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Biomedical subjects

M J Ryan

Publications and source records attributed to M J Ryan.

At least 19 recordsLinked to original sources

Animal communication: complex call production in the túngara frog.

Animals' sound-producing organs often act as an integrated whole--particular vocal structure are not directly associated with the creation of discrete syllables. But here we show that the 'chuck' of the 'whine-chuck' mating call of the túngara frog, Physalaemus pustulosus, is caused by a fibrous mass attached to the vocal folds; the chuck is eliminated by removal of this structure, although the frog still tries to produce the sound. Sexual selection affects the acoustic complexity of the frog's call, so evolution may have shaped this unusual vocalization, which is akin to the two-voiced song of songbirds.

Animals↗

Temporal trends of organochlorine contaminants in burbot and lake trout from three selected Yukon lakes.

Historical studies have demonstrated that organochlorine (OC) concentrations in top predators can vary considerably from lake to lake within a small geographic region but temporal trends of these contaminants have rarely been monitored in a sub-Arctic area for a long period of time. This study examined OC concentrations, including chlordane (CHL), DDT, hexachlorocyclohexane (HCH), toxaphene (CHB), PCB and chlorinated benzenes (CBz) in lake trout and burbot, from three Yukon lakes (Laberge, Kusawa, Quiet), over a span of 11 years (1992-2003). Temporal and spatial differences continue to exist in the OC concentrations of burbot and lake trout between these lakes. There is strong evidence that these contaminants are declining at various rates in lake trout (Salveninus namaycush) in Laberge, Kusawa and Quiet Lakes. For example, SigmaDDT concentrations have decreased 39%, 85% and 84% in Kusawa, Quiet and Laberge Lakes, respectively. Conversely, no consistent trends were observed in OC concentrations for burbot (Lota lota). For example, there is no evidence of a decline in toxaphene concentrations of Kusawa burbot yet a 58% decrease was observed in Laberge samples. Increases were also observed in the SigmaHCH levels of Kusawa Lake burbot, as well as increases in all OC groups (except SigmaHCH) for the Quiet Lake burbot samples. Decreases in burbot were evident in SigmaHCH and SigmaCHB for Lake Laberge fish and in SigmaCHL for Kusawa Lake samples. Spatial variations in OC levels are quite evident as Lake Laberge trout and burbot continued to maintain the highest levels over the eleven-year period from 1992 to 2003 followed by Kusawa Lake and then Quiet Lake. These differences were related to a variety of factors especially the species morphological characteristics such as log age, log weights and fish lipid content. A decreasing trend in Quiet and Laberge Lake trout lipid content, coupled with fluctuating condition factors and increases in body masses, suggest biotic changes may be occurring within the food webs due to fish population variations related to the cessation of commercial fishing or potentially an increase in lake plankton productivity related to annual climate variation. It is suspected that biotic factors rather than atmospheric inputs are the primary factors affecting the contaminant concentrations in lake trout and burbot in the study lakes.

Animals↗

Transgenic mice for studies of the renin-angiotensin system in hypertension.

Hypertension is a polygenic and multi-factorial disorder that is extremely prevalent in western societies, and thus has received a great deal of attention by the research community. The renin-angiotensin system has a strong impact on the control of blood pressure both in the short- and long-term, making it one of the most extensively studied physiological systems. Nevertheless, despite decades of research, the specific mechanisms implicated in its action on blood pressure and electrolyte balance, as well as its integration with other cardiovascular pathways remains incomplete. The production of transgenic models either over-expressing or knocking-out specific components of the renin-angiotensin system has given us a better understanding of its role in the pathogenesis of hypertension. Moreover, our attention has recently been refocused on local tissue renin-angiotensin systems and their physiological effect on blood pressure and end-organ damage. Herein, we will review studies using genetic manipulation of animals to determine the role of the endocrine and tissue renin-angiotensin system in hypertension. We will also discuss some untraditional approaches to target the renin-angiotensin system in the kidney.

Animals↗

Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C.

BACKGROUND AND AIM: In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment naïve patients with chronic hepatitis C virus (HCV). METHODS: In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment. RESULTS: At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects. CONCLUSION: Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.

Adult↗

Thirteen-week inhalation toxicity of N,N-dimethylformamide in F344/N rats and B6C3F1 mice.

