bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of T cell‐mediated immunity by tumor cells: Immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors
Authors: Ting Chou‐Chik , Rodrigues Dennis , Ting Robert C. , Wivel Nelson , Collins Michael J.
Published: February 2007

In studying the immunogenicity of spleen cells and tumor cells in the generation of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell‐free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus‐induced leukemia FBL‐3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non‐viral origin. The viral component was sensitive to UV‐irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non‐viral component was UV‐resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromi‐croscopy, and by the virus focus‐inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune response in the tumor‐bearing hosts.
Transfer of natural resistance to Marek's disease (JMV) with non‐immune spleen cells. I. Studies of cell population transferring resistance
Authors: Lam Kenneth M. , Linna T. Juhani
Published: February 2007

A “natural” resistance to Marek's disease, as well as to the malignancy caused by the laboratory JMV line of Marek's disease, develops with age. Resistance to this malignancy can be transferred from non‐immunized, 8‐week‐old resistant chickens to newly hatched susceptible ones with spleen cells in a B‐locus isogeneic combination. The cell transferring resistance does not seem to belong to the major T‐cell, B‐cell, or macrophage populations, and seems consequently to belong to the functionally heterogenous “third cell” population.
Influence of selective breeding on the incidence of melanomas in sinclair miniature swine
Authors: Hook R. R. , Aultman M. D. , Adelstein E. H. , Oxenhandler R. W. , Millikan L. E. , Middleton C. C.
Published: February 2007

The influence of selective breeding on the incidence of cutaneous melanomas was studied in the Sinclair miniature swine melanoma model. Evaluation of the results of a large breeding study that produced 349 live progeny indicated that the incidence of melanomas (54%) was highest in newborn progeny derived from melanoma female × melanoma male (MF × MM) matings. Newborn progeny from normal female × melanoma male (NF × MM) and melanoma female × normal male (MF × NM) matings had incidences of 22% and 21% respectively; normal female × normal male (NF × NM) progeny had an incidence of 2%. Although most of the progeny were black, melanomas were observed in swine of various colors. Tumors occurred at differing cutaneous sites and did not demonstrate a predilection for any particular area of the body. During the first year of life, additional melanomas developed in some animals from all groups of progeny. At 1 year of age, the incidence of melanomas (85%) remained highest in MF × MM progeny. The incidence had increased to 57% and 50% in progeny from NF × MM and MF × NM matings while NF × NM progeny had an incidence of 4%. Although tumors were observed in newborn swine, most of the tumors (75.5%) developed after birth either from flat melanocytic lesions (19.3%) or from skin free of detectable melanocytic lesions (80.7%). An age effect was observed in tumor development; tumor development decreased as the age of the animals increased. These results demonstrate that selective breeding influences the incidence of melanomas in Sinclair swine and provide basic information required for further studies of tumor development, growth and regression in this unique spontaneous tumor system.
In vitro lymphocyte reactivity to soluble tumor extracts in sinclair melanoma swine
Authors: Aultman M. D. , Hook R. R.
Published: February 2007

An antigen‐stimulated active rosette assay was adapted as an in vitro assay for the detection of lymphocyte reactivity to soluble tumor extracts. The specificity of this assay was demonstrated with lymphocytes from non‐sensitized swine and swine sensitized to either mammalian tuberculin or DNCB‐bovine serum albumin conjugates (DNCB‐BSA). An increase in active rosette‐forming cells (A‐RFC) occurred only when sensitized lymphocytes were stimulated with specific sensitizing antigen. Lymphocytes from melanoma swine reacted in vitro to 3 M KCl extracts of autologous and allogeneic melanomas but did not react to 3 M KCl extracts of autologous and allogeneic swine skin. Lymphocytes from 33 melanoma swine and 17 normal swine were tested for in vitro reactivity to an allogeneic melanoma extract; 84.8% of the melanoma swine demonstrated lymphocyte reactivity to allogeneic melanoma extract and 23.5% of the normal swine reacted positively to allogeneic melanoma extract. The reactivity of melanoma swine lymphocytes to allogeneic melanoma extract was not due to reactivity of the lymphocytes to normal skin antigens or fetal swine antigens present in melanoma extracts; normal and melanoma swine lymphocytes demonstrated only low in vitro reactivity to 3 M KCl extracts of normal swine skin and fetal swine tissue. Lymphocytes from three melanoma swine increased in A‐RFC after incubation with each of nine allogeneic melanoma extracts, indicating that the ability to stimulate lymphocyte reactivity was not limited to a single allogeneic melanoma extract. The results of this study indicate that a tumor‐related immune response occurs in melanoma swine and that in vitro lymphocyte reactivity is directed towards a tumor‐associated antigen or tumor‐associated antigen‐like substance present in 3 M KCl extracts of swine melanoma.
Sister chromatid exchange in PH1‐positive chronic myelocytic leukemia
Authors: Becher Reinhard , Schmidt Carl G. , Theis Gabriele , Hossfeld Dieter K.
Published: February 2007

