bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies reacting with human T‐lymphotropic retrovirus (HTLV‐1) or related antigens in lymphomatous and healthy hamadryas baboons
Authors: Voevodin A. F. , Lapin B. A. , Akovleva L. A. Y , Ponomaryeva T. I. , Oganyan T. E. , Razmadze E. N.
Published: February 2007

The sera of lymphomatous and healthy hamadryas baboons of the main, lymphoma‐prone Sukhumi stock were tested for antibodies reacting with HTLV‐1 antigens in the indirect immunofluorescence test. Antibodies of this specificity were found in all but one of 58 lymphomatous baboons and in 45% of 177 healthy ones. The prevalence of HTLV‐1 reactive antibodies in lymphoma‐free baboon populations (including 118 Sukhumi „forest”︁ stock animals and 195 baboons imported in 3 groups from Ethiopia) was consistently lower (5–8%). The specificity of baboon antibodies reacting with HTLV‐1 or a related agent is supported by the following evidence: (1) Concordant reactivity pattern of baboon sera with several HTLV‐1‐positive and ‐negative human cell lines; (2) elimination of baboon sera anti‐HTLV reactivity by absorption with purified HTLV‐1, but not by other retroviruses; (3) significant correlation between immunofluorescence titers of baboon sera and their reactivity in enzyme‐linked immunosorbent assay with purified HTLV‐1; (4) competition of baboon anti‐HTLV with monoclonal antibodies GIN‐14 for binding of the epitope on p19HTLV‐1. The prevalence of anti‐HTLV positives in the main Sukhumi stock increased by age, reaching its maximum (approx. 80%) at 5–15 years, and showed no significant sex‐related variation. The level of anti‐HTLV antibodies in lymphomatous baboons and in age‐, sex‐ and population‐matched healthy ones did not differ. However, in pre‐lymphoma sera these antibodies reached significantly higher levels than in sera of lymphomatous baboons (obtained in the terminal stage) or of matched, healthy controls.
Differential enhancement of melphalan cytotoxicity in tumor and normal tissue by fluosol‐DA® and oxygen breathing
Authors: Teicher Beverly A. , Holden Sylvia A. , Rose Christopher M.
Published: February 2007

The addition of Fluosol‐DA® carbogen breathing to melphalan treatment of the FSa‐IIC fibrosarcoma was assessed by tumor growth delay and cell survival assays. Melphalan (10 mg/kg) administered intraperitoneally (i.p.) was preceded by Fluosol‐DA (0.3 ml) administered intravenously (i.v.) and followed by 1 hr of carbogen breathing; this resulted in a tumor growth delay of 9.5 ± 1.4 days or an approximately 3‐fold increase compared to melphalan alone. Melphalan produced about 1.7 logs of cell killing; neither carbogen breathing nor Fluosol‐DA pretreatment altered the cell killing observed. There was a 10‐fold increase in tumor‐cell killing when Fluosol‐DA was administered immediately prior to melphalan administration followed by carbogen breathing for 1 hr. Density gradient separation identified a population of denser FSaIIC cells which showed increased sensitivity to melphalan after Fluosol‐DA administration. There was no additional toxicity to bone marrow as measured by CFU‐GM with the combination of melphalan/Fluosol‐DA/O2 compared to melphalan alone.
Glycoconjugates of murine tumor lines with different metastatic capacities. II. Diversity of glycolipid composition
Authors: Schwartz Reinhard , Kniep Bernhard , Müthing Johannes , Mühlradt Peter F.
Published: February 2007

A syngeneic tumor system in DBA/2 mice consisting of a methyl‐cholanthrene‐induced, weakly metastatic lymphoma, L5178YE (= Eb), its spontaneous strongly metastatic variant, L5178YES (= ESb), and an unrelated, methylcholanthrene‐induced, metastasizing tumor, MDAY‐D2, were used to study the relationship between metastatic behavior and composition of GSLs. The D‐I‐14C galactose and D‐I‐14C glucosamine‐labelled neutral GSL and gangliosides of these tumor cells, and additionally ConA‐stimulated spleen T cells from normal mice, were analysed by thin‐layer chromatography. Unlabelled GSLs of the tumors were also characterized by (HPLC) after perbenzoylation. Results obtained with the radioactively labelled GSLs correlated with those of the HPLC analysis of unlabelled GSLs. All tumors contained neutral GSL of the ganglio‐series. Weakly metastatic tumor Eb showed neutral GSL patterns comparable to those from ConA‐stimulated spleen cells, whereas strongly metastatic tumors ESb and MDAY‐D2 had an enhanced expression of lactosylceramide. Gangliosides of metastatic ESb and MDAY‐D2 had a higher degree of polarity than those of weakly metastatic Eb. Eb cells expressed primarily GM1. Metastasizing ESb and MDAY‐D2 had significantly higher amounts of GM3, GM2 and GD1a. An unusual ganglioside, IV3GalNAc‐GMI, was found in MDAY‐D2 cells and ConA blasts. When the extent of label was compared in neutral GSLs and gangliosides, metastasizing ESb and MDAY‐D2 were more heavily labelled in the ganglioside fraction (62%, 58%) than Eb (39%). ESb and MDAY‐D2 also contained larger amounts of gangliosides than Eb.
Extracellular material secreted by human colonic adenocarcinoma cell lines promotes spreading in serumfree medium and induces neurite outgrowth of PC‐12 cells
Authors: Bellot F. , Luis J. , El Battari A. , Secchi J. , Pichon J. , Cau P. , Marvaldi J.
Published: February 2007

