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Biomedical subjects

F F Becker

Publications and source records attributed to F F Becker.

At least 55 records · Page 3Linked to original sources
PubMed1991

Specific reduction of I-compound levels in DNA from spontaneous hepatomas of 22-24 month old male C3H mice.

As previously shown by 32P-postlabeling, I-compound levels are reduced in target tissue DNA of animals exposed to one of several non-genotoxic hepatocarcinogens, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin, carbon tetrachloride, peroxisome proliferators and choline-devoid diet. I-compound levels are further reduced, sometimes to undetectable levels, in chemically induced, transplantable rat (Morris) hepatomas and hepatocellular carcinomas induced by peroxisome proliferators or choline-devoid diet. The current study investigated I-compounds in spontaneous hepatic adenomas of genetically susceptible male C3H mice. DNA samples from individual tumors, background livers (non-tumor bearing lobe from tumor bearing mouse) and non-tumor bearing normal livers taken from 22-24 month old animals were analyzed by 32P-postlabeling. I-compound profiles were qualitatively comparable among the three types of tissues. However, levels of most I-compounds were 2.6-5.0 times lower in tumors than in background liver and non-tumor bearing normal liver. There were virtually no differences between background liver and normal liver. Taken together with the previously reported I-compound deficiency in carcinogen-induced hepatomas, the present observations on genetically initiated neoplasms suggest that this phenomenon may play a role in hepatocarcinogenesis and maintenance of neoplasia.

Aging↗
PubMed1991

Suppression of in vitro chemical transformation by the carcinogenesis-promoting, viable yellow gene Avy.

The presence of the viable yellow Avy and lethal yellow Ay genes has been demonstrated to accelerate the process of tumorigenesis in mice bearing genetically, chemically or virally initiated cells. This promoting effect has been reported in the liver, lung, breast, bladder and skin. Although it has been demonstrated that the accelerated process is associated with systemic, pathophysiologic alterations such as an alteration in the lipogenic pathway, which in turn leads to obesity, alteration in glucose metabolism and/or random immunologic alterations, no examination of the in vitro 'tumorigenic' susceptibility of the cells of animals bearing the yellow genes has yet been reported. In the current study, spontaneous and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced transformation was determined in skin-derived fibroblasts from C57BL/6N-Avy/a mice (Hy) and their black a/a litter mates (B1-). The growth rate of untreated fibroblasts was greater for those from the yellow mice than from the black, while susceptibility to MNNG toxicity was equivalent. However, the rate of spontaneous and chemically induced transformation was consistently and significantly higher in the cells obtained from the black a/a mice than in those from yellow, Avy/a litter mates. These findings, with others from the literature, suggest that the Avy gene may suppress transformation and carcinogenic susceptibility in specific cells, such as fibroblasts, while the systemic effects of the gene are promotional in other cells.

Animals↗
PubMed1991

IL-2-dependent murine T-cell lines and clones expressing gamma/delta T-cell antigen receptors. I. Functional and biochemical characterization.

We have developed two stable IL-2-dependent T-cell lines designated AKV-I and AKV-N from the enlarged spleens, respectively, of an AKV1 and an NFS mouse. Immunofluorescence staining with the appropriate monoclonal antibodies revealed that cells of the AKV-I cell line were alpha beta TCR-CD3+CD4-CD5-CD8+CD25+, whereas cells of the AKV-N cell line were alpha beta TCR-CD3+CD4-CD5+CD8-CD25+. A number of T-cell clones were developed from the AKV-I or AKV-N T-cell lines by limiting dilution and analysed by immunofluorescence. All clones tested were alpha beta TCR-CD3+CD4-CD25+. Certain T-cell clones expressed the CD5 antigen, whereas others expressed the CD8 antigen. The AKV-I cell line responded by proliferation to rIL2, rIL4, phorbol myristate acetate (PMA), PMA plus IL-4 and PMA plus PHA or Con A. In contrast, the AKV-N cell line did not respond to rIL-4 or rIL-4 plus PMA and exhibited only a modest proliferative response to PMA alone. Both AKV-I and AKV-N T-cell lines as well as a large number of T-cell clones examined were able to lyse cells of the PU5-IR murine cell line in the presence of the anti-CD3 (clone 145-2C11) MoAb, demonstrating their ability to mediate cytotoxicity in this system. Biochemical analysis of both AKV lines and a number of clones by immunoprecipitation with the anti-CD3 MoAb, followed by one-dimensional (either non-reducing or reducing) or two-dimensional (non-reducing/reducing) SDS-PAGE, revealed that the AKV lines and clones expressed a disulphide-linked dimer. Under non-reducing conditions, a band in the range of 75-85 kDa was observed and upon reduction it was resolved into two discrete polypeptide chains of 43-44 kDa and 48 kDa in certain AKV-I cells or 38 kDa and 42 kDa in certain AKV-N cells. In other T-cell clones or lines a broad band of 42-47 kDa was observed in AKV-I cells or 38-45 kDa in AKV-N cells. These results suggest the presence of different forms of disulphide-linked dimers on these cells. Northern blotting analysis using probes specific for the constant regions of the alpha-, beta-, gamma- and delta-chains of the T-cell antigen receptor revealed that all the AKV cell lines or clones tested expressed full-length alpha-, gamma- and delta-chain mRNA, whereas beta-chain mRNA was absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel electrophoresis of their AMP-binding domains in the trypsin-digested protein fragments. The results also suggested that these isozymes have been derived from the same primordial DNA sequence or from the same precursor protein. The purification scheme and the data obtained will be instrumental for the further elucidation of the biological roles of various DNA ligases from human cells.

