Search PubMed⌕ Search

Biomedical subjects

M A Ryan

Publications and source records attributed to M A Ryan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Specific linoleate deficiency in the rat does not prevent substantial carbon recycling from [(14)C]linoleate into sterols.

Compared with classic essential fatty acid deficiency or the feeding of a fat-free diet, little is known about specific linoleate deficiency in the rat. Carbon recycling into de novo lipogenesis has been reported to be an obligatory feature of linoleate metabolism in the liver, even in extreme linoleate deficiency (LA-D). The present study had two objectives: 1) to report a brief summary of the tissue n-6 polyunsaturated fatty acid (PUFA) profiles in specific LA-D, and 2) to quantify whole body carbon recycling from [(14)C]linoleate in specific LA-D. Rats consumed a linoleate-deficient diet for 12 weeks and then received a bolus of [1-(14)C]linoleate by gavage. In linoleate-deficient rats, the triene/tetraene ratio in several organs increased by 18- to 100-fold. The amount of (14)C appearing in organ sterols (dpm/g) of linoleate-deficient rats was 2- to 10-fold higher than in the controls and equaled 16.3% of the [(14)C]linoleate dose given, compared with 7.4% in the controls. We conclude that a similar amount (about 10%) of the carbon skeleton of linoleate is normally recycled into lipids synthesized de novo, as remains in the whole body pool of n-6 polyunsaturates.

Animals↗
PubMed1999

Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression.

Recent data indicate that the heat shock response inhibits nuclear translocation of the proinflammatory transcription factor NF-kappaB. Under basal conditions NF-kappaB is retained in the cytoplasm by an inhibitory protein called I-kappaB which exists as two major isoforms: I-kappaBalpha and I-kappaBbeta. Induction of the heat shock response in BEAS-2B cells, a human cell line representative of bronchial epithelium, increased expression of I-kappaBalpha mRNA in a time-dependent manner. Coincubation with actinomycin-D inhibited heat shock-mediated expression of I-kappaBalpha mRNA. Transient transfection assays with a plasmid containing the reporter gene firefly luciferase, under the control of the human I-kappaBalpha promoter, demonstrated that heat shock activated the I-kappaBalpha promoter. Heat shock-mediated induction of I-kappaBalpha was associated with inhibition of NF-kappaB activation. We conclude that heat shock increases I-kappaBalpha mRNA expression in BEAS-2B cells by activating the I-kappaBalpha promoter, and propose that heat shock-mediated up-regulation of I-kappaBalpha is a potential mechanism by which the heat shock response inhibits proinflammatory responses in lung cells.

Cell Line↗
PubMed1999

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet.

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.

Aged↗
PubMed1998

The heat shock response inhibits RANTES gene expression in cultured human lung epithelium.

The chemokine RANTES is thought to be involved in the pathophysiology of inflammation-associated acute lung injury. Although much is known regarding signals that induce RANTES gene expression, relatively few data exist regarding signals that inhibit RANTES gene expression. The heat shock response, a highly conserved cellular defense mechanism, has been demonstrated to inhibit a variety of lung proinflammatory responses. We tested the hypothesis that induction of the heat shock response inhibits RANTES gene expression. Treatment of A549 cells with TNF-alpha induced RANTES gene expression in a concentration-dependent manner. Induction of the heat shock response inhibited subsequent TNF-alpha-mediated RANTES mRNA expression and secretion of immunoreactive RANTES. Transient transfection assays involving a RANTES promoter-luciferase reporter plasmid demonstrated that the heat shock response inhibited TNF-alpha-mediated activation of the RANTES promoter. Inhibition of NF-kappaB nuclear translocation with isohelenin inhibited TNF-alpha-mediated RANTES mRNA expression, indicating that RANTES gene expression is NF-kappaB dependent in A549 cells. Induction of the heat shock response inhibited degradation of the NF-kappaB inhibitory protein, I-kappaBalpha but did not significantly inhibit phosphorylation of I-kappaBalpha. We conclude that the heat shock response inhibits RANTES gene expression by a mechanism involving inhibition of NF-kappaB nuclear translocation and subsequent inhibition of RANTES promoter activation. The mechanism by which the heat shock response inhibits NF-kappaB nuclear translocation involves stabilization of I-kappaBalpha, without significantly affecting phosphorylation of I-kappaBalpha.

