PubMed HealthSearch

Biomedical subjects

C Hayes

Publications and source records attributed to C Hayes.

At least 19 recordsLinked to original sources

Expression of the neu oncogene under the transcriptional control of the myelin basic protein gene in transgenic mice: generation of transformed glial cells.

We have taken a transgenic approach in an effort to specifically transform oligodendrocytes, the myelinating glial cells of the central nervous system (CNS). Transgenic mice were generated with a DNA construct that contained the activated neu oncogene under the transcriptional control of the myelin basic protein (MBP) gene. The MBP/c-neu transgenic animals have experienced a low incidence of brain tumors that express molecular markers specific to oligodendrocytes, providing a mouse model to study the formation and progression of oligodendrocyte tumors. A tumor from a transgenic animal has been dispersed in culture, and transformed cells that express properties of oligodendrocytes and astrocytes have been maintained. The degree to which these cells express phenotypic characteristic of oligodendrocytes or astrocytes is influenced by culture conditions. These transformed cells should serve as a valuable resource with which to study various molecular and biochemical aspects of the myelination process, as well as the lineage interrelationship of CNS glial cells.

Animals

Protein increases glomerular eicosanoid production and activity of related enzymes.

We examined the in vitro production of PGE2, 6-keto PGF1 alpha and TxB2 by isolated glomeruli from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately eight weeks. Glomeruli from high protein-fed rats produced significantly greater amounts of PGE2, 6-keto PGF1 alpha and TxB2 under basal conditions and in response to the addition of 100 nM angiotensin II (Ang II) than glomeruli from low protein-fed rats. To elucidate the mechanisms by which greater protein intake enhanced the glomerular production of eicosanoids, we explored phospholipase (A2 and C) and cyclooxygenase activity in glomeruli isolated from low- or high-protein fed rats. PE-specific PLA2 activities were significantly increased in glomeruli from rats fed a high protein diet when compared to a low protein diet. On the other hand, PC-specific PLA2 activities were significantly decreased in glomeruli from rats fed a high protein diet. No significant difference in PIP2-PLC activities was detected between glomeruli of the two dietary groups. The cyclooxygenase content and activity was significantly greater in glomeruli from rats fed a high protein diet than in glomeruli from rats fed a low protein diet. Glomeruli of rats fed a 50/50 mixture of the diets (23% casein) had amounts and activity of cyclooxygenase and activities of PE-specific PLA2 intermediate between those of high and low protein-fed animals. In conclusion, increased synthesis of eicosanoids by glomeruli from rats fed a high protein diet may be mediated by increases in the amount and activity of cyclooxygenase coupled with enhanced activity of PE-specific PLA2.

Angiotensin II

Quality assessment and meta-analysis of systemic tetracycline use in chronic adult periodontitis.

The use of systemic tetracycline in the treatment of periodontal disease has been controversial. To investigate this controversy, we performed a quality assessment and attempted to perform a meta-analysis of 13 published studies. We evaluated the quality of the study protocol and data analysis and presentation for each study. We were unable to combine data from the majority of studies due to heterogeneity of the outcomes evaluated and limitations in data reported in the individual studies. Therefore, only 2 studies were included in the quantitative meta-analysis. On a scale of 0-1, the mean score for this group of studies was 0.27 (+/- 0.19) for study protocol and 0.31 (+/- 0.11) for data analysis and presentation. Mean reduction in probing depth for the group treated with tetracycline plus scaling was 2.45 mm; for the group which received only scaling, 2.02 mm; for the group that received only tetracycline, 1.98 mm; and for the control group, 0.65 mm. We conclude that analysis of data from the published literature does not demonstrate that the use of systemic tetracycline is more beneficial than conventional treatment in the management of adult periodontal disease. More information is needed in order to perform an extensive meta-analysis of this subject.

Adult

Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients.