The sister chromatid exchange (SCE) frequency in bone‐marrow cells of 12 untreated patients with chronic myelocytic leukemia (CML) was analysed and compared with the SCE frequency in bone‐marrow cells of nine healthy persons. In normal persons the SCE ranged from 3.64 to 5.15 per cell. In CML patients the SCE was significantly lower, ranging from 2.32 to 3.44 per cell. The differences found were unrelated to patients' age and contraction state of the chromosomes. It is suggested that the leukemic process could account for the low SCE rate.
Isozyme studies on the association of the herpes simplex virus type 1 thymidine kinase gene with human chromosomes in somatic cell hybrids
Authors: Kit Saul , Qavi Hamida , Hazen Marion , Dubbs Del Rose
Published: February 2007

To investigate chromosomal site(s) of integration of the herpes simplex virus type 1 (HSV‐1) thymidine kinase (TK) gene in biochemically transformed [HeLa(BU25)/KOS 8–1] cells, these human cells which had been transformed by ultraviolet light‐irradiated HSV‐1 were fused with TK‐negative mouse LM(TK−) cells, human‐mouse somatic cell hybrid clones (LH81 clones 1–20) were isolated by HATG‐ouabain selection and their chromosomes and isozymes were analyzed. Electrophoretic and serological analyses showed that all 20 clones expressed type‐specific HSV‐1 TK. Isozyme analyses on 29 gene‐enzyme systems representing 22 human chromosomes revealed that all of the HSV‐1 TK‐positive clones expressed human aminoacylase‐1 (ACY‐1) and esterase D (ESD), which have been mapped to human chromosomes 3 and 13, respectively. Other human isozymes were detected in only one to four clones or in none of the clones. Chromosome analyses showed that: (1) the hybrid clones retained only a few human chromosomes; (2) a marker chromosome, designated M7, consisting of a chromosome 17 translocated to the short arm of chromosome 3, occurred in 36 out of the 41 metaphases examined of LH81‐4 clones 1 to 4 and in 31 out of the 33 metaphases examined of LH81–12 clone 10; (3) a modified M7 chromosome, (M7/m), in which the distal 2/3 of the long arm of M7 was translocated to a small acrocentric mouse chromosome, was the only human chromosome found in metaphases of LH81–13 clone 17; and (4) an intact human chromosome 13 was not present in LH81–12 clone 10 or LH81–13 clone 17 cells. Counterselection with BrdUrd resulted in the isolation of subclones lacking HSV‐1 TK, human ACY‐1 and ESD, and the human marker M7 chromosomes. The experiments indicate that the HSV‐1 TK gene is probably associated in HeLa (BU25)/KOS 8–1 cells with marker chromosome M7, but the possibility is not excluded that the segment of human chromosome 13 which codes for ESD is involved.
Metastasis of human tumors in athymic nude mice
Authors: Sharkey Francis E. , Fogh Jørgen
Published: February 2007

The incidence of metastasis of xenogeneic tumors transplanted to nude mice is controversial. We studied 106 malignant human tumor lines in a total of 1,045 nude mice, and observed metastasis in only 14 instances (1.3%), involving 11 different tumor lines. Three of the lines showed repeated metastasis. Breast tumor lines metastasized with significantly greater frequency than other tumor types. None of the sarcoma lines metastasized. Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites. However, deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis (p<0.001). Such factors as nude mouse health, tumor size and growth rate, and age and sex of the host mouse were not correlated with metastasis. Serial passage in nude mice did not select for a more malignant tumor line, since the incidence of metastasis did not differ at various passage levels. Thus, metastasis of human malignant tumors in nude mice would appear to depend primarily upon the site of tumor growth in the nude mouse, and upon the intrinsic metastasizing capability of the tumor line employed.
14q translocations, having a break point at 14q13, in lymphoid malignancy
Authors: Fukuhara Shirou , Ueshima Yoshimi , Shirakawa Shigeru , Uchino Haruto , Morikawa Shigeru
Published: February 2007

In three patients with non‐Hodgkin lymphomas and in one cell line (HPL‐Hod) derived from pleural effusion cells of a patient with Hodgkin's disease, rearrangements of the long arm of chromosome No. 14(14q) were observed. These rearrangements appeared to be consistently associated with a 14q translocation, suggestive of occurrence of a break at 14q13. The translocation in an individual case could occur with 1p, 2q, 4q, and another 14q. A 14q13 translocation may be comparable with a 14q32 translocation, which has often been observed in various types of lymphoid malignancy.
Alterations in chromosomal proteins in C3H/HeN mice with spontaneous primary hepatocellular carcinomas
Authors: Rodriguez Lewis V. , Becker Frederick F.
Published: February 2007

