Myelosuppression after methotrexate, mitozantrone, and mitomycin C for treatment of advanced breast cancer.
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Adult↗
Biomedical subjects
A Marks
Publications and source records attributed to A Marks.
Reduction in S100 protein beta subunit mRNA in C6 rat glioma cells following treatment with anti-microtubular drugs.
S100 protein is a calcium-binding protein found in vertebrate nervous tissue. Synthesis of S100 protein in the rat glioma cell line, C6, is inhibited by the addition of anti-microtubular drugs. We have cloned a cDNA for the beta subunit of S100 protein from rat brain in a lambda gt 11 expression vector and used this cDNA to measure the amounts of S100 beta subunit mRNA in C6 cells after treatment with anti-microtubular drugs. Levels of alpha-tubulin and beta-actin mRNAs were also measured. All measurements were performed using RNA-RNA hybridization techniques at high stringency with rat mRNA-specific probes. After 24 h of treatment, the S100 beta subunit mRNA was reduced to levels of 25% by colchicine and 32% by vinblastine when compared to untreated controls. In contrast, the levels of tubulin and actin mRNAs were only slightly changed by these treatments. These studies demonstrate that disruption of the microtubular cytoskeleton causes a specific reduction in the level of S100 protein mRNA in C6 cells.
Amino Acid Sequence↗
Comparative analysis of the effectiveness of the diaphragm and birth control pill during the first year of use among suburban adolescents.
Little attention has been paid to the diaphragm as a contraceptive option for adolescents. To compare diaphragm and birth control pill use by adolescents, 124 females (aged 13-20 years) in a suburban-based adolescent health service were interviewed at least one year after receiving a contraceptive prescription. The 73 diaphragm choosers did not differ from the 51 pill choosers in age, race, or reason for their original visit to the health service. Diaphragm choosers, however, were better students, of higher socioeconomic status, and had had fewer prior pregnancies. In the year following prescription, continuous use for 12 months was reported by 43% of diaphragm choosers and 45% of pill choosers, with significantly more pill (26%) than diaphragm (8%) choosers reporting discontinued use for at least one month while remaining sexually active. Regular use (diaphragm every intercourse, missing less than or equal to 1 pill/month) was reported by 36% of diaphragm choosers compared to 88% of pill choosers; and at least one pregnancy during the year was reported by 15% of diaphragm choosers and 18% of pill choosers. At follow-up interviews, diaphragm subjects disliked the immediate annoyances of the diaphragm, and pill users expressed concern about the potential side effects of the pill. No single factor or set of factors correlated with continuous and regular use of either method. Because both methods present specific problems for certain patients, we suggest that in addition to the pill, the diaphragm should receive serious consideration as a contraceptive option for adolescents.
Adolescent↗
Characterization of binding of four monoclonal antibodies to the human ovarian adenocarcinoma cell line HEY.
Four mouse monoclonal antibodies (mAb) (10B, IgG1; 8C, IgG2a; M2A, IgG2a; M2D, IgG2b) were characterized with respect to their binding to the ovarian adenocarcinoma cell line HEY, using displacement assays and Scatchard plot analyses. The four mAb reacted with different antigens on the surface of HEY cells, with affinity constants ranging from 1 X 10(9) to 3 X 10(9) M-1. The number of binding sites per cell for each antibody was approximately 2 X 10(4). mAb 8C and M2D remained associated with the cell surface following binding to their respective antigens, while mAb 10B was rapidly internalized, with 50% of the bound mAb being lost from the cell surface during 4 h of incubation at 37 degrees C. These different binding characteristics of the mAb may influence their ability to target radioactivity and cytotoxic drugs to HEY cells.
Adenocarcinoma↗
Gunshot wounds. Incidence, cost, and concepts of prevention.
