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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 757 records · Page 42Linked to original sources

Transplantation of human cancers to nude mice and effects of thymus grafts.

Human cancers were transplanted to nude mice; a cell line originating in the foregut (distal stomach or first portion of the duodenum) produced exponential nonmetastasizing growth, preventable by prior thymus implantation. Implantation of thymuses into mice with established tumors resulted in increased animal survival and in four instances in complete regression of the neoplasm. Cell lines of pancreatic carcinoma and melanoma and surgical specimens of melanoma and of neoplasms from the pancreas and colon showed variable growth patterns in this system. Repeated attempts to transplant gastric adenocarcinoma were unsuccessful.

Adenocarcinoma↗

Altered allotransplantability of BALB/c Leydig cell tumor after organ culture or cell suspension.

In confirmation of prior studies, fragments of testicular interstitial (Leydig) cell tumors from BALB/c mice were found to be transplantable to H-2d (BALB/c and DBA/2) or allogeneic H-2q (DBA/1 and BUB/BnJ) recipients after organ culture, whereas noncultured fragments were accepted only in H-2d recipients. Lymphocyte cytotoxicity assays showed that while transplantability was altered by the organ culture process, tissue immunogenicity in vitro was unchanged. Cell suspensions from the same tumor were also found to be transplantable to both H-2d and H-2q recipients and occasionally even to H-2a and H-2k recipients, irrespective of whether the cells were obtained from fragments previously organ-cultured or from dispersed fresh tissue. We suggest, therefore, that rather than modifying cell surface antigens, it is possible that organ culture explanation serves to (1) allow free dispersal of the tumor cells which leads to progressive tumor growth, and/or (2) raise the ratio of dead to living cells in the transplanted fragments, which has previously been shown to direct host immune responses toward enhancement.

Animals↗

Skin grafting across H-Y incompatibility after organ culture.

Mouse skin maintained in organ culture for 7 days was transplanted across the H-Y histocompatibility barrier in two inbred strains: C57BL/6 and C3H/An. Cultured grafts were invariably rejected and at a faster rate than noncultured control grafts. Recipients of the cultured male skin grafts rejected subsequent noncultured male skin grafts in accelerated fashion.

Animals↗

Detection of measles antibodies in cerebrospinal fluid and serum by a radioimmunoassay.

Evidence that different structural components of the measles virus may act as antigens has been provided by the serologic methods of hemagglutination inhibition hemolysin inhibition, and nucleocapsid complement fixation. Using radioiodinated measles viral antigens, and immune precipitation assay has been designed that is capable of discriminating among various reactivities to measles viral structural components in serum or cerebrospinal fluid (CSF) and of distinguishing whether IgG and IgM antibody is involved. This technique has been applied to the study of measles antibodies in CSF and sera of patients with multiple sclerosis (MS) and other neurologic diseases. From data presented here, it was found that both groups of patients have individual reactivity to measles proteins, present in CSF and serum, whereas three normal CSF samples were found not to have such antibodies. It appears that oligoclonal immunoglobulins in CSF of MS patients may be detected by this method, and one patient with MS was found to have CSF IgM anti-measles antibodies.

Antibodies, Viral↗

Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499).

Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer 344 Ficoll-Hypaque separated spleen lymphocytes. Clincal GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.

Animals↗

In vitro studies of axillary lymph node cells in patients with breast cancer.

A total of 170 axillary lymph nodes were obtained from fresh mastectomy specimens from 81 women with breast cancer. Lymph node cells were tested in vitro for T and B cells by the rosette technique and immunofluorescence microscopy and for functional capacity by response to the mitogens phytohemagglutinin (PHA) and concanavalin A. T cells showed a wide range of relative values: 32-80 percent, with a mean of 63.5 percent. B cells defined by the presence of surface immunoglobulins ranged from 14 to 61 percent (mean, 35.8 percent); those defined by the presence of C3 receptors, from 8 to 54 percent (mean, 24.9 percent); and those defined by the presence of IgG-specific (Fc) receptors, from 10 to 45 percent (mean, 27.5 percent). Cells with the C3 and Fc receptors constituted approximately two-thirds of the cells not binding spontaneously to sheep red blood cells (non-SRBC-R), whereas virtually all non-SRBC-R stained for surface immunoglobulins. The proportion of T and B cells and the response to mitogens varied widely among nodes and among patients. Differences were significant between values observed in young and old patients, nodes with and those without metastatic disease, and lymph nodes with different morphology. Lymph nodes from patients over 60 years old showed a higher proportion of B cells and a lower proportion of T cells than did those from patients 45 years of age or younger. Lymph nodes with disease metastic to them also showed a higher percent of B cells and a lower percent of T cells than the nodes that did not have metastatic disease. Lymph nodes with lymphocyte predominance showed a relatively high proportion of T lymphocytes, a high PHA response, and a low content of B lymphocytes. By contrast, lymph nodes with germinal-center predominance showed a relatively low content of T cells, a low PHA response, and a relatively high proportion of B lymphocytes.