A completely defined medium has been designed to promote cell proliferation of 2 colonic adenocarcinoma cell lines of epithelial origin (HT 29 and HRT 18). The spreading of both cell types, especially of HT 29 cells, was not possible in a serum‐free medium supplemented with growth factors. Spreading was obtained in a defined medium (a I/I mixture of DMEM and F12 media supplemented with 5 μ g/ml transferrin, 5 ng/ml EGF, 10 ng/ml selenite and 15 mM HEPES PH 7.3) with an extracellular matrix‐like material (ECM) secreted by the cells themselves. The properties of the ECM have been studied: (I) ECM secreted by the 2 cell lines induced very quick spreading of HT 29 and HRT 18 cells (1 to 2 hr vs. 12 to 24 hr in serum‐supplemented medium). (2) ECM induced morphological differentiation of a rat pheochromocytoma cell line (PC 12). PC‐12 cells grown under these conditions began to develop neurite extensions as early as 2 hr after seeding.
Premature chromosome condensation: Evidence for in vivo cell fusion in human malignant tumours
Authors: Kovacs Gyula
Published: February 2007

Premature chromosome condensation (PCC) was studied in direct preparations of tissues from patients with haematological diseases and carcinomas of various histological types. PCC was found in 6 out of 166 malignancies (128 haematological cases, 35 carcinomas and 1 malignant effusions) analysed with the GTG‐technique. Chromosome analysis revealed S‐phase and G1‐phase PCC in each case; the frequency of PCC varied between 1, 4 and 8.6% of the metaphases analysed. It is suggested that PCC chromosomes, which represent cell fusion in vivo, are not very rare in naturally‐occurring human malignancies. and that cell fusion may affect the malignant phenotype. In conjunction with other factors they may also explain the heterogeneity of tumour cell populations.
The diagnostic value of a hepatoma‐specific band of serum gamma‐glutamyl transferase
Authors: Xu Ke‐Cheng , Meng Xian‐Yong , Shi Yi‐Cai , Ge Zheng‐Ju , Ye Ling , Yu Zhi‐Jian , Yang Da‐Min
Published: February 2007

Using a vertical slab electrophoretic apparatus loaded with polyacrylamide stage gel plate, we observed a total of II bands of gamma‐giutamyl transferase (EC 2.3.2.2, GGT) on a gel plate and designated these GGT I‐XI by order of distance beginning at the positive pole. Positive GGT II was found in 81(90%) of 90 cases of primary hepatic carcinoma (PHC), in 9(90%) of 10 cases of secondary hepatic carcinoma (SHC), and in only 4 (3.1 %) of a total of 128 cases of acute and chronic liver disease. There was one case with positive GGT II among 45 cases of cancer of ampulla of Vater, but the possibility of hepatic metastasis could not be excluded. No GGT II was found in a total of 250 healthy persons and 21 pregnant women. PHC patients with negative alpha‐fetoprotein (AFP) had a positive GGT II rate of 84.6%, whereas in those with negative GGT II the positive rate for AFP was only 44.4%.
Human T‐cell leukemia virus type I: Pseudotype neutralization of Japanese And American isolates with human and rabbit sera
Authors: Hoshino H. , Miwa M. , Clapham P. R. , Weiss R. A. , Miyoshi I. , Yoshida M.
Published: February 2007

CCC/2M, CCC/10Y and CCC/MT‐2 cat kidney cells producing Japanese isolates of human T‐cell leukemia virus type I (HTLVs) and HOS/PL human osteosarcoma cells producing an American isolate of HTLV were infected with vesicular stomatitis virus (VSV) to prepare VSV pseudotypes bearing envelope antigens of HTLVs. VSV propagated in CCC/2M cells contained plaque‐forming fractions that were not neutralized by treatment with anti‐VSV serum alone: VSV pseudotypes bearing envelope antigens of HTLV2M and CCC cat endogenous virus were formed by infection of CCC/2M cells with VSV. Japanese HTLV2M, HTLV10Y and HTLVMT‐2 and American HTLVPL pseudotypes were neutralized by sera of Japanese, American and British patients with ATL. Each serum, including the serum of the patient from whom HTLV2M or HTLV10Y had been derived, gave similar antibody titers against Japanese and American HTLV pseudotypes. The HTLV pseudotypes were also neutralized by rabbit serum raised against HTLVMT‐2. A rabbit antiserum against the C‐terminal half of the HTLV env protein produced in E. coli also neutralized Japanese and American HTLV pseudotypes. Thus, VSV pseudotype analyses indicated that envelope antigens of HTLVs represent a single serotype worldwide. The env protein produced in E. coli may be used to raise neutralizing antibody against HTLVs.
Monoclonal antibody (anti‐leu 7) directed against natural killer cells reacts with normal, benign and malignant prostate tissues
Authors: Wahab Zeinab A. , Wright George L.
Published: February 2007

The reactivity of monoclonal antibody (MAb) antileu 7 (HNK ‐ I) on formalin‐fixed sections of prostate tissues was determined by an immunoperoxidase assay. Anti‐Leu 7 was found to react with both primary and metastatic tissues from 6/6 normal prostate, 15/15 benign prostatic hyperplasia, and 37/39 prostate carcinoma samples. Anti‐Leu‐7 reactivity was localized in the cytoplasm of the supranuclear region of prostatic epithelial cells and the fibromuscular stroma did not stain. Myelinated nerve fibers in the stroma were stained with anti‐Leu 7 and this served as an internal control. Anti‐Leu 7 did not bind to prostatic acid phosphatase (PAP) or prostate‐specific antigen (PSA) in direct or competitive binding radioimmunoassays. Anti‐Leu 7 was more effective (5/5) in the identification of metastatic tumors of prostate origin than an MAb to PSA (2/5). The differential pattern of reactivity of anti‐Leu 7 compared to anti‐PSA on serial sections of prostate tissues suggests that Leu 7 may be a useful diagnostic and prognostic marker of prostate cancer.
The relationship between 17β hydroxysteroid dehydrogenase and breast tumour site and size
Authors: Beranek P. A. , Folkerd E. J. , Newton C. J. , Reed M. J. , Ghilchik M. W. , James V. H. T.
Published: February 2007

