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Biomedical subjects

C Meyers

Publications and source records attributed to C Meyers.

At least 55 records · Page 3Linked to original sources
PubMed1993

Amino acid residues essential for biological activity of a peptide derived from a major histocompatibility complex class I antigen.

The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) and Dk-(69-85). We now show that systematic alanine substitution in Dk-(69-85) identifies residues that are essential for biological activity. Ordered structure of the peptides, estimated by circular dichroism, was found in all peptides with activity, but with a complex variety of spectra. Inactive peptides were in either a random coil or an ordered structure. Ordered structure, therefore, is not sufficient for activity. The peptides self-interact in the absence of cells and form aggregates that precipitate upon centrifugation. The tendency to aggregate is correlated with biological potency. Only MHC class I molecules have significant homology to the peptides studied here. The peptide self-interaction suggests that the biological effects in cells, which result from inhibition of receptor and transporter internalization, may be due to the binding (tantamount to self-interaction) of the peptide to the homologous sequences in the alpha 1 domain of the MHC class I molecule.

Adipose Tissue↗
PubMed1993

c-Myc induces the expression and activity of ornithine decarboxylase.

The role of the product of the c-myc protooncogene in the regulation of cellular proliferation and differentiation is well established. Recent reports that c-Myc can serve as a sequence-specific transcriptional activator have begun to elucidate the mechanism by which c-Myc exerts such a profound effect on the mitotic status of a cell. To identify a potential target gene for Myc-mediated trans-activation, we examined the regulation of the ornithine decarboxylase (ODC) gene by c-Myc. ODC is the first and rate-limiting enzyme involved in the synthesis of the polyamines and has been shown to be required for entry into and progression through the cell cycle. Using a conditionally active c-Myc-estrogen receptor chimeric protein, we found estrogen-dependent activation of ODC expression and enzymatic activity. The induction of ODC mRNA expression was not dependent upon de novo protein synthesis. These data suggest that one downstream pathway for Myc-directed cell cycle control is the induction of ODC expression.

3T3 Cells↗
PubMed1992

Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation.

The study of the human pathogen papillomaviruses (HPVs) has been hampered by the inability to propagate the virus in tissue culture. The addition of 12-O-tetradecanoyl phorbol-13-acetate to the media of organotypic (raft) cultures increased expression of physiological markers of keratinocyte differentiation and concomitantly induced production of virions. Capsid production was detected in differentiated suprabasal cells. Virions approximately 54 nanometers in size were observed by electron microscopy in raft tissue cross sections in the suprabasal layers. Virions purified through isopycnic gradients were found to contain type 31b DNA and exhibited an icosahedral shape similar to that of papillomaviruses found in clinical samples.

Capsid↗
PubMed1992

Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes.

We have been interested in identifying proinflammatory molecules which might play a role in attracting monocytes and T cells to the kidney. Some of the new intercrines are potential candidates. In this report we have isolated cDNA encoding murine Rantes (MuRantes) from renal tubular epithelium (MCT cells). MuRantes is a 91 amino acid member of the -C-C- or intercrine beta subgroup of the Scy superfamily. The amino acid sequence for mature MuRantes was deduced from its coding cDNA and was found to be 90% homologous to its mature human counterpart (HuRantes). MCT epithelium expresses a single mRNA transcript for MuRantes of approximately 1100 bp. The MuRantes protein could be detected in cell lysates of MCT epithelium by western blotting and in the cytoplasm of MCT cells by immunofluorescence using a polyclonal antibody generated against HuRantes fusion protein. A search protocol using MuRantes-specific primers and cDNA amplification revealed that mRNAs for MuRantes are expressed additionally in syngeneic mesangial cells (MMC cells), whole kidney, liver, and spleen, as well as in nephritogenic antigen-specific CD4+ helper and CD8+ effector T cells. cDNA amplification studies also demonstrated a significant elevation in mRNA transcripts encoding MuRantes in response to the stimulation of MCT epithelium with TNF alpha and IL-1 alpha in culture, but not with TGF beta, gamma IFN, or IL-6. Our findings indicate that proximal tubular epithelium is an authentic source of MuRantes, and that transcripts encoding MuRantes are responsive to the modulating influence of paracrine factors having a known role in the development of parenchymal injury.