Adult↗

B lymphocytes in primary and secondary deficiencies of humoral immunity.

The quantitative studies of B lymphocytes in peripheral blood have been performed in various forms of primary and secondary immunodeficiency disease in man. X-linked agammaglobulinemia was found to comprise two sub-types, one lacking B-cell population, the other showing low numbers of B lymphocytes. The absence of B cells in severe combined immunodeficiency was corrected by marrow transplants in 3 children. Cases of DiGeorge syndrome and lepromatous leprosy showed an absolute increase in numbers of B lymphocytes in peripheral blood, probably a compensatory mechanism in the market deficit of T-cell population and function. The reconstitution of DiGeorge syndrome by fetal thymus transplant reversed the abnormally high percentage of B lymphocytes.

Agammaglobulinemia↗

RNA and protein synthesis in spontaneous rosette formation by T lymphocytes.

Formation of rosettes with sheep red blood cells (SRBC) by peripheral blood lymphocytes and thymocytes has been studied. Trypsinization of these cells abolishes the capacity to form SRBC-rosettes. The process of re-establishment of this capacity to form SRBC-rosettes, in vitro, has been shown by use of metabolic inhibitors to require transcription, translation, and protein synthesis. These observations are interpreted in terms of the T cell markers as the expression of a definitive process or step in lymphoid cell differentiation.

Amanitins↗

In vitro differentiation of human marrow cells into T lymphocytes by thymic extracts using the rosette technique.

The manner by which human and calf thymic extracts induce precursor cells of human marrow to differentiate in vitro into T lymphocytes has been studied using as a T-cell marker the spontaneous rosette formation technique of human T lymphocytes with sheep erythrocytes (E rosette). These findings confirm previous observations made in the study of the same process using a different T-cell marker, specific antigenicity recognizable by a heterologous anti-human T-cell serum in a microcytotoxicity test. The number of cells revealing evidence of differentiation demonstrated by the E rosette formation technique is smaller than that obtained with the anti-human T-cell serum, indicating perhaps that a different stage of maturation of T lymphocytes is recognized by the antiserum from the one detected by spontaneous rosette formation. Based on the effects of specific inhibitors of nucleic acids and protein synthesis, it can be concluded that these thymic extracts ultimately act by influences exerted in the cell nucleus and that RNA and protein synthesis are required for the differentiation of precursor cells into T lymphocytes induced by thymic extracts. In addition, continued protein synthesis appears to be required for maintenance of receptors for sheep erythrocytes on the cell surface.

Amanitins↗

Quantitative assessment of thymus-dependent (t)-cell function in human peripheral blood.

A new micromethod for evaluating lymphocyte responses to phytohemagglutinin (PHA) has been developed and used for the survey of T-cell function in human peripheral blood. The results of lymphocyte responses to PHA stimulation in whole blood culture were expressed in terms of unit volume of blood (50 mul). This new method has eliminated the major uncontrollable factors of conventional methods, and appears to be more correlated with the cell-mediated immunity in vivo.

Agammaglobulinemia↗

Some characteristics of human rosette-forming cells.

Some evidence for identification of human rosette-forming cells as thymus and thymus-dependent lymphocytes (T cells) is presented. Application of the rosette assay to several clinical conditions including primary immunodeficiency diseases indicates the usefulness of this assay in quantitating the number of T cells in peripheral blood.

Animals↗

T Cells in immunodeficiencies as evaluated by an antihuman T-cell serum.

