bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface glycoprotein patterns of normal and malignant human lymphoid cells. II. B cells, B blasts and epstein‐barr virus (EBV)‐positive and ‐negative B lymphoid cell lines
Authors: Nilsson Kenneth , Andersson Leif C. , Gahmberg Carl G. , Wigzell Hans
Published: February 2007

Surface glycoproteins of normal human B lymphocytes, B blasts and various types of lymphoid cell lines were labelled by the galactose oxidase‐tritiated sodium borohydride method. The labelled glycoproteins were separated by polyacryUmide slab gel electrophoresis in the presence of sodium dodecy! sulfate and visualized by modified autoradiography (fluorography). The battery of examined hematopoietic cell lines included Epstein‐Barr virus (EBV) carrying lines of proven malignant origin (Burkitt's lymphoma) and presumed non‐neoplastic origin (lymphoblastoid cell lines), and EBV‐genome‐negative lymphocytic lymphoma, histiocytic lymphoma, myeloma and myeloid leukemia lines. The presence of possible EBV‐associated surface glycoproteins, detectable by the labelling method, was studied by use of two EBV‐negative cell lines (BJAB and Ramos) and their EBV‐converted sublines. The six Burkitt lymphoma and three lymphocytic lymphoma lines had all the basic surface glycoprotein pattern of resting B cells and, in addition to individually distinct bands, two characteristic pairs of glycoproteins sf apparent molecular weights of 87,000/85,000 and 71,000/69,OOO. These glycoproteins were not detected on the normal B celts, B blasts or non‐neoplastic lymphoblastoid lines. Neither were they found on the other types of neoptastic line. No consistent difference in the surface glycoprotein patterns was detected between the EBV‐genome‐negative and EBV‐con‐verted BJAB and Ramos sublines. The glycoprotein pattern of the six lymphoblastoid lines resembled that of the B blasts. The histiocytic lymphoma, myeloma and leukemia lines all had distinct patterns. These results confirm that the Burkitt's lymphoma and the lymphoblastoid cell lines represent two biologically distinct EBV‐carrying B lymphoid celts and that the galactose oxidase NaB[3H]4 surface labelling technique can be used as a reliable molecular mapping method to distinguish between these two and other types of lymphoid cell lines.
Geographic variations in tumor prevalence among marine fish populations
Authors: Stich H. F. , Acton A. B. , Dunn B. P. , Oishi K. , Yamazaki F. , Harada T. , Peters G. , Peters N.
Published: February 2007

A global epidemiological study on the frequency of skin papillomas among various flatfish species (Pleuronectids), papillomas of eels and the virus induced lymphocystis disease has revealed particular distribution patterns. Skin papillomas are prevalent among at least 20 flatfish species of the northern Pacific Ocean, Bering Sea, Sea of Okhotsk, and Japan Sea but appear to be absent from the Atlantic, North Sea, and the Caribbean Sea. The opposite is found for lymphocystis, which is common among flatfish species off the Atlantic shores of Europe and North America. Similarly the skin papillomas of eels are restricted to a relatively small region along the European coast extending from the Baltic countries to Denmark, Germany and Holland. Superimposed on this global distribution pattern are local variations in tumor prevalences which can vary from about 58% to 0.01%. The geographic distribution pattern points to the existence of areas around the globe in which flatfish or eels are able to develop skin papillomas. Outside these areas of “potential skin papilloma risk,” flatfish and eel populations are not afflicted with papillomas even if they inhabit estuaries or rivers with a high man‐made or naturally‐occurring pollution.
Immunologic identification of fetal calf serum‐derived proteins on the surfaces of cultured transformed and untransformed rat cells
Authors: Phillips Edwin R. , Perdue James F.
Published: February 2007

The antigens of rat embryo fibroblasts (REF) and of rat Rous sarcoma cells (derived by in vivo passage of oncogenically transformed REF) were studied using the technique of non‐ionic detergent solubilization of radiolabelled cells. Solubilized antigens were complexed with rat immune IgG, and precipitation of the complexes was accomplished with rabbit anti‐rat IgG. The precipitated radiolabelled antigens were then dissolved in sodium dodecyl sulfate and separated by poly‐acrylamide gel electrophoresis. This investigation disclosed the existence of cell surface antigenic proteins which are derived from the fetal calf serum (FCS) used in the cell‐culture medium. These FCS‐dependent antigens include at least three molecular species of approximate molecular weights 95,000, 80,000 and 68,000 daltons. They are probably derived from simple adsorption of FCS proteins to the cell surface, although more complex interactions are possible. One of these proteins (95,000 daltons) is of particular interest. It tenaciously adheres to the cell surface so that a trace amount remains even after subculture in the absence of FCS. Rat Rous sarcomas which are morphologically highly transformed appear to bind very little or none of this protein to their surfaces, whereas untransformed rat embryo fibroblasts bind large quantities. A rat Rous sarcoma line which is intermediate in morphological transformation binds an intermediate amount of this antigen. These findings invite speculation that the interaction of certain serum components with the cell surface may be related to plasma membrane properties which distinguish untransformed and transformed cells.
Induction of tumor resistance with BCGa‐associated tumor antigen
Authors: Crum E. D. , McGregor D. D.
Published: February 2007