Adenosine Monophosphate↗
PubMed1990

Role of the AKR gene locus AKv-1 in susceptibility to chemical induction of thymic lymphomas.

Various strains of mice demonstrate widely differing susceptibility to chemical induction of thymic lymphomas, in both timing and incidence. In AKR mice tumors appear very early and at high incidence after a single dose of N-methyl-N-nitrosourea, while in other strains they appear later and at lower incidences. In an attempt to determine the potential role of AKR ecotropic murine leukemia virus loci in this process, congenic mice of NFS/N background, into which the highly productive ecotropic murine leukemia virus loci AKv-1 or AKv-2 has been transferred, were challenged with N-methyl-N-nitrosourea. Although they had a lower incidence of thymic lymphomas than did the parental donor AKR, the NS.AKv-1 mice had a tumor incidence twice that of NFS/N or NS.AKv-2. However, no difference in timing was noted, and these three strains demonstrated tumor appearance much later than that of AKR/N. It is suggested that the presence of the AKv-1 loci, or a gene of the closely associated genomic region, increases the number of target cells that are susceptible to N-methyl-N-nitrosourea.

Alleles↗
PubMed1990

Dielectrophoretic characterisation of Friend murine erythroleukaemic cells as a measure of induced differentiation.

Dielectrophoresis measurements, the study of the motion of particles in non-uniform a.c. electrical fields, have been made on three cell lines (DS19, R1 and DR1) of Friend murine erythroleukaemia cells as a function of hexamethylene bisacetamide (HMBA) treatment. The effects of saponin treatment on R1 cells and neuraminidase on human red blood cells were also studied. It is shown that the dielectrophoretic behaviour can be interpreted in terms of cell surface charge and cell membrane conductivity effects. HMBA reduces the cell surface charge on all three cell lines, and in lines DS19 and DR10, where the cells are induced to differentiate, there is an increase in effective cell conductivity. This gain in conductivity is concluded to be associated with either an enhanced lateral electrophoretic motion of delocalised ions or of the polarisability of dipoles at the membrane surface.

Acetamides↗
PubMed1990

Heme synthesis in normal mouse liver and mouse liver tumors.

Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors 55FeCl3 and [2-14C]glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated [2-14C]glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool.

Animals↗
PubMed1990

Submental W-plasty for correction of 'turkey gobbler' deformities.

There are many causes and types of submental contour deformities. One such deformity called a turkey gobbler, is caused by an excess of flaccid submental skin and as an isolated defect is seen more commonly in men. We have found that skin excision and a running submental W-plasty for correction of this deformity yields a superior cosmetic result with excellent camouflage of the submental scar. Two cases are illustrated.

Chin↗
PubMed1990

Alterations in electrophoretic mobility, diaphorase activity, and terminal differentiation induced in murine erythroleukemia lines by differentiating agents.

The electrophoretic mobilities (EPMs) and semiquinone reductase activities of two clones of Friend murine erythroleukemia (MEL) cells were investigated as a function of treatment with the inducing agents dimethylsulfoxide (DMSO) and hexamethylene bisacetamide (HMBA). As reported previously by others, the inducible clone DS19 lost its ability to grow in soft agar and expressed hemoglobin as judged by benzidine/H2O2 staining after 96 hours of treatment with 1% DMSO or 4 mM HMBA. In addition, its EPM fell by 14%, its semiquinone reductase activity by 40%, and its mean diameter by 10%. The second clone, R1, retained its ability to grow in soft agar and lacked hemoglobin expression after treatment with HMBA and DMSO, characterizing it as noninducible. However, R1 did demonstrate alterations in EPM, semiquinone reductase activity, and cell diameter that closely paralleled those found in DS19. Such responses were not seen in three non-MEL cell lines exposed to HMBA or DMSO, suggesting that clone R1 responded to these inducing agents in a cell-line specific manner but that its ability to complete the sequences necessary for differentiation may be blocked at an unknown point distal to the block characteristic of untreated cells. The data show that while a reduction in EPM, semiquinone reductase activity, and cell diameter accompany induced differentiation in MEL cells, such changes can occur in the absence of a commitment to terminal differentiation.

