Search PubMed⌕ Search

Biomedical subjects

L M Ryan

Publications and source records attributed to L M Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Overfeeding fat as monoglyceride or triglyceride: effect on appetite, nutrient balance and the subsequent day's energy intake.

OBJECTIVE: To examine the effect of overfeeding isoenergetic diets enriched in 1-monoglyceride or triglyceride on nutrient oxidation and appetite throughout the day that it was given and the subsequent day's food and energy intake. DESIGN: Six men [mean (s.d.) weight; 76.89 (7.00) kg, height; 1.77 (0.05) m, age; 26.4 (6.0) y], were each studied twice in a 3 d protocol. On day 1 (maintenance day) they were fed a medium fat (MF) maintenance diet (MF: 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6 x resting metabolic rate (RMR). Subjects entered the calorimeter at 06.30 on day 2 for 49.5 h. On day 2 (manipulation day) subjects consumed a MF diet at 1.6 x RMR with an additional 0.45 x RMR as either 1-monoglyceride or triglyceride. On day 3 (outcome day), subjects had ad libitum access to isoenergetic, isoenergetically dense MF (40 :47: 13, 550 kJ/ 100 g) foods. Subjective hunger and satiety were tracked hourly, during waking hours throughout days 1-3. RESULTS: There was no significant effect of diet on nutrient oxidation or balance either during day 2 (manipulation day) or day 3 (outcome day), fat oxidation was similar on both diets. Subjective hunger was not affected by diet on either day with mean values of 34.3 and 35.0 mm (SED 5.2) on manipulation day (day 2) and outcome day (day 3), 35.3 and 40.8 mm (SED 5.2) on the 1 -monoglyceride or triglyceride diets respectively. Day 3 food and energy intake were unaffected by the previous day's dietary treatment, with mean intakes of 15.9 and 15.6 MJ (SED 1.07) on the 1-monoglyceride or triglyceride treatments, respectively. CONCLUSIONS: This study suggests that when 1-monoglyceride is covertly incorporated into a diet at unusually high levels, it behaves in a manner that is very similar to triglyceride, in its effects on appetite, feeding behaviour and net nutrient balance.

Adult↗
PubMed1998

Basic calcium phosphate crystal-induced collagenase production: role of intracellular crystal dissolution.

OBJECTIVE: To investigate the potential therapeutic effects of inhibiting intracellular dissolution of basic calcium phosphate (BCP) crystals in tissue culture by raising lysosomal pH using bafilomycin A1, a specific vacuolar pump inhibitor. DESIGN: 45Ca-labeled crystals were used to demonstrate intracellular crystal dissolution in human foreskin fibroblasts (HF). Mitogenesis was evaluated using [3H]thymidine incorporation assays and cell counts. Northern blot and Western blot were used to study collagenase [matrix metalloproteinase-1 (MMP1)] mRNA accumulation and protein secretion, respectively. RESULTS: Bafilomycin A1 inhibited intracellular dissolution of BCP crystals and caused a concentration-dependent inhibition of BCP crystal-induced mitogenesis. Doses of bafilomycin A1 which inhibited intracellular crystal dissolution and mitogenesis had no effect on BCP crystal-induced MMP1 mRNA accumulation or protein secretion. CONCLUSION: Raising lysosomal pH to inhibit intracellular BCP crystal dissolution attenuates the proliferative response to BCP crystals in HF but does not prevent metalloprotease synthesis and secretion. The therapeutic potential of lysosomotropic agents for preventing joint destruction in BCP crystal deposition disease is limited.

Anti-Bacterial Agents↗
PubMed1998

Reproductive hormone profile among pesticide factory workers.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.

Adult↗
PubMed1998

Basic calcium phosphate crystals induce synthesis and secretion of 92 kDa gelatinase (gelatinase B/matrix metalloprotease 9) in human fibroblasts.