The traditional practice of elevating the head in order to lower intracranial pressure (ICP) in head-injured patients has been challenged in recent years. Some investigators argue that patients with intracranial hypertension should be placed in a horizontal position, the rationale being that this will increase the cerebral perfusion pressure (CPP) and thereby improve cerebral blood flow (CBF). However, ICP is generally significantly higher when the patient is in the horizontal position. This study was undertaken to clarify the issue of optimal head position in the care of head-injured patients. The effect of 0 degree and 30 degrees head elevation on ICP, CPP, CBF, mean carotid pressure, and other cerebral and systemic physiological parameters was studied in 22 head-injured patients. The mean carotid pressure was significantly lower when the patient's head was elevated at 30 degrees than at 0 degrees (84.3 +/- 14.5 mm Hg vs. 89.5 +/- 14.6 mm Hg), as was the mean ICP (14.1 +/- 6.7 mm Hg vs. 19.7 +/- 8.3 mm Hg). There was no statistically significant change in CPP, CBF, cerebral metabolic rate of oxygen, arteriovenous difference of lactate, or cerebrovascular resistance associated with the change in head position. The data indicate that head elevation to 30 degrees significantly reduced ICP in the majority of the 22 patients without reducing CPP or CBF.

Adult

Upper respiratory disease in deployed U.S. Navy shipboard personnel.

A study was conducted to determine the risk of upper respiratory disease among deployed U.S. Navy shipboard personnel. Between January and June 1989, a Patient Encounter Form was used to collect disease information from 10 U.S. Navy ships. Patients with a diagnosis of upper respiratory infection (URI) on initial sick-call visit were used in this study. Information on time spent in various ports and time at sea for each of the 10 ships was also collected. A classification scheme was developed to permit daily estimates of URI rates and to indicate whether the ship was in port or at sea. Of 967 cases of URI, 64.4% occurred while at sea, with an average daily rate of 0.5/1,000 crew members; 35.4% of the cases occurred while in port, with an average daily rate of 0.4/1,000 crew members. There was an increase in URI rates after 9 days at sea or in port. These data suggest that there are defined periods of increased transmission of upper respiratory infections aboard ships, both at sea and in port.

Humans

Chemical form of selenium, critical metabolites, and cancer prevention.

Methylated selenides are prominent metabolites at the dietary levels used for obtaining anticarcinogenic effects with selenium. The present study reports the chemopreventive activities of 2 novel selenium compounds, Se-methylselenocysteine and dimethyl selenoxide, in the rat dimethylbenz(a)anthracene-induced mammary tumor model. Other treatment groups were supplemented with either selenite or selenocystine for comparative purposes. Each selenium compound was tested at different levels and was given to the animal starting 1 week before dimethylbenz(a)anthracene administration and continued until sacrifice. Results of the carcinogenesis experiments showed that the relative efficacy with the four compounds was Se-methylselenocysteine greater than selenite greater than selenocystine greater than dimethyl selenoxide. In correlating the chemical form and metabolism of these selenium compounds with their anticarcinogenic activity, it is concluded that: (a) selenium compounds that are able to generate a steady stream of methylated metabolites, particularly the monomethylated species, are likely to have good chemopreventive potential; (b) anticarcinogenic activity is lower for selenoamino acids, such as selenocysteine following conversion from selenocystine, which have an escape mechanism via random, nonstoichiometric incorporation into proteins; and (c) forms of selenium, as exemplified by dimethyl selenoxide, which are metabolized rapidly and quantitatively to dimethyl selenide and trimethylselenonium and excreted, are likely to be poor choices. We also undertook a separate bioavailability study using Se-methylselenocysteine, dimethyl selenoxide, and trimethylselenonium as the starting compounds for delivering selenium with one, two, or three methyl groups, and measured the ability of these compounds to restore glutathione peroxidase activity in selenium-depleted animals. All three compounds were able to fully replete this enzyme, although with a wide range of efficiency (Se-methylselenocysteine greater than dimethyl selenoxide greater than trimethylselenonium), suggesting that complete demethylation to inorganic selenium is a normal process of selenium metabolism. However, the degree to which this occurs under chemoprevention conditions would argue against the involvement of selenoproteins in the anticarcinogenic action of these selenium compounds.

9,10-Dimethyl-1,2-benzanthracene

Patients 21 days or more in an acute hospital bed: appropriateness of care.

