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Biomedical subjects

G F Miller

Publications and source records attributed to G F Miller.

At least 19 recordsLinked to original sources
PubMed2001

IFN-gamma is effective in reducing infections in the mouse model of chronic granulomatous disease (CGD).

Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p<0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p<0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD.

Abscess↗
PubMed2000

Cryptococcus neoformans STE12alpha regulates virulence but is not essential for mating.

The Cryptococcus neoformans STE12alpha gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)alpha cells. In S. cerevisiae, STE12 was required for mating and filament formation. In C. neoformans, haploid fruiting on filament agar required STE12alpha. The ability to form hyphae, however, was not affected by deletion of STE12alpha when convergently growing MATa strains were present. Furthermore, ste12alpha disruptants were fertile when mated with MATa strains, albeit with reduced mating frequency. Most importantly, the virulence of a ste12alpha disruptant of serotype D strain was significantly reduced in a mouse model. When the ste12alpha locus was reconstituted with the wild-type allele by cotransformation, virulence was restored. Histopathological analysis demonstrated a reduction in capsular size of yeast cells, less severe cystic lesions, and stronger immune responses in meninges of mice infected with ste12alpha cells than those of mice infected with STE12alpha cells. Using reporter gene constructs, we found that STE12alpha controls the expression of several phenotypes known to be involved in virulence, such as capsule and melanin production. These results demonstrate a clear molecular link between mating type and virulence in C. neoformans.

Animals↗
PubMed2000

Shoulder impingement in front-crawl swimming: I. A method to identify impingement.

PURPOSE: The impingement of subacromial structures has been proposed as a major cause of the shoulder problems experienced by athletes who use repetitive overhead actions. The purpose of this study was to develop a noninvasive method to identify instances at which the shoulder was experiencing impingement during front-crawl swimming. METHODS: Shoulder impingement has been reported to occur when an arm is: (a) elevated above shoulder height while being rotated internally; and (b) forcibly elevated at, or beyond, the maximum active elevation angle. In this study shoulder configurations that satisfied the above two conditions were sought throughout the functional range of each shoulder; and a boundary that distinguished configurations that would cause shoulder impingement was defined. The shoulder movements exhibited during performance of the front-crawl stroke were measured using three-dimensional videography and compared with the boundary defined for each shoulder. The shoulder was considered to experience impingement if the shoulder configuration observed exceeded the boundary defined for that shoulder. RESULTS: For a male collegiate swimmer, impingement occurred for 12% of the stroke time for each shoulder. CONCLUSIONS: The analysis permitted the identification of the instances at which the shoulders were experiencing impingement during the front-crawl swimming. In this study, the measurement of the boundary was based entirely upon the mechanism of impingement described in the literature. Further studies are needed to confirm the occurrence of impingement by means of advanced visualization techniques, such as magnetic resonance imaging (MRI) and ultrasonogram.

Acromion↗
PubMed2000

Colitis in a female tamarin (Saguinus mystax).

An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp.) in the abdominal cavity. Campylobacter sp. was recovered from the colon. With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia. Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease. In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal.

Animals↗
PubMed1999

Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys.

Systemic infection by an unclassified yeast-like organism has been encountered sporadically in wild-caught owl monkeys (Aotus sp.) from South America. The infection is presumably acquired in the wild; the incubation period ranges from months to years. The disease is indolent and clinical signs are non-specific. The diagnosis is based on histopathologic observation of yeast-like cells in multiple internal organs. Most cells appear to be phagocytized by macrophages, however, many are apparently free in the extracellular space. Other inflammatory infiltrates, including neutrophils, lymphocytes, plasma cells, and multinucleated giant cells, are conspicuously absent. Cells are thick-walled, globose to oval, range from 5 to 8 micron in diameter, and reproduce by narrow-based budding of single daughter cells. Attempts to cultivate the organism on artificial media have failed. Yeast cell ultrastructure was studied using transmission electron microscopy. The cell wall is multilayered, and the internal structure is markedly heterogenous. In some cells, the cytoplasm is lightly electron-opaque, finely granular and lacks recognizable organelles or nuclei. In others, the cytoplasm is electron dense and contains mitochondria, ribosome-like granules, and a multilobulated nucleus. This organism differs from other recognized pathogenic yeast in its combined light microscopic appearance, organ involvement and host response. Ultrastructurally, it most closely resembles Loboa loboi.