OBJECTIVE: Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe joint degeneration accompanied by synovial hypertrophy. The metalloprotease 92 kDa gelatinase (MMP-9) has been implicated in the degradation of extracellular matrix in osteoarthritis, but the ability of BCP crystals to induce gelatinase in human fibroblasts or in adult porcine chondrocytes has not previously been studied. The hypothesis that the mitogenic response to BCP crystals is accompanied by induction and secretion of MMP-9 was studied. METHODS: MMP-9 messenger RNA (mRNA) was detected by northern blot and reverse transcription-polymerase chain reaction (RT-PCR). Gelatinase secretion was identified by western blot and zymography of conditioned media. RESULTS: BCP crystals caused a concentration dependent induction of MMP-9 mRNA accumulation and protein secretion in human fibroblasts but not in adult porcine chondrocytes. CONCLUSION: BCP crystals induce MMP-9 production by HF but not adult porcine chondrocytes. Fibroblast MMP-9 may be an important mediator of the joint destruction associated with synovial fluid BCP crystals.

Animals↗
PubMed1998

Testing for trend with count data.

Among the tests that can be used to detect dose-related trends in count data from toxicological studies are nonparametric tests such as the Jonckheere-Terpstra and likelihood-based tests, for example, based on a Poisson model. This paper was motivated by a data set of tumor counts in which conflicting conclusions were obtained using these two tests. To define situations where one test may be preferable, we compared the small and large sample performance of these two tests as well as a robust and conditional version of the likelihood-based test in the absence and presence of a dose-related trend for both Poisson and overdispersed Poisson data. Based on our results, we suggest using the Poisson test when little overdispersion is present in the data. For more overdispersed data, we recommend using the robust Poisson test for highly discrete data (response rate lower than 2-3) and the robust Poisson test or the Jonckheere-Terpstra test for moderately discrete or continuous data (average responses larger than 2 or 3). We also studied the effects of dose metameter misspecification. A clear effect on efficiency was seen when the 'wrong' dose metameter was used to compute the test statistic. In general, unless there is strong reason to do otherwise, we recommend the use of equally spaced dose levels when applying the Poisson or robust Poisson test for trend.

Animals↗
PubMed1998

Serum nucleotide pyrophosphohydrolase activity; elevated levels in osteoarthritis, calcium pyrophosphate crystal deposition disease, scleroderma, and fibromyalgia.

OBJECTIVE: Quantification of serum nucleotide pyrophosphohydrolase (NTPPHase) activity in healthy subjects and in patients with various rheumatic diseases or with quad/hemiplegia, hemodialysis, or renal transplant. METHODS: Colorimetric assay of enzyme activity in serum. RESULTS: Serum NTPPHase activity in 85 healthy subjects was independent of age or sex and was highly reproducible in each individual. The biologic and methodologic coefficients of variation were nearly identical. Elevated enzyme levels were found in sera from patients with osteoarthritis/spondylosis, calcium pyrophosphate dihydrate (CPPD) crystal deposition, scleroderma, fibromyalgia, or hemodialysis. Renal transplant patients receiving cyclosporine had the highest enzyme activity of any group, whereas transplant patients not taking this drug had normal levels. Histograms of values in all groups showed a normal distribution. CONCLUSION: Serum NTPPHase activity levels were significantly elevated in patients with degenerative arthritis whether or not CPPD crystals were present, in patients with either scleroderma or fibromyalgia, and in patients receiving hemodialysis therapy or taking cyclosporine.

Chondrocalcinosis↗
PubMed1997

Molecular cloning and expression of a porcine chondrocyte nucleotide pyrophosphohydrolase.

