Showing papers on "Transplantation published in 1978"

Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow.

Abstract: In two situations, transfer of normal unsensitized bone marrow cells into heavily irradiated H-2-identical allogeneic mice caused a high incidence of lethal chronic graft-versus-host disease (GVHD), i.e. mortality occuring between days of 20 and 80 postirradiation. Minor histocompatibility determinants appeared to be the main target for eliciting GVHD. Removing mature T cells from the marrow with anti-Thy 1.2 serum and complement before injection prevented GVHD. On the basis of adding purified T cells to T-cell-depleted marrow cells, it was concluded that contamination of the marrow with as few as 0.3% T cells was sufficient to cause a high incidence of lethal GVHD in certain situations. No GVHD was found with the injection of non-T cells (Thy 1.2-negative cells) or with tolerant T cells. Irradiated recipients of T-cell-depleted marrow cells remained in good health for prolonged periods. These mice showed extensive chimerism with respect to the donor marrow, normal numbers of T and B cells and were immunocompetent. The data provide no support for the view that chronic GVHD developing after bone marrow transplantation in man is the result of an attack by the progeny of the donor stem cells. The results imply that mature T cells contaminating marrow inocula are probably the main cause of GVHD seen in the clinical situation.

Malignant neoplasms of genetic origin in Drosophila melanogaster

Abstract: Malignant neoplasms that develop in 12 recessive-lethal, larval mutants of Drosophila melanogaster are discussed. These mutations affect the adult optic neuroblasts and ganglion-mother cells in the larval brain, the imaginal discs, and the hematopoietic organs. The malignant neoplasms exhibit fast, autonomous growth, loss of the capacity for differentiation, increased mobility and invasiveness, lethality in situ and after transplantation, and histological, fine structural, and karyotypic abnormalities. Intermediate neoplasms are also found. These combine both benign and malignant qualities. They grow in a noninvasive, compact fashion, typical of benign tumors, yet they also exhibit malignant qualities such as fast, autonomous, and lethal growth, loss of differentiation capacity, changes in cellular morphology, and lethal growth after transplantation into wild-type hosts. Thus Drosophila and vertebrate neoplasms show striking similarities.

Improvement of kidney-graft survival with increased numbers of blood transfusions.

Abstract: In a study of 1360 cadaver-donor kidney transplants we found a striking correlation of increased numbers of pretransplant blood transfusions with Improved transplant survival (P 20 transfusions was 71±5 per cent at one year as compared with 42±2 per cent for recipients with no transfusions; at four years the survival rates were 65±5 per cent and 30±3 per cent (P<10-6). Frozen blood was less effective than nonfrozen blood in producing this effect. In contrast to previous reports based on fewer numbers of transplants, a single pretransplant transfusion or transfusions given during transplantation had no statistically significant influence on graft outcome. The beneficial effect of pretransplant transfusions was apparent at transplant centers with high or low overall success rates. Deliberate transfusion trials in prospective transplant recipients should consider this strong dose dependence of graft prolongation by transfusions. (N Engl J Med 299:799–...

Severe Candidal Infections: Clinical Perspective, Immune Defense Mechanisms, and Current Concepts of Therapy

Abstract: Disseminated candidiasis has become an important infection, particularly in immunocompromised and postoperative patients. Although serologic tests may, in some settings, facilitate a premortem diagnosis, the disease is usually diagnosed by comprehensive clinical evaluation. Detection of the relatively newly recognized peripheral manifestations of candidemia may be vital to early diagnosis: endophthalmitis, osteomyelitis, arthritis, myocarditis, meningitis, and macronodular skin lesions. Studies in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell). The primary drugs for the treatment of disseminated candidiasis are still amphotericin B or amphotericin B plus 5-fluorocytosine; the mainstay of therapy for chronic mucocutaneous candidiasis is amphotericin B. Other antifungals and immune system-stimulating modalities (transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol) may be useful for chronic mucocutaneous candidiasis in some settings and deserve further evaluation.

