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Biomedical subjects

R Hong

Publications and source records attributed to R Hong.

At least 145 records · Page 8Linked to original sources

Fatal cytomegalovirus bronchiolitis in a patient with Nezelof's syndrome.

A 4-year-old girl who had received a fetal thymus gland by intraperitoneal transplantation 41 months previously sustained acute, fatal bronchiolitis due to culture-proven cytomegalovirus despite the fact that a specific antibody response to this organism was detected. While the thymic transplantation had increased the number of circulating T lymphocytes and had permitted immune sensitization to delayed-hypersensitivity skin test antigens, there was still an incomplete state of T lymphocyte function. In particular, isolated lymphocytes failed to respond to stimulation with phytohemagglutinin at several concentrations and, more important, the pathologic examination demonstrated a severe anatomic deficiency of lymphoid tissue associated with T lymphocyte function. The unusual infection that caused the death of this child emphasized the necessity of acquiring sufficient T lymphocyte function in immunologic reconstitution attempts.

Antibodies, Viral↗

Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs.

Heart and kideny allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney; genetic disparity was ruled out, since the heart and kidney from the same donor were placed into one recipient. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence from the work of Slavin and his colleagues and from our study that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

Animals↗

Fatal lymphoma after transplantation of cultured thymus in children with combined immunodeficiency disease.

A fatal, widespread, polyclonal, B-cell immunoblastic lymphoproliferative disorder developed in three children with combined immunodeficiency shortly after intra-abdominal transplantation of cultured thymus epithelium for immunoreconstitution. All three had surface immunoglobulin-bearing cells (15 to 20 per cent) in the peripheral blood before transplantation and polyclonally elevated immunoglobulins afterward. Abnormal immunoregulation was demonstrated by a lack of concanavalin A-induced suppressor-cell activity in mixed leukocyte culture in all three patients before transplantation and in two afterward. We suggest that the transplant acted as a promoter through immunostimulation or production of promoter factors, and that excessive polyclonal B-cell proliferation resulted because of inadequate immunoregulatory mechanisms. Although this complication occurred in only three of 30 patients with various forms of immunodeficiency treated with cultured thymus, these cases illustrate a potential problem in immunoreconstitution of combined immunodeficiency disorders.

B-Lymphocytes↗

Transplantation of cultured thymic fragments. II. Results in nude mice.

Nine nude mice were transplanted with cultured thymic fragments derived from syngeneic (three recipients) or allogeneic (six recipients) sources. All transplanted mice survived for periods of up to 8-10 mo thereafter, at which time they were sacrificed. Weight gain had been progressive and the animals were in excellent health. Four nontransplanted littermates housed in the same cages died at the age of 4 mo. In the nontransplanted mice, the usual deficits of T and B cells were observed. In transplanted mice, normalization of IgG1 and IgA levels as well as IgG antibodies to sheep erythrocytes and precipitating antibodies to rabbit serum occurred. Lymphocyte counts and Thy-1 bearing cells increased to approximately 50% of normal values. Proliferative responses to phytohemagglutinin and concanavalin A, mixed leukocyte reactivity, and cell-mediated lympholysis were variably restored from approximately 10-100% of normal. Attained responses were the same in recipients of syngeneic or allogeneic tissues and these, in turn, were equal or superior to responses measured in animals transplanted with whole noncultured thymuses. Skin grafts from third party donors were vigorously rejected, whereas those derived from second party (allogeneic thymus donor strain) may have been accepted or slowly rejected. Cultured thymic fragments, consisting primarily of epithelial elements, can effectively repair the thymic deficiency of nude mice. Experiments to date do not indicate that syngeneic tissues enjoy an advantage over allogeneic grafts in this restoration procedure.

Animals↗

A micro method for enumerating T and B cells in mouse peripheral blood.

A micro method has been devised to assess T and B cells in mouse peripheral blood. This technique permits simultaneous determination of B lymphocytes and monocytes. T lymphocytes are determined by a cytotoxicity assay. Tests require only 0.2 ml of whole blood and avoid the loss of certain cell populations secondary to flotation separation techniques. Percentages of IgM and IgG bearing B lymphocytes, Thy-1 bearing T lymphocytes as well as monocytes in mouse peripheral blood were determined in a total of 50 mice of 11 different strains.