The activity of 17β hydroxysteroid dehydrogenase (17OHSD) was measured in adipose tissue adjacent to benign or malignant breast tumours. 17OHSD activity was signficantly correlated with tumour size in malignant tumours (r = 0.75) but not with benign tumours (r = 0.28). Enzyme activity was reduced in adipose tissue adjacent to tumours obtained from inferior breast quadrants.
Studies on components of immunotoxins: Purification of ricin and its subunits and influence of unreacted antibodies
Authors: Vidal H. , Casellas P. , Gros P. , Jansen F. K.
Published: February 2007

Two ricins were purified from the seeds of Ricinus communis by a simple method based on affinity chromatography allowing large‐scale preparations. Separation of these 2 ricins was achieved by ion‐exchange chromatography and studies of purified submits demonstrated that the 2 forms of ricin differed only in their B‐chains which showed widely differing isoelectric points. The A‐chains isolated from both ricins showed similar biological properties and contained 2 variants, A1 and A2, differing in their molecular weights and carbohydrate contents. These variants could be separated by affinity chromatography on Con‐A‐Sepharose which bound the A2 variant more tightly than A1. This property allowed us to obtain immunotoxin preparations devoid of free antibodies and to study the in vitro influence of free antibody on immunotoxin activity.
The rauscher‐MuLV‐induced leukemia, RBL‐5, bears two tumor‐associated transplantation antigens expressed on distinct molecules
Authors: Galetto Giorgio , Law Lloyd W. , Rogers Michael J.
Published: February 2007

Tumor cells frequently express on their surface a new antigenic determinant which renders them immunogenic in the host animal. When immunity to this antigen results in rejection of a syngeneic tumor transplant, it is referred to as a tumor‐associated transplantation antigen (TATA). RBL‐5 is a Rauscher murine leukemia virus (MuLV}‐induced leukemia of C57BI/6 origin that is potently immunogenic and shares a TATA with other tumors induced by the closely related Friend and Moloney‐MuLVs (FMR‐TATA). We have recently isolated a 175 kilodalton (kd) glycoprotein (gp175) which has all the properties expected of the FMR‐TATA (Rogers et al., 1984). When this molecule was separated from a purified total glycoprotein fraction by DEAE chromatography, the remaining glycoproteins still contained a highly immunogenic TATA. Control experiments involving radioimmunoassay and immunoprecipitation with rabbit anti‐gp 175 indicated that this immunogenicity was not due to residual gp 175 or breakdown products of gp 175. We therefore conclude that RBL‐5 expresses at least two distinct TATAs: gp175 and another glycoprotein distinguished from gp 175 by its elution from a diethylaminoethylcellulose (DE52) column. These results, from a completely in vivo system, support data with other tumors obtained by in vitro methods and indicate that tumor cells may express several immunogenic molecules.
Recognition with a monoclonal antibody of a cytoplasmic mammary carcinoma antigen, correlated to the estrogen receptor status
Authors: Krohn Kai , Helle Markku
Published: February 2007

Immunohistochemical reactivity of mammary carcinomas with monoclonal antibodies (MAbs) to human milk fat globule (HMFG) membrane antigens was compared with the estrogen (ER) and progesterone receptor (PR) status of the tumors. Antibody III D 5 stained 55 of the 74 tumors studied, the reaction being of borderline intensity in 19 cases and unequivocally positive in 36 cases. The staining was always cytoplasmic; in addition occasional extracellular III D 5‐positive secretory material was observed. Positive reactivity of the tumor with antibody III D 5 was significantly correlated with ER and/or PR content of the tumors. The presence of extracellular, III D 5‐positive secretory material correlated to the ER but not to the PR status of the tumors.
Correlation of macrophage‐mediated tumor‐cell lysis with the production of macrophage cytolytic factor (CF). preliminary characterization of a factor inhibiting cf production
Authors: Gifford George E. , Loewenstein James , Yamin Aviva , Gallily Ruth
Published: February 2007

Macrophage‐mediated cytolysis of thymidine‐prelabelled murine A9 fibrosarcoma cells was compared to the level of cytolytic factor (CF) present in the cultures by assaying supernatant aliquots on actinomycin (AcD)‐treated A9 fibrosarcoma cells. A good correlation between the level of A9 killing and CF titer was observed when different concentrations of lipopolysaccharide (LPS) were added to various macrophage populations: murine peritoneal cells, short‐term bonemarrow (BM)‐derived macrophages and JBMø macrophage lines. Optimal A9 killing and CF secretion, equivalent to the killing of about 1000 AcD‐pretreated A9 cells by a single macrophage, were obtained following activation of JBMø by LPS. CF production by BM‐derived macrophages was enhanced in serum‐free medium when compared to its release in the presence of fetal calf serum. The LPS‐activated macrophages could be restimulated by the activating agent to produce CF following one week of propagation in the absence of LPS. On the other hand, CF activity was absent from the supernatants of activated macrophages co‐cultured with normal embryonic fibroblasts, which are resistant to macrophage‐mediated killing. This effect could be attributed to a factor, secreted by normal fibroblasts but not by A9 cells, which suppressed CF release from the activated macrophages. Our data strongly support earlier observations, suggesting that CF [which appears to resemble the tumor necrosis factor (TNF)] is responsible for LPS‐induced macrophage‐mediated tumor cell lysis. It is suggested that suppression of the latter process by the fibroblast‐derived factor proceeds via inhibition of CF/TNF production from the macrophage.
Human tumor cells synthesize and secrete alpha‐2‐macroglobulin in vitro
Authors: Bizik Jozef , Vaheri Antti , Saksela Olli , Kalkkinen Nisse , Meri Seppo , Grófóva Marta
Published: February 2007

