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F Langer

Publications and source records attributed to F Langer.

At least 91 records · Page 5Linked to original sources

Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing.

Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.

Animals↗

The biology, pathology and immunology of a virus induced rat osteosarcoma. I. Biological behaviour and histopathology.

The biological behaviour and histopathology of an experimental osteosarcoma in rats are described as a model to study the human disease. The tumour was developed by injection of Moloney murine sarcoma virus into the tibial marrow space of three strains of inbred new-born rats. The resulting neoplasm was highly malignant and arose after a short latent period of only 10 days. It was readily maintained in tissue culture and was transplantable to adult rats. The virus induced tumour resembled human osteosarcoma in pattern of growth, tumour osteoid production, reaction of adjacent bony tissues and distribution of metastases, being an excellent model for the study of the interaction between oncogenic viruses and skeletal tissues. The analogies and differences between this and other virus-induced murine tumours and human osteosarcoma are discussed.

Animals↗

The biology, pathology and immunology of a virus induced rat osteosarcoma. II. Immunological studies.

The immunogenicity of a virus-induced rat osteosarcoma was studied utilizing the lymphocyte microcytoxicity test. Lymphocytes from "progressor" animals (in which the tumour progressed and metastasized) demonstrated an ability to kill osteosarcoma cells in vitro, while serum from these animals abrogated or blocked the cell-mediated cytotoxicity. Lymphocytes from "regressor" animals (in which tumours failed to develop or regressed spontaneously) also showed cytolytic activity against osteosarcoma cells in vitro, but their serum failed to block the lymphocyte-mediated cytolysis. Both progressor and regressor animals demonstrated the presence of humoral cytotoxic antibodies to tumour antigens on the basis of the ability of their serum to kill tumour cells in vitro. In an attempt to alter the fatal course of the disease in progressor animals, immunoprophylaxis and immunotherapy of the osteosarcoma in F1 hybrid rats war carried out by injecting them with parentalor, third party, allogeneic lymphoid cells. Injection of parental spleen lymphocytes into F1 hybrids produced a transient graft versus host reaction (GVHR), and prolonged the survival of the animals when lymphocytes were injected three days before, seven days after and on the day of tumour induction. Injection of allogeneic, third party lymphoid cells produced no detectable GVHR and prolonged the survival of F1 hybrids with osteosarcoma only when injected on the day of tumour induction. The prolonged survival of the groups treated with parental lymphoid cells was a result of stimulation of the host's immunological mechanisms during a transient GVHR, whereas the prolongation of survival in the group given allogeneic cells was most likely the result of a direct action of the donor lymphocytes on tumour cells, and not connected to a GVHR.

Animals↗

Orthotopic bone transplantation in mice. I. Technique and assessment of healing.

A technique for orthotopic bone transplantation in mice has been developed. A section of recipient tibia was removed and replaced by a similar section from the donor animal. The graft was held in place by internal fixation. Bone healing was assessed clinically, histologically, radiologically, and by torsion testing. The most objective measurements of bone healing were the maximum torque and the energy absorbed by the bone to failure, which were derived from torsion testing. The degree of bone healing in donor-recipient combinations differing at H-2, non-H-2, or H-Y antigens was compared to the degree of healing in syngeneic controls. The incidence of nonunion was significantly increased in the H-2-disparate group. Furthermore, the extent of bone healing as measured by torsion testing was significantly reduced in both the H-2-and the H-Y-disparate groups. Thus, in the strain combinations tested, the order of importance of the genetic disparities influencing allogeneic bone grafts was H-2 greater than H-Y greater than non-H-2. The impaired healing of allogeneic bone grafts was probably immunologically mediated, as suggested by the observation that recipients of bone allografts rejected subsequent skin allografts in an accelerated manner.

Animals↗

Orthotopic bone transplantation in mice. II. Studies of the alloantibody response.