Adenocarcinoma↗
PubMed1998

Induction of the stress response with prostaglandin A1 increases I-kappaBalpha gene expression.

I-kappaBalpha is an intracellular protein that functions as a primary inhibitor of the proinflammatory transcription factor NF-kappaB. Induction of the stress response with heat shock was previously demonstrated to induce I-kappaBalpha gene expression. Because the stress response can also be induced by nonthermal stimuli, we determined whether induction of the stress response with prostaglandin A1 (PGA1) would induce I-kappaBalpha gene expression. Treatment of human bronchial epithelium (BEAS-2B cells) with PGA1 induced nuclear translocation of heat shock factor 1, thus confirming that PGA1 induces the stress response in BEAS-2B cells. Induction of the stress response with PGA1 increased I-kappaBalpha mRNA expression in a time-dependent manner and increased I-kappaBalpha peptide expression. Transient transfection assays involving a human I-kappaBalpha promoter-luciferase reporter construct demonstrated that induction of the stress response with PGA1 activated the I-kappaBalpha promoter. Induction of the stress response with PGA1 and concomitant induction of I-kappaBalpha were associated with inhibition of TNF-alpha-mediated secretion of interleukin 8 and with inhibition of TNF-alpha-mediated nuclear translocation and activation of NF-kappaB. These data demonstrate that induction of the stress response, by a nonthermal stimulus, increases I-kappaBalpha gene expression by a mechanism involving activation of the I-kappaBalpha promoter. Coupled with previous data demonstrating heat shock-mediated induction of I-kappaBalpha gene expression, these data suggest that I-kappaBalpha may be considered to be one of the stress proteins. The functional consequences of stress response-mediated I-kappaBalpha gene expression may involve attenuation of cellular proinflammatory responses.

Cell Line, Transformed↗
PubMed1998

Increased expression of heat shock protein-70 protects A549 cells against hyperoxia.

Acute and chronic lung injury secondary to hyperoxia remains an important complication in critically ill patients, and, consequently, there is interest in developing strategies to protect the lung against hyperoxia. Heat shock proteins (HSPs) confer protection against a broad array of cytotoxic agents. In this study, we tested the hypothesis that increased expression of the 70-kDa HSP (HSP70) would protect cultured human respiratory epithelium against hyperoxia. Recombinant A549 cells were generated in which human HSP70 was increased by stable transfection with a plasmid containing human HSP70 cDNA under control of the cytomegalovirus promoter (A549-HSP70 cells). A549-HSP70 cells exposed to hyperoxia had greater acute survival rates and clonogenic capacity compared with wild-type A549 cells and with control cells stably transfected with the empty expression plasmid. Hyperoxia-mediated lipid peroxidation and ATP depletion were also attenuated in A549-HSP70 cells exposed to hyperoxia. Increased expression of HSP70 did not detectably alter mRNA levels of the intracellular antioxidants manganese superoxide dismutase, catalase, and glutathione peroxidase. Collectively, these data demonstrate a specific in vitro protective role for HSP70 against hyperoxia and suggest that potential mechanisms of protection involve attenuation of hyperoxia-mediated lipid peroxidation and ATP depletion.

Adenocarcinoma↗
PubMed1998

Substantial carbon recycling from linoleate into products of de novo lipogenesis occurs in rat liver even under conditions of extreme dietary linoleate deficiency.