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate‐polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB‐2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2‐terminal amino‐acid sequence determination of the purified glycoprotein showed that it is identical to human α2‐macroglobulin (α2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with α2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S‐methionine‐labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to α2M. α2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.
Difluoromethylornithine enhances inhibition of melanoma cell growth in soft agar by dexamethasone, clone a interferon and retinoic acid
Authors: Bregman Marvin D. , Meyskens Frank L.
Published: February 2007

Five human melanoma cell lines (C8146C, C8161, C82‐7A, C83‐2CY and MIRW5) were shown to contain a significant number of melanoma colony‐forming units resistant to single‐agent treatment by dexamethasone, alpha‐interferon and trans‐retinoic acid. These biological modifiers were combined with difluoromethylornithine into a low‐dose combination using concentrations below pharmacologically achievable levels. The suppression of melanoma colony formation induced by this combination was consistent and significantly higher than that seen with any single agent, colony formation being reduced by an average of 90%. Leaving either DEX or DFMO out of the 4‐agent combination resulted in a significant decrease in the observed inhibition. This was also verified by the addition of putrescine which inhibited only the DFMO activity. Median effect analysis of the DFMO + IFN inhibition of C8161 cells demonstrated that the 2 agents interacted synergistically over the entire doseresponse curve. Of the high‐dose combination‐treated melanoma colony‐forming units, 97% did not form small growth units; most remained as arrested single cells, but the cells and small growth units could still metabolize tetrazolium stain after the experiment, suggesting that the high‐dose combination arrested the growth of the melanoma colony‐forming units via a non‐cytotoxic mechanism.
Autonomous proliferation of mewo human melanoma cell lines in serum‐free medium: Secretion of growth‐stimulating activities
Authors: Sauvaigo Sylvie , Fretts Ruth E. , Riopelle Richard J. , Lagarde Alain E.
Published: February 2007

The growth properties of a human melanoma cell line (MeWo) and of a variant (MeWo‐LCI) endowed with higher metastatic potential in nude mice were compared using hormonally‐defined serum‐free media. The two cell lines failed to arrest in Go following serum deprivation, and responded to INS and MSA but not to EGF, PDGF or FGF. Only MeWo‐LCI cells divided persistently in completely serum‐free medium, and formed a high percentage of spheroids in agarose supplemented or not with serum or individual growth factors. The conditioned media of serum‐free cultures of MeWo and MeWo‐LCI cells exhibited mitogenic activities. These were detected without prior concentration, fractionation or acid treatment. They stimulated DNA replication into sparse monolayers of autologous (MeWo, MeWo‐LCI) or homologous (SKMEL28 melanoma) cells and into NRK‐49F normal rat fibroblasts, and acted in synergy with INS in a dose‐dependent manner. Over a period of 5 days in culture, MeWo‐LCI cells produced bioactive material at a 2 to 3‐fold higher rate than MeWo cells, in both the absence and presence of INS. MeWo‐LCI‐conditioned medium promoted or enhanced colony formation of MeWo and NRK‐49F cells plated in serum‐free (± INS) agarose. The two cell lines expressed the same amount of NGF and EGF receptors. On the basis of these results we suggest that: (i) MeWo and MeWo‐LCI melanoma cells have obviated allocrine stimulation of the division process characteristic of normal cells by responding to their own mitogens; (ii) some of these mitogens are akin to TGFs; (iii) the less efficient synthesis of autostimulatory factors by MeWo cells may account for their weaker proliferative capacity in vitro, and possibly in vivo.
Interferon‐activated tumor inhibition in vivo. Small amounts of interferon‐gamma inhibit tumor growth by eliciting host systemic immunoreactivity
Authors: Giovarelli M. , Cofano F. , Vecchi A. , Forni M. , Landolfo S. , Forni G.
Published: February 2007

Ten international units (IU) of recombinant (r) or natural (n) murine interferon (MulFN)‐gamma were used for the in vivo immunotherapy of a chemically induced fibrosarcoma (CE‐2) of BALB/c mice. In vitro, doses of r‐IFN‐gamma below 100 units have a marginal antiproliferative effect on CE‐2 cells and do not induce expression of H‐2d class‐II antigens, whereas they do increase that of class‐I antigens. In vivo, 10 daily injections of 10 IU of r‐ or n‐MulFN‐gamma at the challenge site provide significant protection against increasing doses of CE‐2 tumor cells. This protection was enhanced when non‐reactive T‐lymphocytes from CE‐2 tumor‐bearing mice were admixed at a 10:1 ratio with the CE‐2 tumor cells. Combined lymphocyte and r‐MulFN‐gamma treatment also inhibited the growth of already established tumors when it was started before these reached a mean diameter of 5 mm. Tumor inhibition depends upon activation of the host immune system. The antitumor activity of r‐MulFN‐gamma and T‐lymphocytes was null when mice were first irradiated with 450 rads. Moreover, host leukocytes massively infiltrated the area of tumor growth and the small r‐MulFN‐gamma doses injected daily activated various host immunoreactivity mechanisms.
Genetic and epigenetic factors that influence the occurrence of spontaneous lymphoid tumors in crosses of mice of high‐ and low‐incidence strains
Authors: Duran‐Reynals Maria L. , Kadish Anna S. , Lilly Frank
Published: February 2007

