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Biomedical subjects

M E Perry

Publications and source records attributed to M E Perry.

54 records · Page 3Linked to original sources
PubMed1989

Orotic aciduria fibroblasts express a labile form of UMP synthase.

Orotic aciduria (type 1) results from a mutation in the gene for UMP synthase, a bifunctional protein containing the two enzyme activities which convert orotic acid and 5-phosphoribosyl-1-pyrophosphate to UMP and CO2. In fibroblasts from individuals with orotic aciduria, these two enzymatic activities are about 1% of normal but increase dramatically when deficient cells are grown in the presence of 6-azauridine. Using a polyclonal antiserum to sodium dodecyl sulfate-denatured, pure human UMP synthase, we show that fibroblasts from a patient with orotic aciduria have a low level of immunoreactive UMP synthase protein. Pulse-chase analysis reveals that the UMP synthase is degraded rapidly in the deficient cells. Growth of deficient cells in 6-azauridine leads to an increase in UMP synthase protein and its two enzymatic activities via a decreased rate of proteolytic degradation of UMP synthase. UMP synthase in extracts from deficient cells is more readily denatured by heat and is stabilized after growth of cells in 6-azauridine. These data suggest that the detrimental deficiency of this one patient results from a structurally altered UMP synthase that is probably present in low steady-state amounts due to proteolysis and that this labile protein can be stabilized against heat denaturation and proteolytic degradation by 6-aza-UMP.

Azauridine↗
PubMed1989

A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene.

Differentiation of skeletal myoblasts is accompanied by induction of a series of tissue-specific genes whose products are required for the specialized functions of the mature muscle fiber. The program for myogenic differentiation is subject to negative control by several peptide growth factors and by the products of mutationally activated ras oncogenes, which persistently activate intracellular cascades normally triggered by specific growth factors. Previously, we reported that induction of the muscle creatine kinase (mck) gene during myogenesis was dependent on a distal upstream enhancer that cooperated with a proximal promoter to direct high levels of expression in developing muscle cells (E. A. Sternberg, G. Spizz, W. M. Perry, D. Vizard, T. Weil, and E. N. Olson, Mol. Cell. Biol. 8:2896-2909). To investigate the mechanisms whereby ras blocks the induction of muscle-specific genes, we have examined the ability of mck 5' regulatory elements to direct expression of the linked reporter gene for chloramphenicol acetyltransferase (cat) in C2 myoblasts bearing mutant N-ras and H-ras oncogenes. In this paper we report that expression of activated ras alleles abolishes activity of the mck upstream enhancer but does not affect the activity of the mck promoter. The ability of ras to repress the expression of mck-cat fusion genes that have been transfected either transiently or stably into myoblasts suggests that ras may exert its effects on muscle-specific genes through mechanisms independent of chromatin configurations or DNA methylation. These results also suggest that ras blocks establishment of the myogenic phenotype by preventing the accumulation of regulatory factors required for transcriptional induction of muscle-specific genes.

Animals↗
PubMed1988

Structure of the crypt epithelium in human palatine tonsils.

Material from human palatine tonsils from a group of 18 tonsillectomised patients aged 22 months to 8 years was studied by LM, TEM and SEM. Special attention was focused on the structure of the epithelium lining the tonsillar crypts. This is of a dynamic nature in the living organism. In contrast to the stratified squamous epithelium covering the oropharyngeal surface of the tonsil it was often reticulated and invaded by non-epithelial cells. However, it was not uniform throughout. When studied by LM and TEM, adjacent patches of epithelium varied in degree of reticularity. The reticulated epithelium was either covered by a thin layer of squamous cells, or this was disrupted in places where non-epithelial cells passed through. Hence the intact surface, as seen on the SEM, is not a reliable indication of the nature of the underlying structure of the epithelium. Small blood vessels were frequently observed in association with the reticulated epithelium. They formed numerous finger-like projections surrounded by a sleeve of subepithelial connective tissue, and also a fine capillary network within the epithelial thickness. It is proposed that such an organisation of the crypt epithelium offers favourable means for the capturing and processing of antigens by the palatine tonsils.

Blood Vessels↗
PubMed1986

Incidence of fever and bacteremia following transbronchial needle aspiration.

Fiberoptic bronchoscopy and transbronchial needle aspiration were performed on 50 occasions in 47 afebrile patients. The aspirations were followed by endobronchial or transbronchial biopsies in 22 patients, as well as bronchial brushings and washings where appropriate. Blood for cultures was drawn at 5 and 30 minutes following needle aspiration, as well as at the time of any temperature above 38 degrees C during the 24 hours following the procedure. In five (10 percent) of the 50 cases, there was temperature greater than 38 degrees C (100.4 degrees F) in the 24 hours following the bronchoscopy; in no patient were cultures of blood positive, whether done early after the procedure or at the time of fever. We conclude that transbronchial needle aspiration, a new procedure gaining widespread popularity in diagnostic thoracic medicine, is not associated with clinically detectable bacteremia. This procedure should not require antimicrobial prophylaxis in patients susceptible to endocarditis.

