Steroid economising effects of a calf thymus extract in three patients with juvenile chronic arthritis.

Recent therapeutic trials in rheumatology using different immunomodulating agents have given encouraging results. In this study an aqueous calf thymus extract (CTE) was administered to three patients, two with systemic juvenile chronic arthritis (JCA), Still's disease, who could not be weaned from steroids during 2 years of conventional therapy, and one girl with a chronic juvenile monarthritis who had responded unsatisfactorily to nonsteroidal antirheumatics for 19 months. A striking clinical improvement was observed in all three patients. Prednisone (PRED) was discontinued in one case with systemic (JCA) and 0.25 mg/kg body weight/day is presently being given to the other patient. The girl is doing well on 4 mg chloroquin kg body weight/day; indomethacin (IND) was discontinued. Laboratory data including cellular immunoreactivity normalized in all three patients.

A comitogenic serum glycoprotein in T lymphocyte activation.

The production of Interleukin-2 is induced in helper cells, probably of T-cell origin, after stimulation by Interleukin-1. PHA is known to induce production of Interleukin-1 and Interleukin-2 in human PBL. We observed that PHA-induced mitogenesis in PBL requires the presence of a 90-KD-serum glycoprotein, which we were able to distinguish from other known serum proteins of similar molecular weight. Its biological activity can be destroyed by removal of its sialic acid residues. Evidence presented in this paper indicates that the function of this protein is related to the induction of synthesis and/or release of Interleukin-2. The presence of PHA does not seem to be essential at the level of Interleukin-2 production; the glycoprotein is able to induce Interleukin-2 in cooperation with a soluble mediator, which is produced by adherent cells. This mediator causes T-cell mitogenesis in PBL, provided serum or the 90-KD glycoprotein is present in the culture. It is not able to support the growth of a CTL line. We suggest the name PHILIP (Plasmatic Human Interleukin-2-Inducing Protein) for the 90-KD molecule.

[Retrospective follow-up study on 476 patients admitted for the first time to a nursing-home]. / Retrospektive Verlaufskontrolle von 476 erstmalig in Pflegeheime verlegten Patienten.

During a seven-months' observation period the death-rate of 476 patients referred for the first time to a nursing home were checked up. In the first three months the rat of mortality was extremely high. With patients transferred from a hospital to a nursing-home the rate was much higher than among patients coming from their own home. The male mortality rate was higher than the female rate. The patients' age and the number of diseases diagnosed did not exercise any great influence on the mortality rate. Before admittance to the nursing-home, more males than females had been living in partnership.

[T-lymphocyte activation. Studies on the function of mediator proteins (author's transl)]. / T-Lymphocyten-Aktivierung. Untersuchungen zur Funktion von Mediatorproteinen.

The functions of several mediator proteins involved in the T-cell blastogenesis have been investigated 1. Newly described is the Plasmatic Human IL-2 Inducing Protein (PHILIP), a glycoprotein from human serum with a molecular weight of about 85,000 D. Its presence is mandatory for the synthesis and/or secretion of Interleukin-2 (T-cell growth factor). The mediator protein can be distinguished from other known serum glycoproteins (e.g., transferrin and plasminogen) by affinity chromatography. Desialylation completely abolishes its biologic activity. 2. PMSF- and DFP-treatment of conditioned culture medium inhibit the blastogenesis in the peripheral mononuclear blood-cell fraction. However, the growth of a permanent T-cell line in the inhibitor-treated medium is not affected. This indicates the existence of a blastogenic factor with serine-protease activity.

[Functional disorders of the thymus-dependent immune system after surgery]. / Funktionsstörungen des thymusabhängigen Immunsystems nach operativen Eingriffen. Mögliche Bedeutung für die Tumorchirurgie.

In patients, who underwent surgery for inguinal hernia, a profound suppression of T-lymphocyte functions was found as revealed by a new T-cell function assay. Conventional tests, such as PHA stimulation of lymphocytes and T/B-lymphocyte quantitation showed no changes after this rather minor operation. Thus it must be assumed, that aside from the short-lasting immunosuppression described in the literature after more extensive surgery, even smaller surgical procedures cause a rather long-lasting and severe impairment of T-lymphocyte functions. Since the immune system may play a possibly important role in the defence against autologous tumors, the indications for surgical treatment not concerning the tumor itself in malignoma patients should be severely considered.

