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S T Ildstad

Publications and source records attributed to S T Ildstad.

119 records · Page 7Linked to original sources
PubMed1985

Characterization of mixed allogeneic chimeras. Immunocompetence, in vitro reactivity, and genetic specificity of tolerance.

Mixed allogeneically reconstituted mice (B10 + B10.D2----B10) that specifically accept B10.D2 tail skin allografts were examined for in vivo and in vitro immunocompetence, patterns of hematopoietic repopulation, and in vitro reactivity. In vitro, mixed allogeneic chimeras (B10 + B10.D2----B10) manifested specific tolerance in mixed lymphocyte reactions and cell-mediated lympholysis to B10 and B10.D2 splenocytes, with normal responses to third-party (B10.BR) cells. Such chimeras were immunocompetent in B cell and helper T cell responses, as assessed by their primary plaque forming cell responses to in vivo sheep red blood cell immunization. This is in contrast to fully allogeneic chimeras, which responded less well. In addition, survival of the mixed allogeneic chimeras in a conventional animal facility was superior to that of fully allogeneic chimeras, and similar to syngeneically reconstituted (B10----B10) mice. Specific tolerance to skin grafts, degree of allogeneic engraftment, and persistence of chimerism was also assessed in a noncongenic mixed allogeneic combination (B10 + C3H----B10). Such animals manifested specific hyporeactivity to C3H skin allografts, but eventual chronic rejection of the grafts occurred in spite of stable and persistent mixed chimerism. MHC-congenic (B10.BR) skin grafts were accepted indefinitely in the same animals, suggesting that skin-specific non-major histocompatibility complex antigens were responsible for rejection of the C3H skin allografts.

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PubMed1985

Clinical behavior and results of current therapeutic modalities for squamous cell carcinoma of the buccal mucosa.

A retrospective analysis of 28 patients who received therapy for squamous cell carcinoma of the buccal mucosa at the Massachusetts General Hospital from January 1962 through December 1976 is presented. The patients ranged in age from 42 to 78 years; the majority of patients presented with disease at 50 years or more. The proportion of females in this series (43 per cent) represented a dramatic increase compared with previous reports from other large centers. The 29 per cent rate of metachronous or synchronous second primary malignant disease is increased significantly over that expected for the general population. Uncontrolled disease above the clavicle continues to be the major site of therapeutic failure. The development of co-operative multicenter randomized prospective protocols to evaluate the efficacy of various combinations of current therapy methods in order to improve patient survival from this devastating disease are encouraged.

Adult↗
PubMed1984

In vivo and in vitro characterization of specific hyporeactivity to skin xenografts in mixed xenogeneically reconstituted mice (B10 + F344 rat----B10).

Mixed xenogeneically reconstituted mice (F344 rat + C57BL/10Sn----C57BL/10Sn), which specifically retain F344 tail skin xenografts, were studied for the specificity of such hyporeactivity and for in vitro reactivity and immunocompetence. Survival of mixed reconstituted animals was excellent, without evidence for graft vs. host disease. Donor-type tail skin grafts were specifically prolonged (mean survival time = 80 d) in comparison with normal controls and syngeneically reconstituted animals. In vitro, such animals manifested specific hyporeactivity by mixed lymphocyte reaction and cell-mediated lympholysis to F344 rat and B10 cells, with normal response to third-party rat (Wistar-Furth) and mouse (B10.BR). Examination of lymphoid tissues with a fluorescence-activated cell sorter revealed low levels, if any, of donor-type cells detectable. This system offers a model for investigation of xenogeneic transplantation tolerance.

Animals↗
PubMed1984

Effect of class II antigen matching on renal allograft survival in miniature swine.

The benefit of class II major histocompatibility complex (MHC) antigen matching to renal allograft survival, in the absence of immunosuppression, has been studied in partially inbred miniature swine. Permanent (greater than 6 mo) renal allograft survival was found in 30% of recipients of either class II only or fully matched grafts. Analysis of the survival of the class II-only matched grafts by specific recipient/donor haplotype combinations indicated that survival was regulated by at least three genetic factors, including antigen gene dose, a class I MHC allele-dependent effect, and non-MHC-linked immune response phenomenon. Animals accepting class II-matched kidneys developed spontaneous tolerance to the graft, despite mounting an initial immune response marked by renal damage and the development of serum cytotoxic antibodies directed at the donor MHC antigens. The antibodies were only of the IgM class, suggesting that conversion of the humoral response to IgG was blocked. After acceptance of the kidney, three out of five animals showed specific prolongation of donor skin grafts. At the time of rejection of these skin grafts, no decrease in renal function nor reappearance of anti-donor antibodies was observed.

Animals↗
PubMed1984

Squamous cell carcinoma of the alveolar ridge and palate. A 15-year survey.

A retrospective review of 82 patients treated at the Massachusetts General Hospital from 1962 through 1976 for squamous cell carcinoma of the maxillary and mandibular alveolar ridge and soft and hard palates is presented. Stage at first presentation, clinical features of the disease, analysis of current therapeutic modalities, survival statistics, and prevalence of second primary malignancies are analyzed and compared with reports from other large centers.

Adult↗
PubMed1983

Squamous cell carcinoma of the mobile tongue. Clinical behavior and results of current therapeutic modalities.