Patients occupying beds for 21 days or more in acute hospitals were studied. Using predetermined objective criteria, the appropriateness of the previous day's hospitalisation was assessed. Barriers to appropriate care and the level of care required were identified in those deemed inappropriate. Of the 421 patients identified, 194 were considered to be inappropriately placed in an acute hospital bed. Patients deemed inappropriate were more likely to be older (p less than 0.05), female (p less than 0.05), have lost a spouse (p less than 0.05), have been admitted through the Accident and Emergency Department (p less than 0.05), and have longer lengths of stay (p less than 0.001) than those considered appropriate. The most frequently identified barrier to appropriate care (N = 143) was that the patient was awaiting another level of care. The level of inappropriate use of acute beds in Dublin is unacceptably high. Additional longstay accommodation especially for geriatric patients is needed. Alternatives to acute hospital care for patients requiring rehabilitation or nursing care should be explored.

Acute Disease

DNA sequence, genomic organization, and chromosomal localization of the mouse peripheral myelin protein zero gene: identification of polymorphic alleles.

We have cloned and characterized the mouse gene, P0, that encodes the predominant protein of peripheral myelin. Similar to the rat gene, the mouse P0 gene is encoded by six exons that span about 7 kb of DNA. The DNA sequence of the mouse gene is highly homologous with the rat gene, including the regions believed to be important in transcriptional control. Furthermore, the P0 protein appears well conserved throughout evolution. The gene was mapped to mouse chromosome 1 by Southern analysis of a Chinese hamster x mouse somatic cell hybrid panel. Several polymorphic restriction enzyme sites were identified within the P0 locus. Recombinant inbred strain mapping has linked the P0 gene to Ly-9/Ly/Sap in a region corresponding to band 1H3.

Alleles

Effects of single- and multiday ozone exposures on respiratory function in active normal children.

Ventilatory function was measured twice daily on 46 healthy children aged 8-14 years on at least 7 days for each child during a 4-week period at a northwestern New Jersey residential summer camp in 1988. The highest 1-hr O3 concentration was 150 ppb, while the highest 12-hr H+ concentration (as H2SO4) was 18.6 micrograms/m3. The highest temperature-humidity index was 81 degrees F. The regressions of FVC, FEV1, FEF25-75, and PEFR on O3 in the hour preceding the afternoon function measurements yielded slopes essentially the same as those measured on other children at the same camp in 1984. Regressions of the changes in function between the late morning and late afternoon function measurements on average O3 concentration between them produced significant, but somewhat smaller effects, while regressions of morning function on O3 during the previous day indicated small but still significant effects. There were no significant correlations with other measured environmental variables including H+. Based on the results of this study and similar previous studies, we conclude that O3 exposures in ambient air produce greater lung function deficits in active young people in natural settings then does pure O3 in controlled chamber exposure studies because of: (1) longer exposures; (2) potentiation by other factors in the ambient exposures; (3) the persistence of effects from prior day's exposures; and (4) the persistence of a transient response associated with the daily peak of exposure. It follows that projections of likely effects in the real world from controlled chamber exposure studies should either have a large margin of safety, or the judgment of the extent of effects likely to occur among populations should be based directly on the effects observed in field studies.

Adolescent

Changes in lipid environment decrease Na, K-ATPase activity in obstructive nephropathy.

Unilateral ureteral obstruction markedly alters sodium and water reabsorption by the affected kidney. These abnormalities may be due, at least in part, to decreased Na,K-ATPase activity in various segments of the nephron during obstruction. The reason for this decreased activity has, however, remained speculative. The present study examines the potential mechanisms underlying the decreased Na,K-ATPase activity in obstruction. The Na,K-ATPase activity was markedly reduced in basolateral membrane vesicles prepared from the cortex of the obstructed kidney of rats with unilateral ureteric obstruction of 24 hours duration when compared to basolateral membrane vesicles from contralateral kidneys of the same rats or to basolateral membrane vesicles from kidneys of sham operated animals. However, no such difference was present three days post-release of unilateral ureteric obstruction. When basolateral membrane vesicles were incubated with sodium dodecyl sulphate to permeabilize the vesicles, no difference in the proportion of enzyme latency was detected between the basolateral membrane vesicles from obstructed kidneys and those from sham operated rats. Immunoblotting with antibodies to the alpha subunit of Na,K-ATPase revealed equal amounts of enzyme in the basolateral membrane vesicles from contralateral kidneys, obstructed kidneys and sham operated rats. When incubated with liposomes under conditions conducive to fusion and lipid exchange the activity of Na,K-ATPase in basolateral membrane vesicles from obstructed kidneys was reconstituted almost to normal levels. This increase in enzyme activity did not occur in basolateral membranes from contralateral kidneys or in membranes from kidneys of sham operated rats incubated in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases

Localization and polar distribution of several G-protein subunits along nephron segments.

