bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity of solubilized tumor antigen extracted from P1798 murine lymphoma cells or isolated from tumor‐bearer ascites fluid and reactivity with anti‐thy‐1.2 antiserum
Authors: Gordon William C. , Baechtel F. Samuel , Goetz Gregory , Prager Morton D.
Published: February 2007

Solubilized antigen was prepared from P1798 lymphoma cells by sonication, 3 M KCI extraction, or isolated from the ascites fluid of syngeneic tumor‐bearing BALB/c mice. Antigen was detected and quantitated by its ability to block activity of anti‐P1798 serum raised in syngeneic mice, as assayed by cytotoxic and indirect immunofluorescence tests. It was established that the reaction was immunologically specific as the P1798 antigen did not inhibit the binding to L1210 lymphoma cells of antisera raised against L1210 in syngeneic DBA/2 or allogeneic BALB/c mice. Vaccination of BALB/c mice with different subcellular fractions of sonicated antigen or with ascites fluid resulted in protection against a live P1798 challenge with results comparable to those obtained using iodoacetamide‐modified tumor cells. Solubilized antigen prepared by each of the three methods eluted from a Bio‐Gel A5m agarose column exclusively in an early peak that had a molecular weight estimated to be greater than 2×106. This column‐fractionated antigen was shown to cross‐react with antiserum raised against Thy‐1.2 antigen, which is present on P1798 cells. The purified P1798 antigen sedimented at 200,000 g and was shown to protect syngeneic mice in immunoprophylactic tests.
Immunologic responses to a murine mammary adenocarcinoma. I. Passive transfer of immunity by sera from tumor‐bearing mice
Authors: Yamamura Yasuhiro , Virella G. , Haskill J. S.
Published: February 2007

DBA/2 mice bearing a syngeneic mammary adenocarcioma T1699 produced high levels of tumor‐specific antibody, detected by indirect immunofluorescence and subsequently identified as the IgG2a subclass. Tumor‐bearer sera passively administered to normal recipients protected the animals from subsequent challenge with T1699 tumor cells but not from challenge with a non‐cross‐reacting syngeneic tumor, SaD2 fibrosarcoma. Administration of sera prior to tumor challenge was found to be more effective than treatment after the challenge. The protective effect of sera appeared to parallel both antibody titers and appearance of concomitant immunity; however, sera absorbed with T1699 cells, with the indirect fluorescent antibody titers reduced more than 100‐fold, conferred an almost identical level of protection. Immune suppression of serum recipients before serum transfer abolished the effect, suggesting that protection depended on a cellular immune response by the host in addition to the possible protective effect(s) of humoral antibody.
Alpha‐1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ‐cell neoplasms: Value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour)
Authors: Talerman A. , Haije W. G. , Baggerman L.
Published: February 2007

Serum alphafoetoprotein (AFP) and serum alpha‐1 antitrypsin (AAT) were determined in 24 patients with germ‐cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ‐cell neoplasms had tumours containing endodermal sinus tumour (yolk‐sac tumour) elements. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ‐cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.
K cell mediated lysis of cultured colon carcinoma and urinary bladder carcinoma cells induced by monospecific antisera against carcinoembryonic antigen (CEA) and two CEA‐related normal glycoproteins
Authors: Hammarström S. , Troye M. , Wahlund G. , Svenberg T. , Perlmann P.
Published: February 2007

Antibody dependent lymphocyte (K cell) mediated lysis of tumor cells in vitro was used to assay for cell surface associated carcinoembryonic antigen (CEA) and two CEA‐related normal tissue components, “normal glycoprotein” (NGP) and biliary glyco‐protein I (BGP I). Three tumor cell lines were used as target cells. These were HT‐29, colon carcinoma, T‐24, urinary bladder transitional cell carcinoma and Mel‐1, malignant melanoma. To induce lysis we used the IgG‐fraction of specific rabbit and monkey anti‐CEA sera and of specific rabbit anti‐NGP and anti‐BGP I sera, respectively. Purified human lymphocytes were used as effector cells. HT‐29 was efficiently killed by low concentrations of rabbit anti‐CEA and less efficiently by monkey anti‐CEA. T‐24 and Mel‐1 were not lysed by anti‐CEA. HT‐29 and T‐24 were lysed by low concentrations of anti‐BGP I. In contrast only HT‐29 was lysed by anti‐NGP. Only a fraction of the tumor cells was killed by the different antisera although kinetic studies showed that the lytic reaction was complete well before the end of the eighteen hour incubation period used in the assay. Anti‐CEA and anti‐BGP I gave 30–40% corrected lysis of HT‐29. With anti‐NGP the corresponding figure was 10–20%.
Comparative studies on adult donor lymphocytes infected by EB virus in vivo or in vitro: Origin of transformed cells arising in co‐cultures with foetal lymphocytes
Authors: Rickinson A. B. , Finerty S. , Epstein M. A.
Published: February 2007