The porcine 127-kDa nucleotide pyrophosphohydrolase (NTPPHase) had been previously purified from the conditioned culture media of porcine articular cartilage. Protein sequencing of an internal 61-kDa proteolytic fragment of NTPPHase (61-kDa NTPPHase) determined the 26 N-terminal amino acids. This sequence was used to amplify a DNA fragment, which was used as a probe to clone the gene encoding the 61-kDa NTPPHase from a porcine chondrocyte cDNA library. DNA sequence analysis showed the cDNA insert to be 2509 bp, corresponding to a predicted open reading frame (ORF) encoding 599 amino acids. The 26 N-terminal amino acids of the 61-kDa NTPPHase were located within the ORF immediately downstream of a putative protease recognition region, RRKRR. This is consistent with this cDNA insert representing an internal proteolytic fragment of the full length 127-kDa NTPPHase. BLAST and FASTA analysis confirmed that the deduced amino acid sequence of 61-kDa NTPPHase was unique and did not possess a high degree of homology to sequence in the non-redundant protein and nucleotide databases. Proteins that possess limited homology (< 17%) with the 61-kDa NTTPPHase include several prokaryotic and eukaryotic ATP pyrophosphate-lyases (adenylate cyclase). Northern blot analysis of porcine chondrocyte RNA showed that the DNA encoding the 61-kDa NTPPHase hybridized to a single 4.0-kb RNA transcript. This DNA probe also hybridized to a single species of human chondrocyte RNA. Expression of a 61-kDa protein was detected by coupled in-vitro transcription/translation. Western blot analysis of this in-vitro transcription/translation reaction detected a 61-kDa protein, using an antibody raised against the peptide sequence that was originally used to clone the 61-kDa NTPPHase. These data indicate the successful in-vitro cloning and expression of the porcine chondrocyte 61-kDa NTPPHase. Future studies that utilize the gene encoding the 61-kDa NTPPHase may allow the characterization of the role of NTPPHase in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease.

Amino Acid Sequence↗
PubMed1997

Evaluation of effect profiles: Functional Observational Battery outcomes.

The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects.

Animals↗
PubMed1997

Modeling injury outcomes using time-to-event methods.

BACKGROUND: Mortality is an important measurement of injury outcomes, but measurements reflecting disability or cost are also important. Hospital length of stay (LOS) has been used as an outcome variable, but reduced LOS could be achieved either by improved care or by increased mortality. A solution to this statistical problem of "competing risks" would enable injury outcomes based on LOS to be modeled using time-to-event methods. METHODS: Time-to-event methodology was applied to 2,106 cases with complete data from the 1991-1994 registry of a regional trauma center. LOS was used as the outcome variable, modified by assigning an arbitrarily long LOS to any fatal case. A combination of proportional hazards and logistic regression models was used to explore the effects of potential predictive variables, including Trauma Score (TS), Injury Severity Score (ISS), components of TS or ISS, age, sex, alcohol use, and whether a patient was transferred. RESULTS: The "TRISS" combination of TS, ISS, and age previously shown to predict mortality also predicted "modified LOS" (Wald p value less than 0.001 for each variable). Models using only age and certain components of ISS or TS fit our data even better, with fewer parameters. Other variables were not predictive. Modified Kaplan-Meier plots provided easily interpreted graphical results, combining both mortality and LOS information. CONCLUSIONS: With a simple modification to allow for competing risks, time-to-event methods enable more informative modeling of injury outcomes than binary (lived/died) methods alone. Such models may be useful for describing and comparing groups of hospitalized trauma patients.

Female↗
PubMed1997

Milwaukee shoulder with massive bilateral cysts: effective therapy for hydrops of the shoulder.

"Milwaukee shoulder" is often associated with large effusions that cannot be managed with conventional therapy. We describe a 75-year-old man whose massive hydrops of both shoulders was resistant to treatment with nonsteroidal antiinflammatory drugs (NSAID), multiple aspirations, and injections of corticosteroid. The effusions resolved completely after treatment with oral colchicine and an NSAID containing magnesium.

Aged↗
PubMed1996

Inhibition of calcium pyrophosphate dihydrate crystal formation in articular cartilage vesicles and cartilage by phosphocitrate.