Human primary T-cell lines in lectin-free media.

A method of establishing human T-cell lines in tissue culture media containing TCGF but not PHA is described. PBL, initially stimulated by PHA to produce TCGF, continue production for at least 48 hrs after the lectin has been washed off. The TCGF-conditioned medium initiates blast formation of T-cells from freshly isolated PBL and supports indefinite growth of the T-cell blasts from the primary PBL cultures and also from blast-cells obtained from clonally derived T-cell colonies grown in soft agar culture. The established cell lines are identified by cytochemical and biological means as belonging to the T-cell compartment and express spontaneous cytotoxicity against HeLa-cells. The continuously growing T-cells are unable to produce TCGF and depend strictly on external supply of the growth factor. PHA by itself does not support T-cell growth in spite of its ability to elicit a mitogenic response in PBL-cultures. Thus two types of cells must be involved in the mitogenic event: (i) a TCGF-producer and (ii) a TCGF-responder. PHA elicits in the former TCGF production and then TCGF in the later the mitogenic T-cell response. Therefore, not PHA but TCGF might be considered to be the T-cell mitogen.

[Influence of hyperthermia on toxic side effects of cytostatic agents (author's transl)]. / Klinisch-chemische Untersuchungen an Tumorpatienten unter Zytostatica- und Ganzkörperhyperthermiebehandlung.

14 patients with tumors in generalised stages (Hodgkin's disease, oat-cell-carcinoma, Fibrosarcoma, acute leukemia) were treated altogether 54 times with cytostatics in combination with hyperthermia. The temperature was induced by microwaves with a frequency of 27 MHz. A temperature of 40 degrees C was reached after 40 min. At this point cytostatics were applicated; afterwards the temperature was maintained for one hour at 40-40,5 degrees C. Cardia, pulmonary and circulatory complications did not occur. Controls of the laboratory parameters could exclude effects on electrolytes, muscles, blood, liver and kidney. The laboratory controls were made before, during, immediately after and 24 h after hyperthermia. There were no signs for an enhancement of toxicity typical for cytostatics. The observations are compared to the results of other investigators. To date the therapeutic effect of this treatment can not be stated.

[Changes in clinical and immunological laboratory parameters of healthy adults after exposure to a one-hour 40 degree C-whole-body hyperthermia (author's transl)]. / Klinisch-chemische und immunologische Veränderungen bei Gesunden nach einer einstündigen 40 degree C-Ganzkörperhyperthermie.

There are no signs of organ lesions in healthy subjects exposed to an 1-hour 40 degree C whole-body hyperthermia, induced by radiofrequency or infrared light. As to the immunological in vitro parameters, only a slight decrease of the relative T-cell count is seen, T-cell functions however being normal. A leukocytosis appearing during infrared-induced hyperthermia is probably related to the erythema caused by skin heating. About possible indications and clinical values of this treatment, nothing can however be said so far.

Expression of immunoglobulin synthesis in human myeloma x non-lymphoid cell heterokaryons: evidence for negative control.

Heterokaryons formed between human myeloma cells and various types of mouse and human non-lymphoid cells loose their cytoplasmic content of lambda light chains, a component of IgE produced by the myeloma parent. This loss of immunoglobulin content was observed regardless of the species origin (mouse or human) of the non-lymphoid partner cell, suggesting that the factors responsible for extinction of this differentiated function are not specific for a species. The kinetics of the loss of immunoglobulin content was essentially identical in the different experiments, since all myeloma X non-lymphoid cell heterokaryons were scored as negative after immunofluorescence staining for lambda chains 4-6 hr after infusion. Myeloma cells treated with inhibitors of protein synthesis (puromycin and cycloheximide) also lost their cytoplasmic content of immunoglobulin after 4 hr. These results indicate that the fusion of myeloma cells with non-lymphoid cells results in an immediate inhibition of immunoglobulin synthesis.