Co‐cultures were set up between equal numbers of mononuclear cells from the blood of EB virus‐infected individuals, either acute IM patients or healthy seropositive adult donors, and foetal cord blood mononuclear cells of the opposite sex. The cell lines arising in the co‐cultures were of mixed origin, with foetal cells predominating in many cases. In contrast, when mononuclear cells from seronegative adult donors were first infected with EB virus in vitro and then 5 to 12 days later co‐cultured with a large excess of foetal cells of the opposite sex, the cell lines which arose were almost exclusively derived from the adult donor despite the fact that a small minority of the virus‐infected adult cells released infectious virus capable of transforming the co‐cultivated foetal cells. The experiments suggest that EB virus‐infected cells present in the blood of IM patients and seropositive donors do not possess the capacity for unlimited in vitro growth shown by seronegative adult donor lymphocytes experimentally infected with the virus.
Familial leukemia and inherited chromosomal aberration
Authors: Cervenka Jaroslav , Anderson Renner S. , Nesbit Mark E. , Krivit William
Published: February 2007

This communication contributes a family with 12 cases of cancer and two cases of leukemia. Chromosomal analysis was performed on three occasions, 9 months apart, In unaffected first‐degree relatives, we have demonstrated high frequency of tetraradial figures: in parents, 1:243 mitoses, and in all first‐degree relatives, 1:328 mitoses. The rate of chromosomal breakage was moderately elevated in comparison with carefully matched controls, mainly in father (6.17), mother (4.01) and one sister (4.07). G‐banded and C‐banded karyotypes revealed no structural chromosomal abnormality in relatives of leukemic children. This family is one of five leukemic families investigated. Analogous methods of chromosomal analysis have been employed in all, but chromatid exchange figures and elevated chromosomal breakage were detected only in the presently reported pedigree. It has been postulated that in this family there exists a possible relation between increased incidence of chromatid exchange figures and increased tendency to leukemia.
Competition for cytotoxic immune capacity against A ‘syngeneic’ mouse tumour distributed at two sites
Authors: Chassoux D. , Maclennan I. C. M. , Munro T. R.
Published: February 2007

Normal C3H mice will develop fatal ascites after the intraperitoneal injection of as few as 100 BP8 cells. However, mice can be immunized so that they can specifically reject an intraperitoneal challenge of 107 of these C3H‐derived tumour cells. This paper investigates a phenomenon in which the capacity of immunized mice to reject an intraperitoneal challenge of tumour cells is lost between two to seven days after tumour cells have been given subcutaneously. Investigation of this temporary loss of capacity to reject the intraperitoneal challenge of tumour suggests that this might be due to the attraction of cytotoxic immunity to the site of subcutaneous injection. The possibility that this phenomenon is due to blocking factors, tumour overload, suppressor cells or enhancing antibody has been investigated but experimental results are given which do not favour these explanations.
Tumor regression after intralesional injection of emulsified trehalose‐6,6′‐dimycolate (cord factor): Efficacy increases with oil concentration
Authors: Yarkoni Eliyahu , Meltzer Monte S. , Rapp Herbert J.
Published: February 2007

Injection of emulsified trehalose‐6,6′‐dimycolate (TDM), a mycobacterial glycolipid, into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely depended on the amount of oil in the emulsion. The anti‐tumor activity of the TDM emulsion containing the highest concentration of oil was equivalent to that of living BCG.
Expression of viral protein P27 in avian sarcoma virus‐transformed mammalian cells and helper‐dependent rescue of rous sarcoma virus
Authors: Popovič M. , Svoboda J. , Suni J. , Vaheri A. , Pontén J.
Published: February 2007

Avian sarcoma virus (ASV)‐transformed mammalian cells, known to be either virus‐producing, virogenic or non‐virogenic, were tested for viral gene products: for p27 by radioimmunoassay and for group‐specific (gs) antigens by the complement fixation test. Clones of B77 virus‐producing RBI rat tumour cells had p27 concentrations ranging from 10 to 80 ng/mg cellular protein; the poor virus‐producing clone had the lowest levels of p27 and gs antigen. Treatment of the clones with halogenated pyrimidines, BrdUrd and IdUrd, had little effect. Virogenic mammalian cell lines XC, LWC3 cells and human 118MG/EH cells transformed by the Prague, Schmitt‐Ruppin and Engelbreth‐Holm strains of ASV, respectively, were analyzed for p27, for gs antigens, tumour induction in chickens and focus formation after fusion of the X‐ray‐irradiated cells with chicken fibroblasts. Concentrations of p27 and of gs antigens and tumour induction by intact cells were approximately the same in both rat XC cells and human 118MG/EH cells. Treatment with BrUrd or IdUrd increased the level of p27 in the latter cell line. On the other hand, rat LWV3 cells had no detectable p27 or gs antigens but their tumourinducing activity in chickens was fifty‐fold higher. Non‐virogenic rat TWERC cells, transformed by the Prague strain of RSV, had low detectable levels of p27 and of gs antigens. These cells did not produce tumours in chickens or foci when fused with chicken fibroblasts. The only, and very effective, way of rescuing RSV from TWERC cells was the fusion of TWERC cells with RAV‐1‐preinfected cells. After inoculation of a mixture of 2×104 cells treated with inactivated Sendai virus, tumours were induced in 50% of the chickens. Both the host‐range and virus neutralization studies indicated that the rescued TWERC virus had avian subgroup C specificity and not the specificity of the helper virus. The rescued virus had a one‐hit titration pattern in duck embryo fibroblasts, indicating that the virus was non‐defective for infection and transformation of these cells.
Incomplete viral genome in a non‐virogenic mouse tumour cell line (RVP3) transformed by prague strain of avian sarcoma virus
Authors: Svoboda J. , Popovič M. , Sainerová H. , Mach O. , Shoyab M. , Baluda M. A.
Published: February 2007