Articular cartilage vesicles (ACV), isolated by differential centrifugation of adult hyaline articular cartilage collagenase digests, mineralized in the presence of calcium and ATP. Mineral analysis by microscopy, chemical analysis, energy-dispersive analysis, and infrared spectroscopy revealed crystals resembling calcium pyrophosphate dihydrate (CPPD). Adult articular cartilage also underwent ATP-dependent mineralization, supporting the contention that vesicles in situ fostered adult articular cartilage mineralization. Phosphocitrate (PC) is a recognized in vitro inhibitor of hydroxyapatite and calcium oxalate monohydrate crystal formation, but it is not known whether PC can similarly restrict CPPD crystal development. In the present study we examine the effect of PC, citrate, and n-sulfo-2-amino-tricarballylate (SAT, a PC analogue) on the ATP-induced CPPD crystal formation in both ACV and articular cartilage models. Only PC (10-1000 microM) blocked both the ATP-dependent and -independent mineralization in ACV in a dose-dependent fashion. At 1 mM, SAT and citrate blocked the ATP-independent mineralization. Similarly, only PC blocked both the ATP- and non-ATP-dependent mineralization in native articular cartilage slices. PC, SAT, and citrate had no effect on ACV nucleoside triphosphate pyrophosphohydrolase activity, suggesting that none of these agents blocked mineralization through the inhibition of nucleoside triphosphate pyrophosphohydrolase activity, which generates inorganic pyrophosphate from ATP.

Adenosine Triphosphate↗
PubMed1996

A semiparametric approach to risk assessment for quantitative outcomes.

Characterizing the dose-effect relationship and estimating acceptable exposure levels are the primary goals of quantitative risk assessment. A semiparametric approach is proposed for risk assessment with continuously measured or quantitative outcomes which has advantages over existing methods by requiring fewer assumptions. The approach is based on pairwise ranking between the response values in the control group and those in the exposed groups. The work generalizes the rank-based Wilcoxon-Mann-Whitney test, which for the two-group comparison is effectively a test of whether a response from the control group is different from (larger than) a response in an exposed group. We develop a regression framework that naturally extends this metric to model the dose effect in terms of a risk function. Parameters of the regression model can be estimated with standard software. However, inference requires an additional step to estimate the variance structure of the estimated parameters. An effective dose (ED) and associated lower confidence limit (LED) are easily calculated. The method is supported by a simulation study and is illustrated with a study on the effects of aconiazide. The method offers flexible modeling of the dose effect, and since it is rank-based, it is more resistant to outliers, nonconstant variance, and other departures from normality than previously described approaches.

Animals↗
PubMed1996

Head injury in a college population: analysis of epidemiological factors.

Head injuries are frequent occurrences, and the majority are considered mild Most epidemiological studies have used hospitalized cases, and, as a result, those who sustain a head injury but do not receive intensive medical attention are not considered It can be assumed that those not receiving medical attention most likely sustained mild head injuries A few researchers have examined self-reported head injury, but the data is still limited Little is known about those individuals who incur head trauma and resume normal functioning without treatment The purpose of this study was to identify and describe the epidemiological correlates of head injury within a young high functioning population The present study examined head injury and its associated factors in a college sample, which included such areas as demographics, nature of head injury, and prevalence of postconcussion symptoms.

Journal Article↗
PubMed1996

Comparison of matrix vesicles derived from normal and osteoarthritic human articular cartilage.

