The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Summary A protinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD and tumour cells. This enhancement is greater in the tumour-bearing mice.Acknowledgments. We are grateful to Bayer (U.K.) Limited for generous supplies of aprotinin. The PPD was supplied by the Ministry of Agriculture. The work was supported by a grant from the North of England Cancer Research Campaign.     

Accelerated development of a Th-2 type factor in animals with and without an imbalance between help and suppression

Summary A helper factor can be detected in antigen-treated supernatants from spleen T and adherent cells of sensitized animals. This factor promotes an indirect hapten-specific plaque forming response of B cells, irrespective of the identity of the carrier, i.e. provides the Th-2 type of help. Factor production increases with age and occurs most rapidly in strains known to have an accelerated decrease of suppressor capacity. The reason for the inverse correlation between suppressor capacity and the Th-2 type of helper factor is discussed.Acknowledgments. Thanks are due to the Medical Research Council, the National Cancer Institute of Canada and the National Health Research and Development Program for financial support; T.M. is indebted to the Medical Research Council for personal support.     

The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Aprotinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD nd tumour cells. This enhancement is greater in the tumour-bearing mice.     

Quantitation of proinsulin mRNA sequences in hamster insulinoma cells in culture by molecular hybridization

Summary The content of proinsulin mRNA sequences was measured in a cultured cell line established from a transplantable hamster islet cell tumor, by hybridization with proinsulin cDNA. The cells cultured in vitro were found to contain a significant amount of proinsulin mRNA sequences, compared with non-insulin-producing hamster tissues, and seem to be a useful system for the study of insulin gene expression.This work was supported in part by Grants-in-Aid Scientific Research (248129, 387065, 337013, 378052) and a Grant-in-Aid for Cancer Research (301538) from the Ministry of Education, Science and Culture, Japan.     

Réaction immunoallergique provoquée chez le rat par l'injection d'extraits chauffés de la tumeur de Walker

Summary When repeatly injected to Fisher Inbred rats, boiled Walker tumour extracts induced non specific and specific reactions; non specific reactions being catabolism, thymus involution, adrenal hypertrophy and perturbation of serum proteins relative distribution. The specific reactions attributable to the presence of the specific tumoral antigen in the tumour extracts are immunoallergic arthritis, liver and spleen hypertrophy, acceleration of serum albumin electrophoretic migratory rate and the apparition of the specific antigen in the liver.

---

---

Travail subventionné par l'Institut du Cancer du Canada.     

Effect on macrophages of acute stress induced in mice by local irradiation]

In examining the role of radiation in inducing immunosuppression in tumor-bearing Mice it has been shown that the experimental acute stress inadvertently generated by the procedure is profoundly immunosuppressive. It would appear that monocytes under the influence of glucocortico?ds are sequestered in the spleen. This monocyte immobilisation leads to rapid suppression of local inflammatory reactions including delayed hypersensitivity. The increased number of marcrophages in the spleen is co-incident with non-specific non T cell splenocyte anti-tumour activity. Stress induced suppression of inflammation is prevented by previous adrenalectomy and restored by hydrocortisone.     

The role of p53 in tumour suppression: lessons from mouse models

The use of mouse models has greatly contributed to our understanding of the role of p53 in tumour suppression. Mice homozygous for a deletion in the p53 gene develop tumours at high frequency, providing essential evidence for the importance of p53 as a tumour suppressor. Additionally, crossing these knockout mice or transgenic expression p53 dominant negative alleles with other tumour-prone mouse strains has allowed the effect of p53 loss on tumour development to be examined further. In a variety of mouse models, absence of p53 facilitates tumorigenesis, thus providing a means to study how the lack of p53 enhances tumour development and to define genetic pathways of p53 action. Depending on the particular model system, loss of p53 either results in deregulated cell-cylce entry or aberrant apoptosis (programmed cell death), confirming results found in cell culture systems and providing insight into in vitro function of p53. Finally, as p53 null mice rapidly develop tumours, they are useful for evaluating agents for either chemopreventative or therapeutic activities.     