Heterogeneity in Drug Sensitivity among Tumor Cell Subpopulations of a Single Mammary Tumor

Abstract: Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.

Chronic cutaneous graft-versus-host disease in man.

Abstract: This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.

The Influence of Thymus H-2 Antigens on the Specificity of Maturing Killer and Helper Cells

Abstract: The subject matter of this review is highly restricted. It covers only those T cells which exhibit a dual specificity, i. e. antigen specific T cells which are also specific for a particular self major histocompatibility complex (MHC) structure. In the mouse, where the MHC is called the H-2 complex, such T cells are referred to as H-2 restricted cells. In a functional way, H-2 restriction means that T cells from an U-2^ animal immunized against a foreign antigen (call it X) can perform when they are presented with X on H-2t' cells, but are apparantly \"blind\" to the correct antigen, X, on H-2'' or H-2'' cells. Killer and helper T cell functions are H-2 restricted! Obviously a killer cell has to focus its attention on cell membrane antigens to perform its effector function—killing abnormal cells. The signal from a helper T cell to a B cell also needs to be delivered at the B cell surface. The advantage of the dual specificity of these classes of T cells may be just this—to ensure that they do focus their attention on cell-membrane-bound antigen and avoid having their effector functions dissolved out by fruitless interactions with soluble antigens.

Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation

Abstract: Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment. The second patient underwent a successful transplantation after similar preparation, except that procarbazine was omitted. At 11 and five months after transplantation both had normal hematopoiesis and no evidence of graft-versus-host disease. This treatment of the Wiskott-Aldrich syndrome may be a model for the correction of other genetically determined immune and hematologic bone-marrow disorders.

Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.

Abstract: Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.

Bone marrow origin of hepatic macrophages (Kupffer cells) in humans.

Abstract: Hepatic macrophages (Kupffer cells) from two male recipients of bone marrow transplants from females were studied for fluorescent Y body staining and sex chromatin (Barr body). After the transplant, macrophages had the sex karyotype of the donor, indicating that human hepatic macrophages originate in bone marrow.

Characterization of an apparently nononcogenic Marek's disease virus.

Abstract: A new isolate of Marek's disease virus (MDV) was described. This virus, SB, and a clone, SB-1, differed from pathogenic isolates in in vitro growth characteristics as described for other apathogenic isolates. Serologically, as with other apathogenic isolates, SB could be distinguished from pathogenic MDV and the avirulent turkey herpesvirus. SB failed to induce lesions characteristic of Marek's disease (MD) during a 6- to 11-week experimental period. Also, SB was nononcogenic in immunosuppressed chickens or in chickens inoculated with this virus in ovo. However, under those conditions, SB caused a cytolytic infection. The term "nononcogenic" rather than "apopathogenic" was therefore proposed to classify this and similar isolates. SB-1 protected chickens against challenge with either virulent MDV or the non-virus-producing MD tumor transplant, JMV. Possible mechanisms of protection are discussed.

Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins.

Abstract: Mouse bone marrow and spleen cells were fractionated with the aid of soybean agglutinin and peanut agglutinin. A test for spleen colony-forming units in the isolated fractions showed that the hemopoietic stem cells are agglutinated by both of these lectins. The capacity of the agglutinated fractions to reconstitute lethally irradiated allogeneic mice was investigated. A sequential fractionation of splenocytes from SWR donors by soybean agglutinin and peanut agglutinin, or a single fractionation by soybean agglutinin of splenocytes from BALB/c donors, afforded a cell fraction that successfully reconstituted lethally irradiated (BALB/c X C57BL/6)F1 mice, without complications due to graft-versus-host reaction.

Increased Pulmonary Superinfections in Cardiac-Transplant Patients Undergoing Primary Cytomegalovirus Infection

Abstract: CYTOMEGALOVIRUS infection is extremely common after renal transplantation, with evidence of infection in as many as 90 per cent1 to 96 per cent2 of patients. Although many recipients excrete the vi...