Animals↗
PubMed1998

Virulence of catalase-deficient aspergillus nidulans in p47(phox)-/- mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare genetic disorder in which phagocytes fail to produce superoxide because of defects in one of several components of the NADPH oxidase complex. As a result, patients develop recurrent life-threatening bacterial and fungal infections. The organisms to which CGD patients are most susceptible produce catalase, regarded as an important factor for microbial pathogenicity in CGD. To test the role of pathogen-derived catalase in CGD directly, we have generated isogenic strains of Aspergillus nidulans in which one or both of the catalase genes (catA and catB), have been deleted. We hypothesized that catalase negative mutants would be less virulent than the wild-type strain in experimental animal models. CGD mice were produced by disruption of the p47(phox) gene which encodes the 47-kD subunit of the NADPH oxidase. Wild-type A. nidulans inoculated intranasally caused fatal infection in CGD mice, but did not cause disease in wild-type littermates. Surprisingly, wild-type A. nidulans and the catA, catB, and catA/catB mutants were equally virulent in CGD mice. Histopathological studies of fatally infected CGD mice showed widely distributed lesions in the lungs regardless of the presence or absence of the catA and catB genes. Similar to the CGD model, catalase-deficient A. nidulans was highly virulent in cortisone-treated BALB/c mice. Taken together, these results indicate that catalases do not play a significant role in pathogenicity of A. nidulans in p47(phox)-/- mice, and therefore raise doubt about the central role of catalases as a fungal virulence factor in CGD.

Acatalasia↗
PubMed1997

Mate choice: from sexual cues to cognitive adaptations.

Evolutionary psychologists have successfully combined sexual selection theory and empirical research to compile lists of sexual attractiveness cues used in human mate choice. But a list of inputs is not the same as a normative or descriptive model of a psychological adaptation. We need to shift from cataloguing sexual cues to modelling cognitive adaptations for mate choice. This theoretical chapter addresses how to make this transition in three parts. The introduction discusses four general problems with cue cataloguing as an evolutionary psychology research strategy: animals' promiscuous flexibility of cue use; cue use being marginal to cognition; cue use being marginal to the hard game-theoretical aspects of mate choice; and cue use being uninformative about the exact adaptive functions of mate choice. The middle section develops six critiques of current mate choice research: the obsession with sex difference; the over-emphasis on physical rather than behavioural cues; the assumption of weighted linear models of cue integration; the avoidance of game-theoretical problems of mutual choice and assortative mating; the neglect of co-evolution between mate choice heuristics and the cues that they select; and the failure to understand that mate choice is only worth doing if potential mates show significant genetic variance. The conclusion outlines a new normative and descriptive framework for mate choice, centred on the use of brutally efficient search heuristics that exploit the informational structure of human genotypes, phenotypes and populations to make good mate choices.

Adaptation, Psychological↗
PubMed1997

Hepatic hemosiderosis in non-human primates: quantification of liver iron using different field strengths.

Using a non-human primate model of idiopathic hemochromatosis, hemosiderin-induced T2 shortening of the liver was assessed at nine different field strengths over a range of 0.05 to 1.5 Tesla. The 1/T2 values increased linearly with field strength, with all specimens having approximately the same zero-field intercept. The slope of the field increase, termed "field-dependent T2 proton relaxation enhancement (PRE)", appeared to be proportional to the chemically determined tissue iron content, viz. 10.8 s-1T-1(mg Fe/g wet tissue)-1. The correlation between iron content and field-dependent T2 PRE (r = 0.94) was better than the correlation between iron content and 1/T2 values obtained at single field strengths. For livers containing > or = 2 mg Fe/g wet weight, biexponential T2 relaxation behavior emerged at higher field strengths, with the short T2 component (intracellular water) exhibiting a linear dependence of 1/T2 on field, while T2 of the long component (extracellular/sinusoidal water) was nearly field-independent. After maceration of the specimens, all T2 relaxation curves became monoexponential, including those for high iron content at high field strengths. The present data suggest that the use of double-field MR imaging to assess the field-dependent T2 PRE has potential for specific quantification of (liver) tissue iron stores.

Animals↗
PubMed1997

Hepatic hemosiderosis in common marmosets, Callithrix jacchus: effect of diet on incidence and severity.