An antihuman T-cell has been prepared in rabbits by infecting lymphocytes from a patient with Bruton-type agammaglobulinemia and absorption with cultured B-lymphoblast cells. Cytotoxicity of the antiserum was assayed with peripheral blood lymphocytes in the presence of rabbit complement and its specificity for T vs B cells was verified. This anti-T-cell serum killed 66% (range 49-78) of normal blood lymphocytes. In patients with Bruton-type agammaglobulinemia the percentage of cells sensitive to the antiserum was above normal (77-89%), whereas it was decreased in some patients with lepromatous leprosy or under antilymphocyte globulin therapy.

Absorption↗

Immunodeficiency in leprosy.

It is known that the impairment of cell-mediated immunity (CM) exists in lepromatous leprosy patients. This was shown by 1) delayed skin reaction to various test antigens, 2) decreased transformation of lymphocytes by various antigens, 3) delayed rejection of skin allograft, 4) decreased migration inhibitory fa-tor (MIF) formation, and 5) histologic study of the lymph node. In addition to these previous works, we have studied T and B lymphocytes in peripheral blood of leprosy patients; T cells by the technic of rosette formation, and B cells by staining surface immunoglobulins. The result of our study shows decreased numbers of T cells and increased numbers of B cells in peripheral blood of lepromatous patients. A the same time, we found that allogenic leukocyte infusion treatment reversed T and B-cell abnormalities. We know that repeated infusions of allogenic leukocytes dramatically brought about improvement of the clinical status of the patients, resolution of skin lesions, subsidence of erythema nodosum leprosum reaction, clearance of bacteria from the skin and lymph nodes, and reconstitution of peripheral lymph nodes.

Agglutination Tests↗

immunodeficiency in ataxia-telangiectasia.

Ataxia-telangiectasia is characterized by endocrine, neurologic, hematologic, hepatic, cutaneous and immunologic abnormalities. The immunologic deficiencies vary considerably from patient to patient, and in each patient with respect to time. The most frequent deficiencies of humoral immunity are diminished or absent serum and salivary IgA, diminished or absent serum IgE and impaired antibody responses to a variety of bacterial and viral antigens. Deficiencies of cellular immunity are commonly found by both in vivo and in vitro analyses. Histologic confirmation of these immunodeficiencies is readily observed in the lymphoid tissue. The thymus, which may be the seat of the primary abnormality in the immunodeficiency syndrome, regularly shows morphologic characteristics of an embryonic thymus.

Antibody Formation↗

Congenital neutropenia: impaired maturation with diminished stem-cell input.

Children with congenital neutropenia (Kostman disease) present a syndrome of recurrent and eventually fatal bacterial infections. The disease is uniformly lethal and the mean age at death is 24 months. To attempt to better understand the nature of this inborn error, we have studied marrow and peripheral blood of 3 children with the disease. Along with classic morphologic analysis we have used the technic of soft agar bone marrow culture in vitro. All 3 patients showed marked deficiency of numbers of neutrophils in the peripheral blood, intermittent monocytosis especially with infection, and predominant nitroblue tetrazolium (NBT) dye staining in monocytes during infection. The marrow of all 3 patients showed evidence of maturation arrest at the promyelocyte stage and very few or no neutrophils. Two cases showed no neutrophils in the Rebuck skin window inflammatory study. The 3rd case, however, developed small numbers of neutrophils in the peripheral blood, up to 6%, but the first 2 patients, although studied on many occasions, did not show neutrophils above 1%. Evidence from soft agar culture of bone marrow in 1 patient was compatible with the view that development of committed neutrophil stem cells is defective. This patient did not develop neutrophils in soft agar culture and showed loose colonies developing only to promyelocytes. In the 2nd case, where depression of neutrophil development was somewhat less severe clinically, culture of the marrow in soft agar yielded normal neutrophil colonies and none of the loose colonies showing arrested maturation were seen. These findings suggest that the basic mechanism underlying the congenital neutropenias may differ from patient to patient.

Agranulocytosis↗

Clearances of complement components, C3 proactivator and other serum proteins in chronic membranoproliferative glomerulonephritis (CMPGN).

In chronic membranoproliferative glomerulonephritis (CMPGN) the activation of the complement system through the properdin pathway plays an important role. The clearance of complement components and of the C3-proactivator (C3-PA) have been determined in 18 patients. Hemolytically active C5, C6, C7 and C3-PA were detected in the urine for the first time. The clearances of the complement components did not correlate with the clearances of other serum proteins with similar molecular weights. The specificities of the single complement components in the urine were tested by specific complement inhibitors such as hydrazine, KSCN, and the C4-inactivating factor.

Adolescent↗