The occurrence of antibodies to collagen in synovial fluids.
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Animals↗
Biomedical subjects
H H Fudenberg
Publications and source records attributed to H H Fudenberg.
Ontogeny of immunity in humans.
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Animals↗
Standardization of tissue culture conditions for spontaneous thymidine-2-14C incorporation by unstimulated normal human peripheral lymphocytes: circadian rhythm of DNA synthesis.
The rate of DNA synthesis by human lymphocytes was studied in vitro by measuring unstimulated thymidine-2-14C incorporation (spontaneous lymphocyte blastogenesis; SLB). Freezing lymphocytes and extracting DNA after thawing did not alter the radioactive label count rate and was as efficient as extracting DNA immediately after culture. Omission of fetal calf serum also did not alter the rate of DNA synthesis. Standards established as optimal for studies of SLB were: cell concentration, 1.0 times 10(6)/ml/tube; 14C-TdR concentration, 0.4 mjCi/tube; duration of incubation, 8 hr. In sets of identical samples obtained by specimen division, the variation in counts was 6%. To achieve reproducibility of results; it was essential to count the lymphocytes, and then to ensure that each tube contained almost precisely known numbers of cells. Diurnal variations in the rate of DNA synthesis by circulating lymphocytes of healthy men were measured in vitro by SLB at 2-hr intervals for 24 hr. Leukocyte counts, hematocrit, hemoglobin, plasma cortisol, and body temperature were monitored concurrently. The DNA synthesis rate varied in a 24-hr cycle with peaks at 10 A.M. and 11:00 P.M.., depressions at 4 A.M. and 4 P.M. The rate was correlated with body temperature and hematocrit level, and inversely related to the absolute eosinophil count.
Adult↗
The numerical development of lymphoid cells during human embryogenesis.
We have studied the cellular growth rates in the fetal thymus, spleen, and bone marrow of 12 human fetuses ranging in gestational age from 7 to 20 weeks. In all instances growth rates were linear when plotted logarithmically. However, the spleen had a biphasic growth curve. These data are useful in predicting the cellular yields which can be obtained from human fetal lymphoid organs which are to be used for transplantation in immune deficiency diseases and other clinical conditions.
Bone Marrow↗
Phagocytes and C4 in paraproteinaemia.
Immunological studies were performed on patients with multiple myeloma. A defect in polymorphonuclear leucocyte (PMN) function as evidenced by diminished adherence of these cells to nylon fibre columns was detected in 16, and low levels of the fourth component of complement (C4) were observed in 14, of the 26 patients studied. Twelve of the patients with low C4 exhibited the defect in PMN adhesiveness whereas only four of the 12 patients with normal C4 showed the defect. The PMN defect was not caused solely by the low C4, since PMNs from seven patients with hereditary angioedema, which is associated with low levels of C4, did not show the defect. The low C4 and defect in PMN adhesiveness occurred primarily in patients with IgG myeloma; all but one of the patients with IgA myeloma, macroglobulinaemia, or light chain disease were normal in both parameters. Results of skin window studies indicated that patients with the PMN defect also had a defect in the early PMN inflammatory response. The defect in PMN adhesiveness could be completely corrected by incubating the cells in normal plasma. Binding of the C4 to paraprotein could not be demonstrated, and C1 activation was found to be caused only by one of 10 isolated paraproteins studied. These studies indicate that patients with paraproteinaemia have immunological abnormalities in addition to low immunoglobulin levels and suggest that these abnormalities may be involved in the pathogenesis of the recurrent infections commonly associated with this disease.
Adult↗
Clinical immunology, present and future.
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Allergy and Immunology↗
Immunoglobulin Allotypes of European Populations. I. Gm and Km(Inv) allotypic markers in Hungarians.
The distribution of G1m(f, z, a, and x), G3m(b0, b1, b3, c3, c5, g, s, and t) and Km(1) (formerly Inv[1]) allotypic markers have been examined in 184 Hungarians. The results indicate that the frequency of the immunoglobulin haplotypes Gmza;g, Gmzax;g, Gmf;b and Km1 is similar to the frequencies observed in surrounding populations. In addition, Hungarians were found to be polymorphic for the Oriental haplotype Gmza;bst, and had low frequencies of other uncommon haplotypes. Our data indicate that about 5% of the Hungarian genome is of Oriental origin.
Gene Frequency↗
Immunoglobulin allotypes of European populations. II.Gm, Am and Km(Inv) allotypic markers in Czechoslovakians.