Soluble material enriched in tumor‐associated antigen was prepared by affinity chromatography from a KCI extract of the chemically‐induced D‐23 rat hepatoma. Microgram quantities of the above material bound spontaneously to living BCG when the two were incubated briefly in vitro. When injected into normal syngeneic rats, the BCG‐associated tumor antigen induced a measure of resistance against challenge with D‐23 tumor cells. Peritoneal exudate cells (PEC) obtained from such actively immunized subjects were able to suppress the growth of D‐23 tumor cells at a test site in muscle. In contrast, immunization with either BCG alone, tumor protein alone, or tumor protein admixed with BCG in circumstances designed to impede association of the protein, failed to provoke the formation of tumor suppressor PEC. The results encourage the belief that binding of tumor antigen to BCG favors the induction of a cell‐mediated tumor suppressive response.
Tumor‐associated humoral cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy
Authors: Fäldt R. , Ankerst J.
Published: February 2007

Sera of eight unselected adult patients with acute myelogenous leukemia obtained before and after chemotherapy were repeatedly tested for specific complement‐dependent cytotoxicity against autochthonous peripheral white blood cells from the acute leukemia stage and from the remission stage, respectively. Complement‐dependent cytotoxicity against white blood cells from the acute leukemia stage was demonstrated in all of the eight patients, while none of three patients' sera were reactive against white blood cells from the remission stage tested in parallel. The cytotoxicity was increased after chemotherapy, also in those patients in whom remission was not achieved.
Isolation of breast cancer tumour antigen from serum and urine
Authors: Lopez M. J. , Thomson D. M. P.
Published: February 2007

A blocking tube leukocyte adherence inhibition assay (tube LAI) was used to detect and monitor the isolation of blocking factor from the serum and urine of advanced breast cancer patients. The results of the present study indicate that the blocking factor in serum and urine was soluble breast cancer TSA. In the serum, TSA chromatographed in the region of about 80,000 to >150,000 mol. wt and was shown not to be IgG. By the technique of polyanion precipitation, the TSA was shown to be lipoprotein in nature and co‐isolated with high‐density lipoproteins. In the urine, the TSA chromatographed in the region of about 48,000 mol. wt and this suggested that the serum TSA had undergone enzymatic cleavage prior to filtration. By immuno‐adsorbent affinity chromatography with xeno‐antisera directed to the xenoantigenic determinant of HLA, blocking factor (TSA) was isolated from sera from patients with metastatic breast cancer. The specificity of binding of TSA to the immuno‐adsorbent columns and the immunologically specific abrogation of LAI reactivity were clearly shown. Breast cancer TSA was also isolated from serum by immunoadsorbent affinity columns with human cytophilic IgG anti‐tumour antibody to breast cancer. The tumour‐specific antigenic determinant of human breast cancer appeared either to be associated with the major histocompatibility complex or to be a modified HLA antigen. The present study has defined the features of breast TSA present in serum and urine and it is possible that, from these sources and with these methods, sufficient quantities of pure TSA can be isolated.
In vitro assessment of immunocompetence in patients with malignant melanoma
Authors: Golub Sidney H. , Rangel Decio M. , Morton Donald L.
Published: February 2007

Ninety‐four patients with malignant melanoma and 96 healthy controls were tested for lymphocyte proliferative capacity in a microblastogenesis assay. Each lymphocyte sample was assayed for incorporation of (3H)thymidine after stimulation with PHA, PWM, Con A (two doses), PPD, and allogeneic lymphocytes (MLC). MLC was the only assay that revealed a substantial and significant difference between the melanoma patients and controls. Almost all assays showed lower values in patients with more advanced disease. However, it was not possible to accurately predict clinical outcome from data obtained from in vitro immunocompetence tests. These results indicate the relatively limited clinical usefulness of assays of lymphocyte proliferative capacity in melanoma patients.
Human tumour—lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour‐infiltrating, blood and lymph‐node lymphocytes with autologous tumour cells
Authors: Vose B. M. , Vánky F. , Klein E.
Published: February 2007

Lymphocytes prepared from the blood, tumour‐draining lymph node and tumour were tested for immune reactivity with freshly isolated autologous tumour cells from biopsies. Reactivity was assessed by the autologous tumour stimulation assay and by lymphocytotoxicity. Activity was found in 6/11 blood preparations, 7/10 lymph nodes and 1/7 tumour‐infiltrating lymphocytes in tumour stimulation assays and in 6/19 blood, 8/18 lymph‐node and 5/20 tumour‐infiltrating lymphocytes in cytotoxicity assays. Tests with material from patients with nasopharyngeal carcinoma showed a higher frequency of cytotoxicity in the tumour‐infiltrating lymphocytes than in other solid tumours. There was a correlation between results of the two assays when performed on the same preparations and between the levels of reactivity in lymph node and blood from the same patient. Cytotoxicity in the lymph nodes showed specificity in that cells from a long‐term culture (K562) known to be sensitive to natural killer activity and from allogeneic tumour biopsies were only rarely damaged. Cytotoxicity against K562 was more frequently determined in blood lymphocytes. Tumour‐infiltrating lymphocytes were non‐reactive in patients when the blood and lymph‐node lymphocytes were active.
C. Parvum immunotherapy of transplanted rat tumours
Authors: Pimm M. V. , Baldwin R. W.
Published: February 2007

