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Biomedical subjects

R E Ritts

Publications and source records attributed to R E Ritts.

At least 55 records · Page 3Linked to original sources

The influence of nonspecific immunotherapy on the course of murine melanoma.

BCG, Corynebacterium parvum, vitamin A, and levamisole were continuously administered to C57 BL/6 mice bearing B16 melanoma prior to, with following tumor implantation as well as before and coincident with surgical excision of the implanted tumor. Only the group given levamisole prophylactically for 8 weeks before tumor inplantation showed a significant difference from control mice but a tenfold increase in dosage in this drug did not exert a comparable effect.

Animals↗

Abnormal chemotaxis in patients with cutaneous anergy.

Chemotaxis of polymorphonuclear leukocytes and mononuclear leukocytes was studied in six patients who had persistent cutaneous anergy. Four had previous infections (three fungal and one caused by Mycobacterium kansasii), one had sarcoidosis, and one had late-onset immunoglobulin deficiency. Our data indicate that some patients with persistent cutaneous anergy have a combined defect of leukocyte function. Lymphocytes incubated in vitro with mitogen failed to elaborate active lymphocyte-derived chemotactic factor when compared with controls. Polymorphonuclear leukocytes and mononuclear leukocytes responded poorly to normal chematactic factors compared with controls. The abnormal mononuclear leukocyte chemotaxis may play a role in the persistent cutaneous anergy of these patients.

Chemotaxis, Leukocyte↗

An assessment of cell-mediated immunity in acute allograft rejection in man. A prospective study.

A detailed multifactorial computer analysis of several in vitro tests of cell-mediated immunity has been carried out before and after surgery in 15 renal transplant recipients. Factors studied include lymphocyte blastogenesis, T- and B-cell levels, and lymphocyte protein synthesis. Large doses of immunosuppressive agents chnage lymphocyte subpopulations. This is seen especially in transplant patients who have rejection and who have decreased numbers of circulating lymphocytes. The T cells are selectively depressed more than the B cells. This is also reflected in the greater responsiveness of pokeweed mitogen-stimulated lymphocytes compared with lymphocyte responsiveness to phytohemagglutinin and concanavalin A. In this environment, rejection takes place. These observations suggest that rejection may be initiated by cortisone-resistant lymphocytes of the thymic medullary type. Measurements of changes in lymphocyte responsiveness to mitogens or changes in lymphocyte subpopulations do not reliably predict rejection. However, measurement of lymphocyte protein synthesis fills the criterion of providing a reliable test that can be carried out quickly, and in the future may be valuable in predicting rejection.

B-Lymphocytes↗

Inhibitory activity of medium-dialyzed transfer factor on lymphocyte blastogenesis.

Human transfer factor was prepared from normal donors with marked skin reactivity against common microbial antigens by dialysis of lymphocyte extracts versus tissue culture medium (TFmd). Several batches of TFmd were tested for their ability to specifically increase the DNA synthesis of unsensitized lymphocytes in vitro in the presence of the corresponding antigens (PPD, SKSD, Candida, Thistoplasmin). No transfer or immunologic reactivity by TFmd was observed. There was, however, a significant unspecific inhibition by TFmd of lymphocyte cultures stimulated by antigens, PHA or allogeneic cells.

Adult↗

Transfer factor versus combination chemotherapy: a preliminary report of a randomized postsurgical adjuvant treatment study in osteogenic sarcoma.

Twenty-six patients with classic osteosarcoma were randomized to receive either transfer factor or combination chemotherapy. Eight of 14 patients who received transfer factor converted their skin test markers, evidence of activity of the transfer factor. Of these eight patients, all are alive; four are free of disease. Of the 18 patients who received combination chemotherapy, 14 are alive, 12 of whom are free of disease. The immunologic test procedures performed sequentially reveal that transfer factor appears to enhance cell-mediated immunity, but it is evident that in this study, a control (saline) arm in the protocol could not be included. It is of interest that the chemotherapy regimen used does not appear to suppress such activity permanently. The individual test results, however, are not very helpful for predicting response to treatment. The small numbers of patients and the short duration of this study, combined with the exclusion of parosteal osteogenic sarcomas and jaw tumors, do not permit a meaningful comparison with other published studies.

Antineoplastic Agents↗

Phagocytosis and cutaneous delayed hypersensitivity in patients with chronic obstructive pulmonary disease.

