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Biomedical subjects

H Senoh

Publications and source records attributed to H Senoh.

35 records · Page 2Linked to original sources

Enhanced production of interleukin-6 in mice with type II collagen-induced arthritis.

We established an interleukin-6 (IL-6)-dependent cell line from murine plasmacytoma MOPC-104E cells. This cell line (designated PIL-6) was found to respond to murine and to human IL-6, but not to any other cytokines. We used this cell line to investigate the involvement of IL-6 production in type II collagen-induced arthritis in DBA/1 mice. Only marginal IL-6 activity was detected in sera from DBA/1 mice inoculated with Freund's complete adjuvant (FCA) alone, with an unrelated protein (bovine serum albumin) plus FCA, or with type II collagen plus Freund's incomplete adjuvant. However, enhanced IL-6 activity was observed in DBA/1 mice that had been injected with type II collagen plus FCA to induce arthritis. The elevated level of serum IL-6 activity was associated with high levels of IL-6 produced when lymph node cells from arthritic mice were stimulated in vitro with type II collagen. We also found that the L3T4+ T cell subset is responsible for the enhanced production of IL-6 in arthritic mice. The results are discussed in the context of potential roles of IL-6 in the induction and/or expression of chronic, progressive arthritis.

Animals↗

Remarkable effect of endocrine therapy on brain metastasis from prostatic carcinoma.

The brain metastasis of prostatic carcinoma is rare and is distinguished by its poor prognosis in cases which are not surgically resectable. Herein we report on a case of brain metastasis of prostatic carcinoma which showed a dramatic regression through bilateral orchiectomy and doses of diethylstilbestrol diphosphate and estramustine phosphate. Neurologic and psychiatric symptoms diminished within three months, and the patient is alive and well without any subjective symptoms after twelve months.

Adenocarcinoma↗

Plasma extravasation by chemical mediators in rat skin and trachea: a role of neurogenic agents on tracheal edema formation.

The plasma extravasation inducing activities of several chemical mediators (allergic agents: histamine, leukotriene C4 (LTC4) and platelet activating factor (PAF); neurogenic agents: substance P, capsaicin and carbachol) have been investigated and characterized in rat skin and trachea. Substance P, histamine, LTC4 and PAF induced dose-dependent plasma extravasation in rat skin. The activities of these mediators in inducing tracheal plasma extravasation were very different from those in the skin reactions. When these mediators were injected intravenously, substance P induced severe plasma extravasation, and the activities of histamine and PAF were weaker than that of substance P. When injected intratracheally, only substance P and capsaicin induced tracheal plasma extravasation, while none of the allergic mediators tested caused any plasma extravasation in the trachea. Carbachol did not induce any plasma extravasation in either skin or trachea. These results indicate that the stimulation of afferent substance P-containing nerve fibers has a more important role in the induction of tracheal plasma extravasation than that of allergic chemical mediators.

Animals↗

[A case of bilateral necrosis of the basal ganglia after hypotensive shocks].

We reported a case with bilateral necrosis of the basal ganglia after hypotensive shocks. The patient was a 69-year-old woman, who fell into a hypotensive shock (B.P. below 40 mmHg) of unknown origin during examination of her bladder cancer and was admitted into CCU. After admission, hypotensive shocks were repeated four times (B.P. below 50 mmHg each time). Neurological examination revealed a left spastic hemiplegia. Brain CT on 10th day showed bilaterally low density areas around the basal ganglia and a diagnosis of brain infarction was made. She gradually presented quadriplegia and symptomatic changes from pyramidal to extrapyramidal signs. Brain CT on 24th day showed bilateral hemorrhagic infarction of the basal ganglia with enhanced effect. On 79th day, she again fell into shock and died. Neuropathological examination of the brain was as follows. 1) laminar necrosis of the deep layers of the cerebral cortex, 2) bilateral necrosis of the hippocampal Sommer sector, 3) bilateral necrosis of the caudate nucleus, putamen and pallidum with neuronal loss and infiltration of fat granule cells, 4) sparing of the internal capsules, 5) bilateral necrosis of the reticular zone of the substantia nigra, 6) foci of fresh necrosis and loss of Purkinje cells in the cerebellum. These lesions are consistent with those of selective vulnerability in hypoxia as described by Scholz et al. An extensive distribution of cerebral as well as basal ganglia necrosis in this case was caused by repeated shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity.

Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.

Animals↗

[Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice].