C. parvum (Wellcome CN 6134) has been tested for tumour suppression against a range of syngeneically transplanted rat tumours, both carcinogen‐induced and of spontaneous origin. Subcutaneous growth was not prevented by distant subcutaneous or intravenous injection of the preparation, although growth rates were sometimes depressed or accelerated. In contrast, C. parvum injected in admixture with tumour cells consistently suppressed their growth and with highly immunogenic tumours induced systemic tumour immunity. C. parvum injected intravenously retarded development of pulmonary tumour deposits, and intrapleural injection suppressed growth of pleural tumours and malignant effusions. Host immunosuppression failed to abrogate the tumour‐suppressive effect of locally applied C. parvum, but host macrophage depletion with silica totally abolished the response. These studies indicate that in the rat, tumour suppression is most consistently achieved by regional application of C. parvum, and that this response is more dependent upon local macrophage stimulation than generation of systemic immune responses.
Inhibition of RNA and protein syntheses makes non‐differentiating mouse myeloid leukemia cells sensitive to a factor(s) stimulating differentiation
Authors: Okabe Junko , Honma Yoshio , Hozumi Motoo
Published: February 2007

Treatment with ascitic fluid from animals bearing various tumors, can induce mouse myeloid leukemia line cells, M1, to differentiate in vitro into macrophages and granulocytes. Cells were isolated that were resistant to the ascitic fluid factor(s) stimulating differentiation (D‐factor). The resistant cells became sensitive to the D‐factor and differentiated after treatment with various inhibitors of RNA synthesis (actinomycin D, nogalamycin, chromomycin A3 or cordycepin) or protein synthesis (puromycin or cycloheximide). The cells could not be induced to differentiate by treatment with the inhibitors alone. The effective doses of the inhibitors of protein synthesis were toxic to the cells. Among these inhibitors actinomycin D (5 ng/ml) was the most effective for sensitizing the resistant cells. Inhibitors of DNA synthesis did not sensitize the resistant cells. Added actinomycin D was mainly recovered in the nuclear fraction of the cells. The sensitizing effect of actinomycin D on the cells was roughly parallel to the extent of its inhibition of RNA synthesis in the cells. The effective concentration of actinomycin D (5 ng/ml) mainly inhibited the α‐amanitin‐sensitive RNA synthesis, although it also inhibited α‐amanitin‐resistant RNA synthesis to some extent. These results suggest that α‐amanitin‐sensitive RNA synthesis may be involved in sensitization of the resistant cells to the D‐factor.
Cellular immunity to SV40‐induced tumor cells and solubilized tumor‐associated antigens in immune mice using an isotopic footpad assay
Authors: Dean J. H. , Lewis D. D. , Padarathsingh M. L. , McCoy J. L. , Northing J. W. , Natori T. , Law L. W.
Published: February 2007

The 125Iodine isotopic footpad (IFP) assay was used to measure cell‐mediated immune (CMI) responses in vivo to intact tumor cells (TC), crude membrane (CM) preparations and NP40 solubilized tumor cell extracts in BALB/c mice immunized to the SV40‐induced tumor mKSA. A correlation was observed between footpad swelling as measured by calipers and the incorporation of 125I‐labelled human serum albumin into footpads of mice challenged with intact tumor cells. The IFP measurements were favored over footpad swelling measurements since the former lack the subjectivity involved in measuring footpad thickness and appear more sensitive and rapid to perform. These studies indicate that tumor‐associated antigens (TAA) on intact TC from SV40‐induced tumors can be recognized in vivo in the IFP assays and the response is specific to the sensitizing tumor in that other syngeneic tumors do not cross‐react. In addition, these data represent the initial success in using solubilized TAA in the IFP assay. Reactivity to TAA on either CM or NP40 crude soluble extracts of mKSA TC were observed, indicating that the required structural integrity for immune recognition of TAA was preserved following cell disruption and solubilization. Thus, NP40 represents a good method of obtaining solubilized TAA from TC membranes. Local adoptive transfer of CMI reactivity to mKSA TC in the IFP assay was achieved with spleen cells, but not serum, from hyperimmune mice, further implicating the cell‐mediated nature of this in vivo response. Finally, the IFP assay appears to be a rapid, reproducible and sensitive method of measuring CMI reactivity to TAA on either intact TC or solubilized from the cell membrane by detergent.
BCG vaccination and the incidence of lymphomas and leukaemia
Authors: Skegg D. C. G.
Published: February 2007

BCG vaccination has been claimed to prevent leukaemia, but there is also concern that it might increase the risk of Hodgkin's disease and other lymphomas. Both hypotheses were tested by comparing mortality and registration rates in cohorts of children from the North and South Islands of New Zealand. When school‐children were offered vaccination in both islands, subsequent death rates from lymphomas and leukaemia were similar in the two islands. After withdrawal of vaccination in the South Island, mortality and registration rates for Hodgkin's disease remained similar in the two islands, but there was a significant excess of deaths from non‐Hodgkin lymphomas in the North Island. The difference in the registration rates for these tumours was much smaller than the difference in mortality rates and was not statistically significant. There was no evidence that BCG vaccination in the North Island prevented leukaemia. These findings and the results of other studies suggest that proposals for BCG vaccination against leukaemia are unwise.
Human natural cytotoxicity in the blood and lymphoid organs of healthy donors and patients with malignant disease
Authors: Eremin O. , Ashby J. , Stephens J. P.
Published: February 2007