Articular cartilage matrix vesicles (MVs) from normal human adult articular cartilage were examined for protein and enzyme content and biomineralizing capacity for comparison to MVs derived from human osteoarthritic (OA) cartilage. Femoral condylar and tibial plateau cartilage from each of 9 healthy donors ages 17-37 y was enzymatically digested and serially ultracentrifuged to pellet MV's at 3 x 10(6) g-min. MV protein content, nucleoside triphosphate pyrophospho hydrolase (NTPPPH) specific activity (SA) and capacity for 45Ca precipitation were determined. MV precipitated mineral was examined using Fourier transform infrared spectroscopy (FTIR). Normal human cartilage yields 50% less MV protein/g cartilage than OA cartilage (p < .01). Normal human articular MVs possess 30-70x higher NTPPPH SA than cell-free digest. Mean NTPPPH SAs of MVs derived from normal human cartilage are 3x higher than that of OA MVs (p < .05) and normal MV NTPPPH SA appears to decrease with age (p < .01). Normal human MVs support significantly higher calcium precipitation/mg MV protein in both ATP-dependent (p < .01) and -independent (p = .05) systems. The FTIR spectrum of MV mineral generated in the presence of ATP strongly resembles the standard spectrum for calcium pyrophosphate dihydrate (CPPD). The FTIR spectrum of MV mineral generated without ATP resembles that of carbonate-substituted apatite (AP). The fact that isolated MVs from normal cartilage generate pathologically relevant crystal phases in vitro implies that matrix integrity and substrate availability may be crucial factors in the control of pathologic biomineralization.

Adolescent↗
PubMed1996

Latent variable models with fixed effects.

We discuss latent variable models that allow for fixed effect covariates, as well as covariates affecting the latent variable directly. Restricted maximum likelihood and maximum likelihood are used to estimate model parameters. A generalized likelihood ratio test can be used to test significance of the covariates effecting the latent outcomes. Special cases of the proposed model correspond to factor analysis, mixed models, random effects models, and simultaneous equations. The model is applied to birth defects data, where continuous data on the size of infants who were exposed to anticonvulsant medications in utero are compared to controls.

Algorithms↗
PubMed1996

Adenosine triphosphate levels in human plasma.

OBJECTIVE: To quantify extracellular adenosine triphosphate (ATP) levels in human platelet-poor plasma as a potential source of synovial fluid ATP, and to determine variables affecting these levels. METHODS: ATP was measured by the specific luciferase method; platelet beta thromboglobulin was determined by radioimmunoassay. The effects of fasting, feeding, venipuncture, and muscular exercise were determined by serial venipuncture in healthy subjects. Diurnal variation was determined by serial sampling through indwelling venous catheters in 3 healthy subjects and 3 women with knee osteoarthritis. RESULTS: Unlike beta thromboglobulin levels, which did not change, an invariable marked (mean 58%) fall in plasma ATP was noted 15 min after the first venipuncture, whether the subject had eaten or not. Indomethacin treatment had no effect on this phenomenon. Exercise of forearm muscles had no effect on plasma ATP. The drop in plasma ATP occurred between 3 and 15 min, with recovery at about 90 min. A diurnal variation in plasma ATP was found with trough levels at noon and at night during sleep. CONCLUSION: The predictable sharp fall in plasma ATP levels induced by venipuncture and the clear diurnal variation suggest that plasma contains ATP independent of platelet dense body release and endothelial cell needle trauma. Synovial plasma flow at peak (600 nM) levels is insufficient to provide more than one-third of the extracellular ATP needed to generate inorganic pyrophosphate in articular tissues.

Adenosine Triphosphate↗
PubMed1996

Use of historical controls in time-adjusted trend tests for carcinogenicity.

We develop a method for incorporating historical control information into time-adjusted tests for dose effects in carcinogenicity studies. After discretizing the time scale, we use a multinomial distribution to model the number of animals dying with tumor in each interval. Data from past studies are used to estimate the parameters characterizing the prior. A score test derived from the resulting Dirichlet-multinomial generalizes the test of Tarone (1982, Biometrics 38, 215-220) and reduces, in the limit, to the log-rank test in the case of a diffuse prior. The methodology is illustrated with data from a study of the fire retardant 2,2-Bis(bromomethyl)-1,3-propanediol.

Animals↗