The objective of this study was to determine if the phagocytic and intracellular killing capacity of peripheral granulocytes or an expression of cellular-mediated immunity, delayed cutaneous reactivity, as measurements of native and acquired immunity, might be risk factors associated with chronic obstructive pulmonary disease (COPD). Over 100 patients with a value for their forced expiratory volume in one second (FEV1) less than or equal to 70 percent of normal were carefully matched with healthy participants having an FEV1 greater than or equal to 86 percent of normal, and together they served as the study group. Phagocytosis and intracellular killing were normal in patients with COPD; however, these patients demonstrated a significant impairment in the ability of their peripheral leukocytes to reduce nitroblue tetrazolium. The delayed-hypertensitivity response rate and the degree of reactivity were similar in the two groups, except for the patients with COPD having a significantly greater degree of reactivity to Monilia albicans extract ("canadin.") This finding is thought to be a consequence of reduced mucociliary clearance rather than a risk factor. The significance of decreased resting and stimulated cells' reduction of nitroblue tetrazolium in patients with COPD is not clear.

Aged↗

Idiopathic late-onset immunoglobulin deficiency with functional T-cell deficiency.

The common features in our two patients were late onset of infections that are known to complicate both T-cell and B-cell deficiencies, decreased numbers of circulating B-cells with low serum immunoglobulin levels, and normal numbers of circulating T-cells, which were, however, defective in the response to delayed hypersensitivity skin test antigens and to mitogens in vitro. The composite of clinical and immunologic aberrations is consistent with the presence of an immune deficiency involving the B-cell system quantitatively and the T-cell system qualitatively.

Adolescent↗

Lymphocyte blastogenesis in patients receiving hemodialysis.

Lymphocyte blastogenic transformation in response to plant lectins and allogenic cells was studied in patients with nonuremic, far-advanced, chronic renal failure and in healthy controls. Cell cultures were studied in the presence of normal sera, patient's sera, and with media of different buffering capacities. Minimal blastogenic depression was observed when patient's lymphocytes were cultured in indifferent plasma with effective bicarbonate buffering compared with the use of pooled patient's plasma or HEPES buffer. Fresh plasma in culture depressed concanavalin A (Con A) blastogenesis. The data suggest that, under optimal conditions, lymphocytes from patients with chronic severe renal insufficiency are more responsive to stimuli than previously reported and as a group are near normal control values. Further, the defect observed may be a result of intracellular acidosis.

Adult↗

Soluble proteins of human bronchogenic carcinomas.

Solid-phase affinity chromatography has been used to search for tumor-associated proteins of bronchogenic carcinomas. All of the apparently normal proteins were removed from extracts of squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung. The remaining soluble proteins were partially characterized as to heat stability, approximate molecular size, electrophoretic mobility, and biologic function. These tumor-associated proteins were not tumor-specific by current definition. Neither lung cancer patients' lymphocytes nor serum proteins were specifically reactive with these tumor-associated proteins.

Adenocarcinoma↗

Impaired blastogenic response of lymphocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis.

Synovial fluid lymphocytes from patients with rheumatoid arthritis demonstrated a markedly diminished blastogenic response to both phytohemagglutinin and pokeweed mitogens, when compared to normal peripheral blood lymphocytes. The blastogenic response to rheumatoid peripheral blood lymphocytes to both mitogens was also depressed, when compared to the response of normal lymphocytes, but the difference was less marked and was within limits which could be accounted for by recent salicylate therapy. Lymphocytes of both peripheral blood and synovial fluid of rheumatoid patients showed a delayed response to PHA (five days to achieve maximum thymidine incorporation vs four days for normals).

Arthritis, Rheumatoid↗

Leukocyte chemotaxis in diabetic patients and their nondiabetic first-degree relatives.

Leukocyte chemotaxis wasmeasured in 108 subjects: 20 normal controls, 36 insulin-taking diabetics (15 being index patients), and 52 nondiabetic first-degree relatives of index patients. The relatives had a mean chemotactic index (CI) significantly lower than that of the controls (individually, 25 per cent had CIs lower than the lowest of the controls); and the diabetics had a mean CI significantly lower than that of the relatives. The impairment of leukocyte chemotaxis measured in the first-degree relatives of diabetic index patients does not appear to be associated with an increased susceptibility to infection and suggests that the impaired leukotaxis is due to an inherent defect--perhaps genetic--in leukocyte function.