Natural cytotoxicity against CLA‐4 and D6 target cells was determined in the peripheral blood of healthy donors and women with mammary carcinoma (localized to the breast and axilla), and in human normal and regional tumour lymph nodes. The NK cell activity in the blood of women with clinically localized mammary carcinoma showed a wide range of reactivities but was similar to the pattern detected in healthy controls. The NK cell activity in human normal lymph nodes also showed a wide range and was the same irrespective of the anatomical site of origin of the lymph node. Lymph nodes draining a variety of solid tumours had a similar spectrum of NK cell activity, there being no obvious correlation between the level of NK cell activity and such parameters as size and histological type of tumour, hyperplasia or metastatic spread in the regional node. Trypsin treatment of lymphocyte suspensions from the various lymphoid compartments suggested that the cell responsible for natural cytotoxicity in blood was probably different from the NK cell in tonsil and lymph nodes.
Role of endogenous interferon in the anti‐tumor effect of poly I·C and statolon as demonstrated by the use of anti‐mouse interferon serum
Authors: Gresser Ion , Maury Chantal , Bandu Marie‐Thérèse , Tovey Michael , Maunoury Marie‐Thérèse
Published: February 2007

We have determined the effect of sheep anti‐mouse interferon globulin on the anti‐tumor effects of poly I·C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells. Whereas the anti‐tumor effects of poly I·C and statolon were nullified when mice were injected with immunoglobulins, the anti‐tumor effects of pyran copolymer and BCG were not modified by this treatment. We conclude that interferon mediates the anti‐tumor activity of poly I·C and statolon in these experimental systems. It is suggested that anti‐interferon serum provides a direct method of determining whether other biologic effects attributed to viruses, poly I·C, statolon, tilorone, pyran copolymer (and possibly other interferon inducers) are mediated or not by interferon.
Effects of presensitization in vivo on cell‐mediated responses to embryonic antigens in vitro
Authors: Nelson K. , Sjögren H. O.
Published: February 2007

Lymphoid cells specifically reactive with antigens shared by rat bowel carcinomas and mid‐term embryo cells were generated by in vitro culture on monolayers of embryo cells. Spleen cells from WF females were cultured for 5 days on monolayers of syngeneic embryo cells or adult cells and assayed for cytotoxic activity on syngeneic embryo, bowel carcinoma, or adult fibroblast target cells in microcytotoxicity and 51Cr‐release assays. After culture on embryo monolayers, spleen cells were cytotoxic for embryo and tumor but not for adult fibroblast target cells. Enhanced cytotoxicity was recorded when the spleen cells were cultured from females after interstrain (WFxBN) pregnancy rather than from virgin females. In contrast, previous intrastrain (WFxWF) pregnancy appeared to depress the generation of spleen cells cytotoxic for target cells bearing embryonic antigens.
Chromosome findings in effusions from patients with Hodgkin's disease
Authors: Hossfeld Dieter K. , Schmidt Carl G.
Published: February 2007

Effusion cells from six patients with advanced Hodgkin's disease were studied. Even though no Hodgkin or Reed‐Sternberg cells could be identified cytologically in five of the six cases, striking chromosome anomalies of a clonal nature, including a number of recurrent marker chromosomes, were demonstrated in all effusions. It is concluded that the effusion cells with abnormal karyotypes were intimately related to the pathogenesis of Hodgkin's disease.
Relationship between moloney MSV tumor resistance and endogenous virogene expression in AKR mouse strain and its hybrids
Authors: Colombatti Alfonso , de Rossi Anita , Taylor Benjamin A. , Chieco‐Bianchi Luigi , Meier Hans
Published: February 2007

We have examined the induction of Moloney‐MSV tumors in AKR and other mouse strains in relation to endogenous virus expression. All virus‐free strains so far tested were tumor‐susceptible, while AKR was resistant. The selectivity of MSV tumor resistance, characteristic of AKR mice, was associated with AKR virogene segregation in first backcross to MuLV‐negative/MSV‐susceptible mice, and in a few second backcross families. Stronger evidence that AKR ecotropic virogene expression is the major, but not the sole, determinant of M‐MSV tumor resistance in AKR mice was obtained in strains partially congeneic for Akv‐2 viral gene and in recombinant inbred lines derived from an original cross between AKR and C57L mice. These mice or lines, in which inheritance of endogenous viral genes had occurred, at the same time inherited the ability to show strong resistance to tumor induction by an exogenous oncogenic virus. This finding suggests that ecotropic endogenous viruses can exert a beneficial effect in their hosts providing some protective functions. Although the association between AKR‐MuLV and M‐MSV resistance is definite, the mechanisms by which MulV+ mice are refractory to M‐MSV tumors have still to be elucidated.
In vitro measurement of carcinogen‐resistant liver cells during hepatocarcinogenesis
Authors: Laishes Brian A. , Roberts Esther , Farber Emmanuel
Published: February 2007

