagnosis of nonhemorrhagic contusions demonstrated as a high-intensity area on T2-weighted imaging. MRI provided some information to evaluate the severity of diffuse axonal injury or to predict delayed traumatic intracerebral hematoma (DTICH).

Acute Disease↗

Symptoms and social adjustment of schizophrenic patients as evaluated by their family members: a cross-cultural psychiatric study between offshore islands and an urban city.

We conducted a comparative study of symptoms and social adjustment of schizophrenic patients on offshore islands and one urban region in Japan. In the evaluation of symptoms and social behavior by family members, no differences were observed between the two regions. Looking at social adjustment in the two regions, no differences were observed by family members either in the performance level or in the expectation level of socially expected activities. However, on the offshore islands, the expectation level of socially expected activities by family members was significantly higher than the level of self-accomplishment set by schizophrenic patients themselves. As for leisure activities, both family members and patients on the islands evaluated the level of performance to be significantly higher than in the urban region, and the level of satisfaction of the patients themselves was also higher on the islands. Considering both these findings and Japanese traditional views of work and leisure, it is believed that on the islands patients are required to engage in more productive activities and less leisure activities than in the urban region. Further it seems that patients on the islands compared to patients in the urban region may have greater difficulty in social adjustment.

Adult↗

Molecular analysis of primitive hematopoietic cell proliferation control mechanisms.

Cells at two distinct early stages in the development of mature human blood cells from primitive totipotent hematopoietic stem cells can now be defined and quantitated by separate in vitro assays. Current evidence suggests that most, if not all, colony-forming cells--that is, cells that give rise to colonies of mature progeny within one to three weeks in semisolid culture systems, represent an intermediate stage of hematopoietic progenitor. These cells are not self-sustaining; if they are used to initiate hematopoiesis on competent marrow stromal layers, they rapidly disappear as they differentiate or die. However, clonogenic cells can be generated in such cultures from another cell type over a period of four to eight weeks. We have, therefore, assigned the term long-term culture initiating cell (LTC-IC) to this latter type of clonogenic precursor cell. The production and differentiation of cells in both of these compartments in LTC are dependent on, and regulated by, nonhematopoietic "stromal" cells that form a heterogeneous adherent layer in which close-range interactions with hematopoietic cells take place. The use of separate endpoints to monitor the maintenance, differentiation, and reversible activation or arrest of cycling of these cells has recently revealed different molecular mechanisms regulating their respective functions. However, an important common feature appears to be the relative local concentration of positive and negative regulators to which the target hematopoietic cell is exposed. Both gene expression and growth factor release measurements as well as results obtained using genetically engineered stroma and repeated soluble growth factor addition implicate G-CSF as an endogenous positive regulator of primitive hematopoietic cells. Similarly, gene expression, factor production, factor addition, and neutralizing antibody experiments implicate TGF-beta as an endogenous inhibitor of primitive hematopoietic cells.

Bone Marrow Cells↗

Variation in local cerebral blood flow response to high-dose pentobarbital sodium in the rat.

Microvascular bed structure and functions are known to vary throughout the brain. Microvascular responses to high doses of pentobarbital sodium might therefore differ among brain areas. This possibility was examined by measuring local cerebral blood flow (LCBF) with [14C]iodoantipyrine in 52 brain areas at 5, 10, 25, and 60 min after intraperitoneal administration of pentobarbital (50 mg/kg). From 5 to 60 min, LCBF was significantly lowered in 17 of 25 forebrain gray matter areas but in only 1 of 18 hindbrain gray matter structures, the pontine nuclei. Smaller, shorter duration lowering of LCBF was also observed in ten other brain areas. In both control and treated rats, LCBF was found to vary within individual brain structures. The pattern of these LCBF variations was columnar in the cerebral cortex and the hippocampus but was patchy in the caudate-putamen, thalamus, and inferior colliculus. These results indicate that pentobarbital anesthesia more strongly alters LCBF in the forebrain than in the hindbrain and produces different patterns of changes in LCBF than in local cerebral glucose utilization, which was measured with 2-deoxyglucose in a companion study.

Animals↗

Pentobarbital produces dissimilar changes in glucose influx and utilization in brain.

The effects of pentobarbital sodium on local cerebral glucose utilization (LCGU) and 3-O-methylglucose (3-MG) influx were measured by quantitative autoradiography in 52 brain areas of control and treated rats. Pentobarbital (50 mg/kg ip) lowered LCGU to a relatively uniform rate (approximately 35 mumol.100 g-1.min-1) in 24 of 25 forebrain areas. Among the 18 hindbrain areas, LCGU was decreased by pentobarbital by 15-55% (range 50-157 and 28-110 mumol.100 g-1.min-1 in control and treated rats, respectively). In contrast, pentobarbital lowered the 3-MG influx rate constant and permeability-surface area product by 20-30% in nearly all brain structures. The 3-MG results fit a model in which both the half-saturation constant and the maximal velocity of the glucose carrier are decreased by pentobarbital. After pentobarbital treatment, the ratio of local cerebral plasma flow (LCPF) to LCGU was the same as in controls for brain areas in which LCGU was less than 35 mumol.100 g-1.min-1 but was higher in brain areas where LCGU exceeded 35 mumol.100 g-1.min-1. Pentobarbital produced dissimilar changes in LCGU, 3-MG influx, and LCPF; these processes may thus not be closely linked during pentobarbital anesthesia.

3-O-Methylglucose↗

Differential effects of microenvironmentally presented interleukin 3 versus soluble growth factor on primitive human hematopoietic cells.

The effect of IL-3 on hematopoiesis in long-term culture (LTC) was studied by cocultivating normal human marrow cells with human marrow fibroblast feeders engineered to constitutively produce IL-3 and by adding soluble IL-3 to LTC according to a variety of dose-time schedules. Feeders stably producing 7 ng/ml IL-3, or LTC to which 10 ng/ml IL-3 was added daily for 5 wk, but not once or twice weekly for the same time period, increased the output of mature nonadherent cells and progenitors from LTC as compared to control cultures. At the time of the weekly half-medium change, when primitive clonogenic progenitors in the adherent layer of standard LTC are quiescent, such cells were actively cycling in cultures containing a continuous source of an adequate dose of IL-3. In LTC, where the proportion of IL-3-producing cells in the feeder layer was diluted to 10% and no IL-3 was detectable in culture medium, primitive adherent layer progenitors were, nevertheless, maintained as a population of continuously proliferating cells. Thus, the presence of IL-3 in LTC can enhance the proliferation and differentiation of very early human hematopoietic cells, but the concentration, duration of exposure, and method of IL-3 presentation are important determinants of the ultimate effects observed.

Cell Division↗