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Biomedical subjects

N Moriya

Publications and source records attributed to N Moriya.

At least 37 records · Page 2Linked to original sources

Intestinal absorption of serrapeptase (TSP) in rats.

A sensitive sandwich enzyme immunoassay (e.i.a.) for serrapeptase (TSP), an orally available anti-inflammatory proteinase, was established using affinity-purified anti-TSP rabbit IgG and its Fab' fragment conjugated with horseradish peroxidase as the first and the second antibodies respectively. TSP in the plasma was determined by the e.i.a. after its oral administration (100 mg/kg) to rats. The peak concentration was observed between 30 min and 2 h after administration. TSP in the plasma samples was trapped on a microtitre plate coated with the affinity-purified anti-TSP rabbit IgG, and the hydrolysis of a synthetic fluorogenic substrate, butoxycarbonyl-Glu(benzyloxy)-Ala-Arg-4-methylcoumaryl-7-amide, by the trapped TSP was fluorometrically measured (proteinase assay). The values obtained by the e.i.a. and those obtained by the proteinase assay correlated well for various plasma samples. These results indicate that orally administered TSP was absorbed from the intestinal tract and transferred into the circulation in an enzymically active form.

Administration, Oral↗

[Randomized controlled study of sequential methotrexate and 5-fluorouracil therapy with or without 5'-deoxy-5-fluorouridine against advanced gastrointestinal cancer. Hirosaki Cooperative Study Group for Cancer Chemotherapy].

Seventy-five patients with gastrointestinal cancer were entered in this study. The number of eligible cases were 38 in the group treated with sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR) (group A) and 34 in the group without 5'-DFUR (group B). The treatment schedules were as follows: MTX/100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. In group A, 5'-DFUR 1,200 mg/body/day was given orally 5 consecutive days per week. Three of 35 cases in group A showed PR, while no case showed PR in group B. Median survival time was 5.0 months in group A and 5.3 months in group B, respectively. Gastrointestinal toxicity was commonly observed, and diarrhea was more frequent in group A (p < 0.05).

Adult↗

[Sequential methotrexate/5-fluorouracil therapy with 5'-deoxy-5-fluorouridine against advanced gastric cancer: comparison between bolus injection and drip infusion of 5-fluorouracil administration. Hirosaki Cooperative Study Group for Cancer Chemotherapy].

Forty-two patients with gastric cancer were entered in this study. Forty-one of them were eligible and administered sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR). 5-FU was administered intravenously by drip infusion for 2 hours in 22 cases (group A), and was infused by bolus injection in 19 cases (group B). The treatment schedules were as follows: MTX 100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. 5'-DFUR 1,200 mg/body/day was given orally on 5 consecutive days per week. Three of 20 cases (15%) in group A showed PR, while 5 of 15 cases (33%) in group B showed PR. Median survival time was 2.8 months in group A and 3.7 months in group B. There was, however, no statistical difference. Gastrointestinal toxicity was commonly observed. Leukocytopenia was more severe in group B. Alopecia was more frequently observed in group B (p < 0.025). These results suggested bolus injection of 5-FU was a promising way of administration in sequential MTX/5-FU therapy.

Administration, Oral↗

Identification of a novel population of CD8 alpha+ beta- bone marrow-derived dendritic epidermal cells. This unique population is subsequently outnumbered by thymus-independent expansion of the CD8 alpha+ beta+ dendritic epidermal cells.

