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Biomedical subjects

T Hotokebuchi

Publications and source records attributed to T Hotokebuchi.

At least 37 records · Page 2Linked to original sources
PubMed1994

Autologous blood transfusion with recombinant erythropoietin treatment. 22 arthroplasties for rheumatoid arthritis.

12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.

Adult↗
PubMed1994

[Recombinant human erythropoietin (KRN5702) therapy for autologous blood transfusion in patients with rheumatoid arthritis undergoing joint replacement surgery--a multicenter phase II clinical trial].

In order to evaluate the effect of recombinant human erythropoietin (rHuEPO) on autologous blood transfusion in patients with rheumatoid arthritis (RA), we performed a phase II clinical trial in 65 RA patients undergoing elective surgery. rHuEPO was administered subcutaneously once a week and after observing erythropoiesis, autologous blood was collected. Fifty-seven of the 58 patients who completed treatment responded to rHuEPO and could donate more than 400 ml of autologous blood. Among them, 23 out of 28 patients undergoing total hip arthroplasty, 27 out of 28 undergoing total knee arthroplasty and 1 out of 1 undergoing spinal surgery did not need homologous blood transfusion perioperatively. During rHuEPO treatment, no significant changes of clinical parameters of RA activity were observed. Two patients discontinued the treatment because of mild and transient side effects. These results indicate that subcutaneous rHuEPO is safe and effective in eliminate the need for homologous blood transfusion, even in anemic RA patients undergoing elective orthopedic surgery.

Adult↗
PubMed1993

The effects of recombinant human granulocyte colony-stimulating factor on passive collagen-induced arthritis transferred with anti-type II collagen antibody.

Type II collagen-induced arthritis (CIA) is a pathologic process mediated, in part, by humoral immune mechanisms. Because many antibody-mediated reactions are neutrophil-dependent, the role of this cell population was examined in passive CIA transferred with anti-type II collagen (CII) antibody. In cyclophosphamide (CY)-induced leukocytopenic rats, swelling and inflammation associated with the arthritic response were significantly reduced. Concomitant administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to leukocytopenic rats for 7 consecutive days from the day of CY injection resulted in the recovery of peripheral blood neutrophils count and the abrogation of the suppression of arthritis with an optimal dose of anti-CII antibody. Further study demonstrated that a prior administration of rhG-CSF to naive rats for five consecutive days resulted in the significant and specific increase of peripheral blood neutrophils count and enhancement of passive arthritis with a suboptimal dose of anti-CII antibody. It was suggested that neutrophils played an important role in the development of passive CIA.

Animals↗
PubMed1993

Successful long-term storage of rat limbs. The use of simple immersion in Euro-Collins solution.

The effect of simple cold storage in Euro-Collins solution on prolonging successful preservation time was examined on an established rat limb transplant model. Limbs amputated at mid-thigh level were simply immersed in the solution and stored in a refrigerator at 4 degrees C. After varying periods of cold storage, the limb was orthotopically grafted to another isogeneic rat using microsurgical techniques. The survival rates for 12, 24, 48 and 72 hours' storage were 100%, 90%, 67% and 50% respectively, and the longest time of successful preservation achieved was 78 hours. Survival rates were greatly decreased when amputated limbs were initially perfused with Euro-Collins solution and immersed in the same solution. In a third set of experiments, the limbs were preserved by a conventional method of cold storage in air, and the survival rates were decreased even further. Evaluation by measuring postoperative paw swelling and microscopic examination of the grafts further confirmed the effectiveness of the simple immersion method without perfusion.

Amputation, Surgical↗
PubMed1992

Comparative study of effects of cyclosporins A and G on collagen arthritis in mice.

The effects of the immunosuppressive agents cyclosporin G (CsG) and cyclosporin A (CsA) on collagen arthritis were compared in mice. When administered subcutaneously daily on days 0-13 after immunization with type II collagen, CsG and CsA were both capable of suppressing the development of collagen arthritis in mice as well as the immunological response to native type II collagen in a dose-dependent manner. Histopathologically, no marked inflammatory lesions were observed in diarthroidal joints from mice treated with 100 mg/kg per day of CsA or 800 mg/kg per day of CsG. However, an analysis of dose response showed CsG to be 8 times less potent than CsA in inhibiting the development of arthritis.

Animals↗
PubMed1992

Changes in growth-plate morphology associated with rejection of rat-limb allografts.

