Kenji Takagishi

Serum transfer of collagen arthritis to cyclosporin-treated, type II collagen-tolerant rats

Collagen arthritis has been passively transferred with a serum concentrate from immunized donors to immunologically naive recipients as well as cyclosporin-treated, type II collagen-tolerant rats. These findings point to an important role for anticollagen antibody and appear to rule out a role for cellular immunity to type II collagen in the initiation of this disease. The passively transferred arthritis was a transient lesion in the majority of naive recipients and in the cyclosporin-treated, type II collagen-tolerant rats as well when a serum concentrate was transferred after the cessation of cyclosporin treatment. When cyclosporin-treated, type II collagen-tolerant rats received transfer concentrate while cyclosporin was administered continuously, arthritis was significantly enhanced, and lasted as long as cyclosporin was administered and in the majority of rats up to 2 weeks after the cessation of cyclosporin treatment. These results, together with a rapid clearance of anticollagen antibody from the serum, suggest that anticollagen antibody is not the sole regulatory factor and that a cellular suppressor system, sensitive to cyclosporin, might participate in the regulation of this disease process.

Intermediate form of osteopetrosis with recessive inheritance

The clinical and radiographic features of the intermediate form of osteopetrosis in two sibs are presented in which the disorder appears to have been inherited as a recessive trait. Although this form of osteopetrosis has been poorly delineated, its recognition is practically important in order to give an accurate prognosis. This paper also presents an unusual complication of bilateral avascular necrosis of the femoral head in the younger sib. Radiographic changes of the femoral heads suggest those of Legg-Calvé-Perthes disease, though the possibility of avascular necrosis following unrecognized femoral neck fracture is not completely excluded.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy

The clinical and roentgenographic manifestations of six cases suffering from spondyloepiphyscal dysplasia tarda with progressive arthropathy are presented. The roentgenographic features consist of generalized platyspondyly and varying degrees of epiphyseal involvement with conspicuous enlargement of both ends of the short tubular bones of the hands. This disorder appears at an earlier age, and is more crippling than the usual form of spondyloepiphyseal dysplasia tarda. It is suggested that orthopaedic measures are essential for all patients with this disorder, as profound disability may be expected by progressive involvement of the major joints.

Suppression of collagen arthritis in rats by heterologous anti-idiotypic antisera against anticollagen antibodies

Affinity-purified rat anti-type II collagen antibodies were used to prepare anti-idiotypic antibodies in rabbits. It has been demonstrated that such anti-idiotypic antibodies are capable of binding to anti-type II collagen antibodies in vitro. Intravenous administration of heterologous anti-idiotypic antisera at the time of immunization with type II collagen resulted in a significant suppression of anti-type II collagen antibody formation and the development of arthritis, although delayed-type hypersensitivity skin test response to type II collagen was not affected. However, treatment of rats with heterologous anti-idiotypic antisera at Day 7 after immunization was ineffective in altering disease expression. On the other hand, treatment with heterologous anti-idiotypic antisera had no significant suppressive effect on the incidence or severity of adjuvant arthritis. These results indicate that the effect of heterologous anti-idiotypic antisera directed toward anti-type II collagen antibodies is disease specific and is restricted to collagen arthritis.

Generalized enchondromatosis with unusual complications of soft tissue calcifications and hemangiomas

Generalized enchondromatosis is a newly delineated type of enchodromatosis. Radiographically there are multiple enchondromata in almost all metaphyses of the long and short tubular bones and the lesions are in almost the same stage of development with mild platyspondyly and skull deformity. The pelvic changes are characteristic and, together with the metaphyseal changes of the long and short tubular bones, are probably diagnostic of this disorder. The present case demonstrates advanced radiographic features of this disorder associated with unusual soft tissue calcifications and hemangiomas. The presence of hemangiomas in our case as well as three cases in the literature suggests this feature is more than a coincidence.

Hurler-Scheie phenotype: a report of two pairs of inbred sibs.