Maturation of some T cell populations has been suggested to occur in epithelial tissues. The CD8 molecule, which is expressed as heterodimers made of alpha/beta-chains on virtually all peripheral T cells, is preferentially expressed as homodimers made only of alpha-chains on a subset of CD8+ mouse gut intraepithelial lymphocytes, which arise from bone marrow (BM) precursors in a thymus-independent mechanism. This unique population of CD8 alpha+ beta- T cells, however, has not been identified in other lymphoid tissues in normal adult mice. Because our previous study demonstrated that reconstitution of thymectomized irradiated mice with T cell-depleted BM cells resulted in the appearance of CD8+, TCR-alpha beta+ dendritic epidermal cells (DEC) and suggested that a proportion of the BM-derived DEC may mature within the epidermis, we asked whether the unique phenotype of CD8 alpha+ beta- could be detected among the CD8+ BM-derived DEC. In this report for the first time we identified this unique population of CD8 alpha+ beta- cells among the DEC. Although this population comprised the predominant fraction of the BM-derived DEC in the early post-transfer period (2 to 3 mo), gradual shift from the CD8 alpha+ beta+ phenotypes occurred during the late post-transfer period (4 to 6 mo) independently of the presence of the thymus. Kinetic studies on the BM-derived DEC revealed that this phenotypic shift could be caused by the subsequent expansion of the CD8 alpha+ beta+ DEC. In contrast, the CD8 alpha+ beta- population was the major subset of the BM-derived intraepithelial lymphocytes throughout the entire observation period and the phenotypic shift with age was never observed. These results indicate that CD8 alpha+ beta- cells are preferentially detected on T cells that home to the epithelial tissues and that in the epidermis, but not in the gut epithelia, the subsequent expansion of the CD8 alpha+ beta+ DEC would dilute the high number of the CD8 alpha+ beta- cells.

Animals↗

Bone marrow-derived dendritic epidermal T cells express T cell receptor-alpha beta/CD3 and CD8. Evidence for their extrathymic maturation.

The majority of murine Thy-1+ dendritic epidermal T cells (DETC) express virtually identical TCR encoded by V gamma 5 and V delta 1 genes and are derived from early fetal thymic precursors. However, not consistent with this notion is an early finding that DETC arise continuously from bone marrow (BM) precursors by a thymus-independent mechanism. To address this issue, donor-type DETC were characterized in lethally irradiated mice that were reconstituted by Thy-1-disparate BM cells with or without a thymus. The BM-derived DETC, unlike their normal TCR-gamma delta counterparts, were found to express the TCR-alpha beta/CD3 complex and CD8, and their migration to the epidermis dermis occurred independently of the thymus. The numbers of the BM-derived DETC increased with time and reached a plateau 6 mo after BM transfer, at which time the TCR-alpha beta/CD3 complex was expressed on a small fraction of the DETC in athymic BM chimeras. Although no further increase in the number was observed at later times, at 1 yr after transfer most of the BM-derived DETC came to express the TCR-alpha beta/CD3 complex in the absence of thymic influence. By contrast, most of BM-derived T cells in other lymphoid organs from athymic BM chimeras still failed to express the TCR-alpha beta/CD3 complex even at 1 yr after transfer. These results suggest that extrathymic differentiation of BM-derived DETC could occur with the epidermal microenvironment.

Animals↗

Psychotic symptoms in depression and borderline personality disorder.

The authors investigated the prevalence of psychotic symptoms in depression and borderline personality disorder employing the Diagnostic Interview for Borderlines. Clear-cut delusions and hallucinations were rare among the borderlines. However, derealization and depersonalization symptoms were common and were found to be prevalent as among depressives. The prevalence of these symptoms among patients with both borderline personality disorder and depression was similar to that among patients with only borderline personality disorder or depression. The relationship between depression and borderline personality disorder and the significance of psychotic symptoms in these disorders is discussed.

Adolescent↗

Object images of eating disorder patients.

The authors investigated images held by eating disorder patients toward selected stimulus words using the semantic differential method. The concept "object image" was introduced here to designate the images which any person has about the mother, the father, etc. A comparison was made between 22 eating disorder patients with concurrent borderline personality disorder, 20 patients without borderline pathology, and 48 controls. The eating disorder patients were found to have a "weaker" image of "motherliness" and "womanliness" compared to the control group. Another characteristic of eating disorder patients was their unfavorable image of children. The authors also studied the images held by fathers and mothers. In the families with borderline patients, the discrepancies between what we term "object images" held by fathers, mothers, and daughters were conspicuous. The importance of a tripartite (daughter-mother-father) relationship in the psychopathology of eating disorder is discussed.