Two cell lines, RVP3 and RVA4, derived originally from mouse tumours induced by the Prague and Schmidt‐Ruppin strain of RSV, respectively, were studied. All attempts failed to induce infectious virus production in RVP3 cells by fusion with chicken fibroblasts even if the cells were infected with avian leukosis viruses. Also, attempts to rescue the viral genome by transfection were unsuccessful. RVP3 cells harboured 31–45% of the viral genome sequences, as was shown by molecular hybridization, and therefore they were designated cryptovirogenic. The tumour cell line RVA4 did not contain any detectable viral sequences. The significance of the detection of the incomplete Rous virus genome sequences in mammalian cells is discussed.
RNA‐reverse transcriptase complex from cultured human myeloma‐leukemia cells
Authors: Sawada Hiroyoshi , Tashima Masaro , Nakamura Toru , Uchiyama Takashi , Sagawa Kimitaka , Takatsuki Kiyoshi , Uchino Haruto , Ito Yohei
Published: February 2007

A high molecular weight RNA‐reverse transcriptase complex in the culture media of peripheral leukocytes obtained from two Japanese patients with myeloma‐leukemia was detected by demonstration of a 3H‐uridine peak and a peak of DNA polymerizing activity banding at a density of 1.15–1.19 g/ml. The enzyme in the complex was able to utilize poly(rA) · d(pT)10 or poly (rC) · d(pG)12–18, but not poly (dA) · d(pT)10 or (dT)12–18, as template‐primers. The sucrose density sedimentation analysis revealed that RNA in the complex sedimented at a location of approximately 50s and 20–30s.
Characterization of lymphoid cell lines established from multiple epstein‐barr virus (EBV)‐induced lymphomas in a cotton‐topped marmoset
Authors: Rabin Harvey , Neubauer Russell H. , Hopkins Ralph F. , Levy Barnet M.
Published: February 2007

Inoculation of a cotton‐topped marmoset with cell‐free EBV, strain B95‐8, resulted in the induction of lymphomas in liver, spleen, and mesenteric lymph nodes. Continous suspension cell lines were established from tumor tissue from each of these three sites. Cells of each line were positive for intracellular EBV antigens and EB nuclear antigen and released low levels of transforming virus. Early after initial culturing each line had a high frequency of cells (84‐85%) with receptors for activated complement but these receptors were no longer evident on retesting several months later. All three lines initially showed high levels of cells which stained for surface lambda light chain and gamma and mu heavy chains. Cells of all three lines showed a decrease in gamma chain staining and the lymph‐node tumor line showed reductions in surface staining for mu and lambda chains as well after prolonged cultivation. Clonal cells of the three lines resembled their respective parental lines in surface markers. Cytogenetically, all the lines were hypodiploid, 2n = 45, and several karyotypes from all three lines showed the loss of a medium‐sized metacentric chromosome. A marker chromosome with an extra band in the centromeric region was apparent in the lymph‐node tumor line. These results indicate that cells of individual tumors in a cotton‐topped marmoset with multiple EBV‐induced lymphomas are similar to each other in a number of characteristics although a certain degree of divergence was observed. Thus, it is possible that EBV‐induced lymphomas in cotton‐topped marmosets may have a common cell origin as is the case with Burkitt lymphoma in humans.
SV40 tumor rejection induced by vesicular stomatitis virus bearing SV40 tumor‐specific transplantation antigen (SV40‐TSTA). I. Specificity of immunoprotection and effect of enzyme treatment on tsta activity
Authors: Ansel Sandra , Huet Christian , Tournier Paul
Published: February 2007

Highly purified vesicular stomatitis virus (VSV) was obtained from VSV‐infected SV40‐transformed hamster cell lines. Immunization with this virus protected hamsters against challenge with SV40‐transformed cells (TSV5‐cl2). This protection was obtained regardless of the source of the SV40‐transformed cells (e.g. cat, rat, hamster) used to produce VSV, and was therefore associated with the SV40 tumor‐specific transplantation antigen (SV40‐TSTA). Furthermore, when grown on spontaneously transformed cell lines or on cells transformed by a different oncogenic DNA virus, such as polyoma virus, the VSV failed to protect against the SV40‐induced tumor. It was concluded that the SV40‐TSTA activity of purified VSV is due to the incorporation of SV40‐TSTA within the viral envelope. When VSV was treated with proteolytic enzymes (bromelain, trypsin) no loss of TSTA‐induced tumor rejection was observed, although VSV had lost its ability to induce virus‐neutralizing antibody. This clearly demonstrates that the TSTA activity is not related to the viral spikes. Phospholipase C suppressed the TSTA activity but neutralizing activity was still detectable in the anti‐VSV sera. The results presented here demonstrate that the protection afforded by VSV is highly specific. It is particularly interesting that SV40‐TSTA activity may be conveyed by the lipid core of the viral envelope.
Susceptibility to and escape from complement‐mediated lysis of guinea‐pig hepatoma line‐10
Authors: Abe S. , Berczi I. , Sehon A. H.
Published: February 2007