Acetamides↗
PubMed1990

Overexpression of the multidrug resistance gene mdr3 in spontaneous and chemically induced mouse hepatocellular carcinomas.

Overexpression of a family of plasma membrane glycoproteins, known as P-glycoproteins, is commonly associated with multidrug resistance in animal cells. In rodents, three multidrug resistance (mdr or pgp) genes have been identified, but only two can confer the multidrug resistance phenotype upon transfection into animal cells. Using the RNase protection method, we demonstrated that the levels of three mdr gene transcripts differ among mouse tissues, confirming a previous report that the expression of these genes is tissue specific (J.M. Croop, M. Raymond, D. Huber, A. DeVault, R. J. Arceci, P. Gros, and D. E. Housman, Mol. Cell. Biol. 9:1346-1350, 1989). The levels of mdr transcripts were determined for mouse liver tumors spontaneously arising in both C3H/HeN and transgenic animals containing the hepatitis B virus envelope gene and for tumors induced by two different carcinogenic regimens in C57BL/6N and B6C3-F1 mice. The mdr3 gene was overexpressed in all 22 tumors tested. Our results demonstrate that overexpression of the mdr3 gene in mouse liver tumors does not require exposure of the animals to carcinogenic agents and suggest that its overexpression is associated with a general pathway of hepatic tumor development. The overexpression of the mdr3 gene, which is the homolog of human mdr1 gene, in hepatocellular carcinomas may be responsible for the poor response of these tumors to cancer chemotherapeutic agents.

1,2-Dimethylhydrazine↗
PubMed1990

External approach to rhinoplasty.

The external approach to rhinoplasty offers several distinct advantages over the classical endonasal approach for incising, excising, repositioning, and augmenting the framework of the nose for functional and aesthetic improvement. The history of external rhinoplasty, advantages and alleged disadvantages are discussed; personal experience since 1982 is outlined. Various nasal deformities which have been corrected using the external approach are listed and several are discussed and illustrated. This report presents an overview of the technique of external rhinoplasty which will become even more popular as the advantages continue to be recognized by more nasal surgeons.

Female↗
PubMed1989

In vitro DNA cytosine methylation of cis-regulatory elements modulates c-Ha-ras promoter activity in vivo.

The effect of DNA cytosine methylation on promoter activity was assessed using a transient expression system employing pHrasCAT. This 551 bp Ha-ras-1 gene promoter region is enriched with 84 CpG dinucleotides, six functional GC boxes, and is prototypic of many genes possessing CpG islands in their promoter regions. Bacterial modification enzymes HhaI methyl transferase (MTase) and HpaII MTase, alone or in combination with a human placental DNA methyltransferase (HP MTase) that methylates CpG sites in a generalized manner, including asymmetric elements such as GC box CpG's, were used to methylate at different types of sites in the promoter. Methylation of HhaI and HpaII sites reduced CAT expression by approximately 70%-80%, whereas methylation at generalized CpG sites with HP MTase inactivated the promoter by greater than 95%. The inhibition of H-ras promoter activity was not attributable to methylation-induced differences in DNA uptake or stability in the cell, topological form of the plasmid, or methylation effects in non-promoter regions.

Animals↗
PubMed1989

Altered expression of acute-phase reactants in mouse liver tumors.

We studied the expression of eight liver acute-phase genes in spontaneous and diethylnitrosamine-induced mouse liver tumors (MLTs) under basal and induced conditions. Primary spontaneous and chemically induced MLTs were used for RNA isolation and histopathologic analysis. In the noninduced state, all MLTs showed similar levels of mRNA for albumin, serum amyloid A, alpha 1-acid glycoprotein, haptoglobin, and alpha-, beta-, and gamma-fibrinogens compared with control or background livers. The mRNA for the alpha 1-major acute-phase protein, however, was consistently elevated in both spontaneous and diethylnitrosamine-induced MLTs. The expression of these acute-phase reactants in 11 MLTs was examined following exposure of the mice to turpentine. The relative expression of these mRNAs in these MLTs varied widely compared with mRNA expression in controls. Though all MLTs expressed the same three species of fibrinogen mRNAs as did the controls, no MLT demonstrated downregulation of albumin mRNA levels, and only 1 of 11 MLTs showed a marginal increase in serum amyloid A mRNA levels. Synthesis of mRNA for alpha 1-acid glycoprotein and haptoglobin was intermediate. The study of the response of MLTs to specific acute-phase stimuli may make possible a better understanding of the basis for coordinated expression of acute-phase reactants and of the variable phenotypes associated with cancers.

