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Biomedical subjects

A Caputo

Publications and source records attributed to A Caputo.

At least 91 records · Page 5Linked to original sources
PubMed1988

Cooperation in oncogenesis between BK virus early region gene and the activated human c-Harvey ras oncogene.

Rapidly growing, undifferentiated brain tumours were induced in newborn Syrian hamsters by intracerebral inoculation of a recombinant DNA (pBK/c-rasA) carrying the BK virus (BKV) early region gene and the activated human c-Harvey-ras (c-Ha-ras) oncogene. Neither of the two genes inoculated alone nor recombinant DNA of the BKV early region gene and the normal human c-Ha-ras proto-oncogene were tumourigenic. Tumour-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumours and tumour cell lines contained pBK/c-rasA sequences integrated into cellular DNA and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T antigen and c-Ha-ras p21. These findings are discussed in relation to a possible cooperation or synergism between BKV and cellular oncogenes in human neoplasia.

Animals↗
PubMed1988

Expression of hepatitis B surface antigen in human cells by a recombinant BK virus DNA vector.

The construction of the first stable human cell lines that express and secrete authentic hepatitis B virus surface antigen (HBsAg), using a BK virus (BKV) episomal plasmid vector, is described. The amount of HBsAg produced by BKV vectors (up to 600 ng/10(7) cells) was comparable to other eukaryotic vector systems. The level of HBsAg expression remained the same regardless of the orientation of the HBsAg gene, substitution of the HBsAg gene promoter with the mouse metallothionein I gene promoter or the tissue origin of the human cell lines used to establish stable cellular transformants. Northern blot analysis also indicated synthesis of normal HBsAg transcripts. Surprisingly, however, the vectors were maintained at far lower than expected copy number (one to five copies/cell). Reasons for this are discussed.

BK Virus↗
PubMed1988

Biomechanics.

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Crowns↗
PubMed1987

Induction of malignant subcutaneous sarcomas in hamsters by a recombinant DNA containing BK virus early region and the activated human c-Harvey-ras oncogene.

Malignant undifferentiated sarcomas were induced in 11 of 15 (73.3%) newborn Syrian hamsters by s.c. inoculation of a recombinant DNA (pBK/c-rasA) containing BK virus (BKV) early region gene and the activated human c-Harvey-ras(c-Ha-ras) oncogene derived from T24 bladder carcinoma. The two genes inoculated independently as well as a recombinant DNA of BKV early region gene and normal human c-Ha-ras proto-oncogene were not tumorigenic. Tumor-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumors and tumor cell lines showed tandem insertions of pBK/c-rasA in high copy number and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T-antigen and c-Ha-ras protein with a molecular weight of 21,000. We conclude that BKV DNA requires interaction with other oncogenic functions for tumorigenicity. These findings may be relevant to the role of BKV in human neoplasia, where cooperation or synergism between BKV and cellular oncogenes could occur as an aspect of the multifactorial process of carcinogenesis.

Animals↗
PubMed1987

Effect of hyperthermia on electron transport in Ehrlich ascites tumor mitochondria.

The effect of hyperthermia (1 hr, 41 degrees C) on the functional properties of Ehrlich ascites tumor mitochondria was investigated. Mitochondria isolated from Ehrlich ascites tumor after exposure of whole cells to 41 degrees C for 1 hr still phosphorylate and maintain a normal acceptor control ratio (ACR). The temperature decreases state 4 and ADP-and FCCP-stimulated respiration on various substrates entering at three energy-conserving sites of the respiratory chain. The inhibition of oxygen consumption by NAD- and FAD-linked substrates was 40% for state 4 and 70% for ADP- or FCCP-stimulated respiration. State 4 and FCCP-stimulated respiration of mitochondria on TMPD + ascorbate was affected 38% and 45%, respectively. ATPase activity was unaffected by hyperthermia, indicating that under these experimental conditions, the inhibition of ADP-stimulated respiration does not depend on an effect on either Fo F1-ATPase or adenine translocase, the activity of which is required for ATP entry prior to ATPase activity. Because of the inability to detect a specific site of action of temperature, it is conceivable that hyperthermia might inhibit substrate oxidation by altering some components of the inner mitochondrial membrane, which regulates the kinetic properties of the membrane-associated enzymes.

Adenosine Triphosphatases↗
PubMed1987

Effect of lonidamine on the utilization of 14C-labeled glucose by human astrocytoma cells.

