The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 43, Issue 1
Displaying 1-6 of 6 articles from this issue
  • Hidekazu Suzuki, Soichiro Miura, Masayuki Suzuki, Soichiro Terada, Mas ...
    1994 Volume 43 Issue 1 Pages 1-8
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    The integrity of gastric mucosa is well-balanced by an array of defensive mechanisms which protect the mucosa against external aggressive factors. When excessive stimulation of autonomic nervous system (irritation) is induced, microcirculatory disturbances easily lead to the gastric mucosal damage due to the formation of vasoactive mediators and oxygen radicals. In this review, our discussion has been focused on the co-ordinating function of the autonomic nervous system as well as the microcirculation as an important defense bastion. In this context, Helicobacter pylori represents an important pathogenic factor. In particular, we have discussed the contribution of monochloramine, and active oxidant, which is formed by neutrophils in the presence of ammonia derived from H. pylori to the gastric mucosal injury. Microcirculatory disturbances may be also involved in the pathogenesis of H. pylori-induced mucosal injury. On the basis of these considerations, we should not depend solely on the use of anti-acid secretory drugs for the treatment of gastric mucosal injury, but also should be aware of beneficial effect of mucosal protective drugs which may act on microcirculation and the autonomic nervous system.
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  • Seymour S Kety
    1994 Volume 43 Issue 1 Pages 9-14
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    The author presents his development of the techniques for the measurement of total and regional cerebral blood flow, based on the principles that describe the exchange of inert diffusible tracers between blood and tissue. From the recognition that the uptake and distribution of such tracers would be independent of metabolism and neural function, but dependent instead on blood flow and purely physical factors such as diffusion and solubility, it was possible to transform equations of Fick, Bohr, and Krogh developed to describe steady states of oxygen distribution, to the dynamic processes involved in the distribution and equilibration of inert gases and other diffusible and nonmetabolized substances. The equations thus developed made possible the quantitative measurement of total and local blood flow in the brains of animals and man, and ultimately, the imaging of functional activity in the human brain through the coupling between activity and perfusion described 100 years ago by Roy and Sherrington.
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  • Toshio Nakaki
    1994 Volume 43 Issue 1 Pages 15-26
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    Nitric oxide, or NO., is a gas under atmospheric conditions. It is noxious because of its free-radical structure. It is biosynthesized from the amino acid L-arginine. The responsible enzymes are widely distributed in the human body. It has been shown that this simple molecule, NO., plays important roles in mammalian physiology. It is one of the factors regulating vascular tone and blood pressure, inhibition of platelet aggregation, neurotransmission in the peripheral and central nervous systems and macrophage function. Evidence for the pathophysiological significance of NO. is now accumulating.
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  • Thomas A Torda, Garry Graham, Neil R Warwick
    1994 Volume 43 Issue 1 Pages 27-30
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    In attempts to derive pharmacokinetic constants from effect data three methods were explored, using non-depolarizing neuromuscular blocking drugs as the paradigm for obtaining effect data. The first method, based on the simple assumption that following two doses, the drug concentrations at times of equal effect during recovery, were equal. Provided that recovery took place in the log-linear drug elimination phase, the elimination rate constant (β) could be calculated. This method proved rather inaccurate, a second method, again dependent on recovery in the log-linear phase yielded a constant which was the product of f and the exponent of the Hill equation (s). This method yielded results within 20% of values calculated from plasma drug assays, and it was demonstrated that the time-effect curve could be described from knowledge of this constant. The third method, using non-linear curve fitting technique, derived values for the rate constants of plsma redistribution (α) and elimination (β) as well as for the rate constant of elimination from an effect compartment (keo). If the values were derived from the effect of two doses of a drug, the intensity and duration of effect of a third dose could be predicted with reasonable accuracy. The dose dependent constants of the usual compartmental equations for the plasma concentration of a drug (A and B) could be derived in terms of the EC50. The method can be applied to any drug whose effect can be measured and whose maximal effect can be defined. We believe that the method may be useful in rapidly and inexpensively estimating population kinetic parameters, and in screening drugs.
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  • Kazuo Isozumi, Yasuo Fukuuchi, Hidetaka Takeda, Yoshiaki Itoh
    1994 Volume 43 Issue 1 Pages 31-36
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    To elucidate the mechanisms of CBF augmentation during hypoxemic hypoxia, we applied continuous monitoring of CBF and metabolism to examine the participation of prostacyclin, nitric oxide (NO), and/or adenosine in these mechanisms. Cats (n=32) were anesthetized and ventilated artificially. Cerebrovascular reactivity to hypoxia was assessed by changes in CBF, brain tissue oxygen and carbon dioxide tensions, and mean arterial blood pressure (ΔCBF, ΔBrPO2, ΔBrPCO2, and ΔMABP) during a 3-min inhalation of 10% O2+90% N2 before and after the intracarotid administration of (1) indomethacin (1mg/kg, a cyclooxygenase inhibitor, n=11), (2) L-NG-monomethyl-arginine (LNMMA, 1μmol/kg/min, an inhibitor of nitric oxide synthesis, n=11), and (3) caffeine (20mg/kg, an adenosine antagonist, n=10). BrPO2 decreased significantly in all groups during the produced hypoxemic hypoxia. CBF significantly increased in this state before the administration of indomethacin, LNMMA, or caffeine, whereas it contrastively did not significantly increase after the administration of indomethacin or caffeine. In addition, CBF significantly decreased under hypoxia during the administration of LNMMA. Taken together, these results suggest that prostacyclin (PGI2), nitric oxide (NO), and adenosine may jointly participate in CBF augmentation during hypoxia.
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  • Mototsugu Oya
    1994 Volume 43 Issue 1 Pages 37-44
    Published: 1994
    Released on J-STAGE: March 27, 2009
    JOURNAL FREE ACCESS
    Antitumor effects of interleukin-2 entrapped in liposomes (IL-2 liposomes) on Renca, murine renal cell carcinoma of spontaneous origin, were evaluated by in vivo and in vitro experiments. As a local treatment model, IL-2 liposomes at a dose of 1.0×104 units were for 7 days injected adjacent to the Renca tumors inoculated in the back of BALB/c mice. The treatment inhibited the tumor growth and prolonged the survival time of mice significantly compared to the control (p<0.01). Serum IL-2 levels after subcutaneous administration of IL-2 liposomes confirmed its slow releasing mechanism into blood circulation. The spleen cells from mice following the IL-2 liposome treatment showed higher cytotoxicity in vitro than that of IL-2 alone using Renca, YAC-1, and P-815 cells, which was determined by 51Cr-release assay. Indirect immunoperoxidase staining of tumor-infiltrating lymphocytes (TILs) showed that accumulation of Lyt-2+ and L3T4+ cells were seen in the tumor treated with IL-2 liposomes. These results indicate that IL-2 liposomes have a long-acting cytotoxicity against renal cell carcinoma caused by a slow release mechanism generated through the efficient local immune response mediated by TILs.
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