The United States has the highest incidence of firearm-related deaths among the Western industrialized nations. Firearms are the second leading cause of injury death. In 1982, the National Center for Health Statistics showed that firearms killed more than 33,000 individuals: 1,756 unintentionally, 16,573 by suicide, 13,841 by homicide, 376 by legal action, and 540 of undetermined intent. In terms of the total number of years of life lost, trauma in general contributed more years than heart disease and cancer combined for the year 1975. The southern regions of the United States tend to have higher firearm-related death rates than other regions of the country. Data collected within Arkansas are consistent with this trend. Handguns are the most frequently used firearms in fatal injuries. Unfortunately, data on nonfatal injuries are lacking. The emotional and economic costs of firearm-related death and injury are staggering. The estimated daily cost of hospitalization is $2100, and the average length of hospitalization is 10 days. The emotional impact of a gun-related injury or death will be felt immediately by 950,000 people per year. The economic loss resulting from "premature" deaths due to firearms is estimated to be nearly $4 billion annually. Unfortunately, the firearm is so ingrained in the American experience that one must conclude gunshot injuries and fatalities are simply part of the cost of living in America today.
Humans↗
Clinical applications for dentin bonding.
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Adult↗
Health assessment and screening during adolescence.
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Adolescent↗
Torsion of the colon in a rough collie.
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Animals↗
Production of a monoclonal antibody specific for seminomas and dysgerminomas.
A monoclonal antibody (M2A, IgG2a) was produced against a cultured human ovarian epithelial adenocarcinoma cell line, HEY. Monoclonal antibody M2A reacted with a glycoprotein of molecular weight 40,000 on the surface of HEY cells. The affinity constant of the monoclonal antibody M2A for HEY cells was 10(9) M-1, and the number of binding sites on HEY cells was 2 X 10(4) per cell. The monoclonal antibody produced positive immunoperoxidase staining of fetal (but not adult) testis and of seminomas and dysgerminomas but did not stain various normal adult tissues or other gonadal or extragonadal tumors. Monoclonal antibody M2A may be useful for confirming a histological diagnosis of seminoma and dysgerminoma.
Antibodies, Monoclonal↗
Production of a monoclonal antibody against a human osteosarcoma xenograft.
Monoclonal antibodies (MAbs) against a human sarcoma xenograft carried in BALB/c nu/nu mice were produced by immunizing BALB/c mice with tumor cells and fusing their spleens with the SP2/O-Ag 14 mouse myeloma cell line. Hybridoma supernatants were screened using cryostat tissue sections and an immunoperoxidase reaction for ability to stain osteosarcoma xenograft tumor cells but not tonsil lymphocytes. Of 73 supernatants tested, 19 reacted with both osteosarcoma tumor cells and lymphocytes, while three reacted only with osteosarcoma. One of the latter hybridomas was cloned by limiting dilution to establish a line producing an IgG1 MAb (OS-1). By immunoperoxidase, this MAb stained tumor cells in surgical biopsies of primary (6 of 7) and metastatic (1) osteosarcomas and showed limited cross-reactivity with other tumors. It also cross-reacted with some basement membranes, endothelium and muscular media of blood vessels, and smooth muscle, but not with parenchymal cells of various normal tissues. This MAb may prove useful for the immunohistochemical confirmation of a diagnosis of osteosarcoma in surgical pathology.
Animals↗
Protection of adult BALB/c mice against MOPC 315 myeloma by neonatal administration of monoclonal anti-idiotypic antibody to MOPC 315 IgA.