Rabbit xenoantisera produced against diethyl‐nitrosamine‐induced strain‐2 guinea‐pig hepatoma line‐10 cells (L‐10) according to various immunization schedules were compared for their cytotoxicity on L‐10 cells in the presence of guinea‐pig complement. The highest activity was obtained with anti‐sera (Cx‐1) produced by repeated intravenous injections of living L‐10 cells at high cell dosage, whereas intramuscular injections of living or glutaraldehyde‐treated L‐10 cells at similar frequency and cell dosage were less effective for the production of cytotoxic antibodies against L‐10 cells. Intravenous injections of smaller cell doses were less effective. The cytotoxic antibody in Cx‐1 antiserum was shown to be IgG by various methods including gel filtration on Sephadex G‐200, ion exchange chromatography and immunoelectrophoresis of purified tumor‐specific antibodies. It was concluded that L‐10 cells can be lysed by guinea‐pig complement and tumor‐specific antibodies (IgG). Some antisera contained IgM antibodies which were not cytotoxic. A decrease in susceptibility of L‐10 cells to complement‐mediated lysis was observed when the cells were maintained in vivo for a long period (more than 20 passage generations). This was due to a lower density of tumor antigens on the cell surface. When tumor cells were treated with a second antibody directed against rabbit IgG or F(ab′)2, cytotoxicity of Cx‐1 antisera was completely abolished.
Human lymphoblastoid cell lines derived from individuals without lymphoproliferative disease contain the same latent forms of epstein‐barr virus dna as those found in tumor cells
Authors: Kaschka‐Dierich Christine , Falk Lawrence , Bjursell Gunnar , Adams Alice , Lindahl Tomas
Published: February 2007

The physical state of the intracellular Epstein‐Barr virus DNA was characterized in four human lymphoblastoid cell lines, F‐265, NC‐37, U‐303 L, and PG‐1, derived from individuals without lympho‐proliferative disease. For comparison, a previously investigated Burkitt lymphoma line, Raji, and a more recently established cell line of that origin, Rael, were also studied. The techniques employed were CsCl density gradient centrifugation, glycerol gradient centrifugation, and ethidium bromide‐CsCl density gradient centrifugation in combination with nucleic acid hybridization, as well as electron microscopy contour length measurements of purified circular EBV DNA. All six cell lines contained multiple copies of covalently closed circular EBV DNA‐molecules of the same size, as well as viral DNA with the properties of integrated DNA. No differences could be detected between the forms of EBV DNA present in cell lines derived from non‐malignant sources and those present in lymphoma lines.
Differential sensitivity of Xeroderma pigmentosum cells of different repair capacities towards the chromosome breaking action of carcinogens and mutagens
Authors: San R. H. C. , Stich W. , Stich H. F.
Published: February 2007

The sensitivity of cultured fibroblasts obtained from four unrelated Xeroderma pigmentosum patients (XP‐K, XP‐C, XP‐E and XP‐H), which showed different DNA repair levels, was examined. The frequency of metaphase plates with chromosome aberrations and the frequency of breaks and exchanges per chromosome complement were estimated following exposure to the carcinogens 4‐nitroquinoline‐1‐oxide (4N QO), N‐acetoxy‐2‐acetyl‐aminofluorene (N‐acetoxy‐2‐AAF), and N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), and to the mutagen daunomycin. The frequency of chromosome aberrations (breaks and exchanges) increased in the order (XP‐K < XP‐C < XP‐E < XP‐H) with decreasing DNA repair capacity of the XP cells examined (XP‐K > XP‐C > XP‐E > XP‐H) following 4N QO and N‐acetoxy‐2‐AAF. MNNG induced DNA repair synthesis and chromosome aberrations in the four XP cell types at levels comparable to those in fibroblasts of non‐afflicted persons. Daunomycin triggered no DNA repair synthesis but induced similar frequencies of chromosome aberrations in the XP cells and controls. Heterozygous XP cells from parents of XP‐K, XP‐E and XP‐C responded as control cells towards the three carcinogens and the mutagen used. Xeroderma pigmentosum can be considered to be an “induced” chromosome instability syndrome, in contrast to Bloom's syndrome or Fanconi's anaemia, which are “spontaneous” chromosome breakage syndromes according to German's definition.
Expression of alien h‐2 specificities on a chemically induced balb/c fibrosarcoma
Authors: Meschini Angela , Invernizzi Giovanni , Parmiani Giorgio
Published: February 2007

The presence of alien histocompatibility antigens on the cell surface of the 3‐methylcholanthreneinduced BALB/c (H‐2d) fibrosarcoma C‐1, was investigated by serological and transplantation studies. Absorption experiments with monospecific alloantisera showed that C‐1 cells expressed their original private (H‐2.4 and 31) and public (H‐2.3, 8, 28, and 35) specificities. C‐1 cells were also able to absorb monospecific antisera directed to the private specificity H‐2.23 of the H‐2k haplotype, as well as antisera to the public specificities H‐2.1, 5, 11 and 25 (H‐2k and in part H‐2q, H‐2a and H‐2b haplotypes), which are absent from H‐2d normal cells. Conversely, other alien specificities (H‐2.2, 17, 30, 32, and 33) were not detected on C‐1 cells. The C‐1 cells were also unable to absorb the activity of an anti‐la serum (1–28) directed to la.1, 2 and 19 (lak) specificities. Transplantation studies showed that resistance against the challenge of C‐1 cells could be induced in syngeneic BALB/c mice by preimmunization with normal tissues from C3Hf and AKR (H‐2k), A (H‐2a) and C57BL/6J (H‐2b) strains (expressing all or some of the extra H‐2 antigens of the tumor) whereas no protection was obtained with DBA/2 (H‐2d) or with W/Fu rat tissues. The anti‐tumor activity could be passively transferred by BALB/c lymphoid cells immune to normal C3Hf, AKR, A, and NIH (H‐2q) tissues, but no protection was achieved with lymphoid cells immune to DBA/2 or to W/Fu normal rat tissues. These data indicate that foreign H‐2 antigens are expressed on C‐1 tumor and that they might function as tumor‐associated transplantation antigen which was shown to be present and individually distinct on this sarcoma by appropriate in vivo tests.
Tumour‐specific complement‐dependent serum cytotoxicity against a chemically induced rat hep atoma
Authors: Price Michael R. , Baldwin Robert W.
Published: February 2007