Suppressor T Cells for IgE and IgG in Peyer's Patches of Mice Made Tolerant by the Oral Administration of Ovalbumin

Abstract: A single oral dose of ovalbumin (Ov) resulted in inhibition of IgE formation in mice subsequently immunized i.p. with Al(OH) 3 -Ov. Repeated feeding of Ov (on alternate days for 2 weeks) induced the formation of detectable suppressor cells in Peyer9s patches and spleen. Suppression was demonstrated by the ability of adoptively transferred Peyer9s patch or splenic lymphocytes from Ov-fed tolerant mice to inhibit IgE formation in Ov-immunized syngeneic recipients. Suppressor cells could be induced by feeding mice as little as 100 µg of Ov on alternate days for 2 weeks. Suppression was specific and Peyer9s patch lymphocytes were shown to be more effective suppressors than splenic lymphocytes.

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Abstract: Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.

Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts.

Abstract: Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

Granulocyte Transfusions for the Prevention of Infection in Patients Receiving Bone-Marrow Transplants

Abstract: Prophylaxis by granulocyte transfusions against infection associated with granulocytopenia was studied in 69 patients receiving bone-marrow transplants for the therapy of hematologic neoplasia or aplastic anemia. Patients were randomized to receive or not to receive granulocyte transfusions when their circulating granulocyte levels fell to less than 200 per cubic millimeter during the period between transplantation and the development of graft function. During the first 21 posttransplant days, there were two local infections and no septicemias in 29 transfused patients. Seven local infections and 10 septicemias developed among the 40 controls. This protection was afforded by granulocytes collected by reversible leukoadhesion as well as by cells collected by continuous-flow centrifugation.

Influence on blood pressure of renal isografts between spontaneously hypertensive and normotensive rats, utilizing the F1 hybrids.

Abstract: The F1 hybrids (F1) of spontaneously hypertensive rats (SHR) and Wistar rats (W), whose kidneys were transplanted from SHR at the age of 10 weeks and 20 weeks, showed significant elevation of blood pressure (BP) for 11 weeks after the transplantation In F1 with W or F1 kidneys BP was decreased near to the normal level F1 whose kidneys were transplanted from SHR or W showed low renin activity both in plasma and the kidney It is suggested that BP of SHR is probably determined by the renal pro-hypertensive factor(s) other than renin influencing on sympathetic nerves through central nervous systems

Noncompliance in Children With Renal Transplants

Abstract: Fourteen patients (13 of them adolescents) interrupted immunosuppressive treatment following renal transplantation. Twelve were girls and two were boys. Six subsequently lost their allografts and eight had impaired renal function. Noncompliance was suspected when diminution in cushingoid features, unexplained weight loss, or changes in renal function occurred. Noncompliance was comfirmed by interview with psychosocial staff. Available psychosocial data from family interview and personality test obtained earlier as part of systematic follow-up study were analyzed to explore the reasons for noncompliance. Non compliant patient families had lower incomes, more fatherless households, and comunication difficulties within the family and with the medical establishment. Using a stepwise discriminant analysis, a discriminant function was derived which selected 13 of 14 noncompliant patients. Noncompliance may be a preventable cause of allograft failure. These data can aid in identifying high-risk patients and planning intervention programs.

An autoradiographic study of satellite cell differentiation into regenerating myotubes following transplantation of muscles in young rats.

Abstract: Satellite cells were traced autoradiographically during the regeneration of skeletal muscle in young Sprague-Dawley rats. Approximately 31% of the satellite cells in uninjured muscles appeared labelled after three injections of tritiated thymidine; none of the myonuclei were labelled in the same muscles. Four to six days after transplanting the radioactive muscles to non-radioactive littermates, regenerating myotube nuclei in the host appeared labelled. Thus, this study confirms that satellite cells in young rats can differentiate into multinucleated myotubes following muscle injury.