Adolescent↗

Relationship between clinical symptoms and EEG findings in borderline personality disorder.

Borderline personality disorder (BPD) was diagnosed in female patients (N = 41) between the ages of 18 and 30 using the Diagnostic Interview for Borderline Patients (DIB) and DSM-III. Comparing the EEG findings of BPD (N = 18) and non-BPD (N = 21) groups, there were no EEG findings characteristic of BPD. We also assessed the relationship between the EEG findings and DIB items. Positive spikes appeared in patients with high scores for Impulse Action Patterns, while wave and spike phantoms were observed in patients with high scores for Interpersonal Relations. Dividing the patients into BPD and non-BPD groups, a similar tendency to that observed from an analysis of all patients was observed in the non-BPD group, but no such tendency was observed in the BPD group. The results suggest that BPD patients include those in whom vulnerability of cerebral function plays an important role in the development of these two clinical symptoms as well as those in whom vulnerability of cerebral function plays almost no pathogenic role.

Adult↗

Isolation and characterization of native activin B.

To examine whether activin binds to follistatin, an activin-binding protein, to form a complex in vivo, we attempted to purify activin-follistatin complex from porcine follicular fluid. Our results thus obtained indicated that almost equimolar amounts of activins A, AB, and B are present as a complex with follistatin in the follicular fluid. Reverse-phase high performance liquid chromatography of the purified complex yielded follistatin and activins A, AB, and B. The activity of the purified activin B was found to be significantly lower than those of other activins in various assay systems such as stimulation of follicle-stimulating hormone secretion, induction of erythrodifferentiation, and potentiation of expression of gonadotropin receptors on ovarian cells. Moreover, binding of 125I-activin A to erythroleukemic cells which are activin-responsive was competed by activin B with approximately 10-fold lower potency compared with other activins. In contrast to these results, activin B was proved to have a potent Xenopus mesoderm-inducing activity, comparable with that of other activins. This indicates that, unlike activins A and AB, activin B can only elicit mesoderm-inducing activity and cannot function in other biological systems, suggesting a specific role of activin B in early development and unknown biological functions.

Activins↗

[Ultrastructural changes of liver, heart, lung and kidney of mice in a large dose of ethanol injection].

Ethanol was injected intraperitoneally to dd-strain mice (20-25 g) with a dose of 5 g/kg body weight. The animals were sacrificed by the cervical dislocation at 4, 8, 12 and 24 hr after the ethanol injection. The changes of the ultrastructure of liver, heart, lung and kidney were examined by a transmission electron microscope. The results; from 4 hr to 24 hr after ethanol injection, deposition of fat droplets, swelling of mitochondria, enlargement of rough endoplasmic reticulum and loss of glycogen granules were observed in hepatocytes. Also, the edema of hepatocytes and intravascular hemostasis were found. These changes were aggravated with time course. In the heart, intravascular hemostasis, edema of myocardium, remarkable decrease of glycogen, swelling of mitochondria and appearance of I bands of myocardial fibers were observed. The damage to the myocardium by ethanol injection was similar to that associated with ischemia and anoxia. In the lung and the kidney, at early time after ethanol injection intravascular hemostasis and cell edema were observed but no other electron microscopical changes were found during the experiment. At 4 hr and 24hr after ethanol injection the edema of sinusoidal endothelial cell of liver and at 24hr that of endothelial cell of capillaries of heart were observed. These histological results suggest that the cell damages and intravascular hemostasis would be caused mainly by a direct action of ethanol. The damages of the liver and the heart, however, on the time blood ethanol was not detected would be caused by the disturbance of metabolism owing to ethanol oxidation.

Animals↗

Evidence for involvement of lymphocyte function-associated antigen 1 in T cell migration to epidermis.

