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Biomedical subjects

R Hong

Publications and source records attributed to R Hong.

At least 91 records · Page 5Linked to original sources
PubMed1987

Immunologic reconstitution after haploidentical bone marrow transplantation for immune deficiency disorders: treatment of bone marrow cells with monoclonal antibody CT-2 and complement.

Patients with congenital T lymphocyte deficiency disorders received transplants with parental bone marrow depleted of mature T cells by the use of an anti-T cell monoclonal antibody (CT-2) and complement. Our results with 16 consecutive patients (20 transplants) showed rapid engraftment of donor cells; cytoreduction (busulfan, cytosine arabinoside [ara-C], cyclophosphamide) was used in six transplants, and marrow ablation was used in six (ara-C, cyclophosphamide, 1,365-cGy total body irradiation). No patient received prophylactic anti-graft-v-host disease (GVHD) therapy posttransplant, and only one patient developed significant GVHD, which involved the skin, liver, and gastrointestinal tract. Seven others showed some manifestations of GVHD, but these were of minimal clinical significance and required only occasional steroid therapy. Overall, eight patients are alive and well; eight did not survive. Polyclonal immunoglobulin synthesis by donor memory B cells was seen shortly after transplantation, with peak donor-derived serum levels seen approximately 2 months after transplantation. After this initial immunoglobulin synthesis waned, another wave of B cell responses developed. This immunoglobulin response appears to be permanent. T cell functions appeared as soon as 3 weeks after transplantation. This experience in a variety of patients with combined immunodeficiency who received transplants with monoclonal antibody T cell-depleted marrow shows gratifying results with a consistent T and B cell benefit.

Adult↗
PubMed1987

Modification of the sponge allograft model to study the immune response to bone marrow cells.

The sponge allograft model of Roberts & Hayry and of Ascher et al. was modified by introducing bone marrow cells into uncoated sponges 7 days after the sponge was implanted into the mouse. The number and cellular composition of the response in the sponges was essentially the same whether the stimulus was allogeneic or syngeneic bone marrow. However, the allogeneically stimulated sponge derived cells demonstrated allospecific cell-mediated lympholysis at very low effector-to-target ratios. Similar cytotoxic activity was difficult to demonstrate in splenic cells from the same animal tested concurrently. The cytotoxic cells were shown to be Lyt-1-, 2+ and Thy 1+. For a bone marrow impregnated sponge the peak T cell killing was reached after 12 days whereas peak killing occurred on day 14 in peritoneal cell infiltrated sponges as utilized by Ascher et al. Our model was developed to study the response to various antigenic stimuli placed into the sponge. This variation of the sponge allograft model should permit the study of a local cellular immune response to a number of antigens.

Animals↗
PubMed1987

Thymus and B cell reconstitution in severe combined immunodeficiency after transplantation of monoclonal antibody depleted parental mismatched bone marrow.

Two brothers were transplanted with bone marrow which was depleted of mature T cells with monoclonal antibody CT-2 plus complement. One child died of sepsis due to candida present prior to transplant. The other is alive and well with full T and B cell reconstitution over 36 months after transplant. Thymus biopsy taken after transplant demonstrated normal morphology and cellularity. Portions of the marrow that were radiolabeled permitted an assessment of traffic patterns of aliquots that were injected intravenously and directly into the marrow space. The studies reported here document that a one haplotype mismatch is not a sufficient disparity to preclude both B and T cell reconstitution, and that monoclonal antibody plus complement is an effective method for T cell depletion.

Antibodies, Monoclonal↗
PubMed1987

Effect on IgE production of transplanted cultured thymic fragments.

The effect of cultured thymic fragment (CTF) transplantation on the IgE response of nude mice was studied. Nude mice (BALB/c nu/nu) were immunized with a mixture of tetanus toxoid and aluminium gel intraperitoneally. Non-CTF transplanted nude mice could not regulate IgE production nor synthesize specific IgE antibody, and all died at 16 weeks of age. Nude mice that were transplanted with CTF from allogeneic low responder strains (C57BL/6, SJL), allogeneic high responder strain (ASW) and syngeneic high responder strain (BALB/c) could regulate IgE production, and these lived a normal life span. Additionally, the tetanus toxoid-specific IgE antibody response, which was estimated by PCA, paralleled that seen in the strain of the thymus donor, i.e. BALB/c and ASW thymus reconstitution produced the highest response, whereas SJL and C57BL/6 recipients' levels were significantly less (P less than 0.05). We postulate that the lesser responses were due to the determination of the phenotype response by the thymic microenvironment. The low responses were shown to be due to regulator T-cell imbalance. These data show that BALB/c T-cell precursors developing in non-BALB/c thymuses interact with BALB/c B cells to produce levels of IgE antibody that are more characteristic of the non-BALB/c differentiating microenvironment than of their own genetic background.