Adolescent↗

Suppression of lymphocyte transformation after aspirin ingestion.

To learn whether in vitro blastogenesis of lymphocytes is affected by in vivo salicylate ingestion, blood samples were obtained from 19 normal volunteers before and after therapeutic doses of aspirin. Lymphocyte transformation studies performed on these blood samples showed marked and statistically significant suppression of blastogenesis. Maximum suppression was observed in blood samples obtained 12 hours after the last aspirin ingestion. As compared to controls, samples obtained at this time showed mean blastogenic responses to phytohemagglutinin and pokeweed mitogens of 49 and 56 per cent respectively. No correlation could be demonstrated between the plasma salicylic acid level and the degree of suppression of blastogenesis. Aspirin ingestion altered neither the proportions of circulating T and B cells nor the viability of lymphocytes in culture.

Administration, Oral↗

Studies of mitogen-induced lymphocyte transformation by a semi-microtechnic.

The authors have demonstrated that mitogen-induced lymphocyte transformation can be effectively studied in a semi-microsystem allowing multiple studies from a reasonably small volume of blood, which makes the technic more feasible for clinical studies of cellular immune mechanisms. The variability among individuals, and from day to day in the same individual, makes repeated, careful kinetic studies necessary for valid data. Moreover, the very wide range of normal responses in man makes the interpretation of cellular hyporesponsiveness difficult in pathologic states and necessitates the use of several mitogen concentrations and sequential kinetic studies to establish the validity of results.

Adult↗

Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.

A 20-year old women and her infant daughter had recurrent bacterial infections and chronic mucocutaneous candidiasis and were found to have extreme hyperimmunoglobulinemia E, defective neutrophil chemotaxis, and diminished lymphocyte responses to Candida antigen. Studies of members of the mother's family showed mild increases of IgE and mildly depressed chemotactic activity of neutrophils in a brother, the father, and the paternal grandfather. The recurrent bacterial infections in these two patients can be explained by the defective neutrophil chemotaxis. It is not known whether the mucocutaneous candidiasis is related to the neutrophil chemotaxis with the lymphocyte defect being secondary to the Candida infection or, alternatively, the Candida infection being secondary to the lymphocyte defect. Furthermore, the family data suggest a familial pattern of hyperimmunoglobulinemia E and defective neutrophil motility.

Adolescent↗

Clinical studies of methanol extraction residue fraction of Bacillus Calmette-Guérin as an immunostimulant in patients with advanced cancer.

Forty patients with advanced gastrointestinal cancer, all previous chemotherapy failures, were treated with a methanol extraction residue of Bacillus Calmette-Guérin (MER) alone, administered intradermally in either weekly or every-4-week schedules. The only significant side effect was local cutaneous reaction ranging from papules through pustules to draining ulcerations. On the weekly schedule these reactions frequently reached a point of clinical intolerability. In spite of the advanced nature of their disease, 29% of the patients had increased reactivity to recall antigens; 57% showed an increased reaction to dinitrochlorobenzene challenge during MER therapy; 38% had significant increases in lymphocyte blastogenesis to phytohemagglutinin mitogen, 48% to concanavalin A, and 43% to pokeweed mitogen. Increases (greater than 25%) in immunoglobulins A, M, and G were also observed in 31, 41, and 28% of patients, respectively. MER therapy was associated with increased thymus-derived (T) and bone marrow-derived (B) cells and an increased ratio of T-cells to B-cells. Increases in those determinants reflecting cellular immunity (skin tests, phytohemagglutinin and concanavalin A blastogenesis, and T-cells) showed a positive correlation with patient survival. Increases in those determinants associated with humoral immunity (pokeweed mitogen blastogenesis, immunoglobulins, and B-cells) had, if anything, a negative survival correlation. In comparing administration schedules, the weekly method produced more frequent increases in dinitrochlorobenzene response, more rapid increases with higher peaks in lymphocyte blastogenesis transformation, and more frequent increases in circulating T- and B-cells. The every-4-week method was associated with significantly greater frequencies of increases in immunoglobulins A and M. Of 36 patients with measurable disease, 3 showed greater than 50% objective responses, 2 showed a 25 to 50% response, and 1 showed a mixed response. MER is a potent simulus to cellular and humoral immunity in the patient with advanced gastrointestinal cancer. This stimulation may occasionally result in a clinically evident antineoplastic effect.

Adult↗