Following the transfer of rat liver cells from 2‐acetylaminofluorene‐induced, grey‐white hyper‐plastic nodules to a primary, monolayer cell culture system, the proportion of the nodule cells which were resistant to the cytotoxic effects of aflatoxin B1 was determined The proportion of the resistant nodule cells was expressed as a percentage of the number of attached, viable nodule cells remaining after aflatoxin B1 treatment divided by the number of attached, viable nodule cells remaining without aflatoxin B1 treatment. In each experiment, the results were compared with the proportion of resistant liver cells derived from normal, untreated rats. Following a 3‐h attachment period, nodule and normal cell cultures were exposed to aflatoxin B1 concentrations of 10−7 mol/l to 10−5 mol/l for either 24 h or 48 h. Trypan blue was added directly to the culture flasks and viability was scored as the number of attached cells that would not stain with trypan blue. The resistant nodule cell populations demonstrated a remarkable insensitivity to increasing concentrations of aflatoxin B1 compared with resistant normal cell populations. At all doses of aflatoxin B1 tested, the size of the resistant nodule population remained comparatively constant for periods of treatment varying from 24 to 48 h, whereas the size of the resistant normal population diminished greatly over periods from 24 h to 48 h. Morphologic differences between normal and nodule hepatocytes were great following aflatoxin B1 treatment. Aflatoxin B1 treatment inhibited the spreading of normal hepatocytes, whereas the highly resistant nodule hepatocytes continued to spread out on the plastic substratum. Supplementation of the culture medium with dexamethasone routinely increased the proportion of resistant normal cells exposed to some concentrations of aflatoxin B1 but did not significantly increase the size of the resistant nodule cell population.
Natural cell‐mediated cytotoxicity in rats. I. Tissue and strain distribution, and demonstration of a membrane receptor for the Fc portion of IgG
Authors: Oehler J. Ronald , Lindsay Leroy R. , Nunn Myrthel E. , Herberman Ronald B.
Published: February 2007

Studies in mice and in humans have provided most of the available information concerning natural cell‐mediated cytotoxicity. Rats represent a second experimental species which is well suited for the study of natural cytotoxicity. Our studies indicate that the distribution of natural killer (NK)3 cells in rat lymphoid tissues is similar to their tissue distribution in man, with high levels in the blood and spleen and low or undetectable levels in lymph node, thymus, thoracic duct or peritoneal exudate cells. The levels of NK activity varied considerably among various inbred strains of rats. However, the genetic control of levels of NK activity did not appear to be linked to the rat major histocompatibility complex. As recently demonstrated in mice by depletion experiments on antibody‐erythrocyte monolayers, many or most rat natural killer cells were found to have surface receptors for the Fc portion of IgG.
Natural cell‐mediated cytotoxicity in rats. II. In vivo augmentation of NK‐cell activity
Authors: Oehler J. Ronald , Lindsay Leroy R. , Nunn Myrthel E. , Holden Howard T. , Herberman Ronald B.
Published: February 2007

Natural cell‐mediated cytotoxicity in rats as well as in mice has been shown to vary consistently with age, with peak levels detectable at 5–10 weeks. The levels of cell‐mediated cytotoxicity against tumor cells could be augmented in strains of inbred rats with either high or low levels of natural reactivity, by IP injection of a variety of agents, including C. parvum3, LCMV, KRV, and poly I:C. The specificity of the augmented cytotoxicity appeared to be the same as the specificity of natural killer cells which are found in normal rat spleen cells. Similarly, the cells mediating the augmented cellular cytotoxicity were small, non‐adherent, esterase‐negative lymphocytes with Fc receptors, as are rat NK cells. The kinetics and organ distribution of the augmentation of NK activity by poly I:C and C. parvum were compared and the kinetics were found to differ, with a shorter time course of augmented activity seen after inoculation with poly I:C. These data indicate that interferon may play a central role in the augmentation of NK activity in vivo.
Natural cell‐mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic‐polycytidylic acid
Authors: Oehler J. Ronald , Herberman Ronald B.
Published: February 2007

Treatment of rats with high doses of hydrocortisone, X‐irradiation, or cyclophosphamide had a suppressive effect on natural cytotoxicity in vivo. However, when rats were given poly I:C 3 after any of these agents, the levels of NK activity were similar to those in normal rats which had been given poly I:C alone. To explain these findings, we have postulated that a population of pre‐NK cells, resistant to hydrocortisone, cyclophosphamide and X‐irradiation was induced by poly I:C to become cytotoxic NK cells. Treatment of rats with silica, in doses that had no effect on proliferative responses of host lymphocytes to Con A in vitro, sharply diminished NK activity. With this agent, the boosting effect of poly I:C, although still detectable, was diminished. Since there is little if any indication that NK cells are phagocytic, these data suggest that phagocytes may play a role in maintaining high levels of NK activity in vivo and, further, may be involved in the mechanism by which natural cytotoxicity is boosted by poly I:C. Adult thymectomized rats had easily detectable levels of natural reactivity and the response to poly I:C was unimpaired, indicating a lack of thymic dependence for boosting as well as for spontaneous levels of NK activity.
Detection of trophoblastic tumour activity by pregnancy‐specific beta‐1‐glycoprotein
Authors: Seppälä M. , Rutanen Eeva‐Marja , Heikinheimo M. , Jalanko H. , Engvall Eva
Published: February 2007

Pregnancy‐specific beta‐1‐glycoprotein (PSBG) and human chorionic gonadotrophin (hCG) were measured by specific radioimmunoassays in 73 serum samples from eight patients treated for gestational choriocarcinoma. Both markers were initially present in all cases, but at the time of writing both had levelled off in six cases and decreased markedly in two. Usually hCG was detectable for longer than PSBG during the course of chemotherapy. Both PSBG and hCG reappeared on clinical recurrence. However, at times during the follow‐up period one trophoblastic marker only was expressed This was hCG in most cases, but in one case PSBG alone was encountered. These results suggest that PSBG may serve as an additional marker for the detection of residual tumour growth in patients with trophoblastic tumours.
Relationship between T lymphocyte levels and lymphoproliferative responses to mitogens and alloantigens in lung and breast cancer patients
Authors: Jerrells Thomas R. , Dean Jack H. , Herberman Ronald B.
Published: February 2007