Ascitic fluid containing monoclonal anti-idiotypic antibody (AIA) to MOPC 315 IgA was administered to newborn BALB/c mice, and the mice were challenged in adulthood with IgA-producing MOPC 315 myeloma cells. Administration of AIA D10 (a hybrid molecule containing IgG1 and IgG2a heavy chains), G3 (IgG2b), and A2 (IgG1), all of which reacted with MOPC 315 cells in a cell-binding radioimmunoassay, prolonged survival and reduced the percentage of IgA-producing spleen fragments derived from mice challenged with MOPC 315 myeloma cells, but not with cells of a related IgA-producing myeloma, MOPC 460. Reduction in the percentage of IgA-producing spleen fragments was prevented by treatment of spleen cells prior to culture with anti-Thy 1.2 antibody and complement. Administration of AIA F1 (IgG2a), which did not react with MOPC 315 cells in vitro, or of an antibody with no AIA activity did not produce a similar protection. These results suggest that administration of AIA to MOPC 315 IgA to neonatal BALB/c mice induces idiotype-specific T-lymphocytes that protect these mice against a challenge with MOPC 315 myeloma cells in adulthood.
Animals↗
Monoclonal antibodies to an epithelial ovarian adenocarcinoma: distinctive reactivity with xenografts of the original tumor and a cultured cell line.
Four monoclonal antibodies (mAb) (8C, 10B, M2A, and M2D) were produced against the human epithelial ovarian adenocarcinoma cell line, HEY. The affinity constants of binding of the mAb to cultured HEY cells were 8 X 10(8) M-1 (M2D) and 10(9) M-1 (8C and 10B). mAb 8C reacted with a major glycoprotein of Mr 90,000 on the surface of HEY cells. The four mAb differed from previously reported mAb to epithelial ovarian adenocarcinomas on the basis of their reactivity with cultured ovarian adenocarcinoma cell lines using a cell-binding radioimmunoassay, and their staining of cryostat sections of various human normal and tumor tissues using an immunoperoxidase reaction. All four mAb reacted with s.c. tumors derived by injecting cultured HEY cells into thymectomized CBA/CJ mice. However, only two of the four mAb (8C and 10B) also reacted with s.c. tumors of the original HEY xenograft from which the cultured cell line was derived. In addition, mAb 8C and 10B reacted by immunoperoxidase staining with 2 and 4 different cases, respectively, of 11 epithelial ovarian adenocarcinomas examined. Cultured HEY cells were adapted to grow i.p. in BALB/c-nu/nu mice and the i.p. tumors retained their reactivity with the monoclonal antibodies. These tumor-bearing mice offer a useful model system for studying the potential of mAb, especially 8C and 10B, for the diagnosis and treatment of patients with peritoneal extension of epithelial ovarian adenocarcinomas.
Adenocarcinoma↗
Immunohistochemical staining of macrophages in the skin lesions of leprosy: the role of antibody to mycobacteria in human serum and various polyclonal immune rabbit antisera.
Immunohistochemical staining of tuberculoid and lepromatous leprosy skin lesions was performed using various rabbit antisera. Macrophages in both stained with serum containing antibodies against lysozyme and alpha-1-antitrypsin, while macrophages in lepromatous leprosy also reacted with other antibodies. An immunoglobulin fraction of positive serum stained following pepsin digestion, indicating that reactivity was not Fc dependent. Positive serum contained antibody against Mycobacterium butyricum, which caused macrophage staining, since affinity-purified antibody did not stain and absorption with M. butyricum removed staining. Staining was also produced by serum of subjects with leprosy or a positive tuberculin test. By immunoblotting, the anti-mycobacterial antibody was directed against surface components of M. butyricum of molecular weights 20 000-70 000. Electron microscopy showed M. leprae in phagolysosomes of macrophages, while immunoelectron microscopy demonstrated labelling along bacterial cell membranes. Therefore, macrophages in lepromatous leprosy skin lesions stain because they contain M. leprae, which reacts with antibody to either M. leprae, M. tuberculosis or atypical mycobacteria in human serum and with antibody to M. butyricum in serum from rabbits immunized with various antigens and Freund's complete adjuvant. These results indicate that immunohistochemical studies on leprosy are misleading if performed using intact polyclonal immune sera rather than affinity purified or monoclonal antibodies.
Antibodies, Bacterial↗
Characterization of two epitopes on insulin using monoclonal antibodies.