Male and female F-344 rats and B6C3F1 mice (10/sex/group) were exposed to N,N-dimethylformamide (DMF) by whole body inhalation exposure at 0, 50, 100, 200, 400, or 800 ppm, 6 h/day, 5 days/week, for 13 weeks. A concentration-dependent depression in body weight occurred in rats of both sexes at 400 (6-11%) and 800 ppm (20-22%). In contrast, all weight changes in both sexes of mice were within 10% of controls. No rats died, while 5 mice died from nonexposure-related causes. Relative liver weights were significantly increased at all DMF concentrations in both sexes and both species. Activities of serum sorbitol dehydrogenase (SDH) were statistically increased in male and female rats (200 to 800 ppm) on study days 4, 24, and 91 (13 weeks). Activities of alanine aminotransferase (ALT) and isocitrate dehydrogenase (ICD) were statistically increased in both sexes of rats exposed to 800 ppm DMF at all time points. Cholesterol (CHOL) levels were statistically increased in male and female rats (50-800 ppm) at all sampling time points. Levels of total bile acids (TBA) were statistically increased in both sexes of rats (400-800 ppm) on days 24 and 91. Centrilobular hepatocellular necrosis (minimal to moderate) was seen in rats of both sexes exposed at 400 and 800 ppm, with the lesions more severe in females. Centrilobular hepatocellular hypertrophy (minimal to mild) was found in all groups of DMF-exposed male mice, and in female mice exposed at 100-800 ppm. For male and female rats the no-observed-adverse-effect concentration (NOAEC) for microscopic liver injury was 200 ppm. The NOAEC was 50 ppm for female mice, but an NOAEC based upon the absence of microscopic liver injury was not determined in male mice.

Administration, Inhalation↗

Phenotypic degeneration occurs during sector formation in Metarhizium anisopliae.

AIMS: The formation of sectors was observed during subculturing of an isolate of the entomopathogenic fungus Metarhizium anisopliae, a fungus used for biological control of insect pests. The aim of the investigation was to establish whether sector formation was accompanied by changes in physiological characters. METHODS AND RESULTS: Four degenerative morphological states, with reduced sporulation capacity, were characterized. Subcultures were taken from each sector and four new culture lines established. The new lines were further subcultured every 21 d. A physiological assessment of each line was undertaken after 42 d using TLC of secondary metabolites and fluorogenic enzyme tests. Full sporulation capacity was not regained on subculture, although some cultures recovered partially. Changes in secondary metabolite profiles and the loss in detection of activity of specific enzymes were observed. CONCLUSIONS: Sector formation was frequently accompanied by changes in the ability to produce secondary metabolites and enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results illustrate the importance of maintaining the stability of important cultures during routine subculture. The consequences could have significant implications if degenerate cultures are used as inocula for liquid fermentation cultures or industrial scale production.

Enzymes↗

Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate.

Methylene blue trihydrate is used widely as a dye and therapeutic agent. Methylene blue was administered by gavage to 30 animals/sex/dose group in a 0.5% aqueous methylcellulose suspension at doses of 0, 25, 50, 100, and 200 mg/kg. Blood samples from 10 animals/sex/dose group were collected at the end of study weeks 1, 6, and 13. Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. There was a dose-related increase in absolute and relative spleen weight for both species. Microscopic examination revealed increased splenic hematopoiesis in all mice treatment groups and in rats at the 50 mg/kg dose level and above. Splenic congestion and bone marrow hyperplasia were also observed in these rat-dose groups. Mice at the higher doses showed hematopoiesis in the liver and accumulation of hemosiderin in Kupffer cells. These gross and microscopic findings are consistent with the development of hemolytic anemia. A dose-related increase in the reticulocyte count during study weeks 6 and 13 suggested a compensatory response to anemia.

Anemia↗

Comparative gavage subchronic toxicity studies of o-chloroaniline and m-chloroaniline in F344 rats and B6C3F1 mice.

ortho-Chloroaniline (o-CA) andmeta-chloroaniline (m-CA) are chemical intermediates for pigment production in the textile industry. Comparative subchronic gavage studies were conducted to determine the effect of structure on toxicity.o-CA orm-CA was administered to 10 animals/sex/species in deionized water at dosages of 0, 10, 20, 40, 80, and 160 mg/kg for 13 weeks. Blood samples for clinical pathology were collected after 3 and 23 days in rats and at study termination (Day 93) in rats and mice. No mortalities occurred that could be directly attributed to treatment. Transient clinical signs of toxicity observed after dosing included cyanosis in rats and ataxia and tremors in mice. Methemoglobin formation was directly related to dosage (rats and mice) and duration of treatment (rats). At study termination, Heinz body formation in erythrocytes in association with decreased hemoglobin, hematocrit, and red blood cell count was a prominent treatment-related effect. Enlarged spleens (gross necropsy observation) and increased spleen weight were treatment effects of each chemical in both species. Microscopic lesions typical of increased red blood cell production were found in hematopoietic tissues (bone marrow, spleen, and liver), while lesions due to increased red cell destruction were found in these tissues and also the kidneys (rats). Microscopic changes were more frequently seen and severe, and involved more body organs, in rats than mice, and in m-CA-treated animals thano-CA-treated animals. Sex differences in lesion incidence/severity were not evident.