Lung and breast cancer patients were studied for relationships between lymphocyte function, as measured by lymphoproliferative (LP)3 assays, and levels of circulating thymus‐derived lymphocytes (T lymphocytes) measured by rosette formation with sheep erythrocytes (E rosettes). LP responses to the T lymphocyte mitogens phytohemagglutinin (PHA) and concanavalin‐A (Con‐A) and to alloan‐tigens in one‐way mixed leukocyte cultures (MLC) were assessed in a microculture assay. Total T lymphocyte levels were determined using an E rosette assay performed at 4°C and a subpopulation of T lymphocytes with high affinity receptors for E rosettes was measured in a 29°C assay. Using the relative proliferation index (RPI) which compares patient reactivity to normal reactivity, we found that one‐third to one‐half of the lung and breast cancer patients had depressed LP responses to at least one of the stimulants. In contrast, only 21% of the breast and 25% of the lung cancer patients had low levels of total E‐rosette‐forming cells (E‐RFC) as measured by the 4°C E rosette assay. Using the 29°C E rosette assay, we found that a significantly higher proportion of the patients demonstrated decreased levels of this subpopulation of lymphocytes and in both patient groups the depression noted in functional assays was closely paralleled by the percentage of patients with abnormal levels of high‐affinity T lymphocytes. To further examine this apparent relationship between high‐affinity E‐RFC levels and LP results, the correlation between these measures in individual patients was examined. Regression analysis indicated a significant correlation between mitogen and alloantigen responses in both patient groups as well as between total T lymphocyte and high‐affinity T lymphocyte levels. However, there was no significant correlation between LP responses and T lymphocyte levels. Studies in which MLC and PHA reactivities, 4°C and 29°C E rosette levels were determined on the same peripheral blood leukocyte (PBL) sample demonstrated that a number of lung and breast cancer patients with abnormal LP responses had normal total and high‐affinity T lymphocyte levels. Patients with a decrease in high‐affinity E‐RFC but normal levels of total T lymphocytes had a high incidence of depression to PHA (56 and 82% in breast and lung cancer patients respectively) but fewer had depressed MLC reactivity (33 and 71% in breast and lung cancer patients, respectively). In patients with low levels of total and high‐affinity T lymphocytes, there was a high incidence of depression in responses to both PHA and MLC. The results of this study indicate that some cancer patients may have depressed LP responses in association with depressed levels of T lymphocytes, but that other patients may have depressed functional reactivity despite normal levels of E‐RFC.
Spontaneous human lymphocyte‐mediated cytotoxicity against tumor target cells. V. The role of serum‐derived heterologous membrane antigens
Authors: Pross Hugh F. , Luk Samuel S. , Baines Malcolm G.
Published: February 2007

The effect of serum on the K562 assay for spontaneous human lymphocyte‐mediated cytotoxicity (SLMC) was examined systematically at the level of the assay system and with respect to the serum used for the long‐term maintenance of the K562 target cells. It was found that the assay did not require the presence of serum, but all sera tested increased the level of cytotoxicity observed. Lymphocyte and target cell preparation in serum‐free medium led to a high non‐specific cell loss which could be avoided by substituting 5% human serum albumin for fetal calf serum. With this serum‐free assay, the effect of long‐term culture of K562 in 5% human serum was examined. High SLMC by normal donors was obtained in spite of the fact that the target cells had been cultured in human serum. This occurred even when the serum used for long‐term culture was autologous to the lymphocyte donor, and as long as the experiment was continued (10 months). The relative cytotoxicity of each donor relative to the other two tested in this series of experiments was similar for each of the K562 sources tested, and every time that the experiment was performed. Persistence of susceptibility to cytotoxicity after 10 months of culture in 5% human serum, partial sensitivity to pronase and trypsin, and resistance to neuraminidase, all indicated that the antigen recognized by the effector cells in this assay is distinct from the heterologous membrane antigen described by Irie et al. (1974a, b). The ability of lymphocytes to lyse target cells cultured in serum autologous to the lymphocyte donor indicated that SLMC is not mediated by lymphocyte recognition of serum‐derived antigens or serum‐derived mitogenic factors. The “recovery” of the SLMC susceptibility of pronase or trypsin‐treated target cells in serum‐free medium also suggests that the K562‐SLMC “antigen” is intrinsic to the K562 target cell and is independent of the serum used to culture these cells.
Production of rabbit antibodies against the viral capsid antigen (VCA) of the epstein‐barr virus (EBV)
Authors: Vestergaard B. F. , Hesse J. , Norrild B. , Klein G.
Published: February 2007