Effects of Y-8894 on learning and memory were studied using a radial maze task in intact and scopolamine-induced amnesic mice. The following results were obtained: 1) Repeated administration of Y-8894 (1, 2.5 and 5 mg/kg, i.p.) significantly increased the number of initial correct responses (ICR) in the training session in intact mice, facilitating the learning of the maze task. Dihydroergotoxine (5 mg/kg, i.p.) significantly facilitated the learning of this task in the initial stage of the training session, but non-specifically inhibited the performance in the late stage of training. Ca-hopantenate did not modify the learning of this task. 2) A single administration of Y-8894 (2.5 or 5 mg/kg, i.p.) showed an antagonistic effect on scopolamine (1 mg/kg, s.c.)-induced amnesic mice. Dihydroergotoxine (5 mg/kg, i.p.) and Ca-hopantenate (500 mg/kg, i.p.) also significantly antagonized the ICR-decreasing effect of scopolamine. These results suggest that Y-8894 has an ameliorative and/or facilitative effect on learning and memory in the radial maze task, and Y-8894 is more potent than dihydroergotoxine and Ca-hopantenate.

Amnesia↗

[Host mediated anti-tumor effect of Nocardia rubra cell wall skeleton on syngeneic tumor in mice].

The mode of action of Nocardia rubra cell wall skeleton (N-CWS) on Meth A fibrosarcoma (Meth A) was studied in BALB/c mice. N-CWS suppressed or regressed the intradermal growth of syngeneic Meth A cells in normal BALB/c and athymic BALB/c mice. The intradermally and subcutaneously infiltrated cells harvested from injection sites of N-CWS in normal mice showed in vitro cytotoxic activity against Meth A cells. Pretreatment of normal BALB/c mice with immunosuppressing agents such as hydrocortisone, carrageenan, or silica particles significantly reduced the anti-tumor effect of N-CWS. The growth of Meth A cells, rechallenged into BALB/c mice in which Meth A cells had once been suppressed or regressed by N-CWS treatment, was also inhibited, but not in similarly treated athymic nude mice. This resistant mechanism was shown to be dependent out cellular components but not on humoral components by the Winn Assay. The present results suggest that N-CWS exerts its anti-tumor activity by mediation of the immune system of the host and that the main effector cells in the early stage of tumor rejection are macrophages; T cells may also be involved in the later stage.

Animals↗

Effect of auranofin on autoimmune disease in a mouse model.

The effect of an oral gold preparation, auranofin, on the autoimmune disease mouse MRL/l was examined. Oral administration of auranofin on consecutive days from 6 weeks of age reduced anti-DNA antibody production, IgM rheumatoid factor production, hypergammaglobulinemia, polyclonal B cell activation and renal disease, but did not prevent massive lymphadenopathy or restore the low level of either IL-2 production or mitogen response associated with 1pr gene. In contrast to the effect on autoantibody production, little suppressive activity on the immune response to exogenous antigen SRBC was observed. These results indicate that autoimmune disease in MRL/l mice can be prevented without abrogation of T cell abnormalities and that autoimmune-selective suppression can be induced by chemical compound(s) like auranofin.

Animals↗

Cavernous hemangioma of scrotum and penile shaft.

We report a 13-year-old boy with two independently detected cavernous hemangiomas of the scrotum and the penile shaft. A right scrotal cavernous hemangioma was incidentally found at the age of 6 years by a histological examination of a right scrotal hematoma attributed to contusion. The patient noticed a soft tumor of the penile shaft at the age of 10 and gradual enlargement of the tumor during the next 3 years. He consulted our department at the age of 13. An ultrasonic echogram revealed a heterogeneous tumor, a hemangioma, having dimensions of 3.5 X 2.5 X 1.5 cm and no connection of the corpus cavernosum penis. The tumor was completely removed surgically by means of circumcision on March 30, 1984, and histological examination demonstrated a cavernous hemangioma.

Adolescent↗

[The antiinflammatory effect of budesonide].