The alloantibody response of mice receiving cortical bone allografts was investigated. Such grafts were highly immunogenic, resulting in antibody responses at least as strong as those to skin allografts in the same combinations. The duration of the response to a single bone allograft was very prolonged (greater than 10 months). The antibody response was shown to be directed against H-2K, H-2D, Ia, and at least two non-H-2 antigens. Although the great majority of the parenchymal cells of the graft were dead, the immunogenicity of the graft required living cells, since bone that had previously been frozen and thawed was nonimmunogenic. By retransplanting bone allografts to a second recipient it was possible to demonstrate that the grafts remained immunogenic for at least 4 weeks after transplantation, indicating that the living immunogenic cells survived in the recipient for at least 4 weeks. Such cells may be certain cells of the cortical bone itself, or else residual bone marrow elements which adhere to the endosteal surface of the bone. The observation that a small subpopulation of living cells can provoke strong immune responses against a wide variety of antigens may have implications for understanding the immunogenicity of other types of allografts.

Animals↗

The immunogenicity of allograft knee joint transplants.

Joint allotransplantation has been employed in the management of osteoarthritis affecting primarily one compartment of the knee. Biological resurfacing and realignment of the knee has been the goal. The immunological results of six patients posttransplant were studied with the lymphocyte microcytotoxicity test. Definite immunogenicity was demonstrated at an early stage. The sera from the recipients posttransplant was noted to abrogate the in vitro cytotoxicity suggesting the presence of blocking factors. The actual clinical significance of this phenomenon was difficult to judge insofar as no evidence of allograft joint rejection was seen.

Female↗

[Scintigraphy of the myocardium. Comparative study between thallium and perfusion scintigrams (author's transl)].

In a total of 51 patients (26 with coronary heart diseases, 25 with primary myocardial diseases), the myocardial scintigrams after intracoronary particle injection (perfusion scintigraphy) and after intravenous nuclide injection with accumulation in the myocardium (thallium scintigraphy) were compared with each other and set against the coronary angiographic and levocardiographic findings. It was shown that extensive myocardial failures (aneurysms) can be represented by both nuclear medical procedures, but that perfusion scintigraphy is more sensitive and correlates more closely to the levocardiogram findings. Smaller abnormalities of contraction of the left ventricle (hypokinetic and akinetic areas) were always shown in the perfusion scintigram, more seldom in the thallium scintigram. The outstanding advantage of thallium scintigraphy is that it is non-invasive, it can be repeated as often as desired and is easily performed during ergometric stress.

Adult↗

Articular cartilage transplantation.

This report describes the biopsy findings in four of 30 patients treated with cadaver osteochondral shell allografts for osteoarthritis in the knee. This study demonstrates that graft cartilage cells can survive in excess of 25 months, and that host bone can completely replace graft bone by creeping substitution. An inflammatory reaction in synovium and bone marrow was found in only one of four cases. Graft failure was related to prolonged down time of donor cartilage in one case and mechanical factors related to osteoarthritis in the apposing femoral surface in other cases. The clinical success of these grafts is attributed to the prolonged viability of cartilage cells, the capacity of host bone to join graft cartilage without histologic reaction, and the host's immunologic tolerance, which obviates the need for immunosuppressive therapy.

Aged↗

The significance of low back pain in older adults.

A retrospective study of the practice of an orthopedic surgeon at a university teaching hospital was done to evaluate the significance of low back pain in older adults. All 259 patients in a 3-year period 50 years of age and over whose presenting complaint was low back pain or sciatica or both were identified and classified by final diagnosis. A comparison was similarly identified and classified. Systemic disease, particularly cancer, was much more prevalent in the older group. It was demonstrated that a simple screening routine consisting of measuring the erythrocyte sedimentation rate and serum concentrations of alkaline phosphatase and calcium would identify all cases of unsuspected malignant disease--that is, at least one of the values would be abnormal in every case.

Alkaline Phosphatase↗

Virus-induced osteosarcoma in rats.