SummaryFour cases from two families with dermatan sulfate mucopolysacchariduria who lack α-L-iduronidase in peripheral leukocytes are described. The clinical and roentgenographic features of these cases represent an intermediate phenotype between Hurlers syndrome and Scheies syndrome, and both parents in each family are first cousins. In the presence of parental consanguinity, a phenotypic variation or a third mutant allele at the iduronidase locus seems to be a more reasonable explanation for these cases than a genetic compound.

Reversal of antigen-induced resistance to collagen arthritis by cyclophosphamide

Treatment of rats with intravenous injection of 1 mg of soluble native type II collagen induced resistance against the subsequent induction of active arthritis by type II collagen immunization. This resistant state was accompanied by suppressed antibody response and delayed-type hypersensitivity (DTH) skin reaction to type II collagen. However, pretreatment of rats with 20 mg/kg of cyclophosphamide (CY), an agent reputed to damage suppressor T-cell function, 2 days before intravenous injection of soluble type II collagen abrogated the antigen-induced resistance against the subsequent induction of active arthritis. The DTH skin reaction to type II collagen was completely restored and the antibody response to type II collagen was significantly though not completely restored by CY pretreatment. These results provide evidence that antigen-induced resistance to collagen arthritis is mediated, at least in part, under the control of CY-sensitive events.

Effect of cyclophosphamide and its analogs on collagen arthritis in rats

The effects of cyclophosphamide (CY) and its structurally related analogs, ifosfamide (Ifo), sufosfamide (Sufo), and mafosfamide (Mafo), on collagen arthritis in Sprague-Dawley rats were examined. Prophylactic treatment with 7.5-10 mg/kg/day of CY. 15 mg/kg/day of Ifo, and 10-15 mg/kg/day of Sufo for the first 10 days starting on the same day as the type II collagen immunization suppressed arthritis induction as well as humoral immune response to type II collagen. Prophylactic treatment with Mafo at doses ranging from 10 to 40 mg/kg/day for 10 days was ineffective in suppressing the disease development. When drug treatment was started only during the immediate preclinical phase of arthritis, the development of arthritis was suppressed in the animals treated with 10 mg/kg/day of CY and 15 mg/kg/day of Ifo from Day 5 to Day 14. Additional studies demonstrated that treatment with 10 mg/kg/day of CY and 15 mg/kg/day of Ifo started at the time of disease onset significantly suppressed the severity of arthritis compared with the control group. These results show the effectiveness of Ifo and CY on this animal model of polyarthritis and suggest the possibility of clinical use of Ifo for the treatment of human arthritides similar to CY.

Short rib-polydactyly syndrome type I, Saldino-Noonan

A case of the Saldino-Noonan type of short rib-polydactyly syndrome is reported. Although multiple internal malformations have been described in this syndrome, no significant visceral abnormalities were detected in this case except for the hypoplastic lungs. A similar case was reported by Spranger et al. in 1974.

Enhancing effects of tilorone on collagen arthritis and humoral immune response to type II collagen

The effect of tilorone, which is known to suppress adjuvant arthritis, on the induction of collagen arthritis in rats was investigated. Combined data of the present experiments show that all of the tilorone-treated rats except one in the lowest dosage group developed arthritis but that the incidence of arthritis in the tilorone-treated groups was not significantly different from that of the control group. The results also show that the two higher dosages (12.5 and 25 mg/kg/day) of tilorone caused a significant increase in the severity of collagen arthritis. Humoral immune response to type II collagen was significantly augmented in these two higher dosage groups; however, delayed-type hypersensitivity response to type II collagen was suppressed while tilorone was administered continuously. In addition, treatment with tilorone caused a significant increase in the concentration of anticollagen IgG extractable from the joint tissue. Anticollagen IgG subclass analysis revealed that the major subclass was IgG2a in both the serum and paw extract, with minor amounts of IgG2b, IgG2c, and IgG1. The response of all these subclasses was almost equally activated by tilorone treatment.