We examined the effect of dietary iron concentration on the incidence of hepatic hemosiderosis in common marmosets (Callithrix jacchus) and assessed the impact of hemosiderosis on animal health. Thirteen young adult common marmosets were fed nutritionally balanced natural-ingredient diets formulated to contain either 100 or 500 ppm of iron. Six were fed the low-iron and seven received the high-iron diet. Baseline blood values and liver iron content were determined for each animal. Animals were weighted monthly, blood work (hematologic analysis, serum iron concentration, total iron-binding capacity, percent of transferrin saturation) was performed semi-annually, and liver biopsies for iron analysis were obtained after marmosets had consumed the test diets for 13 months or at necropsy. Midway in study, the high-iron diet was reformulated to contain 350 ppm of iron because of the death of a male which had consumed that diet for 7 months. Four of seven marmosets fed the high-iron diet died during the first year of the study, compared with one death in the low-iron cohort. The mean increase in liver iron content of the marmosets fed the high-iron diet was 6,371 micrograms/g, dry weight analysis. In contrast the low-iron cohort had a mean decrease of 621.5 micrograms/g. These results indicate that liver iron content can be affected by dietary iron intake. The increased mortality in the marmosets fed the high-iron diet also suggests that hepatic hemosiderosis can be detrimental to marmoset health.

Animals↗
PubMed1996

Effects of media, serum, oviductal cells, and hormones during maturation on bovine embryo development in vitro.

Our objective was to optimize in vitro maturation conditions of bovine oocytes as assessed by embryo development. In Experiment 1, cumulus-oocyte complexes were matured in either M-199 or RPMI-1640. Each medium was supplemented with an antibiotic-antimycotic solution (1%) and estrous cow serum (20%). Cumulus cell expansion after 24 h was greatest for cumulus-oocyte complexes matured in RPMI-1640. Morulae development on d 7 was greater (21.1%) for oocytes matured in M-199 than for oocytes that matured in RPMI-1640 (9.6%). In Experiment 2, cumulus-oocyte complexes were matured in M-199 supplemented with antibiotic-antimycotic solution (1%). Main effects were serum type (20%; estrous cow serum vs. superstimulated estrous cow serum) and coculture (with or without bovine oviductal epithelial cells). The percentage of oocytes developing into blastocysts (d 9) was higher for oocytes matured in estrous cow serum regardless of coculture. In Experiment 3, effects of estradiol-17 beta (0, 1, and 2 micrograms/ml) and equine LH (0, 10, 20, and 30 micrograms/ml) on cumulus cell expansion and development after fertilization were determined. Cumulus cell expansion and blastocyst development decreased with estradiol-17 beta in the maturation medium, but LH in the medium enhanced expansion of cumulus cells and blastocyst development.

Animals↗
PubMed1995

Perception of arm orientation in three-dimensional space.

The purpose of this investigation was to determine the preferred coordinate system for perception of arm (humerus) orientation in three-dimensional space. Perception of arm orientation relative to trunk-fixed versus earth-fixed axes were compared in seven human subjects. The experimenter first moved the subject's trunk and arm into a target configuration (in which the arm's orientation relative to the trunk and/or earth was perceived and memorized by the subject) and then moved the trunk and arm to a new configuration. The blindfolded subject then attempted to reproduce the target orientation of their arm relative to either the trunk (i.e., reproduce shoulder angles--intrinsic kinesthetic coordinate system) or earth-fixed axes (extrinsic kinesthetic coordinate system). Perceptual errors were similar for both shoulder (arm relative to trunk) and extrinsic (arm relative to earth) angles. However, elevation angles were perceived with greater accuracy than yaw angles in the two coordinate systems. Also, perceptual errors for arm yaw angles in the extrinsic kinesthetic coordinate system task were better predicted from changes in trunk orientation than the errors for other angles. Furthermore, four subjects matched arm yaw angle relative to the trunk-fixed axis more accurately than to the earth-fixed axis in the extrinsic coordinate system task. These results suggests a bias toward perception of yaw angles relative to trunk-fixed axes (i.e., in an intrinsic coordinate system). These data suggest that the preferred coordinate system for kinesthetic perception of arm orientation is probably fixed in the trunk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Addition of penicillamine, hypotaurine and epinephrine (PHE) or bovine oviductal epithelial cells (BOEC) alone or in combination to bovine in vitro fertilization medium increases the subsequent embryo cleavage rate.