The systemic and topical antiinflammatory activities of budesonide (B) were studied in rats and mice and compared with those of commercially available steroids. Betamethasone 17-valerate (BV) was used as the main reference compound, and fluosinolone acetonide (FA), hydrocortisone 17-butyrate (HB) and hydrocortisone 21-acetate (HA) were also used. B given systemically had stronger antiinflammatory effect than BV on carrageenin edema, cotton pellet granuloma, adjuvant arthritis, croton oil edema, PCA reaction, Arthus reaction, contact hypersensitivity and histamine or serotonin skin reaction. The potency of antiinflammatory activity of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was in the order of FA, B, BV, HB and HA. B given locally also produced stronger antiinflammatory effects than BV on carrageenin edema, cotton pellet granuloma, croton oil edema and contact hypersensitivity. The order of potency of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was the same as by systemic application. In general, the ratio of the dose required to cause atrophy of the thymus and adrenals to the dose required to produce the antiinflammatory effect was the greatest with B by both systemic and local application. The results suggest that B has a stronger antiinflammatory activity with fewer systemic side effects than conventional steroid compounds.

Adrenal Gland Diseases↗

[The antiinflammatory effect of budesonide ointment and cream].

The antiinflammatory effect of topically applied budesonide ointment on carrageenin induced paw edema in rats, croton oil induced ear edema in rats, passive cutaneous anaphylaxis (PCA) in rats and picrylchloride induced contact hypersensitivity in mice was studied and compared with those of commercially available ointments containing betamethasone 17-valerate, hydrocortisone 21-acetate, hydrocortisone 17-butyrate or fluocinonide. The five ointments had almost the same degree of activity against the carrageenin induced paw edema. Budesonide ointment was strongest in inhibiting the croton oil induced ear edema. Budesonide and fluocinonide ointments were stronger than the other 3 ointments in inhibiting PCA and picrylchloride induced hypersensitivity. No clear atrophic effect on the thymus or adrenal was observed with any of the ointments at the doses tested. When the effect of budesonide ointment was compared with that of budesonide cream, there were no differences in activity between the two formulations. The results suggest that budesonide is a useful drug with a superior topical antiinflammatory activity.

Administration, Topical↗

[The anti-inflammatory effect of auranofin].

The anti-inflammatory effects of auranofin were studied and compared with those of indomethacin, gold sodium thiomalate (GST) and D-penicillamine. Auranofin was active as indomethacin in inhibiting carrageenan induced paw edema in rats, but was less potent than indomethacin in inhibiting UV-induced erythema in guinea pigs. Auranofin inhibited Arthus type paw edema and reverse PCA reaction in rats, on which indomethacin was ineffective. The inhibitory activity of auranofin on adjuvant arthritis was weaker than that of indomethacin. In in vitro experiments, auranofin did not show any suppression of cyclooxygenase activity, but was capable of suppression of lysosomal enzyme release and chemotaxis of neutrophils and macrophages. In addition to these anti-inflammatory activities, auranofin had almost equal anti-analgesic and anti-pyretic activity to that of indomethacin. The above results indicated that the anti-inflammatory profiles of auranofin and indomethacin differ, so we can expect new therapeutic activities of auranofin. GST had similar anti-inflammatory and anti-analgesic profiles to those of auranofin; however, the activities were less potent than auranofin and devoid of anti-pyretic activity. D-penicillamine did not show any anti-inflammatory, anti-analgesic or anti-pyretic activity.

Animals↗

An abnormal ratio of cytochromes in the respiratory chain of mouse and human myelomas.

Mouse myeloma cells and mitochondria had the same kinds of cytochrome components in the respiratory chain as the normal ones. Their constitution, however, was abnormally different from that found in normal cells and mitochondria. The cytochrome aa3 concentration was especially low in the myeloma as compared with cytochrome c concentration, and the resulting cytochrome aa3/c ratio was 0.25, which was the lowest ever reported in animal mitochondria. Normal lymph node cells, producing the immunoglobulin similar to the myeloma cells, had a ratio of 1.1. Human myeloma mitochondria had the same characteristics as the mouse myeloma. Ascite form myeloma originated from mouse solid from myeloma grew faster, and yet aa3/c of 0.5 in the ascites myeloma was found to be quite similar to that observed in various ascites tumor cells such as hepatomas, Ehrlich and sarcoma 180. A significant part of the cytochromes in the respiratory chain of the mouse myeloma remained in the oxidized form in the cyanide-inhibited or anaerobic states, and was reduced only by the addition of dithionite. The properties of the b cytochromes in mouse myeloma mitochondria are also described and discussed in the context of multiple forms of the b cytochromes in the respiratory chain.

Anaerobiosis↗

Clinical benefits and tolerability of increased fill volumes in Japanese peritoneal dialysis patients.

