Mechanisms of cellular cytotoxicity mediated by effector cells from rats with spontaneous tumors.

We have previously shown that effector cells from BD X rats bearing spontaneous tumors display increased cytotoxicity towards syngeneic tumor cells compared to effector cells from untreated rats (Zöller and Matzku, 1980 a). The increased in vitro cytotoxicity of lymphoid cells from tumor-bearing (TB) animals was not T-cell mediated and the question was raised, whether it was due solely to increased natural killer (NK) cell activity, or whether humoral factors could also be involved. We now prove that in a long-term assay, the presence of B cells is indeed mainly responsible for increased TB cytotoxicity, since: (1) After depletion of surface immunoglobulin positive cells (s-Ig+), TB cytotoxicity no longer exceeds cytotoxicity of effector cells from untreated rats; (2) Mixtures of s-Ig+ cells from TB animals with Fc-receptor positive (Fc-R+) cells from untreated rats restore the increased TB cytotoxicity; (3) Addition of rabbit Fab' anti rat F(ab')2 reduces TB-effector cell cytoxicity.

Natural killer cells do not belong to the recirculating lymphocyte population.

Natural Killer (NK) cells constitute a cell type with an as yet undefined lineage, although certain similarities with T lymphocytes have been found in the mouse. Our present results show that NK cells have a significant difference compared with T and B cells in their capacity to traverse the blood-lymph barrier. Thoracic duct lymphocytes from mice or rats are thus devoid of NK activity, when at the same time potential, cytotoxic T lymphocyte (CTL) activity or antibody-dependent cellular cytotoxicity function can be demonstrated.

Identification of the catalytic subunit of casein kinase II by affinity labeling with 5'-p-fluorosulfonylbenzoyl adenosine.

Casein kinase II, purified from reticulocytes, was covalently labeled with the ATP affinity analog, 5'-p-fluorosulfonylbenzoyl adenosine. The reaction was monitored by the decrease in enzyme activity and showed saturation kinetics with respect to the sulfonyl compound. This suggested a rapid equilibrium was established between the enzyme and affinity reagent prior to a slower, rate-determining step in the overall inactivation process.

Affinity labeling of cAMP-dependent protein kinase with p-fluorosulfonylbenzoyl adenosine. Covalent modification of lysine 71.

p-Fluorosulfonylbenzoyl 5'-adenosine (FSO2BzAdo) was shown previously to be an irreversible inhibitor of the catalytic subunit of cAMP-dependent protein kinase II from porcine skeletal muscle (Zoller, M. J., and Taylor, S.

Electronystagmography in congenital and acquired syphilitic otitis.

This study is an analysis of the electronystagmogram (ENG) changes in 17 patients with luetic vestibular disease with early and late acquired syphilis and congenital syphilis. Vestibular disturbances occurred in 80% of patients with luetic otitis. Among these patients the ENG gives signs of peripheral rather than central vestibular injury, and reduced vestibular response to caloric stimulation is the most common finding.

Organ-related and malignancy-associated reactivity of cancer patients' leucocytes: a leucocyte migration study with tumour and foetal extracts.

Leucocytes from patients with a variety of tumours including gastric, colorectal, lung, kidney and mammary cancer, were tested in the leucocyte migration test (LMT) against organ-related and non-organ-related tumour and foetal extracts. The reactivity of cancer patients' leucocytes against a panel of organ-related tumour extracts was found to be 71-93%, depending on the tumour system tested. Cross-reactivity with a panel on non-organ-related tumour extracts was found in 0-38% of patients.

Specific cytotoxicity in vitro by T-cell-enriched lymphocyte subpopulations from rats bearing chemically induced but not spontaneous tumors.

Effector cells from inbred BD X and WAB rats bearing either spontaneously arising or chemically induced tumors were cytotoxic for target cells of both kinds of tumor. The level of cytotoxicity of tumor-bearing animals regularly surmounted that of natural cytotoxicity observed in age-matched untreated controls. These findings were obtained by a visual-countin microcytotoxicity assay (48 hr) and by a 51Cr label assay (12 hr).

Lack of correlation between carcinoembryonic antigen content of tumor extracts and leukocyte migration reactivity of tumor patients.

Tumor extracts varying in carcinoembryonic antigen (CEA) content (0.4--2,280 ng/mg protein) did not affect the reactivity of cancer patients' leukocytes in the leukocyte migration inhibition test (LMIT). In addition, variations in the plasma CEA levels of tumor-bearing leukocyte donors did not influence the frequency of significant LMIT reactivity.

Characterization of natural cytotoxicity in vitro in a spontaneous rat tumor model.