The distribution of G1m(f,z,a, and x), G2m(n), G3m(b0, b1, b3, b5, c3, c5, g, s, t, and v), A2m(1 and 2) and Km(1) (formerly Inv[1]) allotypic determinants has been examined in a series of Czechoslovakian blood donors. The results indicate that Gmza;-;gvA2m1, Gmzax;-;gvA2m1, Gmf;n;bvA2m1 and Gmf;-;bvA2m1 are present in polymorphic frequencies. Further, 9 idiomorphic phenotypes were observed; however, without family data it was not possible to exactly define the majority of these. The observed frequencies of Gmza;g, Gmzax;g and Gmf;b and Km1 are similar to those observed previously in Czechoslovakians and similar to those observed in adjacent populations, though different from those observed in Western Europeans, primarily due to a higher frequency of Gmf;b in Czechoslovakians.
Czechoslovakia↗
Osteogenic sarcoma. Immunologic parameters before and during immunotherapy with tumor-specific transfer factor.
18 patients with osteogenic sarcoma were followed by serial measurements in vitro of tumor-specific cell-mediated cytotoxicity and of "active" and total rosette-forming T-cells. 13 of these patients have had or are currently receiving injections of osteogenic sarcoma-specific dialyzable transfer factor derived from healthy donors. In three patients with very small lesions, cytotoxicity was high before amputation and decreased within 2 mo after removal of tumor. Cytotoxicity was low at time of diagnosis in all patients with large tumor masses. The cytotoxicity of the patients' lymphocytes increased after administration of tumor-specific transfer factor in all patients so treated. Patients receiving nonspecific transfer factor showed evidence of declining cell-mediated cytotoxicity. Tumor-specific transfer factor may produce an increase in cell-mediated cytotoxicity to the tumor in patients with osteogenic sarcoma. This possibility is suggested by the pain and edema that occurred in the area of the tumor in patients who had metastatic disease when therapy was started and by lymphocytic infiltrates in the tumor, as well as by the increase in cell-mediated cytotoxicity and the increase in percentage of active rosette-forming cells from subnormal to normal. Serial measurements of cell-mediated cytotoxicity are helpful in monitoring the efficacy of transfer factor and other modes of therapy in these patients, and these measurements are the best available criteria for selection of donors of tumor-specific transfer factor.
Adenocarcinoma↗
Tumor-specific cell-mediated immunity in household contacts of cancer patients..
Patients with osteogenic sarcoma (and related tumors), hypernephroma, and breast carcinoma, and their household contacts were tested for tumor-specific cell-mediated immunity against these tumors with the use of a short-term chromium-51 release assay. This assay, reproducible over many months and well-correlated with the clinical course of the patients, was used to demonstrate that household contacts of patients with osteogenic sarcoma and breast carcinoma have specific immunity against the tumor type with which they have been in contact. In both types of tumors, the range of cytotoxicity values produced by lymphocytes from the household contacts was significantly higher than that of the normal population. The incidence of immunity was much higher in household contacts of patients with breast carcinoma than in those of patients with osteogenic sarcoma. Immunity was found with equal frequency in men and women, as well as in genetically and nongenetically related household contacts (guardians, adopted children, spouses). Immunity against hypernephroma was not demonstrated in either patients with hypernephroma or their household contacts.
Adenocarcinoma↗
Studies on cystic fibrosis using isoelectric focusing. I. An assay for detection of cystic fibrosis homozygotes and heterozygote carriers from serum.
We have developed a standardized biophysical assay for the rapid detection of individuals homozygous or heterozygous for cystic fibrosis (C/F). The assay employs isoelectric focusing in thin layer polyacrylamide gels to analyze microliter quantities of whole serum for the presence of a C/F factor protein and for deletions in a group of proteins called proteins B, C, and D (Fig, 1). A pH 5-10 gradient is used (Fig. 2) and each sample is screened using a serum volume which contains 300 micrograms immunoglobulin G (IgG). Individuals homozygous or heterozygous for C/F are distinguished from normal unaffected individuals on the basis of the presence of a C/F factor protein band (Table 1). Heterozygous carriers for C/F are distinguished from C/F homozygotes 75 percent of the time, on the basis of a deletion in either band B, C, or D (Table 2). On the basis of screening 65 patients with cystic fibrosis, 61 heterozygous carriers for C/F, and 105 normal control subjects, it was concluded that no obvious correlation existed between either sex, age, or severity of the disease in the individual C/F patient, and the absolute presence or absence of the C/F factor. In addition, no correlation existed between sex or age and the presence of the C/F factor or deletions in proteins B, C, and D in the individual heterozygous carrier for C/F or normal control subjects. Analysis of serum samples from 68 patients with a variety of other diseases, many with clinical symptoms resembling those seen in the patient with cystic fibrosis (Table 3), indicated that the C/F factor protein described in this study appears to be diagnostic for C/F genotypes, with the possible exception of patients with certain types of leukemia.