A retrospective review of 122 patients who received therapy at the Massachusetts General Hospital for squamous cell carcinoma of the mobile tongue from January 1962 through December 1976 was analyzed for clinical patterns of behavior and results of current therapeutic modalities. The results were compared with a previously reported series from our surgical service. Our series showed a dramatic increase in the proportion of women with carcinoma of the tongue from the 10 to 30 percent distribution reported 20 to 30 years ago to the 45 percent female to male ratio we observed. Only 38 percent of patients who had a regional recurrence of disease after initial therapy responded to secondary therapeutic measures. We therefore encourage that initial treatment offer the patient the optimal chance for cure. No significant increase in survival with the current therapeutic modalities of surgery, radiation, or combined therapy was noted; we observed 55 percent 2 year and a 34 percent 5 year overall survival rates. It is our belief that randomized, prospective, therapeutic protocols are essential for further progression of treatment success for patients with this devastating disease.

Adult↗
PubMed1983

Squamous cell carcinoma of the tongue: a comparison of the anterior two thirds of the tongue with its base.

A retrospective analysis of 176 patients with squamous cell carcinoma of the tongue has been reported. The tongue base and mobile tongue, believed to behave as two clinically distinct anatomic areas, have been compared and contrasted. Women comprised 25 percent of the patients with tumors of the base of the tongue and 45 percent of those with mobile tongue lesions, an increase over previous reports for both locations. The majority of patients with squamous cell carcinoma of the tongue base (77 percent) presented with advanced (stage III or IV) lesions at time of initial clinical and diagnostic staging, compared with only 33 percent of those with cancer of the mobile tongue. There was no significant difference in survival between the two locations when survival rates were compared stage by stage. The decreased overall survival frequently reported for patients with squamous cell carcinoma of the tongue base compared with the survival for patients with tumors of the mobile tongue may be due to the disproportionately high number of patients with cancer of the tongue base who present with advanced disease. Survival rates have not significantly improved when compared with other retrospective series reported in the past 40 years. We strongly urge the development of intercenter, multidisciplinary, cooperative, prospective, protocols to assess combinations of currently accepted therapeutic modalities in the hope of improving treatment of this devastating disease.

Adult↗
PubMed1983

Intra-oral cancer at the Massachusetts General Hospital. Squamous cell carcinoma of the floor of the mouth.

A retrospective review of 163 consecutive patients with biopsy-proven, invasive squamous cell carcinoma of the floor of the mouth who underwent inpatient treatment at the Massachusetts General Hospital during the 15-year period from January 1962 through December 1976 is presented. The stage at first presentation, clinical features of the disease, incidence of second primary tumors, analysis of therapeutic modalities, and survival statistics are compared with reports from other large centers. Floor of mouth tumors comprised 28%, (163/592) of oral squamous cell carcinomas seen at the Massachusetts General Hospital during that time period. Seventy-one per cent of floor of mouth tumors were in men and 29% in women; women tended to present earlier in the course of their disease. Thirty-seven patients (23%) developed a secondary primary malignancy, and four of these 37 patients developed two second primaries. Distant metastatic disease appeared in 6% of patients with Stage I, II, or III disease and 26% of patients with Stage IV disease. Radiation therapy alone and surgery alone resulted in equivalent long-term survival rates for early stage disease. In more advanced stages (III and IV), a combined approach utilizing surgery and radiation therapy obtained superior results for short-term survival than either modality alone. The importance of early diagnosis and treatment and suggestions for development of cooperative protocols in an attempt to improve salvage of patients with this disease is discussed.

Adult↗
PubMedDate not supplied

Baboon bone marrow transplantation in humans: application of cross-species disease resistance.

Xenotransplantation is a newly evolving field. A renewed interest has emerged coincidentally with the shortage of donor organs for transplantation. Bone marrow (BM) chimerism has been suggested as a potential strategy to induce tolerance to xenografts and control the immune response across a species barrier. Bone marrow transplantation (BMTx) displays unique features compared to solid-organ transplantation or transplantation of other cellular grafts. To achieve engraftment of the pluripotent hematopoietic stem cell, which generates all lineages of the hematolymphopoietic system, conditioning of the recipient (usually a combination of irradiation and cytoablative chemotherapy) is required. Once engraftment is achieved, graft function is stable and rejection does not occur, even without immunosuppression. On the other hand, the graft itself is able to generate an immune response against the host, resulting in graft-versus-host disease (GVHD). A newly recognized advantage to xenotransplantation is species-specific disease resistance. In terms of BMTx, important questions arise: Can xenogeneic BM generate a competent immune response across species barriers? Will cross-species GVHD occur? What are the possible applications to humans? This review addresses these questions. Problems emerging from xenogeneic BMTx are summarized and strategies for their solution discussed.

Animals↗
PubMedDate not supplied

Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts.

Clinical organ transplantation between genetically disparate individuals currently requires the use of chemotherapeutic agents to suppress the rejection reaction. The deleterious side effects of these reagents and their inability to prevent rejection completely has led to a continuing search for methods to induce specific transplantation tolerance in adult recipients. Numerous experimental animal models utilizing irradiation and bone marrow transplantation coincident with organ transplantation have been proposed. Bone marrow transplantation, however, has its own major complications, including graft-versus-host reactions and immunoincompetence, probably resulting from a failure of appropriate immune cell interactions in the reconstituted host. We have now attempted to overcome these difficulties by reconstituting the irradiated host with T-cell depleted bone marrow containing both host (syngeneic) and donor (allogeneic or xenogeneic) components. This technique leads to long-term survival of the reconstituted animals and specific prolongation of subsequent skin grafts of donor type. Animals reconstituted in this fashion are fully reactive to third-party allografts and xenografts and do not appear to manifest signs of graft-versus-host disease.

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