Although it is well known that in various T cell-mediated skin diseases T cells migrate preferentially to epidermis, no direct evidence has been presented in which molecules on T cells are important in directing T cell traffic to epidermis. We have previously established CD4+ autoreactive cloned T cells with a special tropism for epidermis in vitro as well as in vivo. Antibody inhibition studies demonstrated that only anti-lymphocyte function associated Ag 1 (anti-LFA-1) mAb completely inhibited the in vitro migration of the T cells toward the epidermis, whereas mAb against other T cell surface molecules had little or no effect. Monovalent F(ab) fragment of the anti-LFA-1 mAb, although less efficient, also inhibited the T cell migration. The apparent dependency of the inhibition on the anti-alpha-chain mAb suggested a major role for the alpha-chain of LFA-1 in T cell migration to epidermis. The relevance of an LFA-1-dependent mechanism to the epidermotropic migration of T cells was further strengthened by the findings that the T cell migration to epidermis was inhibited by divalent cation depletion, cytochalasin B, and low temperature. These findings indicate that the LFA-1 molecule, which is thought to be primarily involved in cell-to-cell adhesions, also plays an important role in directing T cell migration to epidermis.

Animals↗

Loss of epidermal integrity by T cell-mediated attack induces long term local resistance to subsequent attack. II. Thymus dependency in the induction of the resistance.

Our previous study showed that in cutaneous graft-vs-host disease (GVHD) induced by intradermal injection of autoreactive T cells the epidermal structures spontaneously recovered from the destruction became resistant to the subsequent attempts to induce the cutaneous GVHD and that the resistance correlated well with a 30-fold increase in the number of Thy-1+ epidermal cells (Thy-1+EC). We show that the resistance to the cutaneous GVHD was never induced in athymic nude mice and adult thymectomy lethal radiation and bone marrow reconstitution (ATXBM) mice under the same conditions, indicating that the induction of the resistance is dependent on the presence of thymus. A great increase in the number of Thy-1+EC was similarly observed in the epidermis of the athymic nude and ATXBM mice that spontaneously recovered from the cutaneous GVHD and that remained susceptible to the induction of the cutaneous GVHD. However, the results with B10Thy-1.1----B6 radiation chimeras clearly demonstrate that the vast majority of the increased Thy-1+EC found in the "susceptible" epidermis of the ATXBM mice were of donor bone marrow origin and there was no increase in the number of host-derived Thy-1+EC, whereas in the "resistant" epidermis of the XBM mice both Thy-1+EC populations were equally increased. The overall results indicate that the expansion of Thy-1+EC that mature in the thymus is crucial to the induction of the resistance, although the migration of bone marrow-derived Thy-1+EC precursors to the epidermis occurs quite independently of the presence of thymus.

Animals↗

Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy-1+ epidermal cell numbers.

The cutaneous graft-versus-host disease (GVHD) lesions induced by intradermal injection of cloned autoreactive T cells have been shown to subside rapidly and the epidermis returns to normal 2 wk after injection. Those mice that had spontaneously recovered from the cutaneous GVHD became resistant to subsequent attempts to induce the cutaneous GVHD by the T cells while maintaining their activity to mount delayed-type hypersensitivity (DTH) responses and to induce the enlargement of the popliteal lymph nodes (PLN). The resistance appeared to be restricted to the epidermal structures of the injection sites, suggesting the involvement of locally acting suppression mechanisms. This local resistance was not specific for the clonotype used for the induction of the resistance. A loss of the epidermal integrity by an attack of T cells capable of producing cutaneous GVHD was a prerequisite for the induction of the resistance. By up to at least 8 mo after injection of the T cells, no mice became susceptible to the cutaneous GVHD again, provided that the T cells were injected into the same footpad sites that had initially received the T cells. This resistance correlated well with the great increase (20-30-fold) in Thy-1+ EC number. The great increase in the number of Thy-1+ EC following destruction of epidermal structures may be important in protecting the epidermal integrity from an additional attack by T cells.

Animals↗