The chromosomal proteins from chromatins of normal and background liver and spontaneous primary hepatocellular carcinomas (PHC) of C3H/HeN mice were examined by high resolution acid‐urea and sodium dodecyl sulfate (SDS) polyacryl‐amide gel electrophoresis. Before gel analysis, the histone and non‐histone chromosomal proteins (NHCP) from the various tissues studied were separated by affinity chromatography. No qualitative or quantitative differences in histone content were detected in any of the chromatins studied. Tumor and background chromatins did, however, exhibit higher NHCP content than normal tissues. When NHCP were fractionated on SDS polyacrylamide gels, the appearance of 10 new unique NHCP, many of which were of high molecular weight, was found to accompany the manifestation of malignancy in these C3H/HeN mice. Conversely, the abundance of a number of individual NHCP decreased precipitiously in PHC chromatin; and, additionally, two high‐molecular‐weight NHCP present in normal chromatins were not detectable in background and PHC chromatin. A number of NHCP were found to be unique to each of the chromatins studied. The progressive increase in total number of NHCP in background and PHC chromatin when compared to normal chromatin suggested that such changes in NHCP might indicate progression towards malignancy. The acquisition of new high‐molecular‐weight NHCP, the loss of some high‐molecular‐weight NHCP, and the decrease in individual NHCP found for mouse PHC correlate well with findings of previous studies in other systems in which malignant transformation was induced with some agent. It appears then that changes in NHCP accompany both spontaneous and induced malignant transformation, and that such changes may reflect alterations in gene expression known to accompany malignancy.
Mouse mammary tumor virus (MMTV) antigen(s) are present on B lymphocytes of BALB/c mice
Authors: Charyulu Vijaya , Sigel M. Michael , Durden Donald L. , Lopez Diana M.
Published: February 2007

Immunofluorescence studies using a polyvalent anti‐MMTV serum revealed the presence of MMTV antigen(s) on the surface of spleen cells from the low mammary tumor incidence mouse strain BALB/cCrgl. Upon separation of the splenocytes on nylon‐wool columns the populations of cells exhibiting positive fluorescence were nylon‐adherent. These cells were considered to be B lymphocytes by the following criteria: presence of surface immuno‐globulin (Slg), absence of Thy‐1 antigens, enhanced responses to B‐cell mitogens and decreased reactivity to T‐cell mitogens. In order to ascertain the specificity of the cell surface immunofluorescence reaction, blocking studies were performed. Immunofluorescence was blocked by preincubation of the antiserum or with purified MMTV, but not by R‐MuLV. Non‐specific binding of the anti‐MMTV to Fc receptors present on B lymphocytes was ruled out by the use of Fab′2 fragments of IgG from the various sera. Double label immunofluorescent studies with rhodamine‐conjugated anti‐mouse Slg Fab′2 fragments and rabbit anti‐MMTV Fab′2 with fluorescein‐conjugated goat anti‐rabbit Fab′2 showed the simultaneous appearance of both labels in the nylon‐adherent splenocytes. These results suggest the expression of viral polypeptide(s) encoded by an endogenous MMTV on the surface of B‐type splenocytes in mice devoid of intact viral particles.
Lymphocyte‐mediated lysis of tumor cells in vitro (ADCC), induced by serum antibodies from patients with urinary bladder carcinoma or from controls
Authors: Troye M. , Hansson Y. , Paulie S. , Perlmann P. , Blomgren H. , Johansson B.
Published: February 2007

IgG fractions from serum of patients with transitional‐cell carcinoma of the urinary bladder (TCC), patients with carcinoma of the prostate (CC) and healthy donors (HD) were tested for their capacity to induce antibody‐dependent lymphocyte‐mediated cytotoxicity (ADCC) to tumor cells in vitro. Lymphocytes from healthy donors were selected for low natural cytotoxicity to the target cells from established cell lines of TCC or other origins. IgG was prepared by adsorption of serum to Sepharose‐bound protein A from Staphylococcus aureus and subsequent acid elution. When tested against a panel of six different target cells, most individual IgG preparations from all three donor groups contained antibodies inducing ADCC to some of the target cells. When IgG preparations from 11 untreated TCC patients were studied for ADCC induction to the TCC target T24 and the colon carcinoma HT29, cytotoxicity to T24 was, on an average, significantly higher than that to HT29. For IgG preparations from 18 TCC patients, treated with radiotherapy, a similar difference was seen but was not statistically significant. IgG preparations from 11 patients with carcinoma of the prostate and from 12 healthy donors did not show this difference. Moreover, while individual IgG preparations from untreated TCC patients were, on the average, significantly more cytotoxic to T24 than those from either of the two control groups, no such differences were seen when HT29 was the target. On the contrary, IgG preparations from patients with prostatic carcinoma were significantly more cytotoxic to HT29 than those from healthy donors. The results suggest that TCC patients develop a disease‐related humoral immune response, superimposed on a “natural” immunity to a variety of antigens on the target cells used. The nature of the antigens involved in these reactions remains to be established. However, the results are compatible with previous findings, in these patients, of a bladder‐tumor‐related cellular cytotoxicity, to a large extent caused by the patients' own antibodies.
Surface glycoproteins of normal and neoplastic glia cells in culture
Authors: Lubitz Werner , Westermark Bengt , Peterson Per A.
Published: February 2007

Two normal and seven malignant human glia lines grown in vitro were labelled by lactoperoxidase catalysed iodination. The labelled cell surface glycoproteins were isolated by lectin affinity chromatography and compared by SDS gel electrophoresis. The glia and the glioma lines possess a common characteristic glycopro‐tein pattern. Seven glycoproteins in the molecular weight range between 70,000 and 220,000 daltons and several minor components of low molecular weight could be distinguished. The expression of the glycoproteins was independent of the passage number or the growth conditions although the expression of the different glycoproteins showed quantitative differences for the individual cell lines. The differences found in the tumor lines were either due to an amplification or decrease in the expression of the different glycoproteins and/or their accessibility to the lactoperoxidase‐catal‐ysed labelling.
Long‐term T‐cell‐mediated immunity to epstein‐barr virus in man. IV. Development of T‐cell memory in convalescent infectious mononucleosis patients
Authors: Rlckinson A. B. , Moss D. J. , Pope J. H. , Ahlberg N.
Published: February 2007

Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response of T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB‐virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 × 105/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within I week of onset, a much higher mean lymphocyte concentration (3.7 × 106/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 × 1O6/ml). Six additional IM cases were tested 23–83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 × 1O5/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T‐cell‐de‐pleted and T‐cell‐enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB‐virus‐specific memory T‐cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5–23 weeks after onset, and reaches a maximum after about 6 months.
H‐2 associated resistance to leukaemia transplantation: Natural killing in vivo
Authors: Carlson George A. , Melnychuk David , Meeker Mary Jane
Published: February 2007

Natural resistance in vivo was studied by injecting non‐immunized mice with leukaemia cells prelabelled with the thymidine analogue 131I‐iododeoxyuridine. There was a decrease in the survival of the leukaemia cell inoculum as determined by whole‐body gamma counting, and a failure of the leukaemia cells to survive in the spleens of mice which were not H‐2 identical with the transplant. H‐2‐associated resistance could be measured within 24 h of leukaemia inoculation and was strongest in the spleen and absent from the liver. Although all strains of mice tested were able to resist H‐2 non‐identical cells, resistance in irradiated (800‐900 R) mice was restricted to certain strains and their F1 hybrids, notably those of the C57BL family. Resistance in both non‐irradiated and irradiated mice was not due to classical immunological rejection. Mice with either genetic or induced T‐cell deficiency showed full resistance, and circulating preformed antibody could not account for the rejection observed. Treatment with silica or with 89Sr abrogated natural resistance in non‐irradiated as well as irradiated animals; these treatments had previously been shown to abolish both bone‐marrow graft rejection in irradiated mice and in vitro natural killing. Resistance against leukaemia transplantation in irradiated C57BL mice appeared to depend on Hh‐I (H‐2D) incompatibility between the host and the graft, again suggesting that bone‐marrow graft rejection, and perhaps natural killer activity, is a subset of a more general paraimmune or non‐adaptive rejection mechanism.
Carcinogenicity of dapsone in mice and rats
Authors: Griciute Laima , Tomatis L.
Published: February 2007

Dapsone (4,4′‐diamino‐diphenyl sulfone) has been tested for possible carcinogenicity in long‐term animal experiments. BDIV rats and C7BL mice received a 3.5% aqueous suspension of dapsone by intragastric intubation. Treatment was started in pregnant females during the last part of pregnancy, continued during lactation, then given to the offspring after weaning, five times a week for 104 weeks. The dose administered was 100 mg/kg to both rats and mice; total doses ranged from 10–16 g per rat and 1.2–1.4 g per mouse. Separate groups of animals received a combined treatment of dapsone with urethane or benzo (α) pyrene, to investigate the possible additive or synergistic action of dapsone with known carcinogens, as well as the possible inhibiting effect of dapsone on carcinogenesis. Unusual tumours, viz. spleen sarcomas (related to severe fibrosis of the spleen) were detected in male rats, and higher morbidity from C‐cell thyroid carcinomas was observed in treated rats of both sexes than in control rats. There was no evidence that dapsone can modify the action of other chemical carcinogens. It was noted that: (1) although the increase in the incidence of turnours in dapsone‐treated animals over that observed in untreated controls is statistically significant, the increase is relatively low; (2) the tumours appeared after lifetime treatment with maximum tolerated doses; (3) in rats, spleen sarcomas were observed mostly in males; this may indicate a possible hormone‐dependence of the observed carcinogenic effect. The present results therefore provide only limited evidence of carcinogenicity of dapsone in rats.
Protein‐A antibody‐binding (PAAB) technique for detection of tumor‐associated membrane antigen (TAMA) of lewis lung carcinoma
Authors: Veltri Robert W. , McKolanis John R. , Rockoff S. David , McIntire K. Robert
Published: February 2007

Xenoantisera were prepared in rabbits against intact paraformaldehyde‐fixed Lewis lung carcinoma (LLCa) cells and membrane solubilized proteins extracted with Triton X‐100 and 3M KCI. The antisera were analyzed for antibodies to tumor‐associated membrane antigens (TAMA) by means of a solid‐phase radioimmunoassay (RIA). The immunoassay employed 125I‐labelled Staphylococcus aureus protein A (SPA) to detect specific antibody binding to glutaraldehyde‐fixed Lewis lung tumor target cells. The protein‐A antibody‐binding (PAAB) method is rapid, sensitive and reproducible. The PAAB revealed a possible LLCa‐TAMA as evidenced by the reactivity of xenoantisera raised to LL paraformaldehyde tumor cell vaccine (TCV) and LL tumor Triton X‐I00 (TTri) and 3M KCI (TKCI) extracts of membrane preparations. The reactivity of our antisera followed linear dose‐response kinetics but the degree of reactivity decreased from anti‐TCV to anti‐TTri to anti‐TKCI respectively. The LL‐TAMA demonstrated specificity since our antisera did not significantly cross‐react with normal C57BL/6 cellular antigens or other known murine tumor‐associated surface antigens of virally and chemically‐induced tumor systems.
HLA antigens in stomach cancer
Authors: Nomura Abraham , Glober Gary A. , Terasaki Paul I. , Stemmermann Grant N.
Published: February 2007