Amino Acid Sequence↗
PubMed1992

Identification of three transforming proteins encoded by cottontail rabbit papillomavirus.

Cottontail rabbit papillomavirus (CRPV) provides an animal model for human papillomaviruses associated with a high risk of cancer development. So far, nothing is known about the transforming functions of CRPV genes because of the lack of an assay system. We have recently developed two systems to assay for CRPV transforming functions. One is based on the finding that transformation of NIH 3T3 cells by CRPV is considerably increased by deleting sequences in open reading frame L2. The second one is based on the use of a cottontail rabbit skin epithelial cell line, sf1Ep (C. Meyers and F. O. Wettstein, Virology 181:637-646, 1991). Mutations were introduced which abolished expression of the full-length E6 protein (LE6), the short E6 protein (SE6) initiated at the second ATG of E6, the E7 protein, or the E5 protein. Mutations affecting LE6 or E7, but not SE6, reduced transformation of NIH 3T3 and sf1Ep cells. Transformed NIH 3T3 cell lines with mutations in LE6 and E7 did not grow in soft agar, while those with mutations in SE6 and E5 grew with a reduced efficiency. The cell lines with mutations in LE6, SE6, or E7 still did induce tumors in nude mice. These mutations, however, abolished the ability to induce papillomas in rabbits. When expressed individually with a retroviral vector, LE6, SE6, or E7, but not E5, conferred anchorage-independent growth. The level of viral protein expression in these cell lines was generally low, and a comparison of the abundance of virus-specific mRNA showed that cell lines contained 20 to 50 times less mRNA than a cottontail rabbit papilloma. These data demonstrate that CRPV encodes at least three transforming proteins.

3T3 Cells↗
PubMed1992

The impact of physician denial upon patient autonomy and well-being.

It is now widely accepted that a patient's ability to engage in autonomous decision-making can be seriously threatened when she denies significant aspects of her medical condition. In this paper I use a true case to reveal the harmful effects of physician denial upon patient autonomy and well-being. I suggest further that such physician denial may be more common than is generally acknowledged, since aspects of the contemporary medical ethos likely serve to reinforce rather than to undercut such denial.

Attitude to Death↗
PubMed1992

Hmong children and their families: consideration of cultural influences in assessment.

Occupational therapists assessing young Hmong children with developmental problems must consider their families' cultural beliefs as they affect the design of assessment procedures and practices. Choices that families make about health and educational services are influenced by their beliefs. Developmental status can be affected by unresolved medical problems and the child's general health condition. Assessment components based on cultural awareness may improve the effectiveness of early identification of Hmong children with developmental delay. Appropriate use of interpreters, creation of the most beneficial assessment environment, parental report, and observation of functional skills and play provide needed information when determining the child's eligibility for early intervention services. The author has found that trained interpreters provide the most reliable communication between family members and the therapist. Assessments in the home environment are encouraged due to the child's age and the need for family support and interaction. Parents are an excellent source of information about the child's current and past functional abilities. Observations of the child's interaction with family members, with objects and toys during play, and during functional daily living activities provides the therapist with valuable information about the child's need for intervention.

Attitude to Health↗
PubMed1991

The late region differentially regulates the in vitro transformation by cottontail rabbit papillomavirus DNA in different cell types.