Histological and electron microscopic studies were performed to demonstrate the changes in the morphology of the growth plate that occur in allografts obtained from the limbs of growing rats. A genetically defined model was used in which the right hindlimbs of Lewis rats were orthotopically transplanted into Fischer-344 recipient rats. These strains are matched for major histocompatibility antigens but mismatched for minor histocompatibility antigens. The disparity at the minor histocompatibility complex between the Lewis donors and the Fischer recipients creates a weak histocompatibility barrier to transplantation. Lewis-to-Lewis syngeneic limb grafts were used as controls. The proximal parts of the transplanted tibiae were excised during acute rejection of the allograft on days 1, 5, 8, 11, 14, and 28 postoperatively. During rejection, a widened zone of calcified cartilage in the growth plate was observed at eleven days; this zone increased progressively thereafter. The number of chondroclasts in the primary spongiosa of the metaphysis had decreased significantly at eleven days, and chondroclasts had disappeared completely at fourteen days, in association with mononuclear cell infiltration. Electron microscopic examination revealed inactive morphology in some chondroclasts at eight days, and the number of inactive chondroclasts had increased significantly on day 11. At fourteen days, there were no viable chondroclasts in the primary spongiosa, and only remnants of degenerated chondroclasts were present. These findings suggest that the chondroclasts were early targets of rejection and their loss resulted in the cessation of resorption of the calcified cartilage. However, the proliferation and maturation of chondrocytes in the growth plate and the calcification of the matrix continued, despite progression of rejection in the metaphysis. Thus, survival of the chondrocytes and rejection of the chondroclasts apparently led to the formation of a widened calcifying zone in the growth plate.

Animals↗
PubMed1992

Transtrochanteric anterior rotational osteotomy for idiopathic and steroid-induced necrosis of the femoral head. Indications and long-term results.

From 1972 until 1988, transtrochanteric rotational osteotomy was used to treat 474 hips in 378 patients with idiopathic and steroid-induced osteonecrosis of the femoral head. Two hundred twenty-nine of 295 hips with anterior rotation and follow-up periods ranging from three to 16 years had excellent surgical results (success rate, 78%). Outcome was chiefly dependent on the ratio of transposed intact posterior articular surface to the acetabular weight-bearing area after osteotomy. This relationship suggested that the transposed intact area should occupy more than 36% of the acetabular weight-bearing area by adequate rotation and intentional varus position in addition to rotation, especially for extensive lesions. Salvage operations, such as total hip arthroplasty, were performed on 18 hips, of which ten hips were cases of either relative indication for extensive lesions in young patients or other misindications for rotational osteotomy. Four hips sustained neck fracture, including three hips after 180 degrees of posterior rotation; two hips were complicated with avascular necrosis, and another two hips developed osteoarthrosis. Histologically, femoral heads with osteoarthrosis removed at the time of salvage operation showed complete healing of the necrotic lesion. The overall findings indicate that healing of the necrotic lesion of the femoral head may be brought about by rotational osteotomy if it spares the vulnerable site from the brunt of mechanical stress.

Acetabulum↗
PubMed1991

Comparative studies of the effects of FK506 and cyclosporin A on passively transferred collagen-induced arthritis in rats.

We investigated the effect of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA) on the development of passive arthritis induced by anti-type II collagen (CII) antisera in rats. FK506 pretreatment shortly before serum transfer markedly suppressed the incidence and the severity of passive arthritis, while CsA pretreatment had no observable effects on this disease when used in doses sufficient to suppress the development of active arthritis induced by CII immunization. In an additional study, we examined whether these agents affect antibody-mediated tolerance induction. CII-specific immunological tolerance was induced by serum transfer, but was unaffected by either FK506 or CsA pretreatment in our regimen. While its precise mechanism of the immunosuppressive activity remains to be elucidated, FK506 can act on the antibody-mediated effector phase of arthritis and may offer new insights into the possible role of potential therapeutic utility in human autoimmune diseases.

Animals↗
PubMed1990

Effects of deoxyspergualin on collagen arthritis in mice.

We have studied the effect of the immunosuppressive agent deoxyspergualin (DSG) on collagen arthritis in mice. DSG, when given prophylactically, was capable of suppressing the development of collagen arthritis in mice as well as the immunological response to native type II collagen in a dose-dependent manner. Further, treatment of DSG, started 7 days after the primary immunization, also resulted in the inhibition of development of arthritis and immunity to collagen. The treatment of DSG, started after a booster injection, did not suppress the development of arthritis, despite suppression of antibody production in collagen. These findings suggest the possibility that a threshold level of anti-type II collagen antibodies may exist which must be exceeded before arthritis develops. Its therapeutic use in mice did not affect the clinical course of arthritis or the immune response to collagen, which is similar to the results obtained with cyclosporin.

Animals↗
PubMed1990

Inhibition by FK506 of established lesions of collagen-induced arthritis in rats.