The cleavage rate of in vitro-matured bovine oocytes was compared after fertilization in 1) TALP medium alone (control); 2) in TALP+BOEC; 3) in TALP+PHE; or 4) in TALP+BOEC and PHE. The overall cleavage rate at 45 h post insemination was greater for embryos in Treatments 2 (52%), 3 (55%) and 4 (66%) than for Treatment 1 (32%). The oocyte cleavage rates for Treatments 2 and 3 were similar, but were lower than that of Treatment 4. Addition of PHE or BOEC, alone or in combination, to the fertilization medium resulted in more embryos at the 3- or 4-cell stage than the 2-cell stage by 45 h post insemination. After 5 d of co-culture with BOEC in M-199 medium, 21, 28, 25 and 35% of the cleaved embryos in Treatments 1, 2, 3 and 4, respectively, developed to the morula or blastocyst stage. The rate of development to morulae and blastocysts was similar among Treatments 1, 2 and 3, and between Treatments 2 and 4. Across treatments, a correlation of 0.98 was noted between the portion of embryos that had reached the 3- or 4-cell stage by 45 h post insemination and the percentage of embryos in each treatment that continued to develop to the morula or blastocyst stage in vitro.

Journal Article↗
PubMed1994

Coordination of index finger movements.

The purpose of this investigation was to describe the patterns of coordination among the joint motions of the index finger, and among the EMGs of index finger muscles. Index finger movements involving all three joints were varied in speed and direction. Joint motions were recorded along with fine-wire EMG from all the muscles that insert into the index finger. We observed nearly linear relationships for angular position between the two interphalangeal (IP) joints, and between the metacarpophalangeal (MP) and proximal IP (PIP) joints regardless of movement, speed and direction. The activities of the extrinsic flexors were of similar magnitude and were highly correlated when they acted as agonists but were poorly correlated when they acted as antagonists to the movement. Extrinsic extensor muscles behaved in this way also. The activation patterns of the intrinsic musculature correlated weakly except for extension movements voluntarily limited to the IP joints. We conclude that the highly coordinated action of the extrinsic flexors during flexion contribute importantly to the linked motions of the IP joints in part because these muscles span two or all the three index finger joints. Hence, interjoint movement patterns appear not to arise solely from restraints imposed by passive tissues, especially for fast flexion movements. The weakly correlated intrinsic muscle activity does not uncouple the flexion motions at the PIP and DIP joints because these muscles exert extensor torques at both IP joints. However, the actions of the intrinsic muscles are necessary for stabilizing the MP joint in flexion postures during IP motion and in producing motions voluntarily limited to the MP joint.

Electromyography↗
PubMed1994

Effects of protein source and co-culture on bovine embryo development in synthetic oviductal fluid medium.

Experiment 1 compared the development of 2- to 4-cell bovine embryos cultured in synthetic oviductal fluid with 20% fetal calf serum or 3.2% BSA and in the presence of oviductal cells, cumulus cells, or medium alone. More embryos developed in medium with serum, regardless of culture method (P=0.063). Oviductal cell co-culture resulted in more embryos developing to at least the morula stage (P or=0.400). Addition of serum to oviductal cell co-culture medium increased the number of excellent or good quality embryos (P=0.019). Experiment 2 further compared the development of 2-cell or 3- to 4-cell embryos co-cultured with oviductal cell suspensions in serum-supplemented synthetic oviductal fluid or M-199 medium. More 3- to 4-cell than 2-cell embryos developed to at least the morula stage (P<0.001). More embryos developed to at least the morula stage in synthetic oviductal fluid (P=0.083). Neither initial embryo cell stage nor medium type influenced the percentage of developing embryos that achieved the blastocyst stage or final morphological quality of embryos (P>or=0.535).

Journal Article↗
PubMed1994

In vitro development of bovine embryos as affected by different lots of bovine serum albumin and citrate.

The effect of bovine serum albumin (BSA) lots on the development of in vitro-derived bovine embryos in synthetic oviductal fluid was investigated. Citrate concentration was determined for each lot of BSA, and then correlated with differences noted in the ability of BSA lots to support embryo development. Development of bovine embryos to the blastocyst stage was also compared after culture in chemically-defined medium with varying levels of citrate. There were distinct differences in the ability of the different BSA lots to support embryo development to the blastocyst stage (P<or=0.05). Citrate content (based on 3.2% BSA) of the medium varied from 320 to 1280 microM. Although there was an overall linear trend (P<0.001) for increased number of blastocysts with increasing concentrations of citrate in the medium, there were also substantial deviations (P=0.024) from this linear trend, suggesting that factors other than citrate could be responsible for stimulating blastocyst development. In the second experiment, the percentages of cleaved embryos that developed to the blastocyst stage in defined medium with 0, 100, 300 or 900 microM citrate ranged from 18.2 to 27.8% and were similar among treatments (P=0.441). The mean number of cells in the embryos developing to the blastocyst stage did not differ among treatments (P=0.545). Overall, these results indicate citrate has little affect on development of bovine embryos to the blastocyst stage in vitro.

Journal Article↗