Aniline Compounds↗

Vestigial preference functions in neural networks and túngara frogs.

Although there is a growing interest in understanding how perceptual mechanisms influence behavioral evolution, few studies have addressed how perception itself is shaped by evolutionary forces. We used a combination of artificial neural network models and behavioral experiments to investigate how evolutionary history influenced the perceptual processes used in mate choice by female túngara frogs. We manipulated the evolutionary history of artificial neural network models and observed an emergent bias toward calls resembling known ancestral states. We then probed female túngara frogs for similar preferences, finding strong biases toward stimuli that resemble a call hypothesized for a recent ancestor. The data strongly suggest that female túngara frogs exhibit vestigial preferences for ancestral calls, and provide a general strategy for exploring the role of historical contingency in perceptual biases.

Animal Communication↗

Geographical variation in reproductive character displacement in mate choice by male sailfin mollies.

Female Amazon mollies, Poecilia formosa, are a unisexual species that reproduce by gynogenesis. They must coexist and mate with males of other species (usually the mollies Poecilia latipinna or Poecilia mexicana) to induce embryogenesis, but inheritance is strictly maternal. We examined the mating preference of the male sailfin molly, P. latipinna, for female sailfin mollies versus Amazon mollies, P. formosa. We compared the mating preferences of sympatric and allopatric populations collected throughout the Gulf Coast of North America. Male P. latipinna from six populations sympatric with Amazon mollies showed a significantly greater strength of preference for conspecific sailfin females than males from five populations that were allopatric with Amazon mollies. These results provide strong evidence for reproductive character displacement of male mate choice in sympatry. Furthermore, the large geographical range of populations that we tested revealed variation among populations within sympatry and allopatry, indicating that it is important to evaluate a large number of populations when examining reproductive character displacement.

Animals↗

Hypocalcemia: a pervasive metabolic abnormality in the critically ill.

Hypocalcemia has been reported in critically ill patients, most commonly in association with sepsis syndrome. However, the severity and incidence of hypocalcemia in nonseptic but critically ill patients has not been well defined. Therefore, the goal of this study was to identify and compare the frequency and degree of hypocalcemia in critically ill patients with differing underlying illnesses (those admitted to medical, surgical, trauma, neurosurgical, burn, respiratory, and coronary intensive care units [ICUs]; group A; n = 99). Results were compared with the frequency and degree of hypocalcemia in non-critically ill ICU patients (initially admitted to an ICU but discharged within 48 hours; group B; n = 50) or hospitalized non-ICU patients (group C; n = 50). Incidences of hypocalcemia (ionized calcium [Ca] < 1.16 mmol/L [less than normal]) were 88%, 66%, and 26% for groups A, B, and C, respectively (P: < 0.001). In group A, the frequency of hypocalcemia did not depend on the ICU setting or presence of sepsis. However, the occurrence of hypocalcemia correlated with both Acute Physiology and Chronic Health Evaluation II score (r = -0.39; P: < 0.001) and patient mortality (eg, hazard ratio for death, 1.65 for Ca decrements of 0.1 mmol/L; P: < 0.002). Hypomagnesemia, number of blood transfusions, and presence of acute renal failure were each associated with depressed Ca levels. A weak association (r = -0.12; P: = 0.09) was noted between serum Ca level and QT interval. Clinical concern stemming from hypocalcemia was underscored by the substantial use of intravenous (IV) Ca therapy ( approximately 2 to 3 g IV). We conclude that hypocalcemia is extremely common in hospitalized patients (up to 88%) and correlates with severity of illness, but not with a specific illness per se. Whether it directly impacts patient survival remains unknown. Resolution of this issue appears to be critical because of the frequency with which it leads to high-dose IV Ca therapy.

APACHE↗

Risk factors and mortality associated with calciphylaxis in end-stage renal disease.