Three monoclonal antibodies (MAb), 21 (IgG1), I10 (IgG1) and H38 (IgG2b), to insulin have been tested for cross-reactivity with 11 species variants of insulin and three of proinsulin. Correlations of differences of reactivities between the MAb and the species variants of insulin with the respective amino acid sequences of the latter have permitted the identification of two epitopes recognized by the MAb which encompass the regions in the A- and B-chains of insulin subject to frequent evolutionary amino acid substitutions. MAb 21 and H38 are directed to an epitope which includes residues B27-30 and A1 or A4 and can discriminate between human and pig insulins which differ only at B30. MAb 21 reacts with human (B30 thr) but not with pig (B30 ala) insulins, whereas MAb H38 exhibits a reciprocal specificity. Neither MAb 21 nor MAb H38 react with human or pig proinsulins respectively indicating that the presence of the C-peptide joining A1 to B30 masks the epitope. MAb 21 reacts with human insulin 125I-labeled at tyr A14 but not B26 suggesting that incorporation of the I atom at B26 also masks the epitope. MAb I10 is directed to an epitope which includes A8-10 and A4 or B3 with a specificity for the human A8-10 sequence. MAb I10 reacts with human proinsulin and human insulin 125I-labeled at either tyr A14 or B26.
Amino Acid Sequence↗
Are adolescents able and willing to pay the fee for confidential health care?
We studied the ability and willingness of adolescents attending a suburban-based Adolescent Health Service to pay a fee for health care. Self-administered, anonymous questionnaires were distributed to 180 predominantly middle-class adolescent patients prior to the establishment of a fee-for-service payment plan. One hundred sixty-five respondents planned to continue as patients of the Adolescent Health Service; of these, 155 (94%) indicated that they would be able and willing to pay a fee. All of the 155 respondents indicated they could pay $5 per visit, two thirds could pay as much as $10, half could pay $15, and one fifth could pay $20 or more. Sources of fee money would be job earnings, a friend, allowance, and savings; 75% of respondents planned to pay without any help from parents. Analysis revealed few significant correlates of ability and willingness to pay with demographic, socioeconomic, and attitudinal factors. These data demonstrate that, although few of these middle-class adolescent patients indicated that they were able and willing to pay a full fee of $20 or more, most were able and willing to pay more than a token amount for health care.
Adult↗
Suture materials and suturing techniques.
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Animals↗
Myoepithelial cells in salivary gland tumors. An immunohistochemical study.
Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.
Actins↗
Interspecies Lewis lung carcinoma x Chinese hamster ovary hybrids as protective agents against Lewis lung carcinoma tumor growth.
Interspecies somatic cell hybrids formed between a clone of Lewis lung carcinoma (LLC/9) and Chinese hamster ovary cells were assessed for tumorigenicity in C57BL/6 mice and capacity to protect mice against a challenge with LLC/9 cells. LLC/9 cells were fused with ouabain-resistant-Chinese hamster ovary cells deficient in hypoxanthine guanine phosphoribosyl transferase. Hybrids were selected in medium supplemented with hypoxanthine: aminopterin: thymidine and 5 mM ouabain. Hybrids were shown to contain chromosomes and surface antigens of both parents. At doses up to 10(7) cells, uncloned hybrids and hybrid clones obtained by limiting dilution were nontumorigenic in C57BL/6 mice, while 10(4) LLC/9 cells were tumorigenic in 80% of mice. In protection experiments, hybrid cells were injected i.p., followed by foot pad challenge with 10(6) LLC/9 cells. Three injections of live uncloned hybrids produced complete protection, while one or two injections gave partial protection. Individual live hybrid clones conferred no or partial but never complete protection. Administration of hybrids or LLC cells killed by freezing and thawing or arrested in division by treatment with mitomycin C failed to confer protection against subsequent challenge with LLC/9 cells. These LLC/9 X CHO hybrid cells will be useful for studying therapy of primary LLC tumors and their pulmonary metastases.
Animals↗