Acute-Phase Proteins↗
PubMed1989

The modulation of astrocytic differentiation in cells derived from a medulloblastoma surgical specimen.

Medulloblastomas are cerebellar tumors which are primarily composed of sheets of uniform, small malignant cells and may have astrocytic, neuronal or no features typical of these cell types. The assessment of astrocytic differentiation in medulloblastoma rests largely on the detection in malignant cells of glial fibrillary acidic protein (GFAP), a marker present in the later stages of normal astrocyte differentiation. It is still not known whether cells that do not contain GFAP in medulloblastomas with astrocytic differentiation correspond to highly proliferative astrocyte progenitors in maturation arrest at earlier stages of differentiation. The purpose of the current study was to examine whether cells in short term culture derived from a medulloblastoma tumor specimen with astrocytic differentiation were of the astrocytic lineage and if so, whether they represented proliferative astrocyte progenitors which would morphologically and antigenically mature in response to differentiating agents. A portion of tumor specimen from a 10-month-old child with recurrent posterior fossa medulloblastoma (RB2) that contained GFAP focally in tumor cells was grown in monolayer culture. We examined cellular structure and appearance of western immunoblotting and immunohistochemical studies for GFAP and neuron-specific enolase (NSE) in RB2 cells before and after treatment with retinoic acid (RA) and dibutyryl cyclic AMP (dBcAMP). RB2 in culture consisted of small polygonal cells (93%), large flat cells (3%), and polygonal cells with cytoplasmic processes (4%). In untreated RB2, 30% of cells expressed GFAP and staining for NSE was negative. RA treatment produced flattened cells and decreased GFAP. DBcAMP reversibly induced fine cytoplasmic processes containing GFAP in 85% of cells within 96 h. Neither agent induced NSE. The results suggest that cultured cells which are derived from a medulloblastoma with astrocytic differentiation do not spontaneously differentiate but that treatment with dBcAMP suppresses proliferation, enhances cytoplasmic process formation and increases cytoplasmic GFAP. Cells in culture and in medulloblastoma tumor specimens which do not contain GFAP may represent astrocyte progenitors in maturation arrest.

Astrocytes↗
PubMed1989

[The removability of pesticides during the production of dialysis water (2)].

In many cases it can be demonstrated that the amount of plant protectives and plant treatments (pesticides) in drinking-water exceeds the permitted levels of the drinking-water decree which will be effective on October 1st, 1989. These components are in parts toxicologically important. Therefore, an examination was made on how far pesticides are removed during the conventional purification of dialysis water, but especially during the reverse osmosis. Retention rates of a reverse osmosis plant for 14 different pesticides were discovered which were used in different concentrations and compositions. In part 2 of this contribution the results of the investigation are presented. The figures demonstrate that almost all of the examined components were retained with an effectiveness of 92-98%. The elimination efficiency did not depend on the basic concentration of the pesticides. After an initial phase of 50 h duration, the permeat concentration reached a constant value which did not alter even after more than 700 h.

Dialysis↗
PubMed1989

[Reducing chloramines in drinking water].

Monochloramine is produced when drinking water containing ammonium is chlorinated. It has long been known that activated charcoal destroys monochloramine. However, exact data for the dimensioning of a dechloramination plant were lacking. Four different commercially available activated charcoals were characterized (size of particle, iodine number) and examined for their effectiveness in removing monochloramines. The degradation of monochloramine by active charcoal is based on a chemical reaction of first order between carbon and monochloramine. The types of activated charcoal considerably differ in terms of reaction velocity, due in part to the mean granular size. The final concentration of the monochloramines is influenced only by their length of stay in the activated carbon filter, the temperature and the inflow concentration. A mathematical model describes the dependence of the degradation rate of the monochloramines on various factors. With its aid a nomogram can be established with which, simply and quickly, the activated charcoal needed in a concrete case can be determined.

Charcoal↗
PubMed1989

[Ability to remove pesticides in the production of dialysis water (1)].

In many cases it can be demonstrated that the amount of plant protective and plant treatment substances (pesticides) in drinking water exceeds the permitted levels of the drinking water ordinance which will come into effect on October 1st, 1989. Since some of these components are of toxicological relevance, an investigation was done on how far pesticides are removed during conventional purification of dialysis water, and especially during reverse osmosis. The retention rates of a reverse osmosis plant for 14 different pesticides applied in different concentrations and compositions were determined. Almost all of the substances examined were retained with an effectiveness of 92-98%. The elimination efficiency did not depend on the initial concentration of the pesticides. After an initial phase of 50 h duration, the concentration in the treated water reached a constant value which no longer changed even after more than 700 h. In part 1 of this contribution at first the fundamentals of dyalisis water purification are reviewed and a selection of the pesticides to be investigated is carried out. In addition experimental set up and procedure are described.

Filtration↗