Rabbits were immunized with nuclear or cyto‐plasmic extracts of the Epstein‐Barr virus (EBV)‐producing marmoset cell line B95‐8. Following extensive absorption with human EBV‐negative cells (Hep‐2, Ramos and BJAB), sera were obtained that no longer reacted with cellular or serum proteins of human origin, but gave a single precipitin band with extracts of the human EBV‐producing line, P3HR‐1. Immunofluorescence tests performed with appropriate parallel human serum controls showed that the rabbit serum contained no activity against EBNA + EA ‐ VCA ‐ Raji cells, or against P3HR‐1 virus superinfected, cytosine arabinoside‐treated Raji cells that contained EBNA and EA, but not VCA. The sera gave a brilliant indirect immunofluor‐escence reaction with the virus‐producing (EBNA+EA+ VCA+) P3HR‐1 lines. Two‐color fluorescence tests, performed with a direct TRITC‐labelled VCA conjugate and indirect FITC‐staining with the rabbit serum, showed that the same cells reacted in both red and green fluorescence, confirming that the rabbit serum was directed specifically against some antigen formed in the virus‐producer cells. Since the synthesis of the relevant antigen was prevented by cytosine arabinoside it cannot be EA and must be a late antigen. The morphology and localization of the antigen support the conclusion that the antigen is VCA or some part of the VCA complex.
Separation of lymphoid cells with a suppressor effect on the activity of cytotoxic cells in vitro during the growth of a syngeneic mouse tumour
Authors: Schaaf‐Lafontaine N.
Published: February 2007

One or 4 weeks after grafting of a syngeneic sarcoma (T2) to C57BL/6 mice, lymph‐node cells (LNC) are cytotoxic in vitro for the cells of this tumour. But after 2 weeks LNC are not cytotoxic or show a non‐significant activity. These second‐week LNC, added to cytotoxic lymphocytes (CL) from the first or fourth week, reduce considerably the cytotoxicity of the latter cells. When velocity sedimentation at unit gravity is used to fractionate 11th‐14th day LNC, some fractions, enriched in small lymphoid cells, kill the cancer cells. Other fractions, containing large blast cells, lack this property but can suppress the activity of the small cells or of fourth week CL. These suppressor cells can also be separated from active CL by passage on a glass bead column. They are “adherent” while CL are non‐adherent at this stage. This suppressor effect is abolished when the lymphoid cell suspension is treated by anti‐θ serum, but macrophage depletion does not modify the inhibition. The cell responsible for the suppressor effect is thus a large T lymphoid cell, adherent and non‐phagocytic. It seems to act essentially on an effector phase of the cell‐mediated cytotoxicity.
Isoniazid tumorigenicity in mice under different experimental conditions
Authors: Bhide S. V. , Maru G. B. , Sawai M. M. , Ranadive K. J.
Published: February 2007

Tumorigenicity of isoniazid in Swiss and A strain mice was studied with three different doses (0.55, 1.1 and 2.2 mg/mouse/day). Mice were fed isoniazid by gastric intubation and killed when they appeared weak. Incidence of tumour ranged from 32 to 100%. Subsequently sex‐specificity in isoniazid tumorigenicity was also studied as well as the effect of vitamin B complex or protein deficiency, and of transplacental exposure of Swiss strain embryos to isoniazid. It was observed that protein deficiency and transplacental exposure stimulated tumour incidence in mice treated with 0.55 mg of isoniazid. No sex specificity was observed in isoniazid tumorigenesis.
Polyadenylated RNA molecules and polyribosomes in tumours of chemical and viral origin
Authors: Shaposhnikov Jacob D. , Ratovitski Edward A.
Published: February 2007

The distribution of poly(A)‐enriched mRNA in nuclei, mitochondria, free and membrane‐bound polyribosomes from normal C3HA mouse and Syrian hamster livers and normal chicken fibroblasts has been compared with that in corresponding subcellular fractions in a transplantable, chemically induced MD hepatoma, non‐virus‐producer hamster and virus‐producer chicken Rous sarcomas. It has been shown that the content of poly(A)‐RNA is increased in all tumour fractions except in free polyribosomes. The distribution of different classes of polysomes i.e. free, membrane‐bound and mitochondrial outer‐membrane‐associated polysomes in tumour cells was changed in comparison to that in normal cells. It is concluded that in tumours of chemical and viral origin, the observed changes in the two components of the protein‐synthesizing apparatus occur simultaneously.
Comparison between the macrophage electrophoretic mobility (mem) and the fixed tanned erythrocyte electrophoretic mobility (fteem) tests in the detection of cancer
Authors: Harlos J. P. , Weiss L.
Published: February 2007

When peripheral lymphocytes from patients with a history of cancer are incubated with encephalitogenic factor (EF), in 90% of cases the resulting products reduce the net surface negativity of guinea‐pig macrophages, used as detector cells, as revealed in the macrophage electrophoretic mobility (MEM) test. The MEM test is positive in 36% of people with no history of cancer. Formaldehyde‐fixed tanned sheep erythrocytes have been used as detector cells in place of guinea‐pig macrophages, in a fixed tanned erythrocyte electrophoretic mobility (FTEEM) test, with lymphocyte products identical to those used in MEM tests. In patients with a history of cancer, positive results were obtained in 28/42 cases with the FTEEM test compared with 32/42 in the MEM test. In people with no history of cancer, negative results were obtained in 16/18 cases with the FTEEM test, compared with 12/18 in the MEM test in the present series, and 51/69 in a more extensive series. These differences are not significant. Cases in which discrepancies are revealed between the two tests are discussed in terms of individual case histories.
Early increase of serum alpha‐fetoprotein in spontaneous hepatocarcinogenesis in mice
Authors: Jalanko H. , Virtanen I. , Engvall E. , Ruoslahti E.
Published: February 2007