BACKGROUND: Increasing fill volume is an effective means of improving clearances in patients on peritoneal dialysis (PD). Since Japanese PD patients are physically smaller than their Western counterparts, there is some concern that PD patients in Japan may be unable to tolerate larger fill volumes. OBJECTIVE: To determine patient tolerance and changes in solute clearance and net ultrafiltration resulting from increased fill volumes in Japanese patients on PD. DESIGN: Prospective double-blind study, randomizing patients to three different fill volumes (2.5% dextrose solution: 1.5 L, 2.0 L, or 2.5 L) administered in random order on three different occasions separated by 1 week. RESULTS: Twenty-one patients with a mean age of 55.4 +/- 2.1 years and a mean body surface area of 1.66 +/- 0.03 m2 were studied. On a scale of 0 to 10, patients' mean discomfort scores were 2.14 +/- 0.59, 3.48 +/- 0.54, and 3.81 +/- 0.63 (p = 0.047) at the end of the 1.5-L, 2.0-L, and 2.5-L dwells, respectively. There were no reports of cramps or shortness of breath with any fill volume. Patients were able to correctly guess the actual fill volume for only 34 of the 63 total exchanges (54.0%). Increasing fill volume resulted in an incremental improvement in peritoneal creatinine clearance, from 3.74 +/- 0.16 to 4.49 +/- 0.21 (p < 0.001, 2.0 L vs 1.5 L) to 5.12 +/- 0.20 mL/minute (p< 0.001, 2.5 L vs 2.0 L) for 1.5-L, 2.0-L, and 2.5-L dwells, respectively. Peritoneal urea clearance also increased significantly, from 5.65 +/- 0.13 to 7.04 +/- 0.17 (p < 0.001, 2.0 L vs 1.5 L) and 8.16 +/- 0.29 mL/minute (p < 0.001, 2.5 L vs 2.0 L), with incremental increases in fill volume. Similarly, net ultrafiltration in a 4-hour dwell increased significantly with fill volume, from 255.24 +/- 24 mL with 1.5 L, to 356 +/- 24 (p < 0.004, 2.0 L vs 1.5 L) and 392 +/- 29 mL (p < 0.086, 2.5 L vs 2.0 L) in patients receiving 2.0 L and 2.5 L, respectively. CONCLUSION: Increasing the fill volume results in improvement in solute clearance and net ultrafiltration in Japanese PD patients, with minimal increase in patient discomfort. A large percentage of patients were unable to identify the actual fill volume.

Body Surface Area↗

Type II collagen-induced murine arthritis. II. Genetic control of arthritis induction is expressed on L3T4+ T cells required for humoral as well as cell-mediated immune responses to type II collagen.

The present study investigates the cellular and molecular mechanisms responsible for expressing genetic control of type II collagen-induced murine chronic arthritis. Analyses were made for both humoral and cellular immune responses, since the induction of arthritis required synergy between both types of immunities. Immunization of high (DBA/1) and low (C57BL/6, C3H/He, BALB/c) responder mice with native bovine type II collagen resulted in the production of the respective high and low levels of anti-collagen antibody. However, polyclonal in vitro stimulation of normal spleen cells from high or low responder mice with lipopolysaccharide (LPS) induced a comparable magnitude of anti-collagen antibody responses, indicating the localization of the genetic defect at cellular levels other than B cells themselves. In contrast to immunization with native collagen, sensitization of DBA/1 mice with heat-denatured collagen failed to stimulate B cells, but resulted in selective generation of L3T4+ T cell-mediated immunity. These included anti-collagen delayed-type-hypersensitivity (DTH) responses and the generation of various interleukins (IL) responsible for antibody production as well as DTH responses. It was demonstrated that there was appreciable difference in the magnitudes of these responses between lymphoid cells from high and low responder mice. Differential effects of sensitization with heat-denatured collagen in high versus low responders were reflected on the genetic difference in the development of chronic arthritis. A typical arthritis was induced neither in denatured collagen-sensitized DBA/1 mice nor in unsensitized mice transferred with anti-collagen antiserum. However, the antiserum transfer into denatured collagen-sensitized DBA/1 mice induced chronic perpetuating arthritis. This sharply contrasted with the failure of the same aliquot of the antiserum to induce a chronic arthritis when inoculated into denatured collagen-sensitized low responder mice. These results indicate that the genetic control of the induction of arthritis is expressed on L3T4+ T cells which are required for generating anti-collagen humoral as well as cell-mediated immunities as assessed by DTH responses in vivo or lymphokine productions in vitro.

Animals↗