Animals↗

Functional relationship of macrophages and basophils to the thymus gland.

Human thymus epithelium, depleted of thymocytes and macrophages by means of organ culture, was used in chemotaxis experiments with peripheral blood cells. Such cultured thymus epithelium can attract specifically macrophages and basophils. T-lymphocytes were attracted only by short-term (8 day) cultured thymus tissue which still retains some of the original macrophage population. Thymic macrophages formed rosette structures with thymocytes. In other experiments 'activated' rabbit macrophages had the capability to destroy thymocytes, whether autochthonous or allogeneic. The possible role of macrophages and basophils in thymus function is discussed.

Animals↗

Transcervical thymic biopsy in children with immunodeficiency.

To more fully characterize immunodeficiency states, thymic biopsies add useful information. The transcervical technique is simple and does not require a sternal-splitting procedure. The thymus was much larger than anticipated in 12 of 12 cases so far biopsied, including six cases of severe combined immunodeficiency. A sample of 2-3 gm was readily removed. A slight wound infection was encountered in only one instance; no generalized septic episode resulted.

Biopsy↗

Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency.

The inherited deficiency of adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in humans is associated with an immunodeficiency. Some of the immunodeficient and enzyme-deficient patients respond immunologically to periodic infusions of irradiated erythrocytes containing adenosine deaminase. It has been previously reported that erythrocytes and lymphocytes from immunodeficient ane enzyme-deficient children contained increased concentrations of ATP, and in the one child studied after erythrocyte infusion therapy, the intracellular level of ATP diminished. Using high-pressure liquid chromatography that resolves ATP and 2'-dATP, we have observed greater than 50-fold elevations of dATP in the erythrocytes of immunodeficient, adenosine deaminase-deficient patients but not in the erythrocytes of an immunocompetent adenosine deaminase-deficient patient. The erythrocyte dATP in two unrelated adenosine deaminase-deficient, immunodeficient patients disappeared after infusion of normal erythrocytes. We propose that deoxyadenosine, a substrate of adenosine deaminase, is the potentially toxic substrate in adenosine deaminase deficiency, and that the mediator of the toxic effect is dATP, a recognized potent inhibitor of ribonucleotide reductase.

Adenine↗

Transplantation of cultured thymic fragments. I. Morphologic and technical considerations.

Thymic fragments were maintained in organ culture until egress or deterioration of the leucocyte component was near completion. These depopulated cultured thymic fragments were then implanted into immunologically competent mouse recipients. Acute immunologic rejection was not observed in mice given cultured thymic allografts. If the organ culture period was approximately 2 weeks, lymphoid repopulation and newly developed Hassall's corpuscles were observed 7-10 weeks after implantation. If the initial culture period was extended to 3 weeks, transplanted fragments developed as unusual repopulation pattern, characterized by eosinophils, macrophages and plasma cells. This finding could be interpreted as a protracted allograft rejection or, more likely, a loss of ability of the thymic epithelium to attract or differentiate the types of precursors usually attracted to the normal gland. When cultured and non-cultured tissues were simultaneously transplanted in a single recipient, the non-cultured tissue was acutely rejected and became fibrous, while the cultured thymus assumed the appearance of a normal lymphoid organ without any neighbouring inflammatory reaction.

Animals↗

Fatal graft-versus-host disease after a small leukocyte transfusion in a patient with lymphoma and varicella.

A child with a poorly differentiated lymphoma developed varicella while being treated with maintenance chemotherapeutic agents. He received a transfusion of nonirradiated leukocytes from 1 unit of whole blood donated by a healthy volunteer who had recently recovered from varicella. The clinical course of varicella was aborted, but a classic graft-versus-host reaction developed and ultimately proved fatal. The host may have presented a large population of antigen-bearing cells to an infusion of presensitized immunocompetent donor cells, leading to an overwhelming aggressor lymphocyte reaction. We speculate that a modified approach using irradiated donor cells could be of benefit in the treatment of varicella infections in the immunosuppressed host.

Chickenpox↗