Aluminum Hydroxide↗
PubMed1986

A case report and literature review of "primary" pulmonary histiocytosis X of childhood.

"Primary" pulmonary histiocytosis X, a well-described entity in young adult males in which pulmonary disease is the overriding site of involvement, is exceedingly rare in children younger than 15 years old. We report a new case in a 2-year-old male and review other reported prepubertal cases. The diagnosis of pulmonary histiocytosis X is based on examination of lung tissue. Langerhans cells containing Birbeck granules, seen by electron microscopy, are virtually pathognomonic of histiocytosis X. These Langerhans cells also react with a monoclonal antibody (OKT6) as well as with antibody to S-100 protein. Based on the lack of consensus for the appropriate treatment of pulmonary histiocytosis X and on our patient's favorable response, we recommend initial therapy with corticosteroids alone, reserving more toxic agents for patients who fail to respond to this initial therapy.

Bone Diseases↗
PubMed1986

Reconstitution of T-cell deficiency by thymic hormone or thymus transplantation therapy.

Correction of T-cell defects by either thymic hormone treatment or thymus transplantation has proven to be more difficult clinically than historically anticipated. Because the precise action of thymic hormones is unknown and because these hormones act upon post-thymic cells, therapeutic attempts may fail owing to lack of sufficient substrate population. Results of thymic transplantation suggest that this procedure may be best utilized for the treatment of mild T-cell defects, rather than as complete replacement treatment for severe deficiency. Future clinical trials of thymic transplantation or thymic hormone appear justified in narrowly circumscribed and well-characterized conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Chronic exposure to aldicarb-contaminated groundwater and human immune function.

Aldicarb, a carbamate pesticide, has been a known groundwater contaminant in Wisconsin since 1981. To assess the effects of chronic ingestion of low-level aldicarb-contaminated groundwater (less than 61 ppb) on the immune function of humans, we identified 50 women, ages 18 to 70, with no known underlying reason for immunodysfunction. Twenty-three of these women (exposed group) consumed groundwater with detectable levels of aldicarb, and 27 (unexposed group) consumed water from a source with no detectable levels of aldicarb. Data were collected on each woman's health status, immune function, and fluid intake. Exposed women as compared with unexposed women showed an elevated stimulation assay response to the antigen Candida (P less than 0.02, t test). The exposed group had increased numbers of T8 cells (P less than 0.05, t test), an increased percentage of total lymphocytes as T8 cells (P less than 0.02, t test), and a decreased ratio of T4:T8 cells (P less than 0.02, t test). Our results suggest an association between consumption of aldicarb-contaminated groundwater and abnormalities in T-cell subsets in women with otherwise intact immune systems.

Adolescent↗
PubMed1986

T-lymphoblasts with erythropoietic helper function in acute T-cell leukemia.

A patient with acute T-lymphoblastic leukemia was found to maintain a normal hemoglobin concentration both at presentation and preterminally several months later, despite a replaced bone marrow and over 80% circulating lymphoblasts on both occasions. Cell surface marker analysis demonstrated the T-lymphoblasts both at presentation and preterminally to belong to the T-helper subpopulation. In vitro culture studies demonstrated that the patient's T-lymphoblasts, as well as conditioned medium derived from these lymphoblasts, significantly stimulated normal bone marrow erythroid colony growth (CFU-E). These findings suggest that in this patient the preservation of erythropoiesis resulted from a helper effect exerted by his T-lymphoblasts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Depletion of T cells from bone marrow for allogeneic transplantation: method for treatment of bone marrow in bulk.

T lymphocytes were depleted from donor marrow for 23 patients undergoing allogeneic bone marrow transplantation using an anti-T-cell antibody, CT-2, and complement. The methodology is described in detail for in vitro depletion of large quantities of bone marrow. The extent of T-lymphocyte depletion using various T-cell markers, the percent of marrow lost in the processing and quantity of antibody, and complement needed are presented. These techniques for in vitro T-lymphocyte depletion were reproducible and did result in an average final yield of 47% of the harvested donor marrow.

Antibodies, Monoclonal↗
PubMed1986

ELISA detection of specific functional antibodies in human serum to Escherichia coli, tetanus toxoid, and diphtheria-tetanus toxoids: normal values for IgG, IgA, and IgM.

An inexpensive, easily performed enzyme-linked immunosorbent assay (ELISA) was developed to measure specific IgG, IgA, and IgM antibodies to the common antigens Escherichia coli, diphtheria-tetanus toxoid, and tetanus toxoid. Normal values were established. Classical antibody deficiency disease states were confirmed and delineated by these assays. Additionally, several instances were discovered when functional antibody levels were abnormal when the serum immunoglobulin levels were normal. The use of ELISA assays for antibodies to common antigens provides a useful technique to measure and monitor isotype responses of the humoral immune system.