The effect of lonidamine (LND), 1-(2,4-dichlorobenzyl)-1H-indazol-3 carboxylic acid, on the utilization of carbon from 14C-labeled glucose by cell cultures of the permanent strain LI derived from a human glioblastoma multiforme (astrocytoma) has been investigated. The results may be summarized as follows. Aerobic glycolysis is the main energy-yielding process as shown by the fact that the greatest part of glucose carbon atoms is incorporated into lactate. Nevertheless, the amount of glucose converted accounts for only 63% of the lactate produced, indicating the presence of an elevated endogenous aerobic glycolysis. The amount of glucose carbon atoms incorporated into CO2, lipids, nucleic acid, and supporting structures is low. LND decreased the incorporation of 14C activity in all the above mentioned isolated compounds because of its ability to inhibit glucose phosphorylation. Consequently, there is a lower concentration of glucose-6-phosphate which, in turn, affects the rate of formation of several metabolites in glycolytic and pentose phosphate pathways. Experiments with [1-14C]-2-deoxy-D-glucose further substantiate the idea of glucose phosphorylation as a main target of LND and strongly suggest the presence of a mitochondrially bound hexokinase. The higher inhibition of glucose phosphorylation in exponentially growing cells indicates a further shift of the enzyme toward mitochondria-bound form and confirms the importance of the energy status of the cell in eliciting the response to LND. The reduced capacity of LND-treated cells to synthetize ATP and glucose-6-phosphate reflects the decreased synthesis of proteins and nucleic acids, which affects cell growth and duplication.

Antineoplastic Agents↗
PubMed1987

Force transmission and retentive capabilities utilizing labial and palatal I-bar partial dentures.

A maxillary photoelastic model was constructed to determine the retention and force transmission characteristics of a bilateral distal extension base partial denture. Comparisons were made using palatal and labial I-bars. It was shown that there were no significant differences in retention and force transmission between palatal and labial I-bars. From a stress and retention standpoint, it may be concluded that the use of palatal I-bars is a viable alternative to the labial I-bars, especially where aesthetics is of primary concern.

Dental Stress Analysis↗
PubMed1986

Transactivation of BKV and SV40 early promoters by BKV and SV40 T-antigens.

The early promoters of BKV and SV40 plasmids were transactivated in both BKV and SV40-transformed cells which failed to support replication of these plasmids. This suggests that the T-antigen of either virus can transactivate BKV and SV40 early promoters by either increasing the availability of cellular transcription factors or by directly interacting with specific sequences which comprise the transcriptional control region of the early promoters. We also observed that removal of 8-bp on the early side of T-antigen binding site I of BKV does not alter viral-plasmid replication.

Animals↗
PubMed1986

Induction of stress proteins by lonidamine in human and murine melanoma cells.

The ability of lonidamine [1-(2,4)-dichlorobenzyl-1H-indazol-3-carboxylic acid], to induce a stress response in human and murine cultured melanoma cells has been demonstrated. In the M14 and M10 human melanoma cell lines, lonidamine enhances the synthesis of a unique set of proteins, characterized by SDS-PAGE by an Mr of about 72 kDa. In the B16 murine melanoma cell line, exposure to lonidamine increases the synthetic rate of two polypeptides of mol mass 86 and 72 kDa, respectively. Lonidamine is a drug which specifically acts on mitochondria. Therefore the observation that it can also promote a stress response indicates that the mitochondria might be one of the primary cellular targets and postulates a causal relationship between an impairment of the energy supply and induction of stress protein synthesis.

Animals↗
PubMed1986

Adenovirus type 12 early region 1A proteins repress class I HLA expression in transformed human cells.

The adenovirus type 12 (Ad12) early region 1A (E1A) gene is thought to play a major role in repressing class I major histocompatibility complex expression in transformed rodent cells. However, since transformation by adenovirus requires both E1A and E1B genes, it has not been demonstrated whether the Ad12 E1A gene acts alone or synergistically with the E1B gene to accomplish this effect. Moreover, it is not known whether the repression of class I antigen synthesis by Ad12-transforming gene products occurs only in rodent cells. We show that the Ad12 E1A gene, in the absence of the E1B gene, is capable of greatly reducing the levels of class I HLA antigens and mRNAs in primary human cells transformed by the E1A gene of Ad12 and the large tumor antigen (T-antigen) gene of BK virus; control cells transformed by BK virus T-antigen gene alone or the highly related simian virus 40 T-antigen gene showed no apparent alteration in class I HLA expression. Human recombinant interferon gamma was able to restore synthesis of class I HLA antigens in transformed cells that produced Ad12 E1A proteins, indicating that these cells were not deficient for class I genes. These results strongly indicate that the Ad12 E1A proteins modulate class I gene expression by similar mechanisms in both transformed rodent and human cells.

Adenovirus Early Proteins↗
PubMed1985

Effect of lonidamine on protein synthesis in neoplastic cells.