A significant portion of the beta-oxidized carbon skeleton of some polyunsaturated fatty acids can be recycled into de novo lipogenesis, i.e., cholesterol, saturates and monounsaturates. The recycling of carbon from linoleate was quantified in liver lipids of severely linoleate-deficient rats to determine whether it is more likely to be a function of redundancy or could be obligatory. After 13 wk on a control (2 energy % linoleate) or severely linoleate-deficient (<0. 05 energy % linoleate) diet, 7 muCi [1-14C]linoleate was given by gavage and the rats were killed 48 h later. A second linoleate-deficient group received an oral bolus of 256 mg linoleate as a supplement with the radiotracer. In comparison to the controls, 14C recovery in liver total lipids of the linoleate deficient group was increased about 5-fold with increased dpm/g in linoleate (13.7-fold higher), arachidonate (2.7-fold higher) and products of de novo lipogenesis (3.5-fold higher). In livers of control rats, 14C distribution was: 41% arachidonate, 29% linoleate, 22% sterols, 3% oleate, 3% palmitate, and 2% stearate. In livers of linoleate-deficient rats, 14C distribution was: 63% linoleate, 19% arachidonate, 11% sterols, 4% oleate, 3% palmitate, and <1% stearate. Thus, in controls, equivalent amounts of 14C were in products of de novo lipogenesis as in linoleate (29-30%), and in livers of linoleate-deficient rats, a similar proportion of 14C was in products of de novo lipogenesis as was converted to arachidonate (18-19%). We conclude that carbon recycling into de novo lipogenesis accounts for a significant, obligatory component of linoleate metabolism even during extreme linoleate deficiency.

Animals↗
PubMed1997

BOX-polymerase chain reaction-based DNA analysis of nonserotypeable Streptococcus pneumoniae implicated in outbreaks of conjunctivitis.

Nonserotypeable isolates predominate in epidemic conjunctivitis caused by Streptococcus pneumoniae. Previous evaluations of outbreaks of pneumococcal conjunctivitis have relied on epidemiologic factors and the nontypeability of the isolates to infer that a single clone was involved. In the present study, BOX-polymerase chain reaction DNA analysis was used to characterize nonserotypeable S. pneumoniae isolated by conjunctival culture during a recent conjunctivitis outbreak and to compare these isolates with those from outbreaks described earlier. The recent outbreak was caused by a single pneumococcal clone. Outbreaks in separate parts of the United States in 1980-1981 were all caused by the same clone. Cluster analysis revealed a high degree of genetic relatedness among isolates causing conjunctivitis compared with that among other nonserotypeable S. pneumoniae, with the closest relatedness being found among the 1996 and 1980-1981 conjunctival isolates.

Conjunctivitis↗
PubMed1996

Tuberculosis in the workplace: OSHA's compliance experience.

OBJECTIVE: Inspections of 272 facilities were performed between May 1992 and October 1994 to determine compliance with applicable Occupational Safety and Health Administration (OSHA) requirements for prevention of tuberculosis (TB) transmission. DESIGN: Retrospective record review of two data sources: (1) OSHA's Computerized Integrated Management Information System and (2) an inspector-completed questionnaire on inspection results. SETTING/PARTICIPANTS: Inspections of five types of facilities: healthcare institutions, correctional facilities, homeless shelters, long-term-care facilities for the elderly, and others, including drug treatment centers that the Centers for Disease Control and Prevention (CDC) identified as having a higher than expected rate of TB. METHODS: The OSHA Compliance Memorandum, based on the 1990 CDC Guidelines, which outlined elements of a TB prevention program, was used in performing 272 inspections of facilities between May 1992 and October 1994. Elements of compliance were recorded and reviewed from the IMIS database and inspectors' questionnaires. RESULTS: Regulated facilities were not fully compliant with OSHA guidance. Generally, healthcare facilities performed better than other facilities. Most facilities (79%) were compliant with administrative elements of a comprehensive TB control program, such as early identification of known or suspected infectious TB patients and skin testing of workers. Only 29% of inspected facilities were found to have acceptable respiratory protection programs for the prevention of occupational TB. CONCLUSION: Facilities have not been fully compliant with the OSHA memorandum describing protection of workers from TB. Facility compliance was better with some traditionally recognized TB infection control elements, but was weaker in the area of respiratory protection programs. This may reflect a lack of familiarity with the latter type of hazard protection.

Facility Regulation and Control↗
PubMed1995

Synthesis of linoleate and alpha-linolenate by chain elongation in the rat.