The concentration of serum alpha‐fetoprotein (AFP) was followed in C3H mice having a high incidence of spontaneous liver‐cell cancer. No general elevation of serum AFP level with age was seen in mice without tumor. With a single exception, mice bearing hepatocellular carcinomas had increased serum AFP levels. In some mice this increase followed a biphasic course. Mice killed within 1 month of the time when an elevation of serum AFP was first observed had small tumors or no detectable tumor. Premalignant lesions were present in the livers of 11 out of 16 mice that had elevated AFP but no cancer, while only one out of 14 mice with normal AFP had such alterations. Our results strongly suggest that spontaneous hepatocarcinogenesis proceeds through almost the same premalignant lesions as chemically induced carcinogenesis, and that an increase in AFP production occurs early during this process, often preceding macroscopic lesions. Autologous antibodies to AFP were produced in a group of C3H mice by immunization with rat AFP. These anti‐AFP antibodies reduced the amount of serum AFP but had no effect on the incidence of spontaneous hepatomas.
Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine c‐type virus
Authors: Kiessling Rolf , Fenyö Eva Maria , Steinitz Michael , Klein George , Haller Otto
Published: February 2007

Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short‐term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C‐type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C‐type virus either by repeated passage through nude mice or by in vitro superinfection with the supernatants of nude‐mouse‐passaged lines. The appearance of surface‐associated MuLV antigens after superinfection was confirmed in a complement‐dependent cytotoxtcity test. Subsequently, the NK sensitivity of each infected line was compared with its non‐infected counterpart in direct cytolytic and competition assays, None of these two assay systems showed a consistent difference in NK sensitivity of infected and non‐infected cell lines. These findings do not lend support to the concept that murine C‐type viral antigens are responsible for NK sensitivity.
Effectiveness of clinically active antineoplastic drugs in a surgical‐adjuvant chemotherapy treatment regimen using the lewis lung (LL) carcinoma
Authors: Merker Philip C. , Wodinsky Isidore , Cantor Margaret L. , Venditti John M.
Published: February 2007

Surgical‐adjuvant chemotherapy studies were done with BDF1 mice bearing Lewis Lung (LL) carcinoma implanted intramuscularly (IM). Ten days (D10) after implantation, the tumor‐bearing leg was surgically amputated, and intraperitoneal (IP) drug treatment was started either 3 or 5 days after surgery using single‐dose therapy or intermittent treatment given every 4 days for three doses or daily treatment for five doses. The percentage increase in life span (%ILS) was used as the primary measure for evaluation. Data for 17 clinically active drugs showed that surgical‐adjuvant, single‐agent chemotherapy was markedly effective (%ILS>100) in prolonging the life span of tumor‐bearing animals given BCNU, MeCCNU, and cytoxan; moderate activity (%ILS, 40–100) was obtained with bleomycin and vincristine, and marginal activity (%ILS, 35–40) was observed with 5‐fluorouracil (5‐FU), hexamethylmelamine (HMM), procarbazine, and dibromodulcitol. Surgical‐adjuvant, two‐drug‐combination chemotherapy treatment with bleomycin plus MeCCNU or cis‐platinum [cis‐PT(II)] plus CCNU were more effective than single‐drug chemotherapy in prolonging the life span of tumor‐bearing animals. When used in a surgical‐adjuvant chemotherapy‐treatment schedule, the solid tumor model was found to be sensitive to certain antineoplastic drugs that are of clinical benefit in the treatment of human lung cancer. Thus, the model is potentially useful in the search for newer single agents and combinations of drugs against cancers.
Neoplastic transformation of hamster brain cells in vitro by polyoma virus
Authors: De Micco C. , Tripier M. F. , Hassoun J. , Lipcey C. , Meyer G. , Toga M.
Published: February 2007

The transformation of cultivated hamster brain cells by polyoma virus is reported. The transformed cell line contained polyoma virus‐specific nuclear, surface and transplantation antigens. Subcutaneous and intracranial inoculations revealed high tumorigenicity of the cells. Brain‐specific S 100 protein was found in these tumors with immuno‐peroxidase staining, suggesting that they were of a nervous nature. Both in vivo and in vitro, the cells had glial features as studied by phase contrast, light and electron microscopy. Type‐H virus‐like particles were found in the tumor cells and might have played a role in the viral transformation.
Altered membrane‐associated functions in chronic lymphocytic leukemia cells
Authors: Godal Tore , Henriksen Aase , Ølandaas Tone , Iversen Jens‐Gustav , Lindmo Tore
Published: February 2007

Peripheral blood lymphocytes consisting mainly of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL cells) showed a markedly reduced response to the human B‐cell mitogens anti‐β2 microglobulin, Sepharose‐bound protein A and Sepharose‐bound anti‐human immunoglobulin (anti F(ab′)2) in all of nine patients studied. On the other hand, CLL cells from three out of eight patients tested responded well to the calcium ionophore A23187. Sepharose‐bound protein A and anti‐β2 microglobulin also failed to induce increased uptake of 86Rubidium (potassium analogue) in CLL cells as compared to B‐cell‐enriched preparations of normal peripheral blood lymphocytes. The capacity of CLL cells to cap various surface markers including β2 microglobulin was reduced. On the other hand, surface concentrations of β2 microglobulin were not reduced as measured by fluorescein‐labelled anti‐β2‐microglobulin in singlecell cytofluorometry. It is concluded that various membrane‐associated events elicited by ligandreceptor interactions are altered or blocked in CLL cells.