Adolescent↗
Chemical studies on a monoclonal immunoglobulin from a patient with carcinoma of the colon.
Structural studies were carried out on a monotypic immunoglobulin (Ig) isolated from a patient suffering from a colon tumor. Results indicated that the light (L) chain of this protein belonged to the VkappaII subgroup and was devoid of known Inv allotypic determinants, whereas the heavy (H) chain variable (V) region belonged to the VHIII subgroup and its constant (C) region was of the gamma1 subclass and was Gm (a+Z+). The amino acid sequence of a total of 106 residues has been determined for this molecule. An extra cysteine was present at the fourth hypervarible region of the heavy chain. Preliminary results indicated that the Fc fragment of this protein did not include the inter-heavy-chain disulfide bonds.
Amino Acid Sequence↗
Immunoglobulin allotypes in symptomatic and asymptomatic pigeon breeders.
Comparison of immunoglobulin allotypes were studied in a group of patients with pigeon breeder's disease and in similarly exposed by asymptomatic individuals. The study revealed that the disease is not correlated with immunoglobulin allotypes. Furthermore, the phenotype Gm(a;g) was not associated with high levels of serum antibodies to pigeon antigens.
Adolescent↗
Transfer factor I: methods of therapy.
Transfer factor was first discovered by Lawrence in 1955, but was not used therapeutically until 1969 when we reported its use in a Wiskott-Aldrich patient. Since that time, it has been used in a wide variety of disorders related to defects in cellular immunity, infectious diseases, and malignant diseases. This report describes our experience with transfer factor. Report number I discusses rationale for patient selection, procedures for transfer factor therapy, procedures for monitoring the efficacy of therapy, untoward effects of therapy, and experience with transfer factor therapy in severe combined dual system deficiency disorder. The results of our study on transfer factor therapy indicate that it is capable of inducing a clinically acceptable level of cell-mediated immunity in approximately 50% of patients with a variety of immunodeficiency disorders. It also appears to be a useful adjunct to chemotherapy, and may possibly act synergistically with transplanted fetal thymocytes to produce a constantly regenerating specifically competent source of T lymphocytes, thereby obviating the need for bone marrow transplant for severe combined dual system deficiency disorder.
Antibody Formation↗
Transfer factor II: results of therapy.
Transfer factor is a dialyzable extract of sensitized leukocytes, which transfers reactivity from skin test-positive donors to skin test-negative recipients. Transfer factor supplied by our laboratory has been used therapeutically to induce cellular immunity in 78 patients around the world. Many patients received multiple doses of transfer factor ranging from 1 unit given every 6 months for 3 years to 1 unit every week for 6 months to as much as 8 units per week for a brief period. A total of 299 units of transfer factor have been given. Diseases in which transfer factor appeared to cause improvement include the Wiskott-Aldrich syndrome, severe combined immunodeficiency disease, mucocutaneous candidiasis, chronic active hepatitis, coccidioidmycosis, dysgammaglobulinemia, Behcet disease, aphthous stomatitis, linear morphea, familial keratoacanthoma and malignancy.
Amphotericin B↗
Human thymus-derived rosette-forming cells and immunologic diseases.
This paper describes some studies done on the human lymphocytes that bind to normal sheep red blood cells in a rosette formation. On the basis of human fetal studies and investigations of markers for B cells, it is demonstrated that rosette-forming cells are valid markers for T cells. These cells were looked at in various immunologic diseases. A modification of the basic technic, one that detects subpopulations of lymphocytes, was mainly used. Results correlate closely with the cellular immune status of the patient.
Agammaglobulinemia↗
The relationship of IgA and IgE deficiency.
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Agammaglobulinemia↗
Ontogeny of cellular immunity in man.
The purpose of this study was to determine the precise developmental sequence of the acquisition of phytohemagglutinin (PHA) and allogenic cell responsiveness (MLR) in the human fetus. Reactivity was determined quantitatively by 3H-thymidine incorporation in various fetal lymphoid tissues. MLR reactivity was the earliest detectable response occurring first in liver lymphoid cells at 5 weeks fetal age. Reactivity to PHA then appeared in thymocytes at 10.5 weeks and at 14 weeks in the spleen and blood. MLR reactivity first appeared in the thymus at 12.5 weeks and in the spleen and blood at 14.5 weeks. Marrow lymphocytes failed to react up to 18 weeks. These results suggest that fetal thymus is immunocompetent by about 10.5 weeks and MLR responsiveness may be under nonthymic (hepatic) control during development.
Blood↗