Adult↗
PubMed1984

Gas washout and pressure waveform characteristics of high-frequency oscillation.

High-frequency oscillation (HFO) minimizes tidal volume. To investigate whether ventilation can proceed when tidal movement (volume) is eliminated, a nondistensible physical model of interconnected chambers was constructed. During HFO, ventilation was related to pressure waveform characteristics recorded within the separate chambers. Ventilation increased up to a critical frequency related to the time constant of the system. Beyond this frequency, ventilation dropped off rapidly.

Humans↗
PubMed1984

Effect of continuous positive airway pressure on lung mechanics during high-frequency jet ventilation.

Six mongrel dogs were studied in a body plethysmograph to ascertain the effects of continuous positive airway pressure (CPAP) during high-frequency jet ventilation (HFJV), using an open system allowing gas entrainment. Increases in CPAP significantly reduced tidal volume. Increases in HFJV and inspiratory fraction caused progressively larger increases in functional residual capacity (FRC). Higher levels of CPAP dramatically reduced HFJV's effect on FRC, but lower levels of CPAP augmented this effect. At constant CPAP, tidal volume correlated well with the difference between peak airway pressure and CPAP, while the FRC change was correlated with the difference between end-expiratory pressure and CPAP. The relationship between end-expiratory airway pressure and total change in FRC was predictable from lung compliance at all levels of CPAP.

Animals↗
PubMed1983

P1,P4-Di(adenosine-5')tetraphosphate inhibits phosphorylation of immunoglobulin G by Rous sarcoma virus pp60src.

Di(adenosine-5')oligophosphate nucleotides of general structure ApnA (n = 2-6) inhibited phosphorylation of immunoglobulin G from tumor-bearing rabbits (TBR IgG) by pp60src protein kinase purified from Rous sarcoma virus-transformed rat tumor cells. Ap4A, a nucleotide associated with eukaryotic cell proliferation, was one of the most effective inhibitors in the series, causing 50% inhibition of TBR IgG phosphorylation at 15 microM. Ap4A inhibited pp60src-dependent phosphorylation of TBR IgG in solution and immunoprecipitates, as well as the phosphorylation of tubulin, microtubule-associated proteins, and vinculin. Under similar assay conditions, Ap4A did not inhibit phosphorylation of histone H2b by cAMP- or cGMP-dependent protein kinases. Ap4A appears to interact noncovalently with the enzyme, because removal of pp60src by immunoprecipitation from solutions containing Ap4A restored activity to uninhibited levels. A 100-fold increase in ATP (4-400 nM) caused a 13-fold increase in the 50% inhibitory concentration of Ap4A (2.5-33 microM), consistent with the interpretation that Ap4A competes for an ATP-binding site on the pp60src molecule. The simplest explanation of these results is that Ap4A binds to the phosphodonor site for ATP.

Adenine Nucleotides↗
PubMed1979

A correlation between nucleosome spacer region susceptibility to DNase I and histone acetylation.

Hepatoma tissue culture (HTC) cell nuclei were digested with either DNase I or micrococcal nuclease and the nucleohistone digestion products fractionated by gel electrophoresis or exclusion chromatography. Under appropriate conditions, gel electrophoresis demonstrates that for both nucleases, only cleavages within the nucleosome spacer regions and not within the nucleosome core lead to freely migrating nucleohistone particles. These particles consist of nucleosome cores, nucleosomes and nucleosome oligomers. Following DNase I digestion and fractionation by exclusion chromatography, analysis of the histones indicates a direct relationship between increased spacer region susceptibility to nuclease and increased nucleosomal histone acetylation. Evidently digestion sites outside the regions of DNA protected by core histones can reflect the degree of acetylation of core histones. Such a relationship is not found when micrococcal nuclease is used to digest the samples.

Acetylation↗
PubMed1976

Retroperitoneal germinoma marked by elevated serum lactic dehydrogenase.

A case of primary retroperitoneal germinoma is presented in which markedly elevated serum lactic dehydrogenase levels were present before diagnosis, but declined to normal with abdominal irradiation. It is the first report of lactic dehydrogenase serving as a tumor marker in germinoma.

Adult↗
PubMed1975

Transcultural attitudes toward homocide and suicide.

Using the concept that homicide and suicide are complex sociopsychiatric phenomena clearly influenced by cultural norms and values that define which behaviors are viewed as deviant, the investigators constructed a small sample model to determine relevant qualitative attributes of public opinion. A stratified factorial sample of 258 subjects distributed among eight large cities throughout the world was selected for interviewing. The 2,603 resulting statements were then subjected to content analysis and categorization. Results indicated that people in cities, regardless of location, are most concerned about crimes of violence, especially homicide, and those against property. Other kinds of life-threatening offenses such as arson, war, and suicide are seldom seen as important "crimes." Many people endorse a problem-solving approach to dealing with crime and criminals, but a reservior of traditional, punitive attitudes clearly remains among the less educated, lower socioeconomic classes. A commonality of many attitudes in these various urban centers does suggest that modern communication techniques may well have a modulating effect on culture-bound orientations toward crime.

Attitude↗