We investigated the superior potency of the immunosuppressive agent FK506 on collagen-induced arthritis in rats. In our initial studies, we demonstrated that only one shot administration of FK506 at a dose of 10 mg/kg on the same day as type II collagen immunization suppressed the incidence of arthritis completely as well as humoral and delayed-type hypersensitivity (DTH) skin test responses to type II collagen. Yet no major side effects were observed in the rats treated with such a high dose of FK506. Additional studies demonstrated that pretreatment with FK506 on day -7 or day -3 was effective in suppressing the severity of arthritis and immune responses to type II collagen. The immunosuppressive effect of a single high-dose administration of FK506 continued for at least 1 week in this animal model of arthritis. A single administration of FK506 at a dose of 10 mg/kg on day 12 or 15, after the clinical onset of arthritis, was also effective in suppressing the severity of arthritis and immune response to type II collagen. We conclude that FK506, in this model, possesses an important, curative action when applied therapeutically. The outlook of FK506 treatment in clinical autoimmunity is promising at present.

Animals↗
PubMed1990

Immunoelectron microscopic analysis of Ia antigen expression in rat skin during limb allograft rejection.

Using a whole-limb graft model in rats, morphologic changes and variations in the expression of Ia antigen on epidermal cells were investigated in the allografted skin during acute rejection. BN right limbs were transplanted to F344 recipients. Skin tissues were excised during acute rejection on days 1, 3, 5, 7, and 9 after the transplantation. Sections were examined for Ia antigen expression using immunohistologic techniques, and in situ quantification of Ia antigen was made using an immunogold method. Epidermal keratinocytes expressed Ia antigen before the grafts were rejected and the amount of Ia antigen expression increased and exceeded the amount of Ia antigen of Langerhans cells during the course of rejection. The progressive increase in class II antigen expression on EKs correlated with the appearance and relative accumulation of dermal lymphocytic cells. On the other hand, Ia antigen was not expressed on vascular endothelial cells during rejection. Our results suggest that the Ia-positive keratinocytes can serve as target cells in skin rejection of limb allografts. The immunogold technique we used seems most pertinent for a quantitative examination of cell-surface antigens in situ.

Animals↗
PubMed1990

[Two cases of Turner's syndrome with spondyloepiphyseal dysplasia like bone appearance].

We report two cases of mosaic karyotype (45XO/46XiXq) Turner's syndrome with unique bone appearance. The cases were 44 and 34 year-old women and latter was complicated by Hashimoto's thyroiditis (hypothyroidism). Following the systemic bone surveys, we found the patients showed not only osteoporotic bone change and short stature, but also spondyloepiphyseal dysplasia (SED) like bone appearance (thinness of vertebral bodies, irregularity of vertebral end-plates, shortness of femoral necks, Coxa valga, Coxa magna and hypoplasia of acetabula). Those findings can not be explained by degenerative bone changes like osteoporosis, rather are suggestive the sequelae of malgrowth of the bone system in Turner's syndrome.

Adult↗
PubMed1989

Limb allografts in rats immunosuppressed with FK506. I. Reversal of rejection and indefinite survival.

We have tested the effects of FK506 (FK), a new immunosuppressive agent, on a rat limb allograft model. Histoincompatible BN limb allografts were rejected in untreated F344 hosts within 11 +/- 1 days (mean +/- SD) after operation. A single injection of 2 mg/kg, 10 mg/kg, or 50 mg/kg of FK on the day of limb transplantation (day 0) significantly prolonged graft survival in a dose-dependent manner--i.e., mean limb survival times (MST) based on gross signs of skin rejection were 16 +/- 3 days, 51 +/- 6 days, or 104 +/- 17 days, respectively (P less than 0.01). Delayed treatment with a single injection of 10 mg/kg of FK at when early signs of rejection were visible (day 7 or day 10) reversed the ongoing rejection. The MSTs in these groups were comparable to that of those treated with the same dosage of FK on day 0. The FK-induced unresponsiveness toward limb allografts was donor-specific because limb-allografted. FK-protected rats could not accept the skin grafts from a third-party donor. In the next set of experiments, rats were given a single administration of 10 mg/kg of FK on the day of limb allograft, followed by intermittent injections of 3 mg/kg of FK once a week. This regimen produced complete graft survival for more than 200 days, though Pneumocystis carinii pneumonia occurred in most of the recipients. These results represent the unique effects of FK in preventing or reversing the graft rejection and in inducing indefinite survival in this animal model of composite tissue allografts.

Animals↗
PubMed1989

Prolonged limb allograft survival with short-term treatment with FK-506 in rats.

The effect of the new immunosuppressive agent FK-506 on rat limb allograft was investigated across the BN-to-F344 histocompatibility barrier. A 14-day course of FK-treatment at doses of 1 mg/kg per day or more, begun on the day of operation, significantly increased the period of graft survival. Additional studies demonstrated that single treatment with FK only on the day of operation prolonged the graft survival in a dose-dependent manner. These results stress the profound immunosuppressive effect of FK and suggest the possible future application of composite tissue allograft in humans.

Animals↗