HLA antigens were identified for 99 Japanese patients with stomach cancer and for 222 controls in Hawaii. There were 68 patients with the intestinal / other histological type of stomach cancer and 31 patients with the diffuse type who may be genetically predisposed towards developing the disease. No significant differences in antigen frequency were noted between cases of the diffuse or intestinal/other histological type and the controls, or between the diffuse and intestinal/other type stomach cancer cases.
Space‐time clustering of Burkitt's lymphoma in East Africa: Analysis of recent data and a new look at old data
Authors: Siemiatycki J. , Brubaker G. , Geser A.
Published: February 2007

Forty cases of Burkitts' lymphoma (BL) in North Mara, Tanzania, with onset between 1971 and 1977, were analysed for evidence of space‐time clustering. Previous analyses in East Africa had produced conflicting results. The Knox method used in those analyses dichotomizes the space and time scales and does not take into account the degree of closeness. The Mantel method, a generalization of Knox's, does permit closeness between pairs of cases to enter into computations. To see whether this method could clarify matters, previously reported data sets from West Nile, Uganda and North Mara were reanalysed. Unexplained differences were found between West Nile and North Mara with respect to age, sex and temporal distributions of BL, and between the eastern and western parts of North Mara with respect to incidence. In West Nile between 1961 and 1965, there was clustering. All of the Mantel analyses and a few of the Knox analyses were highly significant (p< 0.0025). Since 1966, evidence of clustering is weak. In North Mara, there was no statistical evidence of space‐time clustering between 1971 and 1977, as there was none between 1964 and 1970. The conflicting results in East Africa are compatible with a model involving several factors which «move about», or with a single factor which is sporadic in some areas but constant in others. Alternatively, artifactual biases or coincidence may have created or wiped out the appearance of clustering. Results of space‐time clustering analyses permit little discrimination between infectious and non‐infectious etiologic hypotheses. Either one type or both may be operating.
Evidence for type‐C retrovirus production by Burkitt's lymphoma‐derived cell line
Authors: Yaniv Abraham , Gotlieb‐Stematsky Tamar , Vonsover Ami , Perk Kalman
Published: February 2007

Burkitt's lymphoma cell line, P3HR‐1, was found to secrete virions with properties of known type‐C RNA tumor viruses. The viral particles had a buoyant density of 1.16 g/ml in sucrose gradients and contained a highmolecular‐weight RNA and an RNA‐instructed DMA polymerase. The viral polymerase was active in an endogenous reaction requiring the presence of the four deoxyriboside triphosphates and manganese ions, and was sensitive to RNase. The DNA product of the endogenous reaction specifically hybridized to P3HR‐I viral 60 to 70S RNA. Electron microscopic examination of ultrathin sections of P3HR‐I cells revealed immature, mature and budding virions typical of type‐C retroviridae. Nucleic acid hybridization assays showed no sequence homology between the genome of P3HR‐I virus and avian myeloblastosis virus, murine oncornaviruses, simian sarcoma virus or RD114 virus.
Stable bone‐marrow‐derived cell line producing transforming avian acute leukemia virus OK 10
Authors: Pfeifer Susan , Kallio Annikki , Vaheri Antti , Pettersson Ralf , Oker‐Blom Nils
Published: February 2007

A stable bone‐marrow‐derived cell line, OK‐BM, producing transforming avian acute leukemia virus OK 10, was established. The cell line has been maintained in culture for over 4 years and 405 passages. The cells grow rapidly in suspension, have a low serum requirement, display a uniform morphology and perpetually release transforming OK 10 virus. No transforming helper virus was detected by interference assay. The cells have a chromosome complement of the chicken. Characterization of the cells indicates that they are of myeloid origin and have properties characteristic of proliferating transformed macrophages.
Retinoids inhibit the mitogenic activity of tumourpromoting phorbol esters on human lymphocytes
Authors: Abb Jochen , Deinhardt Friedrich
Published: February 2007

The tumour‐promoting agents 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) and phorbol‐12,13‐dibutyrate (PDB)1 are potent mitogens for human peripheral blood lymphocytes. In contrast, the non‐cocarcinogenic substance phorbol lacks lymphocyte‐activating properties. Non‐toxic levels of retinoic acid (RA) or retinyl acetate (RAt) inhibit the phorbol‐ester‐induced lymphocyte proliferation. Selective inhibition of phorbol‐ester‐stimulated lymphocyte blastogenesis required the near‐concurrent addition of retinoids. Differences in the sensitivity of phorbol‐ester‐stimulated lymphocyte subpopulations to the antagonistic action of RA or RAt, respectively, suggest that the inhibitory effect of retinoids may not be due to a common mode of action. Lymphocyte cultures may provide a useful model system for studies of the mechanisms of action of both phorbol esters and retinoids.
Correlation between perchloric‐acid‐soluble serum proteins, cellular immunity and tumor‐cell burden
Authors: Hakim Anwar A.
Published: February 2007