A short‐term 51Cr release test was used for the detection of complement‐dependent cytolytic activity of syngeneic serum for transplanted aminoazo dye‐induced rat hepatoma cells in suspension. Serum samples from rats bearing intraperitoneal implants of one hepatoma (hepatoma D23) were specifically cytotoxic for hepatoma D23 target cells, although this activity was not detected in sera from donors bearing subcutaneous tumour grafts. Other sera containing demonstrable IgG antibodies reactive in membrane immunofluorescence tests with individually distinct tumour‐specific antigens or tumour‐associated embryonic antigens were not cytotoxic for hepatoma D23 cells; and even though serum from donors carrying intraperitoneal tumour grafts contained tumour‐specific IgG antibody, the complement‐dependent reactivity was confined to the 19s region of fractionated tumour‐bearer serum. These findings are discussed in relation to the development of humoral responses in the tumourbearing host and with regard to the significance of the availability of an objective and reproducible assay for measuring humoral responses directed against the tumour‐specific antigens associated with chemically induced rat tumours.
Spontaneous and induced appearance of murine leukemia virus antigen containing cells in organ cultures of embryonic mouse thymus
Authors: Riesenfeld Inger , Alm Gunnar V.
Published: February 2007

The potential of embryonic thymus organ cultures for studies on relations of endogenous MuLV, lymphoid cells and thymic microenvironment to lymphoma development were evaluated. Four main findings are reported. First, thymuses of 14‐day‐old CBA and AKR embryos could be maintained in organ cultures for at least 9 weeks with sustained production of lymphocytes. Lymphopoiesis in CBA and AKR thymuses were not grossly different. Secondly, an indirect immunofluorescence (IF) technique demonstrated spontaneous appearance of MuLV‐antigen‐containing cells in AKR, but not in CBA thymuses. Such spontaneous MuLV expression first occurred after 16 days of organ culture, thereafter infrequently and at random in individual thymus cultures. Thirdly, incubation of AKR and CBA thymuses in lymphoma extract containing AKR‐type MuLV at initiation of organ cultures induced MuLV‐antigen‐containing cells. These were first detected after 7‐14 days in culture, somewhat earlier and initially more frequently in AKR than in CBA thymuses. In the former, induction was accompanied by a clear reduction in the number of lymphocytes per thymus. Fourthly, iododeoxyuridine (IdUrd) treatment of AKR thymuses on culture day 0, 3 or 7 decreased the number of lymphocytes per thymus and induced appearance of MuLV‐antigen containing cells, assayed 8‐20 days later. The IdUrd effect was most marked on day 0, and decreased successively on days 3 and 7. IdUrd had a much slighter effect on CBA thymuses, causing a lower reduction in cell numbers and inducing few MuLV‐antigen cells. These main results clearly demonstrate the potential usefulness of the organ culture system for studies on leukemogenesis. It may be directly applied to answer several questions raised by detailed findings in our study.
Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos—smoking interaction
Authors: Saracci R.
Published: February 2007

Three simple models for the asbestos—smoking interaction on human lung cancer production are considered. In the first model the excess incidence of lung cancer independently due to asbestos and to smoking adds together when both agents are present (additive model). In the second the addition of each one of the two agents produces an effect (increase in lung cancer incidence) which is proportional to the effect of the other (multiplicative model). In the third, asbestos can only increase lung cancer incidence in the presence of smoking. As previously found by other investigators, the additive model appears the least plausible in the light of the data from two published epidemiological studies. A discrimination between the other two models is attempted through a detailed analysis of the five published epidemiological studies today available which provide information on occupational asbestos exposure, smoking habits and lung cancer risk. Although the data do not allow a definitive discrimination, the multiplicative model appears to be more plausible, being also consistent with a multistage carcinogenic mechanism and with evidence from animal (rat) experiments. It is relevant both for biology and for public health that in this model asbestos and smoking are regarded as independently capable of producing lung cancer in humans and that they act synergistically when exposure to both occurs.
Increased ferritin synthesis and release by hodgkin's disease peripheral blood lymphocytes1
Authors: Sarcione Edward J. , Smalley James R. , Lema Mark J. , Stutzman Leon
Published: February 2007