AKR mice, which spontaneously develop >90% incidence of lymphocytic leukemia (LL), crossed with SJL mice, which show >80% incidence of Hodgkin's‐like reticulum‐cell sarcoma (RCS), produced F1 progeny showing incidences of 30% LL and 0% RCS. Thus, each strain possesses one or more dominant genes capable of interfering with the emergence of the tumor type typical of the other strain. Although mice of reciprocal F1 crosses showed a profound difference in expression of endogenous ecotropic murine leukemia virus (E‐MuLV) due to a maternal resistance factor transmitted by SJL females but not males, the two populations did not differ detectably in LL incidence. Like AKR mice, mice of 5 other strains studied (C58, DBA/2, PL, RF and ST/b) possessed one or more genes conferring resistance to RCS in F1 crosses with SJL. Analysis of LL incidences in F1 generations of all possible crosses among these 7 strains revealed 4 different categories of strains with respect to susceptibility/resistance to LL; only ST/b mice, which show no significant incidence of spontaneous LL, lacked genes that could suppress the disease in crosses with high‐ or moderate‐incidence strains. SJL mice treated topically with 3‐methylcholanthrene (MCA) developed a 50% incidence of LL, mostly before one year of age; treated mice surviving after one year of age developed a high incidence of RCS.
Loss of HLA‐A,B,C and de novo expression of HLA‐D in colorectal cancer
Authors: Momburg Frank , Degener Theodora , Bacchus Elisabeth , Moldenhauer Gerhard , Hämmerling Günter J. , Möller Peter
Published: February 2007

One hundred primary colorectal carcinomas and 19 metastases were studied for the expression of HLA‐A,B,C and HLA‐D antigens using monoclonal antibodies (MAbs) against framework determinants and a sensitive immunoperoxidase technique on frozen sections. With MAb W6/32, 65 tumors were intensely stained for HLA‐A,B,C; 22 showed a reduced staining intensity, in 5 carcinomas a minor or major subset of the tumor cells lacked HLA‐A,B,C, and in 8 cases all tumor cells were unreactive. The loss of HLA‐A,B,C was inversely correlated with the degree of differentiation. No relation was found to type, stage and site of the tumor, or to age and sex of the patients. With MAb 2.06, 58 tumors were HLA‐D negative, 20 exhibited small positive foci, 19 showed a patchy staining pattern, and 3 were homogeneously HLA‐D positive. There was no apparent correlation between HLA‐D expression and any of the clinico‐pathological features mentioned, nor was it related to the loss of HLA‐A,B,C. About half of the metastases displayed the same staining pattern for HLA‐A,B,C and ‐D as the respective primary tumors. The remainder differed from the primary carcinoma by gain or loss of HLA antigens.
Occupational exposure and lung cancer risk
Authors: Kvåle Gunnar , Bjelke Erik , Heuch Ivar
Published: February 2007

The importance of occupation held longest as a risk factor for lung cancer was examined in a prospective study in Norway of 11,995 men, among whom 125 cases occurred in a follow‐up from 1966 through 1978. Based on information about occupation held longest, the respondents were classified into 3 groups according to suspected exposure to respiratory carcinogens at the workplace. After stratification for age, place of residence and cigarette smoking, we found a highly significant relative risk of 2.6 for those judged to have experienced definite exposure versus the group with no workplace exposure. The apparent risk‐enhancing effect of occupational exposure was observed for all histologic subtypes. Stratification including a socioeconomic factor score led to a moderate reduction in the relative risk estimate. High risk estimates still obtained, however, for a limited number of occupations, the highest for workers in the mining and quarrying industries. Although the interpretation of the observed effect associated with a crude index of occupational exposure may be difficult, our results suggest that between 13 and 27% of the lung cancer cases observed among Norwegian men in the relevant time period can be attributed to harmful work‐place exposure.
The Epstein‐Barr virus determined nuclear antigen is composed of at least three different anitgens
Authors: Dillner Joakim , Kallin Bengt , Ehlin‐Henriksson Barbro , Rymo Lars , Henle Werner , Henle Gertrude , Klein George
Published: February 2007

The EBV‐determined nuclear antigen, EBNA, is the only known viral product to be regularly detected in all EBV‐transformed cells. The anticomplement immunofluorescence (ACIF) staining detects an EBV‐specific nuclear reaction that has recently been shown to be due to at least 2 different proteins, EBNA‐1 and EBNA‐2, encoded by different parts of the viral genome. We now report the existence of a third antigen of the EBNA complex, designated as EBNA‐3. Serum from a patient with chronic infectious mononucleosis contained no detectable antibodies to EBNA‐1 and had only a low EBNA‐2 antibody level. Nevertheless, it gave an EBV‐specific nuclear reaction of normal intensity and stained EBNA‐2‐positive and EBNA‐2‐negative EBV‐carrying lines equally well. Immunoblotting with the same serum identified a new EBV‐specific nuclear protein of 143‐157 kDa.
Melanoma in Western Australia 1975–76 TO 1980–81: Trends in demographic and pathological characteristics
Authors: English Dallas R. , Heenan Peter J. , Holman C. D'Arcy J. , Armstrong Bruce K. , Blackwell John B. , Kelsall G. Robert H. , Matz Leonard R. , Singh Amarjeet , Seldam Rolf E. J. Ten
Published: February 2007

Trends in incidence rates of cutaneous malignant melanoma in Western Australia from 1975–76 to 1980–1981 have been examined with reference to age, sex, body site, presence or absence of dermal invasion, tumour thickness, histological type, socioeconomic status and occupation. The incidence rates of all melanomas increased from 22.1 to 31.5 per 100,000 person‐years in males and from 23.6 to 28.6 in females. In males, the relative annual increase in the incidence of invasive melanoma was 2.2%, and in females it was 5.6%. In‐situ melanomas had larger relative increases in incidence (28% per annum in males and 10% in females) and the thickness of invasive lesions decreased between 1975–76 and 1980–81. The relative increase in incidence of invasive melanomas was greatest on the body sites with the highest rates initially–the trunk in males and the lower limbs in females. There was an increase in the proportion of invasive lesions classified as superficial spreading melanoma. The increase in incidence of in situ melanomas was largely restricted to the head and neck in older men of high socioeconomic status resident in Perth. This trend in in‐situ melanoma was mainly due to an increase in the recorded incidence of Hutchinson's melanotic freckle. It may have been, in part, an artefact due to increased recognition of Hutchinson's melanotic freckle in this sub‐group of the population.
Studies of cellular retinol‐binding protein (CRBP) in squamous‐cell carcinomas of the head and neck region
Authors: Fex G. , Wahlberg P. , Biörklund A. , Wennerberg J. , Willén R.
Published: February 2007