The action of lonidamine, 1,(2,4 dichlorobenzyl)-1H-indazol-3-carboxylic acid, on protein synthesis of neoplastic cells growing both in vivo and in vitro has been investigated. Lonidamine decreases amino acid incorporation in all cells tested, although the inhibition is partially relieved by glucose. The inhibition of labeled precursors into acid-insoluble material cannot be ascribed to an impairment of amino acid uptake which, on the contrary, is enhanced by the drug. Tests on cell-free systems showed that lonidamine does not inhibit the tobacco mosaic virus (TMV)-mRNA-directed in vitro protein synthesis, thus indicating that protein synthetic machinery per se is not affected. The inhibition of the rate of protein synthesis achieved by lonidamine must be ascribed to an effect on energy-yielding processes with a mechanism similar to that observed in other metabolic inhibitors. Lonidamine, however, because of its capacity to inhibit both respiration and glycolysis in neoplastic cells, is effective at 10 to 20 times lower concentrations. DNP and oligomycin potentiate the inhibitory effect of lonidamine on the rate of protein synthesis. This finding substantiates the idea that neoplastic cells, including those growing in ascitic form, utilize mitochondrial oxidative phosphorylation as the main source of ATP for their biosynthetic processes.

Amino Acids↗
PubMed1985

Occlusal force transfer by removable partial denture designs for a radical maxillectomy.

Several removable partial denture retainers were tested on a photoelastic cast of a human maxilla that had undergone a surgical resection through the midline. The conclusions based on the results of these tests are as follows. Physiologic adjustment of all the designs tested revealed a dramatic reduction in stresses when the framework were placed into position. Under load, the physiologically adjusted frameworks produced less potentially damaging stresses in the supporting structures than the unadjusted frameworks. High stresses were located at the premolar region for all the designs. Lingual retainers produced higher stress concentration than buccal retainers. In the anterior region, the I-bar retainer with a cingulum rest was the best combination for transmitting the occlusal forces along the long axis of the tooth. From the perspective of the equitability of stress transfer, the tested designs from best to worse are infrabulge I-bar retainer, either buccal or lingual retention; light wire circumferential retainer with buccal retention; and the circumferential cast buccal retention, swing-lock system.

Bite Force↗
PubMed1985

Growth-related changes in specific mRNAs upon lectin activation of human lymphocytes.

A cDNA library in lambda gt10 was constructed from the cytoplasmic poly(A) +RNA of human peripheral blood lymphocytes after 72 hr of phytohemagglutinin stimulation, with the aim of assessing selective gene expression as a result of lymphocyte activation. Thirteen recombinants were isolated by the use of an enriched probe and differential screening. These clones were categorized into two groups with respect to their hybridization to mRNA. In the first group three recombinants were isolated, which hybridized to single discrete mRNAs in the size range 0.7-1.7 kb. The mRNAs corresponding to these clones were present at elevated levels in activated lymphocytes, but the kinetics of increase differed. The 0.7-kb mRNA coded for by clone p1L1 increased two-fold at 6 hr and remained elevated over 72 hr, as did beta-actin mRNA. The 1.7-kb mRNA coded for by clone p9L2 increased two- to three-fold after 6 hr and was maximally expressed after 24 hr exposure to phytohemagglutinin, coincident with the onset of DNA replication, and maintained this level up to 72 hr. The 1.0-kb mRNA coded by p10L2F which was rare in resting cells increased 25- to 30-fold after 6 hr, prior to overall transcriptional increases and reached peak levels after 72 hr when a substantial proportion of the cells were in the S and G2 + M phases of the cell cycle. This clone was undetectable or very rare in the leukemic T-lymphoblast cell line CCRF-CEM. The second group of clones, consisting of the remaining 10 recombinants, did not hybridize to discrete bands, but to a smear on RNA blots.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1984

The effect of gossypol and Lonidamine on electron transport in Ehrlich ascites tumor mitochondria.

The effect of the association of gossypol and Lonidamine on the electron transport in Ehrlich ascites tumor mitochondria has been investigated by addition of drugs to isolated mitochondria. The results may be summarized as follows. (1) Low concentrations of gossypol increase the rate of oxygen consumption at the level of three energy-conserving sites of the respiratory chain. Higher concentrations result in an inhibition of oxygen consumption at (or near) both energy-conserving sites 1 and 2, while energy-conserving site 3 is unaffected. (2) Gossypol, at concentrations at which it exerts its uncoupling effect, stimulates ATPase activity. Higher concentrations inhibit the enzyme activity. (3) The addition of gossypol to mitochondria respiring on pyruvate plus malate or succinate induces a more oxidized state of NAD+ and cytochrome b, respectively. (4) Gossypol enhances the effect of Lonidamine on oxygen consumption. Lonidamine does not affect state 4 respiration, but in the presence of gossypol, it determines a marked decrease in the rate of oxygen consumption. The inhibition of oxidation of NAD-linked substrates is greater than that of FAD-linked substrates. (5) It may be concluded that gossypol is very effective in potentiating the effect of Lonidamine. Moreover, it may be suggested that the antitumor activity of Lonidamine is enhanced if it is used in combination with other drugs and/or treatments, such as hyperthermia, which modify the energy status of mitochondria.

Adenosine Triphosphate↗