Peripheral blood lymphocytes from patients with all stages of untreated Hodgkin's disease and from normal healthy adults were shown to synthesize and release ferritin in vitro. Ferritin synthesis was confirmed by immunoelectrophoresis, double immunodiffusion and autoradiography. Hodgkin's disease lymphocytes synthesized ferritin 4.2 times faster and released it 2.4 times faster than did normal lymphocytes, whereas total protein synthesis was faster in normal lymphocytes. Patients with nodular sclerosis and perhaps those with absence of fever had the highest synthetic rates; however no relationship was observed between relative rates of lymphocyte ferritin synthesis and sex, age, anatomical stage and presence of splenic or hepatic involvement by tumor. Addition of iron to normal human lymphocytes produced little or no change in ferritin synthesis. These data indicate that part of the intracellular ferritin detected in peripheral blood lymphocytes from patients with Hodgkin's disease and from normal individuals resulted from de novo synthesis rather than from uptake and storage of serum ferritin, and suggests that elevated ferritin levels detected in the serum and tumor tissue of Hodgkin's disease patients originate from lymphocytes.
Membrane receptor stripping confirms the association between ebv receptors and complement receptors on the surface of human b lymphoma lines
Authors: Yefenof Eitan , Klein George
Published: February 2007

Complement (C3) receptors, EBV receptors, Fc receptors, membrane IgM and beta2microglobulin (β2m) were individually stripped from the surface of human B lymphoma lines. The cells were subsequently tested for their ability to absorb infectious EB virus. Stripping of Fc receptors, IgM and β2m did not reduce EBV absorption. Stripping of either EBV receptors or C3 receptors eliminated or drastically reduced EBV‐absorptive capacity. The results confirm the distinctive association between EBV receptors and C3 receptors on human lymphoma cells.
Detection of herpes simplex virus‐related antigens in the nuclei and cytoplasm of biochemically transformed cells with peroxidase/anti‐peroxidase immunological staining and indirect immunofluorescence
Authors: Kurchak Mark , Dubbs Del Rose , Kit Saul
Published: February 2007

Herpes simplex virus (HSV)‐related antigens have been demonstrated in the nuclei and cytoplasm of human and mouse cells biochemically transformed by ultraviolet light‐irradiated HSV. This was accomplished by using peroxidase/anti‐peroxidase immunological staining and indirect immunofluorescence with rabbit antisera that had high neutralizing titers against the HSV‐specific thymidine kinase activity and virus infectivity. HSV‐1 antisera reacted with antigens in cells biochemically transformed by type 1 HSV, but not with those of cells biochemically transformed by type 2 HSV. Similarly, HSV‐2 antisera reacted with antigens in cells biochemically transformed by HSV‐2, but not with those in cells biochemically transformed by HSV‐1. In contrast, herpes virus‐related antigens were detected in cells cytolytically infected with HSV‐1 and with HSV‐2 by either type 1 or type 2 HSV antisera. These observations suggest that the antigens detected in the biochemically transformed cells were a type‐specific subset of the HSV‐related antigens synthesized in cells undergoing productive infection by HSV‐1 and HSV‐2.
Natural cell‐mediated cytotoxicity in mice against non‐lymphoid tumor cells and some normal cells
Authors: Nunn M. E. , Herberman R. B. , Holden H. T.
Published: February 2007

Lymphocytes from normal mice were found to have cell‐mediated cytotoxicity, in a short‐term 51Cr release assay, against a variety of non‐lymphoid tumor cells as well as against lymphomas. Some of the non‐lymphoid tumors were as susceptible to natural cytotoxicity as the standardly used lymphoid lines. Some tissue culture cell lines and in vivo passaged tumor lines were susceptible to lysis, as were some primary virus‐induced lymphomas. Tumors which arose in nude mice, which have high levels of natural cytotoxic activity, were all resistant to lysis. In addition to the susceptibility of transformed cells to natural cell‐mediated cytotoxicity, some untransformed cultured cells and cells from normal tissues were targets for this mechanism. Low levels of cytotoxicity were seen with normal thymus cells, bone‐marrow cells, and short term cultures of macrophages, whereas normal spleen and lymph‐node cells were completely resistant to lysis. These results indicate a broader spectrum for mouse natural cell‐mediated cytotoxicity reactivity than has been previously recognized.
Soluble tumor antigen‐induced lymphocyte proliferation: Effects of serum from normal and tumor‐bearing mice
Authors: Calderwood Maron B. , Forbes James T. , Smith Richard T.
Published: February 2007

The effect of serum from mice bearing methylcholanthrene‐induced fibrosarcomas on the lymphoproliferative responses of their spleen and lymphnode cells to 3 M KCI‐solubilized tumor antigens has been investigated. Low concentrations of serum (≤2.5%) collected throughout the course of tumor growth were inhibitory. Normal sera collected from age‐matched control mice were often slightly inhibitory, but to a significantly lesser extent at identical serum concentrations. The inhibitory effect of tumor‐bearing serum was not limited to homologous tumors, but was also observed when cross‐reacting syngeneic tumor antigens or serum from animals bearing other syngeneic tumors were added to the assay mixture. At the low concentrations used, tumor‐bearing sera inhibited only tumor‐antigen‐induced proliferation, and not proliferation induced by T cell mitogens. The inhibitory effects of tumor‐bearing sera on lympho‐proliferative responses to soluble tumor antigens appear to be similar to the inhibition seen as “serum blocking” in other assays of tumor immunity.
An analysis of the g‐banded chromosomes of the golden hamster
Authors: Pavia R. A. , Smith L. W. , Goldenberg D. M.
Published: February 2007