Several in vitro‐cultured neoplastic cells, particularly human mammary carcinoma and malignant melanoma cells, shed or secrete glycoproteins which are tumorspecific. These compounds contain N‐acetylneuraminic acid (NANA), and they differ from the bulk of serum proteins and glycoproteins in being soluble in perchloric acid. The present studies examined the relation between perchloric acid soluble serum proteins (PA‐proteins), and N‐acetylneuraminic acid (PA‐NANA) and the number of R3230 AdCa implanted into syngeneic Fischer rats. A graded number of R3230 AdCa cells from a mammary rat adenocarcinoma was implanted into separate groups (20 rats/group) of imbred 12‐ to 16‐week‐old female Fischer rats. At 0, 24,48, 72, 196 h, and at 6, 9, 12, 15 and 21 days after tumor cell implantation, blood was examined for protein and NANA levels, and spleen cells for migration inhibition. Vibrio cholerae neuraminidase (VCN)‐treated formalinized tumor cells were used as the antigen. Animals which received 100 R3230 AdCa cells/animal showed a progressive increase in PA‐proteins and PA‐NANA 48 h after implanting the tumor cells. The serum PA‐protein and PA‐NANA levels were time‐dependent and increased with the number of implanted tumor cells. Maximum levels were found in sera from blood drawn 196 h or later from animals which received 1,000 tumor cells/rat or more. At 72 h or more after tumor cell implantation, spleen cells from animals which received 100 or more R3230 AdCa cells per animal were inhibited on contact with VCN‐treated formalinized R3230 AdCa cells. The magnitude of inhibition increased with time and with number of implanted tumor cells. A maximum of 85% inhibition was attained with spleens from animals 196 h after implantation of 100 R3230 AdCa cell/animal, or from animals 72 h after implantation of 103 or 104 R3230 AdCa cells/animal.
Does whole‐body hyperthermia therapy involve participation of the immune system?
Authors: Roszkowski W. , Wrembel J. K. , Roszkowski K. , Janiak M. , Szmigielski S.
Published: February 2007

The effect of micro‐wave whole‐body hyperthermia on tumor growth and lung metastasis counts was examined in adult BALB/c mice. The effective therapy with hyperthermia prolonging mean survival time of the animals and causing tumor regression resulted in concomitant depression of anti‐tumor immunity measured in vivo. The beneficial effect of preimmunization of animals with killed tumor cells on subsequent challenge with live tumor cells was completely abrogated by hyperthermia treatment. It is postulated that this form of therapy is directly related only to heat sensitivity of tumor cells and that there is no profitable participation of the immune system in the anti‐tumor effect of wholebody hyperthermia.
Cells from chemically induced mouse sarcomas retain tumor‐specific transplantation antigenicity during prolonged passage in vitro
Authors: Walker Rondi , Hellstroöm Ingegerd , Hellström Karl Erik
Published: February 2007

Tumor‐specific transplantation antigens (TSTA) expressed by cells from transplantable lines of 3‐methyl‐cholanthrene‐induced BALB/c sarcomas were maintained over a 26‐week culture period, which represented 2–32 passages in vitro. Cells from in vitro‐passaged sarcomas were immunogenic in that they induced specific resistance in syngeneic mice to challenge with cells from the same sarcoma. They were also immunosensitive in that their outgrowth in syngeneic mice was prevented when they were mixed with lymph‐node cells from mice immunized with in vivo‐passaged cells from the respective sarcoma.
Interaction between cellular and viral genes in the expression of the RSV‐induced transformation‐specific cell‐surface antigen VCSA
Authors: Prat Maria , Tato Franco , Tarone Guido , Comoglio Paolo M.
Published: February 2007

Transformation of BHK hamster fibroblasts by an env strain of Rous sarcoma virus (RSV) leads to the appearance at the cell surface of a virus‐induced nonvirion antigen (VCSA), specific for transformation, whose expression is controlled by the transforming src gene. Previous work has shown that a rabbit anti‐VCSA serum lyses specifically, in the presence of complement, 51Cr‐labelled RSV‐transformed cells from different animal species. Now, by competition experiments with a panel of different unlabelled cells we show that the VCSA expressed on RSV‐transformed hamster fibroblasts is a complex of at least three distinct antigenic specificities: (1)one expressed on all RSV‐transformed fibroblasts, regardless their species and the subgroup or strain of the transforming virus; (2) one cross‐reacting with a cell‐surface antigen (CSA) expressed at various degrees on untransformed avian fibroblasts, but not on mammalian fibroblasts; (3) one species‐specific, present only on RSV‐transformed hamster fibroblasts. It is concluded that VCSA is a complex of several antigenic determinants, and that some of these differ in different cells transformed by RSV. This observation indicates that VCSA expression at the cell suface is likely to be the result of the interaction between the viral src gene product pp60src with host cell gene(s) or gene product(s), rather than the simple expression of this molecule at the cell surface.
Collaboration between specific anti‐tumor immunity and chemotherapeutic agents
Authors: Yamamura Yasuhiro , Proctor Julian W. , Fischer Beth C. , Harnaha Jo B. , Mahvi Thomas A.
Published: February 2007