Guanine nucleotide binding proteins (G-proteins) are heterotrimeric proteins involved in signal transduction in epithelia. In addition to possessing a polarized epithelium the nephron is composed of well defined segments, each with distinct receptors, transporters and other functions. Since different G-proteins interact with different receptors, a differential distribution of the various G-protein subunits would be expected. To investigate this possibility, polyclonal antipeptide antibodies to several G-protein subunits were used to examine the distribution of these proteins in nephron segments and their localization to apical or basal membrane domains. Immunoblotting of cortical membrane vesicles demonstrated the presence of G-proteins in both the brush border and basolateral membrane. Staining with G alpha common and G alpha s antibodies demonstrated more of these G-protein subunits in the brush border than basolateral membrane. G-protein beta subunits were also present in greater quantity in brush border membranes. Immunocytochemical analysis demonstrated good antigenic preservation and basically confirmed the results of immunoblotting of renal cortex. G-proteins were also found to be differentially distributed in the medulla, the amounts increasing with proximity to inner medulla. Only G alpha s and G beta subunits were demonstrated in glomeruli, but all subunits examined were detected in brush borders of proximal and apical membrane of distal tubules in cortex. In outer medulla G alpha s was detected in both basolateral and brush borders of some tubules and only brush borders of others, G alpha i2 and G beta were found in brush border and G alpha i3 was not detected in this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Risk reduction among injecting drug users: changes in the sharing of injecting equipment and in condom use.

In an investigation of risk behaviour among injecting drug users in the North-West of England, information was obtained concerning the sharing of injecting equipment, respondent's sexual partners and the use of condoms. Between six and nine months after the initial contact, 169 respondents (56%) were contacted again. The emphasis in the second phase of the project was on changes, if any, in risk behaviour that had occurred in the intervening period. Significant reductions were found in sharing, mostly in the more indiscriminate use of others' injecting equipment. No reduction was observed in sharing between injecting partners and little in sharing between close friends. The number of sexual partners had decreased and the use of condoms, although it increased among those involved in temporary relationships, remained low. Impediments to further progress in risk reduction are discussed.

Adolescent

The sharing of injecting equipment among drug users attending prescribing clinics and those using needle-exchanges.

Three groups of injecting drug-users were defined in terms of their experience of methadone treatment: treatment for periods longer than 6 months, treatment for shorter periods, and no treatment. Methadone treatment and the use of needle exchanges were related in subsequent analysis to the sharing of injecting equipment. Comparisons between groups were made on other variables believed to be associated with sharing. Significant differences were observed between treatment groups in the recency of sharing and in the use of needle-exchanges. Age and length of drug use were important factors in sharing, which was least prevalent among older respondents in long-term treatment. Regular use of needle-exchanges was associated with the passing on of used equipment to others. Subsequent analysis of regular users suggested respondents in long-term treatment were less likely to pass on their equipment than those in the other two groups.

Adolescent

Effects of heavy industrial pollution on respiratory function in the children of Cubatao, Brazil: a preliminary report.