The objective was to determine whether rats could synthesize longer chain polyunsaturates from hexadecadienoate (16:2n-6) and hexadecatrienoate (16:3n-3). Rats were gavaged with uniformly 13C-labelled hexadecadienoate or hexadecatrienoate, euthanized 24 h later, and total lipids were extracted from liver and carcass. Gas chromatography/combustion/isotope ratio mass spectrometry was used to measure 13C levels in individual liver, carcass, and whole body fatty acids. 13C Enrichment was present in desaturated and chain-elongated polyunsaturates, including linoleate, arachidonate, alpha-linolenate, and docosahexaenoate at 12-13% of the dose of tracer given. 13C Enrichment from hexadecatrienoate was highest in carcass and liver alpha-linolenate, representing 3.5 and 17.9% of the total alpha-linolenate pool, respectively. For linoleate, arachidonate, or docosahexaenoate, the contribution of 13C did not exceed 0.2% of the total body pool. Green leafy vegetables common in the human diet were shown to contain up to 1.2% of total fatty acids as hexadecadienoate and 11.6% as hexadecatrienoate. Hence, humans consuming green vegetables probably synthesize a small proportion of their total body content of linoleate and alpha-linolenate.

Animals↗
PubMed1995

Assessment of pain in advanced cancer patients.

This study tested the feasibility of standardized pain assessment instruments in a population of patients with far advanced cancer at the time of admission to a specialty hospital. As pain is a symptom, pain control must be based on patients' self-report. Cognitive impairment and severe physical illness, however, limited the ability to use these tools. Almost one-half (44.8%) of the patients were unable to use the McGill-Melzack Pain Questionnaire, the Memorial Pain Assessment Card, or the Faces Pain Rating Scale. Patients with far advanced cancer fall into three groups: those who report pain, those who report no pain, and those who are unable to state whether or not they have pain. This study demonstrates the need to undertake pain assessment while the patient is able to respond and to monitor behaviors that could be indicative of changes in pain.

Aged↗
PubMed1995

The new reproductive technologies: defying God's dominion?

Objections that the New Reproductive Technologies pose temptations to "play God" are common. This essay examines three versions of the objection: 1) these technologies "usurp God's dominion in reproduction"; 2) they permit us to "make" our offspring; and 3) they involve us in a denial of human finitude. None proves to generate a decisive case against the New Reproductive Technologies; each requires some further argument to be persuasive. Nonetheless, warning not to "play God" are shown to have an important parenetic function in the debate over medically-assisted reproduction, occasioning needed reflection on the meaning of creatureliness, finitude and responsible co-creation in the context of new forms of reproduction.

Catholicism↗
PubMed1994

Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.

Aged↗
PubMed1990

Thiol protease-thiol protease inhibitor imbalance in cardiac tissue of ageing cardiomyopathic hamsters.

In cardiomyopathic hamsters myofibrillar lesions and loss of muscle specific proteins occur in the heart early in life, and it has been suggested that intracellular proteases are involved in the process of muscle necrosis. In the age-dependent study reported here, we observed that cardiac tissue of dystrophic hamsters contains 30-100% more thiol protease activity than normal hamsters, with the greatest differences found in hearts of older animals. As well, the ratio of thiol protease activity in dystrophic hearts compared to normal hearts increases by 1.5-fold and 2.7-fold, respectively in the lysosomal and non-lysosomal fractions between 1.4 and 14 months of age. Cathepsin B accounted for over 90% of the thiol protease activity in the lysosomal fraction of both normal and dystrophic hamster hearts. In contrast, cardiac tissue of 3 to 14 month old dystrophic hamsters contains 20-45% less thiol protease inhibitor activity than hearts from age-matched normal hamsters. These results demonstrate that at an early age (1.4 to 3 months) an imbalance occurs between the thiol protease activity and thiol protease inhibitor content of cardiac tissue of dystrophic hamsters, which becomes more severe in older animals and associated with progressive myofibrillar lesions and tissue necrosis.

Aging↗
PubMed1990

Hospitalized advanced cancer patients: a profile.

More than half of all individuals diagnosed with cancer will not be cured and will require supportive care for some period. Nonetheless, few large scale studies have documented the prevalence and complexity of the problems of advanced disease. This study examined the demographic treatment and outcome variables for 1,103 admissions to a specialty acute care hospital devoted to the care of patients with advanced cancer. The population is profiled, and significant relationships among these variables are identified. The prevalence of major symptoms is documented. This data base study provides a foundation for further research.

Activities of Daily Living↗