Spontaneous rat tumor cells were tested in a 12-hr Cr-release assay for susceptibility or resistance to cytolysis by lymphoid effector cells from untreated rats. Most target cells were intermediate to highly susceptible (up to 85% lysis at an effector-to-target ratio of 50:1), but we observed nonsusceptible target cells, too. Cold target inhibition experiments confirmed the susceptibility classifications obtained in the direct assay.

Sensitization of leukocytes of cancer patients against fetal antigens: leukocyte migration studies.

Hypertonic extracts from human fetuses (10--22 wk of gestation) were used to test the sensitizaton of leukocytes from cancer patients against fetal antigens in a direct, microcapillary tube assay system. Leukocytes were simultaneously exposed to a panel of allogeneic tumor extracts and a panel of fetal extracts. Leukocytes from 24 gastric cancer patients, 43 colorectal cancer patients, and 13 lung cancer patients were assayed with extracts obtained from gastric, colorectal, and oat cell carcinomas, respectively, and these extracts were also used with leukocytes from 41 patients bearing tumors of various other organs.

Treatment of syphilitic hearing loss. Combined penicillin and steroid therapy in 29 patients.

Twenty-nine patients with presumed syphilitic hearing loss, either congenital or acquired, were treated on one or more occasions according to a three-month protocol using penicillin and prednisone. Changes in hearing were carefully followed during treatment and for at least one year thereafter. Of 58 ears studied in 29 patients, 19 demonstrated significant partial improvement in hearing during treatment.

Detection of syphilitic hearing loss.

Syphilis can cause sensorineural hearing loss that is potentially treatable. To determine the incidence of positive serological findings in patients with sensorineural hearing loss, the rapid plasma reagin card test (RPRCT) and the FTA-ABS test were performed in a study group composed of patients with sensorineural hearing loss of obscure origin. Of the 306 patients with sensorineural hearing loss, 20 (6.

Radioimmunological quantitation of human group-II pepsinogens.

A solid-phase sandwich radioimmunoassay was developed to quantitate human group-II pepsinogens in plasma. The test detected pepsinogen II in a concentration range of 0.25--64.

High incidence of spontaneous transplantable tumours in BDX rats.

Untreated male and female BDX rats were observed over a period of 30 months for spontaneous tumours of a size suitable for transplantation. At the age of 13-30 months 60/97 animals developed tumours, 53 of which were considered as malignant, and 7 as benign tumours. The spectrum of malignant tumours included sarcomas of connective tissue and bone, skin carcinomas, tumours of the lung, the gastrointestinal tract, the genito-urinary tract, the mammary glands, the testis, the adrenal glands and also sarcomas of the neural system and malignancies of the lymphoreticular system.

Guidelines for prognosis in head and neck cancer with nodal metastasis.

Patients with squamous cell carcinoma of the head and neck with cervical node metastasis were studied retrospectively to delineate the prognostic significance of certain clinical and histologic parameters. The patients were divided into radiated and non-radiated groups for analysis purposes. A good prognosis was found in non-radiated patients with an active nodal plasmacytic inflammatory response.

Evaluation of 51Cr release for detecting cell-mediated cytotoxic responses to solid chemically induced rat tumours.

A 51Cr-release test was developed for the detection of cell-mediated cytotoxicity against transplanted solid chemically induced rat tumours, and the findings were compared with those obtained in parallel tests using a microcytotoxicity assay. It was necessary to incorporate several modifications of the original Brunner assay (Brunner et al., 1968) in order to increase the sensitivity of the test as applied to long-term tumour lines maintained as glass-adherent cultures.

Leukocyte migration studies in gastric cancer detection: an approach toward improved specificity and sensitivity.

Peripheral blood leukocytes from patients with gastric cancer and various other malignant and nonmalignant diseases and peripheral blood leukocytes from apparently healthy volunteers were tested in the leukocyte migration inhibition test with the use of 4-5 different 3 M KCl extracts of gastric cancer tissue. An operational criterion for defining sensitization of patients' leukocytes was developed; i.e.

A modified leucocyte migration assay as indicator of malignant and non-malignant gastric mucosal alteration.

When gastric cancer patients' leucocytes were exposed to a panel of tumour extracts, leucocyte migration reactivity was "positive" before operation (90% of cases), it declined after surgery and it reappeared in patients with local recurrence or metastases. In patients with non-malignant gastric diseases, "positive" reactivity against tumour extracts was associated almost exclusively with atrophic gastritis with and without intestinal metaplasia (24/43 cases). "Positive" patients also showed a pathological migration index with an extract of normal gastric mucosa.