Chromosomes from 20 G‐banded karyotypes of golden hamster cheek pouch cells were precisely measured to determine total lengths and arm ratios. Mean values were used t o establish an idiogram which may serve as the basis for a standard hamster karyotype.
Relationship between the Epstein‐Barr virus and undifferentiated nasopharyngeal carcinoma: Correlated nucleic acid hybridization and histopathological examination
Authors: Andersson‐Anvret Maria , Forsby Nils , Klein George , Henle Werner
Published: February 2007

In order to examine critically the closeness of association between Epstein‐Barr virus (EBV) DNA and nasopharyngeal carcinoma (NPC) a correlated histopathological and nucleic acid hybridization study was performed on 51 undifferentiated NPC, 4 NPC with some signs of squamous differentiation, 7 nasopharyngeal tumors of other histological types and 14 head and neck carcinomas located outside the nasopharynx. All 51 undifferentiated NPCs contained significant numbers of EBV‐genome copies per cell. Two of the somewhat differentiated NPCs were also EBV‐DNA‐positive, whereas 2 were negative. Of the 7 other nasopharyngeal tumors, 1 was EBV‐DNA‐positive. Histological examination, however, showed that this was a typical Burkitt lymphoma. The other 6 tumors were all EBV‐DNA‐negative lymphoproliferative malignancies. All 14 head and neck carcinomas located outside the nasopharynx were EBV‐DNA‐negative. The sera of undifferentiated NPC patients had elevated antibody titers against the EBV‐determined antigens, the EA (D) component in particular. These findings confirm that there is a regular association between EBV‐DNA and undifferentiated NPC.
Detection of epstein‐barr virus antigens with enzyme‐conjugated antibody
Authors: Granlund David J. , Andrese Angelo P.
Published: February 2007

Monospecific conjugated (fluorescein isothiocynate and horseradish peroxidase) goat antisera, prepared against three human immunoglobulin classes, IgM (μ), IgG (γ) and IgA (α), were compared for their ability to detect human Ig classes possessing specificity for Epstein‐Barr virus (EBV) viral capsid antigens (VCA) in a chronically infected human lymphoid cell line, P3J‐HRIK. It was determined that the enzyme system was significantly more sensitive than immunofluorescence in detecting most of the immunoglobulins in sera from cancer patients. Some patients with nasopharyngeal carcinomas (NPC) had extremely high levels of EBV‐specific IgA, whereas cancers other than NPC may have lower EBV‐specific IgA titers.
Growth inhibitory effects of interferon on normal and malignant human haemopoietic cells
Authors: Balkwill Frances R. , Oliver R. T. D.
Published: February 2007

A study of the effects of human leukocyte and lymphoblastoid interferon preparations on the growth of normal, immune and malignant haemopoietic cells has been carried out. At a standard dose of 10,000 U/ml, incorporation of tritiated thymidine ([3H] TdR) was reduced by 7–92% of control values, and cell survival by 35–82% in acute myelogenous leukaemia cell cultures, whereas in normal bone‐marrow cultures interferon showed a 58–62% reduction in [3H] TdR uptake but only up to 13% reduction in cell survival. [3H] TdR incorporation by MLC‐stimulated lymphocytes was also significantly reduced by interferon but the blastogenic response to PHA was not. These effects of interferon were shown to be dose‐dependent. The problems of using interferon in the treatment of AML in the light of these findings are discussed.
Lymphocyte cytotoxicity against autologous tumour biopsy cells in humans
Authors: Vose B. M. , Vanky F. , Klein Eva
Published: February 2007

By the application of separation techniques in a stepwise manner to mechanically prepared cell suspensions from human tumour biopsies it has been possible to isolate tumour cells having high viability and low contamination with host cells. These tumour cells have been used as targets in 51Cr release cytotoxicity assays using autologous lymphocytes from blood or lymph node as effectors. It has been possible to investigate this reactivity in 30 patients with malignant and four patients with benign tumours. Significant autologous cytotoxicity in the blood lymphocytes was detectable in two of 12 lung tumours, nine of 18 other carcinomas and sarcomas but in none of the benign cases. Cytotoxicity was not limited by the presence of obvious residual disease at the time of operation although reactivity was less frequently detectable in patients with secondary involvement. Reactivity in the tumour‐draining lymph nodes largely paralleled that in the blood in the limited number of patients examined. The technical problems encountered during this study and the role of natural cytotoxicity in the interpretation of these data are discussed.
Surface immunoglobulins and protease inhibitors of human acute leukemia blasts
Authors: Cotropia J. P. , Gutterman J. U. , Hersh E. M. , Mavligit G. M.
Published: February 2007