Cellular retinol‐binding protein (CRBP) concentration was determined by radioimmunoassay in biopsies from normal mucosa and squamous‐cell cancers of the head and neck region in 26 patients. The plasma concentrations of retinol, retinol‐binding protein (RBP), prealbumin, albumin, orosomucoid and alfa1‐antitrypsin were also determined. In all patients the tumours contained significantly higher concentrations of CRBP (median = 185μg/g) tissue protein; range: 27–1,017μg/g) than normal mucosa (median = 14 μg/g tissue protein; range 6–97 μg/g). CRBP could not be detected in patient plasma. The tumour/normal mucosa CRBP concentration ratio showed a significant inverse correlation to a histopathological malignancy grade score evaluating the tumour‐host relationship, suggesting that tumours with high CRBP relative to normal mucosa are biologically less aggressive. Tumour CRBP showed no correlation either to CRBP concentration in normal mucosa, or to plasma retinol or plasma retinol‐binding protein concentration. CRBP concentration in normal mucosa, however, showed a significant correlation to plasma retinol‐binding protein concentration. Most of the patients had low levels of plasma retinol and retinol‐binding protein compared to matched controls. Whether this has any relationship to the development of the tumour, or whether the active inflammation induced by the cancer leads to a low plasma retinol concentration, is unknown.
Multiple myeloma in Western Australia: A case‐control study in relation to occupation, father's occupation, socioeconomic status and country of birth
Authors: Nandakumar A. , Armstrong Bruce K. , de Klerk Nicholas H.
Published: February 2007

A death‐certificate‐based case‐control study was undertaken covering 249 patients with multiple myeloma diagnosed in Western Australia from 1975 to 1984 whose deaths were registered in Western Australia in the same period (73.4% of the total diagnosed) and 996 control decedents who were matched to the cases by age, sex and death registration district. Death from multiple myeloma was associated with both farming [odds ratio (OR) 1.44 with 95% confidence interval (Cl) 0.81–2.55] and woodworking (OR 1.70 with 95% Cl 0.67–4.31) but not with farming as the father's occupation (OR 0.96 with 95% Cl 0.66–1.41). It was also more frequent in migrants to Australia than in native‐born Australians (OR 1.31 with 95% Cl 0.99–1.74) particularly those born in England (OR 1.57 with 95% Cl 1.11–2.42) and Italy (OR 2.02 with 95% Cl 1.09–3.74). An apparent excess of multiple myeloma in all rural residents appeared to be due to bias introduced by matching for death registration district, as rural residents dying from multiple myeloma were more likely to die and have their deaths registered in the city than other rural residents. A conditional logistic regression analysis showed the above associations to be substantially independent of one another.
Comparison of doxorubicin‐induced DNA damage in doxorubicin‐sensitive and ‐resistant P388 murine leukemia cells
Authors: Capranico Giovanni , Dasdia Teresa , Zunino Franco
Published: February 2007

Doxorubicin‐induced DNA damage was studied in the P388 leukemia cell line and in a doxorubicin‐resistant subline by alkaline elution techniques. DNA single‐strand breaks and DNA‐protein cross‐links were determined. Whereas, in the sensitive line, I hr exposure to drug induced DNA damage in a concentration‐dependent manner, in the resistant line only a marginal effect was observed at high drug concentrations. In contrast, elution kinetics of DNAs from cells irradiated with X‐rays were similar in both lines. Although a reduced intracellular drug accumulation was found in resistant cells, this difference could not account for the marked reduction in doxorubicin‐induced DNA damage. The degree of resistance of the P388 subline was reduced about 7‐fold by verapamil, whereas the extent of DNA damage was unaffected. These results suggest the presence of alternative modes of resistance, independent of membrane changes, in highly resistant cells.
Analysis of structural polypeptides of the lymphoproliferative disease virus (LPDV) of turkeys
Authors: Gazit Arnona , Basri Ruth , Ianconescu Marius , Perk Kalman , Zimber Amatzia , Yaniv Abraham
Published: February 2007

The polypeptide composition of the lymphoproliferative disease virus (LPDV) of turkeys was shown to comprise several polypeptides with apparent molecular weights of 76, 31, 28, 20 and 15 kDa. This polypeptide pattern is distinctly different from the protein profiles of avian leukosis viruses, reticuloendotheliosis virus, or murine leukemia viruses. Moreover, LPD virions contain 2 major structural proteins (p31 and p28), in contrast to only one major internal protein present in most other retroviruses. The 76 kDa protein was established as the major viral envelope glycoprotein. The uniqueness of the LPDV polypeptide pattern is consistent with the lack of genetic relatedness of LPDV genome to other retroviruses, establishing LPDV as a representative of a distinct group of retroviridae.
Elimination of murine erythroleukemic stem cells with a novel anti‐erythroid antibody conjugated to ricin a‐chain: A model for studies of bone‐marrow transplantation therapy
Authors: Tonevitsky A. G. , Mechetner E. B. , Rozinova Emilia N. , Ievleva Elena S. , Poltoranina Valentina S.
Published: February 2007