Adult↗
PubMed1986

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: autologous marrow recovery with specific immune sensitization to donor antigens.

Autologous marrow recovery without engraftment of donor marrow was observed after bone marrow transplantation (BMT) for two patients with acute lymphoblastic leukemia. Each had received marrow from a haploidentical mixed lymphocyte culture (MLC) reactive donor after pretransplant conditioning with total body irradiation and high-dose cyclophosphamide. To minimize graft-vs-host disease, the marrow was depleted of T cells in vitro by treatment with a monoclonal anti-T-cell antibody and complement. Two weeks after each transplant, reactive lymphocytes were noted transiently in the blood of each patient. Analysis of karyotype, HLA type, and in vitro MLC responsiveness proved the lymphocytes to be of host, not donor, origin. MLC studies showed rapid proliferative responses specifically to stimulating cells from the BMT donor, indicating in vivo sensitization to donor antigens. Return of hematopoietic function was markedly delayed, but it eventually normalized after several months, without evidence of chimerism. These studies confirm that some immune and hematopoietic stem cells of host origin survive the high-dose chemoradiotherapy used as transplant conditioning. Because these immune cells are specifically reactive to donor alloantigens, more potent suppression of host immunity may be needed to prevent nonengraftment of T-cell-depleted, HLA-mismatched bone marrow.

Adult↗
PubMed1986

In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

Acute Disease↗
PubMed1985

Familial hemophagocytic lymphohistiocytosis: report of four cases in two families and review of the literature.

Four cases of familial hemophagocytic lymphohistiocytosis (FHL) from two families with first cousins affected in family and siblings in another are presented. The pathological findings, including neuropathology, transmission (TEM), and scanning electron microscopy (SEM), are discussed. This is the first study of this condition to include TEM and SEM. One hundred and fifty-nine cases from the literature, including the author's four cases, are reviewed. The familial occurrence in 116 instances in sibships and consanguinity in 13 of the 73 families support autosomal-recessive inheritance. In five families there were affected first cousins--an observation not readily explained by autosomal-recessive transmission. We suggest that the genetic aspects of FHL be more fully explored and that in future cases parents and other relatives be included in the hematologic, immunologic, and genetic evaluation.

Blood Cells↗
PubMed1985

Reactive hemophagocytic syndrome.

Two cases of reactive hemophagocytic syndrome (RHS) are reported, and the clinical and pathological features are compared with other histiocytic proliferative disorders, including familial hemophagocytic lymphohistiocytosis (FHL) and malignant histiocytosis. RHS can be associated with a variety of infections, including viral, bacterial, fungal, and parasitic. RHS may also be familial as exemplified by our 2 cases in siblings. The isolation of an effective agent appears to be the only criterion by which a diagnosis of RHS can be made.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Omenn disease: termination in lymphoma.

Two brothers with Omenn's disease were seen at the University of Wisconsin. The first died at 3 months. The second developed a chronic measles infection from vaccination with a live virus to which he did not produce an antibody. He received transfer factor and irradiated leukocyte infusions without benefit. After death a lymphoma was found in virtually all tissues. It is unclear whether the treatment predisposed the child to or caused the cancer. Omenn's disease is an autosomal-recessive disorder of the immune system that leads to early death. The pathogenesis remains unknown.

Histiocytosis, Langerhans-Cell↗
PubMed1985

Transplantation of cultured thymic fragments. VI. H-2 recombinant donors.

Athymic (nude) mice were transplanted with cultured thymic fragments from syngeneic, allogeneic, and partially allogeneic (recombinant) mice. Lymphocyte proliferation and cytotoxicity in vitro were measured to assess immunologic reconstitution. Transplanted nude mice were immunocompetent whether donor and recipient were disparate for class I, class II, or both H-2 gene types. Furthermore, allotolerance for thymic H-2 class I antigens was achieved independently of class II antigen allotolerance. Class I antigen tolerance was not broken during lymphocyte responses to unrelated alloantigens, ruling out insufficient help as the tolerance mechanism. Splenocytes, isolated from nude mice transplanted with fully allogeneic or syngeneic thymic fragments and stimulated in vitro with trinitrophenyl-modified cells, displayed H-2-restricted, hapten-specific cytotoxicity. Cytotoxic cells from allotolerant mice were restricted to either host or thymic H-2 antigens, depending on the stimulating cell haplotype. Response levels for thymic and host trinitrophenyl-modified cells were comparable. We have shown that allogeneic thymic epithelium transplanted into adult nude mice can induce allotolerance to class I and II H-2 antigens equally, and permits T lymphocyte interaction with cells bearing thymic donor or host H-2 antigens. Our results are consistent with a model wherein T lymphocyte self-receptors retain their genomic repertoire but can be selectively mutated or expanded by appropriate H-2 antigen presentation by the thymus.

Animals↗