Treatment of DBM/2J mice bearing a T1699 syngeneic mammary adenocarcinoma (Ts) with a single intraperitoneal (i.p.) injection of 100 ug melphalan produced complete tumor regression in about 65% of the animals treated; however, tumors recurred in about 85% of these regressors after 15–22 days' remission. The drug regimen was ineffective against Ts tumors growing in immunosuppressed or immunodeficient animals. Stimulation of immunologically intact Ts tumor‐bearers with bacterial lipopolysaccharide (LPS) or with phytohemagglutinin (PHA) 3 days prior to melphalan therapy, on the other hand, produced not only higher rates of tumor regression but also significant increases in the number of permanent cures. A tumor induced by T1699 subline TR2 was resistant to the same regimen, although Ts and TR2 cells were equally susceptible to the cytotoxic and growth‐inhibiting activities of the drug in vitro. In contrast, the combination of specifically armed monocytes and melphalan in vitro produced enhanced killing of Ts cells but not of TR2 cells. Analysis of the collaborative cytotoxicity between immune effector cells and melphalan indicated that exposure of tumor cells to killer cells increased the drug susceptibility of the tumor cells, but not the reverse. These results suggest a possible mechanism for in vivo resistance of tumors to chemotherapeutic agents that is not directly associated with the drug resistance of the tumor cells in vitro.
Response to chemotherapy of human, malignant melanoma xenografts in athymic, nude mice
Authors: Fodstad Øystein , Aass Nina , Pihl Alexander
Published: February 2007

In attempts to elucidate the factors determining individual differences in response of tumors to chemotherapeutic agents, the sensitivity of six human malignant melanomas growing in athymic, nude mice was studied. Six agents, viz. DTIC, CCNU, vinblastine, procarbazine, as well as the toxic lectins abrin and ricin, were administered in maximum tolerable doses to the tumor‐bearing mice. The response to treatment was expressed as tumor growth delay, i.e. the number of volume doubling times saved by the treatment. The xenografts had very nearly retained the morphology of the parent tumors and were histologically similar. They showed different and characteristic early growth rates and also wide variations in their response to the agents tested. Unexpectedly, in the case of DTIC, CCNU and procarbazine, the response of the xenografts proved to be inversely related to the early growth rates of the tumors. For vinblastine, abrin and ricin, no correlation between response and growth rate of the tumors was apparent. Procarbazine had the best overall effect among the agents here tested. DTIC, CCNU and vinblastine had somewhat less and about equal overall efficiency. The plant toxin abrin, which acts by inhibiting protein synthesis, was at least as effective as DTIC. When abrin was given together with DTIC, the effect on the two xenografts tested was superior to that of each agent given alone. The wide variations observed in the response of the histologically similar xenografts to the different agents demonstrate that testing of the chemosensitivity of human xenografts requires the use of a panel of tumors of each histological type. The clear relationship found between the early growth rate of the xenografts and their sensitivity to three of the drugs most commonly used in the treatment of malignant melanomas, may have clinical implications.
Elevation of serum polyamines in malignant lymphomas and acute myeloid leukemia
Authors: Hospattankar A. V. , Advani S. H. , Vaidya N. R. , Electricwalla S. E. , Braganca Beatriz M.
Published: February 2007

In a study of 89 cases of hematological cancers including 55 cases of Hodgkin's disease, 21 of non‐Hodgkin lymphoma and 13 of acute myeloid leukemia, the serum total polyamines were considerably elevated (1.2–5.7 nmol/ml) as compared to observations on control values for eight healthy individuals (0.62–0.87 nmol/ml). The assay procedure was based on enzymes oxidizing polyamines isolated from Russell's viper venom. Serial determination of polyamines in the sera of eight cases of Hodgkin's disease done before and after chemotherapy or radiotherapy showed positive correlation with clinical status of the disease. Analysis of individual polyamines in four patients with Hodgkin's disease indicated that putrescine may be a more sensitive marker of the diseased state. By the present method it was undetected in the control sera but rose significantly in the sera of patients with Hodgkin's disease. Overall data suggest that serum polyamines may be useful as indicators of onset of relapse in patients with Hodgkin's disease and could thus be helpful in early start of treatment.
Subcellular distribution of simian virus 40 T antigen species in various cell lines: The 56K protein
Authors: Luborsky Samuel W. , Chandrasekaran K.
Published: February 2007

The subcellular distribution of SV40 anti‐T serumspecific species was examined in SV40‐transformed, Tantigen‐positive tissue culture cell lines of rat and of AL/N and BALB/c mouse origin. Cells were labelled with [35S]methionine. The cytoplasm, nuclear and membrane fractions were obtained, and their radioimmunoprecipitates analyzed by gel electrophoresis. Tests were performed to determine the purity of these subcellular fractions, and negligible cross‐contamination was found. The cytoplasm fractions lacked detectable anti‐T serum reactivity. Large amounts of both large T antigen and a 56K protein were always present together both in the nuclear fractions and, in a somewhat lesser amount, in the plasma membrane fractions of all cell lines examined. Analysis of density gradient sedimentation profiles of the immunoprecipitates of whole‐cell extracts indicated these species were associated in some fashion, probably with each other. The activity of the 56K protein may be associated with its presence on the cell surface where, either alone or acting together with the large T antigen, it might provide the surface activity responsible for tumor‐specific surface and/or traneplantation antigen activities.
Non‐T‐cell‐mediated cytotoxicity in MSV tumor‐bearing mice. III. Macrophage‐mediated cytotoxicity against autochthonous MSV tumor‐isolated target cells
Authors: Becker Susanne , Haskill Stephen
Published: February 2007