Under a cooperative agreement between New York University and the Environmental Protection Agency, and in collaboration with the University of Sao Paulo (USP), a study is ongoing in Cubatao, Brazil, to try to establish exposure-response relationships on the impact of specific industrial effluents on respiratory function in school-age children. Cubatao, located on the coast about 44 km from the city of Sao Paulo, is surrounded by U-shaped mountains (approximately 800 m) covered with subtropical forests. Its area is approximately 160 km2, and it has a population of approximately 90,000. The geography is such that it causes a consistent diurnal land-sea breeze pattern and the opposite during the night, with low dispersion of the air pollutants. In a small area (approximately 40 km2) against the mountains there is a concentration of over 20 large plants: oil refinery; iron and steel mill; fertilizer, cement, and gypsum production; coke kilns; and chemical, paint, and many other ancillary plants. During the 1988 school year, March through June, August through November, 600 six-year-old children, attending six different kindergarten schools, underwent monthly spirometry tests. Because the children live within a 500 m radius of their school, pollution monitors were located on each of the six schools. Particles were collected using dichotomous stacked filter units placed on 20 m towers to reduce the influence of dust from unpaved roads. The units use different pore size filters for coarse, 2 to 10 microns, and fine particles, (dp) less than 2 microns, and took separate samples for day and nighttime.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants

A large outbreak of salmonellosis and its economic cost.

In the summer of 1989, a large outbreak of gastroenteritis occurred in persons attending a barbeque. An investigation was carried out to determine the cause, institute control measures, and to estimate the costs involved in the outbreak. Epidemiological investigation revealed that chicken served at the barbeque was the pecant food, which was confirmed by microbiological investigation. Prompt institution of control measures resulted in early containment of secondary spread. Nevertheless, the total cost of the outbreak amounted to 77,995 pounds. The economic impact of this outbreak was therefore considerable.

Diarrhea

Alcohol treatment of defective lambda lysogens is deletionogenic.

We ascertained that transient exposure to ethanol, above 18%, was deletionogenic to an Escherichia coli strain with a fragment (12.5 kb) of bacteriophage lambda integrated within the chromosome. The lambda attL B.P' through P fragment provided a forward selection for mutants, and a target for mutagenesis. The cells were killed by thermal derepression of transcription and replication of the lambda fragment when transferred from 30 degrees to 42 degrees C. Survivor mutants, capable of forming colonies at 42 degrees C, were selected from untreated starting cells. About half no longer supported marker rescue of the lambda fragment imm lambda (immunity) region, comprising the cI repressor, and the PL and PR promoters. Ethanol treatment of starting cells increased the occurrence of imm lambda-defective clones to near 100%. The mutations responsible for the imm lambda defect were found to be large deletions (12 kb or more of DNA). Ethanol treatment of the starting cells also produced a 5- to 18-fold increase in the occurrence of E. coli pgl mutations, which likely arose by the deletion mechanism generating the imm lambda defects, since pgl was closely linked to the integrated lambda fragment. A unifying hypothesis for these observations was that ethanol was deletionogenic. The inclusion or substitution of the int-kil segment of the lambda fragment produced no real change in the spontaneous occurrence of large imm lambda deletions from the untreated cells. Substitution of this segment suppressed the deletionogenic effect of ethanol, implying a prerequisite for sequence homology or gene function from this interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage lambda

Stimulation of mutations suppressing the loss of replication control by small alcohols.

Transient exposure of lysogenic Escherichia coli cells to small alcohols stimulated the frequency of mutations suppressing the lethal loss of replication control from a prophage fragment of bacteriophage lambda. The stimulation in mutation frequency paralleled the effect of mutagenic agents, and in this sense the alcohols behaved as mutagens. 10-min treatments above distinct threshold concentrations at 23%, 18%, 10% and 4% (v/v) were required in order for methanol, ethanol, isopropanol and propanol to evoke mutagenic effects. The selected mutant cells were, in general, equally or more sensitive to ethanol than the starting cells. The mutagenicity of methanol and ethanol was detected only with E. coli strains with lambda fragments that included the site-specific and general recombination genes found within the phage int-kil gene interval; whereas, stimulation of the frequency of phenotypically identical mutations by nitrosoguanidine or ionizing radiation did not require that the lambda fragment encode these genes. Treatments of lysogenic cells with mutagenic concentrations of ethanol did not trigger prophage induction and were concluded not to induce a cellular SOS response nor to denature the prophage repressor, or to disrupt repressor-operator binding. The toxicity of ethanol was pH-dependent. Cellular sensitivity to ethanol toxicity was unaffected by the integrated lambda fragment(s) or by an intact lambda prophage; but, it was increased by deletions of the E. coli chromosome extending rightward from bio into uvrB, and rightward from chlA.

1-Propanol