Papilloma induced by the cottontail rabbit papillomavirus (CRPV) progress at a high frequency to cancers. This property makes the CRPV system unique to study the role of papillomaviruses in cancer development. In contrast to bovine papillomavirus type 1, no convenient in vitro transformation system for CRPV has been available. Here, we describe two in vitro systems that we have developed. Transformation of NIH 3T3 cells is greatly facilitated by deletions in the CRPV late region. Specifically, a 300-bp segment located in the 5' half of open reading frame L2 inhibits transformation of NIH 3T3 cells by CRPV DNA. In a second system involving the natural host cell of CRPV, rabbit skin epithelial cells, transformation is a two-stage phenomenon leading first to cells with an increased growth potential which subsequently become morphologically transformed. Transformation of rabbit skin epithelial cells does not require deletions in the L2 ORF. However, late region sequences located in the 3' half of ORF L1 are needed, as they are for papilloma induction in rabbits.

Animals↗
PubMed1991

Brain function, learning styles, and cancer patient education.

As cancer care moves into the outpatient setting and hospital stays are shortened, patients and their family members are expected to take on tremendous responsibilities in providing their own self-care. At the same time, stress and anxiety about the diagnosis of cancer, the disease itself, and cancer therapy can effect learning. Information processing, learning styles, and learning barriers need to be considered when developing and implementing cancer education programs.

Aged↗
PubMed1991

Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction.

During pregnancy, nucleated fetal erythrocytes enter the maternal circulation and can be isolated efficiently from the maternal cells by multiparameter flow cytometry. Male DNA, implying presence of a male fetus, can be identified in flow-sorted maternal blood by polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific DNA sequences. Among flow-sorted samples, we correctly identified fetal sex in 17/18 (94%) pregnancies of 10-21 weeks gestation. Maternal blood thus provides a potential opportunity for prenatal diagnosis that could preclude the need for invasive procedures in current use.

Base Sequence↗
PubMed1990

Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates.

To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants.

Amphotericin B↗
PubMed1990

Identification and preliminary characterization of protein-cysteine farnesyltransferase.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗
PubMed1990

The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties.

The E7 early viral protein of the oncogenic human papillomavirus type 16 (HPV-16) has been strongly implicated in the maintenance of the malignant phenotype in cervical cancers and cancer-derived cell lines. HPV-16 E7 is a nuclear phosphoprotein that can cooperate with ras to transform baby rat kidney cells, transactivates the adenovirus E2 promoter, and binds to the retinoblastoma (RB) protein. The E7 phosphoprotein of the nononcogenic HPV-6b, which is generally associated with benign genital warts, is similar to the HPV-16 E7 in amino acid sequence but differs dramatically in migration in sodium dodecyl sulfate-polyacrylamide gels, sedimentation in nondenaturing glycerol gradients, and the ability to bind the RB protein. Our results indicate that the RB protein preferentially binds the phosphorylated form of HPV-6b E7, which comprises a minor fraction of the total E7 expressed in transiently transfected COS-7 cells. These characteristics may help to explain the difference in the oncogenic potential of the oncogenic and nononcogenic types of genital papillomaviruses.

Amino Acid Sequence↗
PubMed1989

Genetic analysis of CRPV pathogenesis: the L1 open reading frame is dispensable for cellular transformation but is required for papilloma formation.

Genetic studies to elucidate the role of papillomaviruses in the development and progression of tumors have been severely hampered because the viruses cannot be grown in tissue culture and therefore mutants are not available. We have employed recombinant DNA for papilloma induction to identify essential sequences involved in papillomavirus pathogenesis. Here, we demonstrated that deleting most of the open reading frame (ORF) L2 did not affect the potential of viral cottontail rabbit papillomavirus (CRPV) DNA to induce papillomas. The extrachromosomally maintained DNA in the papillomas was not rearranged and the major transcripts of 1.3 and 2.0 kb encoded E7 and E6, respectively. A recombinant DNA containing a larger deletion lacking the 3' terminal half of ORF L2 and all of ORF L1 (pdlBc/l) did not induce papillomas. The results indicate that sequences in the late region not required for transformation of NIH 3T3 cells by bovine papillomavirus type-1 essential in CRPV for induction of papillomas.

Animals↗