Cytotoxic macrophages have been isolated Moloney sarcoma virus (MSV) tumors induced in uncompromised, immunosuppressed and athymic nude mice. Macrophages from compromised mice were least as active as those from uncompromised mice when tested against the autochthonous MSV target cells. Although both cytolytic and cytostatic activity could demonstrated with all tumor‐derived macrophages, cytostatic and cytolytic effects could be distinguished from each other only at high effector target‐cell ratios. A variety of target cells were compared for sensitivity to various tumor‐associated macrophages. The auto chthonous virus‐infected MSV‐target cells appeared be more sensitive to the macrophage effects than fast growing, established cell lines. Normal embryo fibroblasts were only slightly affected. Peritoneal exudate cells from tumor‐bearers were much less active than either the tumor‐isolated macrophages or bone‐marrow culture‐derived macrophages. Both were more active than control peritoneal cells. Although no quantitative or qualitative differences in macrophage activity could be detected in mice with regressing lesions immuno‐compromised mice with progressing lesions, the ratio of macrophages to «sarcoma» cells was three to five times higher in regressing tumors.
Establishment in continuous culture of a T‐lymphoid cell line (HD‐Mar) from a patient with Hodgkin's lymphoma
Authors: Ben‐Bassat Hannah , Mitrani‐Rosenbaum Stella , Gamliel Haim , Naparstek Elizabeth , Leizerowitz Rachel , Korkesh Aviva , Sagi Michal , Voss Ruth , Kohn Gertrude , Polliack Aaron
Published: February 2007

A new cell line, HD‐Mar, was established from a pleural effusion of a patient with Hodgkin's lymphoma. Formation of E rosettes, sensitivity to anti‐T serum, elevated terminal deoxynucleotidyl transferase activity, presence of T‐cell and the common ALL membrane antigens, morphology, and cytochemical staining indicate that the HD‐Mar line is of thymic derivation. Absence of any immunoglobulin determinants, the lack of EBNA or any other EBV‐associated antigen or function are also characteristics associated with established T‐ cell‐derived lymphoma cell lines. Karyotype analysis indicated a tetraploid origin of the cell line.
Partial characterization of viral DNA from human genital warts (condylomata acuminata)
Authors: Gissmann Lutz , Hausen Harald Zur
Published: February 2007

By centrifuging total cellular DNA derived from human genital warts (condylomata acuminata) in CsCI‐ethidium bromide gradients, supercoiled DNA was isolated. The molecular weight of this DNA was determined by agarose gel electrophoresis and amounted to 5.1 × 106. This DNA isolated from an individual genital wart was annealed to fractions of aqueous supernatants of the same wart after prior centrifugation of this material in CsCI density gradients. Annealing was observed at a density of approximately 1.32 g/ml corresponding to the expected density of papilloma virus particles. Since such particles were also observed in the same preparation by electron microscopy, it was concluded that the supercoiled DNA molecules were derived from papilloma virus nucleocapsids. Positive hybridization was found with six additional preparations from individual genital warts. Therefore, it seems that the isolated DNA prevails in condylomata acuminata. The DNA is different from the other five types of human papilloma viruses described thus far in regard to its restriction endonuclease cleavage patterns. The virus analyzed is tentatively designated as human papilloma virus type 6 (HPV 6).
Killing of normal cells by activated mouse natural killer cells: Evidence for two patterns of genetic regulation of lysis
Authors: Kiessling Rolf W. , Welsh Raymond M.
Published: February 2007

Normal primary mouse thymocytes and peritoneal cells are sensitive for lysis by mouse spleen cells activated by in vivo infection with lymphocytic choriomeningitis virus (LCMV). With both thymocytes and peritoneal cells as targets, the active killer cell seemed to be an NK cell, as judged by high activity in the mouse mutant nude and low activity in the mouse mutant beige. Thymocytes from 1‐ to 3‐week‐old mice were found to be most NK‐sensitive, while peritoneal cells showed highest sensitivity for lysis when harvested from older (6‐ to 8‐week‐old) animals. In a direct comparison the genetic regulation of NK activity against thymocytes and peritoneal cells was analyzed. The same strain origin of both target cells and effector cells in either system was used. With thymocytes as target cells, spleen cells from LCMV‐infected C3H/St mice invariably showed the highest activity closely followed by cells from the BALB/c strain, while the SWR/J and the A/J strains both were considerably less reactive. The same pattern of high‐ or low‐reactive strains was seen regardless of the genotype of the thymocyte target donor, and the same pattern of cytotoxicity was also seen against the YAC‐I lymphoma target. An entirely different genetic regulation was active in the lysis of peritoneal cells, where a unique pattern of reactivity was seen for each effector cell genotype, dependent on the strain origin of the peritoneal target cell. In line with previous findings, syngeneic combinations of effector‐target cells yielded little or no reactivity, while various allogeneic combinations showed considerable levels of activity. Also, primary cultures of embryonic fibroblasts were used as target cells. The genetics of the fibroblast target system was more similar to that seen in the thymocyte‐YAC‐I assay since no evidence for a preferential killing of allogeneic target cells was seen.