We have produced a rat monoclonal antibody (MAb) MAE 15 (IgG), specific for murine erythroid cells, using a murine erythroid cell line as immunogen. This MAb specifically binds to the surface of normal and neoplastic murine erythroid cells. Murine mature erythrocytes and non‐erythroid cells as well as rat and human erythroid and non‐erythroid cells are not recognized by MAb MAE 15. Immunoblotting analysis and mixed precipitation in agar gel showed MAb MAE 15 to be specific for murine epitope of 69 kDa antigen of erythroblasts (Ag‐Eb), an interspecies antigenic marker of nucleated red cells and reticulocytes. A conjugate (immunotoxin) was prepared, comprising ricin A‐chain and MAb MAE15. The immunotoxin inhibited protein synthesis of murine erythroleukemic Ag‐Eb‐positive K‐2 cells and completely inhibited (at the concentration of 2 × 10−7 m) spleen colony formation by erythroleukemic stem cells of the Ag‐Eb‐positive RAL cell line. Approximately 35% of the murine normal stem‐cell (CFU‐S) population was not affected by the immunotoxin at the concentration of 2 × 10−7 m. This experimental system may be a convenient model for studies of bone marrow transplantation therapy of erythroleukemias.
In situ identification of host derived infiltrating cells in chemically induced fibrosarcomas of interspecific chimeric mice
Authors: Deamant F. D. , Vijh M. , Rossant J. , Iannaccone P. M.
Published: February 2007

Chimeric mice have been used to investigate the cellular origin of chemically induced tumors. Interspecific chimeras were formed between the Ha/ICR strain of Mus musculus and Mus caroli. The normal tissues of the chimeric mice were composed of a mixture of cells which originated from each of the 2 species. The species of origin of the cells was determined both histologically with in situ hybridization using a DNA probe which recognizes M. musculus satellite DNA and by electrophoretic analysis of phosphoglycerate kinase‐I (PGK‐I) isozyme expression. The 2 parental species, M. musculus and M. caroli, had comparable levels of inducible cytochrome P‐450‐dependent mixed function oxidase activity. Subcutaneous fibrosarcomas were induced with 3‐methylcholanthrene. Electrophoretic analysis of many samples from the tumors revealed that some demonstrated both isozymes of PGK‐I. However, extensive sectioning with subsequent in situ hybridization revealed that the only cells of mixed genotype were small, infiltrating inflammatory cells. These results confirmed PGK‐I analysis of the tissue culture cell lines derived from the tumors. This is the first report of direct visualization of the lineage origin of various cellular components in chemically induced tumors in a mosaic system and supports the contention that, while the neoplastic cells are clonal in origin, the tumors also contain non‐neoplastic “host” cells which are derived from both sets of parents.
Differential antiproliferatve effects of combinations of recombinant interferons alpha and gamma on two murine tumor cell lines
Authors: Brunda Michael J. , Wright Rosemary B.
Published: February 2007

The in vitro antiproliferative effects of recombinant interferons (IFNs) alpha and gamma against the murine reticulum‐cell sarcoma M5076 and the malignant melanoma B16 F10 were evaluated using the human hybrid IFN‐alpha A/D (rHulFN‐αA/D), which is active on murine cells, and recombinant murine IFN gamma (rMulFN‐γ). An isobologram analysis was used to evaluate the interactive antiproliferative effects of the recombinant IFNs on these two tumor cell lines. The data, in contrast to prior reports, indicate that rHulFN‐αA/D and rMulFN‐γ interact in an additive rather than a synergistic manner against M5076 cells. When a similar analysis was performed on B16 F10 cells, synergy was obtained. Thus, either a synergistic or an additive antiproliferative effect can be obtained by combining IFN‐α and IFN‐γ, depending upon the cell line used in the assay.
Cloning and characterization of putative genes that specify sensitivity to neoplastic transformation by tumor promoters
Authors: Lerman Michael I. , Hegamyer Glenn A. , Colburn Nancy H.
Published: February 2007

Two putative genes (termed pro 1 and pro 2) specifying sensitivity to induction of neoplastic transformation by TPA in mouse epidermal JB6 cells were cloned by sib selection from a size‐selected genomic library of clonal cells sensitive to promotion of transformation. By restriction analysis, heteroduplex analysis, direct hybridization, and sequencing, the putative genes are different from and have no homology to known oncogenes. Both genes are independently and equally active as total DNA in the transfection assay. The transformation‐promoting potential of these putative genes does not appear to result from gene amplification or detectable rearrangements, suggesting that small structural changes might confer the promoting activity. The mouse pro sequences are also found in monkey and human DNAs. The pro‐1 sequence is homologous to middle repetitive elements in the mouse genome, namely the BAM 5 and B1 repeats. The sequence of pro‐1 was determined and suggests that it contains the signals to be transcribed by RNA polymerase 11 and to encode a protein of 7.1 kDa.
Correlation between quantitative expression of H‐2K, H‐2D and mulv antigens on spontaneous AKR lymphomas
Authors: Oudshoorn‐Snoek Margriet , Demant Peter
Published: February 2007