Morphogenesis of human colon cancer cells with fetal rat mesenchymes in organ culture

Summary The morphogenesis and cytodifferentiation of human colon cancer cells (LS174T and HT29) were examined by combining cancer cells with fetal rat digestive-tract mesenchyme in organ culture. LS174T cells migrated into the mesenchyme to form glandular structures composed of single columnar cells with their nuclei oriented basally, while HT29 cells formed cell masses with little lumen formation. Immunohistochemical studies with antibodies against carcinoembryonic antigen and secretory components showed that the composition of cell surface glycoproteins was not necessarily reversed to the normal type, even when neoplastic cells exhibited normal glandular structures.This work was supported by grants-in-aid for Cancer Research from the Ministry of Education, Science, and Culture, Japan, and by the Veterans Administration Medical Research Service, USA. Y.S. Kim is the recipient of a Medical Investigator Award of the Veterans Administration.     

Sensitivity of follicular melanoblasts in newborn mouse skin to tritiated thymidine: Evidence for a long term retention of label

Summary Injection of tritiated thymidine into newborn mice results in a progressive greying of hair that does not begin until after the first hair coat is grown. After a year the depigmentation is appreciable (about 60% of the hair are white). The effect cannot be simulated by external irradiation of newborn mice or by the administration of radioactive uridine or methionine. The effect can best be explained by a long-term retention of radioactivity in the DNA of melanocyte stem cells (melanoblasts) in spite of several rounds of cell division. This could be achieved by labelling the strands of DNA destined to act as templates throughout life by being selectively retained in the stem line as described in Cairns' hypothesis.Acknowledgments. This work was supported by grants from the Cancer Research Campaign. I am indebted to Joan Bullock for her careful, patient help with these experiments. CSP is a fellow of the Cancer Research Campaign.     

Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer

Stable transfection of human ovarian carcinoma cells with survivin cDNA caused a four- to sixfold increase in cell resistance to taxotere and taxol (two-sided Student's t test, p < 0.05), with a concomitant reduction in the apoptotic response to taxol, but did not affect cell sensitivity to cisplatin or oxaliplatin. Such findings were indirectly supported by similar observations obtained with clinical tumours. In fact, high levels of survivin protein expression (>30% positive cells), detected by immunohistochemistry in 90/124 (73%) advanced ovarian carcinomas, were significantly associated with clinical resistance to a taxol/platinum-based regimen but unrelated to tumour shrinkage following cisplatin-including combinations (non-taxol based). In the 95 patients receiving a taxol/platinum-based regimen, survivin overexpression correlated with a lower clinical or pathologic complete remission rate than absent/low protein expression (43 vs 75%, p = 0.0058 by logistic regression adjusted for tumour stage, histological grade and p53 expression). Conversely, in the 29 cases treated with cisplatin-containing regimens (not taxol based), survivin expression was unrelated to tumour response. Cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol.     

Histopathological modifications following immunotherapy with P 40 in rats bearing DMBA-induced mammary carcinoma

Summary Female Sprague-Dawley rats bearing primarily-induced mammary carcinomas were treated with a new immunostimulating agent (P 40). The histopathological modifications encountered in tumors, lymph nodes, liver and spleen are described. Intratumoral injections provoke a more widespread response of the RES, and particularly a more intense reaction in the draining lymph nodes, than systemic treatment.This work was partly supported by a contract from CHU Necker Enfants Malades (Prof. J. Reynier), with the help of the Ligue Nationale Française contre le Cancer, the FEGE-FLUC and the International Society against Breast Cancer.We thank also the Ecole de Chirurgie, Paris, and the Pasteur Institute which kindly provided the immunostimulating agent P 40. The skillfull collaboration of Dr R. Villet, Mlle G. Amichot and Mme J. Garaudel is gratefully acknowledged.     

Occurrence of trichochromes in the urine of a melanoma patient

Summary The presence of two phaeomelanic pigments, trichochrome B and C, was demonstrated in the urine of a patient with malignant melanoma metastases.Supported by grants from the Swedish Cancer Society (No. 626-B75-04XA), 869-B75-01P, the Swedish Medical Research Council (No. B76-04X-00056-12), and the Walter, Ellen and Lennart Hesselman Foundation for Scientific Research. ProfessorProta was a visiting scientist of the Swedish Cancer Society (No. 626-B75-04U).     

Application of the indigogenic principle for the histochemical demonstration of ribonuclease

Zusammenfassung Es wurde ein neues Indolsubstrat für die histochemische Demonstration von alkalischer RNase II und saurer RNase II synthetisiert. Dieses Verfahren ist besser, schneller und präziser als die bisherigen Kupplungstechniken.