BACKGROUND: We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in end-stage renal disease. METHODS: Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. RESULTS: Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI, 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI, 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis, for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001). CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase, and low serum albumin are risk factors for calciphylaxis. Calciphylaxis is associated with a very high mortality.

Alkaline Phosphatase↗

Evolution of calls and auditory tuning in the Physalaemus pustulosus species group.

In species within the Physalaemus pustulosus species group, male frogs produce a whine-like advertisement call consisting of a frequency sweep typically descending from 1,000 to 400 Hz (depending on the species). One species, Physalaemus pustulosus, the túngara frog, has evolved a second call syllable, the chuck, which males place after their whine. Most energy in the chuck is above 1,500 Hz and peaks at 2,400 Hz. We investigated whether the evolution of this new call component in P. pustulosus coincided with evolution of auditory tuning. We used multiunit electrophysiological recordings of auditory-evoked activity in the midbrain to characterize auditory tuning in Physalaemus pustulosus, four other Physalaemus species within the P. pustulosus clade, and three additional, closely related Physalaemus species as outgroups. All eight species had similar sensitivity profiles, with a broad area of enhanced sensitivity from 100 to 1,100 Hz, which we presume represents amphibian papilla (AP) tuning, and a second, narrower area of enhanced sensitivity centered above 2,100 Hz, which we presume represents basilar papilla (BP) tuning. For all species, the whine stimulates the AP. The P. pustulosus chuck stimulates the BP. The frequency with greatest AP sensitivity differed significantly among species. Although in all cases the AP peak lay within the frequency sweep of the whine, phylogenetically corrected correlations revealed no significant relationships between AP tuning and any spectral feature of the whine. BP tuning was similar among all species, with mean BP best excitatory frequencies (BEFs) around 2,100-2,200 Hz, with the exception of P. pustulatus, with a mean BP BEF of 2,549 Hz. Physalaemus pustulosus, the only investigated species that produces a call component stimulating the BP, had a BP BEF that was not significantly different from any of the species within its clade except P. pustulatus, or from any of the outgroup species. A phylogenetic reconstruction of ancestral BP tuning confirms that the only point of evolutionary change in BP tuning is in the line of descent leading to P. pustulatus, not in the line leading to P. pustulosus despite this being the species using the BP for communication. The results indicate that BP tuning around 2,200 Hz is a conserved trait in the Physalaemus pustulosus species group and that no evolution of BP tuning accompanied the subsequent evolution of the call component (the chuck) that stimulates it. This supports the sensory exploitation idea, which posits that signals evolve to match preexisting features of receiver systems.

Animals↗

Culture collections in the twenty-first century.

Culture collections conserve the living tools for biotechnology. Without them there would be no reference organisms, and no stocks of crucial or rare microorganisms that are so valuable for biotechnology and biomedical research. The expertise that drives these collections is under threat, but the collections themselves may survive by pooling their knowledge.

Animals↗

History influences signal recognition: neural network models of túngara frogs.

Animals often attend to only a few of the cues provided by the complex displays of conspecifics. We suggest that these perceptual biases are influenced by mechanisms of signal recognition inherited from antecedent species. We tested this hypothesis by manipulating the evolutionary history of artificial neural networks, observing how the resulting networks respond to many novel stimuli and comparing these responses to the behaviour of females in phonotaxis experiments. Networks with different evolutionary histories proved equally capable of evolving to recognize the call of the túngara frog, Physalaemus pustulosus, but exhibited distinct responses to novel stimuli. History influenced the ability of networks to predict known responses of túngara frogs; network accuracy was determined by how closely the network history approximated the hypothesized history of the túngara frog. Our findings emphasize the influence of past selection pressures on current perceptual mechanisms, and demonstrate how neural network models can be used to address behavioural questions that are intractable through traditional methods.

Algorithms↗

Visual and acoustic communication in non-human animals: a comparison.

The visual and auditory systems are two major sensory modalities employed in communication. Although communication in these two sensory modalities can serve analogous functions and evolve in response to similar selection forces, the two systems also operate under different constraints imposed by the environment and the degree to which these sensory modalities are recruited for non-communication functions. Also, the research traditions in each tend to differ, with studies of mechanisms of acoustic communication tending to take a more reductionist tack often concentrating on single signal parameters, and studies of visual communication tending to be more concerned with multivariate signal arrays in natural environments and higher level processing of such signals. Each research tradition would benefit by being more expansive in its approach.

Acoustic Stimulation↗