An experimental model for osteosarcoma was developed in which, after Moloney murine sarcoma virus was injected into the tibial marrow space of three strains of inbred neonatal rats, a highly malignant neoplasm arose within ten days. This tumor was readily maintained in tissue culture and was transplantable to adult rats. It arose in the metaphyseal marrow of several bones, was locally invasive, metastasized to the lungs, and histologically resembled osteosarcoma.

Animals↗

Immunogenicity of virus-induced rat osteosarcoma.

The immunogenicity of a virus-induced rat osteosarcoma was studied utilizing the lymphocyte microcytotoxicity test. Intratibial injection of murine sarcoma virus (Moloney) resulted in the development of palpable tumors at the injection site which on histopathological examination appeared to be osteosarcomas. In 73 per cent of animals injected these tumors progressed and metastasized to the lungs. Lymphocytes from these "progressor" animals demonstrated an ability to kill osteosarcoma cells in vitro (as quantitated in the microcytotoxicity test) while serum from these animals abrogated or blocked the cell-mediated cytotoxicity. In the remaining animals the tumors either failed to develop or regressed spontaneously. Lymphocytes from these "regressor" animals also demonstrated cytolytic activity against osteosarcoma cells in vitro, but serum failed to block the lymphocyte-mediated cytolysis. Both regressor and progressor groups demonstrated humoral cytotoxic antibodies to tumor antigen on the basis of the ability of their serum to kill tumor cells in vitro.

Animals↗

[Breech presentation and its significance (author's transl)].

From 1959 to 1975, 1060 (3.6%) breech presentations were found among 29,463 infants. The breech deliveries from May 1, 1959 to December 31, 1965 were compared with those from January 1, 1966 to December 31, 1975. Among the 3.6% breech deliveries there were 47% male and 53% female. There were more primigravida breech deliveries in both groups. The mean age of the mothers was 25.4 years for primigravidas and 29.4 years for multiparas. There was a maternal mortality of 0.2% (2 cases) in breech delivery. 29% of the breech deliveries were premature deliveries. There was a strickingly high incidence of frank and full breech deliveries among all patients. Knee presentations were rare. Delivery was primarily accomplished with the Bracht manoeuver in over 80% of the cases. Complete breech extractions decreased and the incidence of Caesarean Sections rose from 6% in the first group to 21% in the second group of patients. During the past 3 years the Caesarean Section rate was approximately 30%. Perinatal complications in the breech deliveries compare well to those reported in the literature. Of 750 mature infants (70.8%), 12 died (1.6%). Discounting children with congenital malformations and intrauterine stillbirth there remained 5 deaths from breech deliveries (0.7%). Of 1032 breech deliveries with a birth weight of 1000 grams or over, 74 infants (over all perinatal mortality 7.2%) died. 110 infants of all breech deliveries had a birth weight of less than 2500 grams (prematurity rate 29.2%). Of 102 cases of perinatal mortality in breech deliveries including those below 1000 grams 90 (88.2%) were premature. Of those 90 premature deaths, 28 infants were less than 1000 grams. 25 infants showed fetal congenital abnormalities. The corrected perinatal mortality of the premature deliveries was therefore 11.9%. The rate of birth trauma was 6.3% in the first group and 2.7% in the second group.

Adult↗

The allotransplantation of partial joints in the treatment of osteoarthritis of the knee.

Nine allografts replacing part of the knee have been carried out in 8 patients. In all patients the graft was incorporated without clinical evidence of rejection. In one case a low grade infection was brought under control without surgery and thus far has not impaired the results. All patients have a good functional range of movement and the alignment of the knee has been maintained by the grafts which display little or no collapse at all. Histological evidence in one case revealed cartilage viability at 14 months. Two years interim observations are encouraging enough to continue on with this technique in the knee with disease severe enough not to be helped by osteotomy but not so diffusely damaged as to require total knee arthroplasty.

Aged↗