Cell‐surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), low pH elution and immunodiffusion (ID). Among AML blasts from 21 patients, the average proportions of blasts positive for IgG, IgM, and IgA were 60%, 9%, and 9% respectively. In contrast, blasts from four CML patients in blast crisis and 14 ALL patients had surface IgG, IgM, and IgA values of 14%, 9%, and 7% respectively for the former group and 1.4%, 1.1%, and 0.8% respectively for the latter group. Blasts from 20 leukemic cell preparations were eluted at pH 2.4 for 30 min at 4° C in glycine. HC1 buffer. Immunodiffusion with appropriate specific antisera demonstrated intact IgG in 3 of 13 AML eluates. Ten of 13 AML eluates, 1 of 3 CML eluates, and 2 of 4 ALL eluates contained intact IgG and Fab fragment, but no Fc fragment. One CML eluate contained intact IgG; the remaining CML eluate contained Fab fragment only. Two ALL eluates contained no IgG or fragments by double diffusion. An eluate from a pool of normal human leukocytes from 20 normal donors contained intact IgG and Fc fragment, but no Fab fragment. Nineteen of 20 leukemic cell eluates also contained the anti‐proteases alpha‐1‐antitrypsin and alpha‐1‐anti‐chymotrypsin which were shown to have been proteolytically modified. Five of 20 leukemic cell eluates contained the anti‐protease alpha‐2‐macroglobulin. The normal leukocyte eluate contained alpha‐1‐anti‐trypsin but no alpha‐1‐anti‐chymotrypsin or alpha‐2‐macroglobulin. The presence of Fab fragment in AML, CML blast crisis and ALL eluates suggests IgG binding by Fab as antibody, while Fc fragment in normal leukocyte eluate suggests binding via Fc to the Fc receptor. The expression of cell‐associated proteolytic enzymes, as revealed by the presence of protease‐modified anti‐proteases, may explain cell‐surface IgG degradation. A consequence of surface proteolytic activity would be the degradation of IgG antibody to yield Fab fragment bound to membrane antigenic determinants. The Fab reaction product is incapable of interacting with either complement or Fc receptors. Therefore, such proteolytic activity may protect the leukemic blasts from lysis by complement‐dependent or antibody‐dependent cell‐mediated cytotoxic mechanisms.
Cell‐mediated immunity against particulate and solubilized tumor‐associated antigens of murine plasmacytomas detected by macrophage migration inhibition assays
Authors: Padarathsing M. L. , Dean J. H. , McCoy J. L. , Lewis D. D. , Northing J. W. , Natori T. , Law L. W.
Published: February 2007

Cell‐mediated immunity (CMI), as detected by the agarose microdroplet macrophage migration inhibition (MMI) assay, was investigated using peritoneal exudate cells (PEC) of BALB/c mice and several crude membrane (CM) and solubilized preparations of murine plasmacytomas. The MMI assay was quite sensitive and detected inhibition of macrophage migration as low as picogram quantities of CM, NP40 detergent‐ and papain‐solubilized preparations (CS) of ADJ‐PCS and LPC‐1 plasmacytomas. The data were highly reproducible from one experiment to the next with the same or different lots of the CM or solubilized extracts. Specificity studies demonstrated that ADJ‐PCS and LPC‐1 plasmacytomas expressed cross‐reactive tumor‐associated antigens (TAA) as detected by MMI and confirmed by tumor challenge and Winn neutralization experiments. No cross‐reactivity was observed with similar extracts prepared from an unrelated syngeneic simian virus 40 (SV40)‐induced sarcoma. The inhibition of macrophage migration observed was mediated by culture supernatants generated from the mixture of plasmacytoma‐immune spleen cells with antigens and then assayed in an indirect MMI assay on normal PEC. The agarose microdroplet MMI assay appeared to be a rapid and sensitive method to measure TAA recognition and to monitor TAA isolation and solubilization with minimum numbers of immune cells.
Latent carcinoma of prostate at autopsy in seven areas. Collaborative study organized by the International Agency for Research on Cancer, Lyons, France
Authors: Breslow N. , Chan C. W. , Dhom G. , Drury R. A. B. , Franks L. M. , Gellei B. , Lee Y. S. , Lundberg S. , Sparke B. , Sternbya N. H. , Tulinius H.
Published: February 2007

A world‐wide comparative study of the frequency and characteristics of latent carcinoma of the prostate was undertaken in seven areas, using standardized methods and “blind” microscopic evaluation in order to reduce selection and observer bias. The morphological features of 350 latent carcinomas found in 1,327 prostates were examined. Two Chinese populations, from Hong Kong and Singapore, showed a low frequency of latent carcinoma in comparison with western Europeans in Sweden and the Federal Republic of Germany and negroes from Jamaica; an intermediate position was found for Israelis and black Ugandans. The frequency of small latent carcinomas was about 12% in all the areas investigated and did not vary with age. Rates for larger latent carcinomas increased sharply with age and showed an area‐to‐area variation resembling that of clinical carcinoma of prostate. The small carcinomas were almost exclusively situated in the outer half of the prostate and latent carcinomas of all sizes were evenly distributed between the anterior and posterior halves of the prostate and the right and left sides of the outer prostatic shell. Certain disagreements in diagnosis were noted when the sections from each area were evaluated independently by a different pathologist. Most of these disagreements were resolved by re‐reading the sections; their occurrence had no significant effect on the geographical comparisons.
Tyrosinase activity in the sera of patients with malignant melanoma: Method and specificity
Authors: Nishioka K. , Romsdahl M. M. , Fritsche H. A. , McMurtrey M. J.
Published: February 2007

Serum tyrosinase activity has been measured by adapting the [3]tyrosine assay for tyrosinase and significant elevations of serum tyrosinase activity were found in patients with malignant melanoma. In contrast to findings in a study which utilized [14C]tyrosine, augmented levels of tyrosinase activity were not observed in sera from patients with other malignancies, including subjects with carcinoma of the breast. The results of the examinations for soluble tyrosinase activity in human malignant melanoma tissue‐cultured lines were all positive, whereas human cell lines from carcinoma of the breast, carcinoma of the colon and sarcoma uniformly showed no activity. The method employed for detecting tyrosinase activity holds promise as a specific diagnostic test and may be valuable for monitoring the response to clinical treatment of patients with malignant melanoma.