---

---

This investigation was supported in part by Public Health Service Research Grants No. CA-02624 and CA-02903 from the National Cancer Institute and in part by an institutional grant to the Detroit Institute of Cancer Research from the United Foundation of Greater Detroit allocated through the Michigan Cancer Foundation and Detroit General Hospital Research Corporation, Newaygo County Cancer Society. We thank MissPat Warzocha for secretarial assistance.     

2/8 translocation in a Japanese Burkitt's lymphoma

Summary A new translocation between chromsomes 2 and 8 t(2p^–; 8q⁺), was found in fresh lymphoma cells from a Japanese patient with Epstein-Barr virus-carrying Burkitt's lymphoma, and in a lymphoma cell line derived from this patient. There was no 14q⁺ translocation, as has been previously described in African and North American Burkitt's lymphomas.Supported by a grant-in-aid for Cancer Research (52-11) from the Ministry of Health and Welfare of Japan.     

Cytotoxic action of nucleic acids

Zusammenfassung Mit einer letalen Dosis von Dimethyl-Myleran vorbehandelte Mäuse überleben nach Transfusion isologer Knochenmarkzellen. Wirken Nukleinsäurenin vitro auf die Knochenmarkzellen ein, so ist ihre lebenserhaltende Kapazität vermindert.

---

---

This investigation was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research: Royal Cancer Hospital, London) from the Medical Research Council, the British Empire Cancer Campaign, the Anna Fuller Fund and the National Cancer Institute of the National Institutes of Health, U.S. Public Health Service.     

Ocular involvement in hamsters transplanted with a human leukemic T-cell line

Summary A leukemic T-cell line (TALL-1) was serially transplanted for 5 passages into newborn hamsters treated with antilymphocyte serum. This cell line was derived from a leukemic patient with clinical evidence of ocular involvement. I.p. implantation of 1–3×10⁷ cells resulted in disseminated growth of tumors in all 15 recipients after 23–41 days and 8 of them showed leukemic infiltration of the uveal tract of one or both eyes.Supported by a Cancer Research Grant from the Ministry of Health and Welfare of Japan.     

Suppression of immunization to tuberculosis and diphtheria by an extract of lymphoid tissue

Zusammenfassung Dank einer neuen Anwendung von Lymphknotenextrakten (statt Röntgenextrakten, Corticosteroiden, Antilymphozytenserum usw.) wird eine erhebliche Reduktion der immunologischen Reaktion erzielt, wenn die Tiere mit diesen Extrakten vorbehandelt und gleichzeitig mit Antigenen behandelt werden.

---

---

This investigation was supported in part by U.S.P.H.S. Research Grant No. CA-02624 from National Cancer Institute; and in part by an institutional grant to Detroit Institute of Cancer Research from United Foundation of greater Detroit allocated through Michigan Cancer Foundation and the Detroit General Hospital Research Corporation, and Newaygo County Cancer Society.     

The fine structure of cloned cells from normal adult rat brain

Summary A cell clone was isolated from a normal adult rat brain culture and maintained in vitro for many passages. It possessed glial characteristics; in particular ultrastructural examination revealed astrocytic features including the presence of filaments 9–11 nm in diameter.Acknowledgments. The work was partly supported by a grant from the Cancer Research Campaign to JPR. The secretarial help of Miss Hilary A. Waddington is gratefully acknowledged.     

Serendipitous precise and unique staining of cell nuclei

Zusammenfassung Frischgefrorene Gewebesektionen verschiedener Gewebe wurden in Kalium-Eisen-Cyanid bei pH 5,2 inkubiert; dabei wurde eine präzise und einzigartige Färbung nur der Zellnuklei beobachtet. Die Ursache dieser selektiven Kernfärbung ist nicht verständlich, doch stellt sie höchstwahrscheinlich eine Färbung von Ferro-Verbindungen in den Nuklei dar.

---

---

This investigation was supported in part by Public Health Service Research Grants Nos. CA 02624 and CA 02903 from the National Cancer Institute and in part by an institutional grant to the Detroit Institute of Cancer Research Division of the Michigan Cancer Foundation from the United Foundation of Greater Detroit, and Detroit General Hospital Research Corporation. Newaygo County Cancer Association. We wish to express our gratitude for stenographic assistance to Mrs.Georgette M. Bellmay.     

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased, alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.