Thymocytes of leukemic AKR mice were analysed with a fluorescence‐activated cell sorter (FACS) using monoclonal antibodies (MAbs) reactive with H‐2Kk and H‐2Dk and conventional hetero‐antibodies against MuLV gp‐70 antigens. Comparison was made with thymocytes of the low‐leukemia H‐2k strain C3H, as well as with thymocytes of young AKR mice, late preleukemic AKR mice (6–9 months old) and mitogen‐stimulated thymocytes of young AKR mice. Expression of H‐2 antigens increased on cells of the majority of tumors, on thymocytes of some late preleukemic mice and on mitogen‐stimulated thymocytes. An increase in H‐2K and H‐2D antigens was noted: imbalance of the K/D ratio in favor of H‐2D was observed mostly in tumors with relatively lower total amounts of H‐2K and D antigens; ratio shifts in favor of H‐2K were also found, mostly in tumors with relatively higher amounts of H‐2K and D antigens. Increased expression of MuLV antigens was found on cells of all tumors and on thymocytes of several late preleukemic mice. We show that in primary spontaneous AKR leukemias, in spite of large individual differences, the expression of high amounts of MuLV gp70 is not random, but is associated with high expression of H‐2K and H‐2D antigens. The same phenomenon is seen in thymocytes of preleukemic mice, but in mitogen‐stimulated thymus cells increase of H‐2 expression is not accompanied by increase of MuLV gp70.
Suppression of human lymphocyte mitogen response by proteins of the type‐D retrovirus PMFV
Authors: Denner Joachim , Wunderlich Volker , Bierwolf Dieter
Published: February 2007

A type‐D retrovirus, derived from a human cell line and designated PMFV, which is related to, but distinct from the Mason‐Pfizer monkey virus (MPMV) suppressed the in vitro mitogen response of human lymphocytes. PMFV was suppressive either as intact virus or after disruption by ether or detergents. In kinetic studies, the time course of the interaction between suppressive virus components and lymphocytes was characterized. Neither cytotoxicity nor time shifts in optimum 3H‐thymidine incorporation of responding lymphocytes were observed. The suppressive activity of the disrupted virus was diminished by heating, freeze‐thawing or treatment with pronase or trypsin, indicating temperature‐sensitive proteins as suppressive components. By Sephacryl S‐200 gel chromatography, molecular weights of approximately 70 and 15 kDa were determined for the suppressive components which were isolated from disrupted virus or virus‐producing cells but not from non‐infected cells.
Clinical analysis of 33 patients with adult T‐cell leukemia (ATL)‐diagnostic criteria and significance of high‐ and low‐risk ATL
Authors: Tamura Kazuo , Nagamine Nobuhiko , Araki Yasuhiko , Seita Masashi , Okayama Akihiko , Kawano Kiyohide , Tachibana Nobuyoshi , Tsuda Kazunori , Kuroki Yasumasa , Narita Hiromi , Inoue Shouhei , Suzumiya Junji , Sumiyoshi Akinobu , Aratake Yatsuki , Ohtaki Sachiya , Torigoe Junichiro , Kawachi Jitsuyo
Published: February 2007

The clinical characteristics of 33 patients with adult T‐cell leukemia (ATL) are described. All patients were born and have lived in Miyazaki Prefecture (south‐west of Japan). Because of a wide range of clinical presentations and courses, they were subdivided into 2 groups. In the high‐risk group, patients presented with high white‐cell counts (WBC ≧ 20,000/μl) and over 30% of abnormal lymphoid cells (18 patients) and hypercalcemia with a low percentage of leukemic cells (5 patients). In this group the median survival time was only 3 months despite various modes of treatment. In contrast, patients of the second group exhibited a low percentage of abnormal lymphoid cells (WBC < 20,000/μl and/or leukemic cells < 30%) and had no hypercalcemia (8 patients). Their clinical course was chronic with a median survival of 8 months, regardless of modalities of treatment. Two patients went through a period when the number of circulating leukemic cells was low ( ≦ 5%) before overt leukemia appeared. Other clinical features, signs, symptoms, routine laboratory data, serum anti‐ATL‐associated antibody, cell membrane markers and cytogenetic studies were similar to those observed in other districts of Kyushu island.
Clonal analysis of T lymphocytes in spleens from patients with Hodgkin's disease. Frequent occurrence of unusual T4‐positive cells which co‐express cytolytic activity and production of interleukin‐2
Authors: Romagnani S. , Maggi E. , Parronchi P. , Macchia D. , Prete G. F. Del , Rossi‐Ferrini P. L. , Ricci M. , Moretta L.
Published: February 2007

T‐lymphocyte populations isolated from spleens of untreated patients with Hodgkin's disease (HD) were grown by combining limiting dilution techniques and an assay system that allows clonal proliferation of virtually all human T cells. Under these conditions, high proportions of splenic T lymphocytes (50‐80%) underwent clonal expansion, so that the set of clones obtained could be considered representative of the starting T‐cell population. A total number of 229 clones from 6 HD spleens (3 uninvolved and 3 histologically involved by the disease) and 133 clones from 3 control spleens (obtained from otherwise healthy individuals, who underwent post‐traumatic splenectomy) were examined for surface markers and tested in functional assays. One hundred and seventy‐five clones from HD spleens and 75 clones from control spleens expressed the “helper/inducer” (T3+ T4+ T8−) phenotype, whereas 54 clones from HD spleens and 58 control clones expressed the “cytotoxic/suppressor” (T3+ T4− T8+) phenotype. As assessed by a non‐specific lectin‐dependent lytic assay, the proportion of HD clones displaying cytolytic activity was higher than that of cytolytic clones derived from control spleens. The majority of T4+ clones obtained from HD spleens (either uninvolved or histologically involved by the disease) were cytolytic, whereas only a small proportion (less than 10%) of T4+ clones derived from normal peripheral blood or spleens displayed cytolytic activity. The cytolytic potential of T4+ clones obtained from HD spleens did not reflect the activity of natural killer (NK) cells, since a minority of these clones exerted NK activity on K562 target cells. In addition, most of the T4+ cytolytic clones derived from HD spleens produced particularly high amounts of interleukin‐2 (IL‐2). These data indicate that T lymphocytes which concentrate in spleens of patients with HD consist at least in part of an infrequent T4+ cell subset co‐expressing cytolytic activity and production of IL‐2. These cells may reflect a cytotoxic reaction against unknown antigens associated with self class‐II histocompatibility antigens.