C. C. Shullenberger

Serum copper observations in patients with malignant lymphoma

A study of 353 serum copper levels (SCL) in 236 patients with non‐Hodg‐kins lymphoma has demonstrated, in general, a clinically useful relationship between SCL and disease activity. Elevated SCL in the active disease decreases as disease activity is reduced in response to therapy, with normal SCL in inactive phases and increased SCL in relapse generally preceding clinical signs. This relationship of SCL to disease activity is noted in all histologic groups and types of malignant lymphoma, with SCL values slightly higher in undifferentiated lymphoma. An analysis of apparently inconsistent SCL has been included. The relationship between SCL and extent of disease is shown by marked elevation of SCL in generalized disease as contrasted to localized disease. A detailed study of sequential SCL in 18 patients undergoing therapy also confirmed its clinical usefulness in the evaluation of status of disease activity and efficacy of therapy.

Prognostic factors in localized Hodgkin's disease treated with regional radiation. Clinical presentation and specific histology.

Abstract One hundred forty-seven cases of clinically localized Hodgkins disease, admitted between 1947 and 1963, are reviewed. The incidence of local control by intensive regional radiotherapy was analyzed in terms of tumor dose, overall treatment time, and therapy techniques for the major areas of clinical involvement. Although overall survival figures for Stages I and II were similar to other recorded results, statistically significant differences became apparent when the material was analyzed by clinical presentation, specific histology, constitutional symptomatology, and from survival and relative incidence of first manifestations of new disease. Significance of these observations is considered.

Stage II Hodgkin's disease. Significance of mediastinal and nonmediastinal presentations.

Case material on 208 patients with Stage II Hodgkins disease has been reviewed. Survival figures and patterns of secondary manifestations including laparotomy findings have been compared for mediastinal presentations versus other Stage II presentations in patients staged prior to lymphography versus patients staged by lymphography. Higher survival was seen in lymphography-staged patients and in both groups for patients with mediastinal presentation. The influence of age and sex was determined for both series. Age has a significant influence on survival. Females showed higher survival rates in the clinically staged group, but there was no difference observed in the lymphography-staged group.

Long-term culture of lymph node tissue from a patient with lymphocytic lymphoma. II. Preliminary ultrastructural, immunofluorescence and cytogenetic studies.

The original cell line was established from a lymph node biopsy specimen from a 59‐year‐old male patient having lymphocytic lymphoma (chronic lymphocytic leukemia). The culture has maintained an identical pattern of growth for 18 months. Two morphologically distinct cell types are present. One is a spindle shaped, flattened element attached to the glass surface, often forming an interlacing network; the other appears as clusters of ovoid or round floating elements. A first report described immunofluorescent studies with antihuman gammaglobulin, in which the round floating elements displayed marked fluorescence. This second report mentions similar results obtained using the patients labeled gammaglobulin. Preliminary ultrastructural studies revealed elementary particles resembling virus in the same cells. Chromosomal analysis of the strain showed a change to aneuploidy at approximately 6 months.

Radiotherapeutic Management of Localised Hodgkin's Disease involving the mediastinum

Abstract Fifty-five patients were treated by radiation therapy for Hodgkins disease clinically localised to the mediastinum or the mediastinum and peripheral node-bearing areas above the diaphragm. Twenty-six have been followed a minimum of five years. Intensive regional irradiation was administered to the neck, mediastinum and, when necessary, the axillae in 48 of 55 patients, the average tumour dose being 3,000 to 4,000 rads. Seven patients were treated less radically. The survival rates for three, five, and ten years, calculated according to the Modified Life Method of Berkson-Gage, were 95·5, 78·4, and 56·5 per cent. Of ten patients who developed a recurrence in the mediastinum, five received tumour doses of 2,500 rads or less. With the exception of those patients who developed complications following retreatment for mediastinal recurrence, no serious complications developed as a result of mediastinal treatment. However, review of serial follow-up radiographs demonstrated an increasing incidence of p...

Leukemogenic effect of human leukemic materials. Attempts to enhance effect in mice by combination of materials with inactivated mouse leukemia virus

Human leukemic bone marrow cells or fluids from cultures of such cells were mixed with heat‐inactivated (56°C for one hour) Rauscher mouse leukemia virus and the mixtures were inoculated into two to three‐day‐old Swiss mice of a low‐leukemia line. Control mice were inoculated with (1) the human material mixed with heat‐inactivated normal mouse spleen extract and (2) the heatinactivated Rauscher virus mixed with fluids from normal human cell cultures. Sixteen human leukemic materials were tested with equivocal results except in one instance. When mixed with heat‐inactivated Rauscher virus, tissue culture fluids from lymph node and bone marrow cells of a 15‐year‐old girl with acute leukemia repeatedly caused leukemia with significantly higher incidence than the corresponding controls. Theoretically, an increased leukemogenic potency of human leukemic materials and inactivated murine leukemia virus can be explained by recombination of human and murine leukemia viruses (“genome rescue”) but other mechanisms, such as phenotypic mixing, multiplicity reactivation of the murine leukemia virus or increased activity of virus‐decoating enzymes, are also possible.

Mouse leukaemia, a dichotomy of virus neutralizing and cytotoxic antibodies

Mice exposed to subliminal doses of live, or to large doses of properly inactivated mouse leukaemia viruses, or cells, will develop antibodies. These antibodies can be detected by virus neutralization (1, 2, 3, 4) and cytotoxic tests (5, 6, 7), among other techniques. I t is not known how these serologic faculties are correlated. Studies in progress suggest tha t the virusneutralizing and cytotoxic antibodies are not identical. The following is a preliminary report on these studies. An immune serum was obtained from mice with adoptive immunity. The cell donors were low leukaemia Timco (Texas Inbred Mouse Company, Houston) S~dss mice vaccinated with photodynamieally inactivated Rauseher mouse leukaemia virus. The technique of photodynamic inactivation of this virus has recently been reported (4, 8). A cell-free spleen extract of leukaemic mice is mixed with high dilution of methylene blue and the mixture is transill~minated with visible light for 25 minutes a t 37 ~ C. Due to photooxidation, the virus loses its infectivity. In the experiment described here, 3 doses of such inactivated virus were injected intraperitoneally into young adult mice a t 3-week intervals. The second dose of the vaccine was given together with Freunds complete adjuvant. These mice produced both virus neutralizing and cytotoxic antibodies. The pooled and inactivated (56 ~ C for 20 minutes) serum neutralized more than 102 LDs0 of the Rauscher virus (8). In the cytotoxic test, 15 per cent of Rauscher leukaemic spleen cells responded with swelling and pinkish