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Biomedical subjects

J B Miller

Publications and source records attributed to J B Miller.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs.

OBJECTIVE: To determine whether phenobarbital treatment of epileptic dogs alters serum thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations. DESIGN: Cross-sectional study. ANIMALS: 78 epileptic dogs receiving phenobarbital (group 1) and 48 untreated epileptic dogs (group 2). PROCEDURE: Serum biochemical analyses, including T4 and TSH concentrations, were performed for all dogs. Additional in vitro analyses were performed on serum from healthy dogs to determine whether phenobarbital in serum interferes with T4 assays or alters free T4 (fT4) concentrations. RESULTS: Mean serum T4 concentration was significantly lower, and mean serum TSH concentration significantly higher, in dogs in group 1, compared with those in group 2. Thirty-one (40%) dogs in group 1 had serum T4 concentrations less than the reference range, compared with 4 (8%) dogs in group 2. All dogs in group 2 with low serum T4 concentrations had recently had seizure activity. Five (7%) dogs in group 1, but none of the dogs in group 2, had serum TSH concentrations greater than the reference range. Associations were not detected between serum T4 concentration and TSH concentration, age, phenobarbital dosage, duration of treatment, serum phenobarbital concentration, or degree of seizure control. Signs of overt hypothyroidism were not evident in dogs with low T4 concentrations. Addition of phenobarbital in vitro to serum did not affect determination of T4 concentration and only minimally affected fT4 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicians should be aware of the potential for phenobarbital treatment to decrease serum T4 and increase TSH concentrations and should use caution when interpreting results of thyroid tests in dogs receiving phenobarbital.

Alanine Transaminase↗
PubMed1999

Coding sequence, genomic organization, chromosomal localization, and expression pattern of the signalosome component Cops2: the mouse homologue of Drosophila alien.

The Drosophila alien gene is highly homologous to the human thyroid receptor interacting protein, TRIP15/COPS2, which is a component of the recently identified signalosome protein complex. We identified the mouse homologue of Drosophila alien through homology searches of the EST database. We found that the mouse cDNA encodes a predicted 443-amino-acid protein, which migrates at approximately 50 kDa. The gene for the mouse alien homologue, named Cops2, includes 12 coding exons spanning approximately 30 kb of genomic DNA on the central portion of mouse chromosome 2. Mouse Cops2 is widely expressed in embryonic, fetal, and adult tissues beginning as early as E7.5. Mouse Cops2 cDNA hybridizes to two mRNA bands in all tissues at approximately 2.3 and approximately 4 kb, with an additional approximately 1.9-kb band in liver. Immunostaining of native and epitope tagged proteins localized the mouse Cops2 protein in both the cytoplasm and the nucleus, with larger amounts in the nucleus in some cells.

Amino Acid Sequence↗
PubMed1999

Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity.

This study was undertaken to determine the modulation of uterine function by chorionic gonadotrophin (CG) in a nonhuman primate. Infusion of recombinant human CG (hCG) between days 6 and 10 post ovulation initiated the endoreplication of the uterine surface epithelium to form distinct epithelial plaques. These plaque cells stained intensely for cytokeratin and the proliferating cell nuclear antigen. The stromal fibroblasts below the epithelial plaques stained positively for alpha-smooth muscle actin (alphaSMA). Expression of alphaSMA is associated with the initiation of decidualization in the baboon endometrium. Synthesis of the glandular secretory protein glycodelin, as assessed by Western blot analysis, was markedly up-regulated by hCG, and this increase was confirmed by immunocytochemistry, Northern blot analysis, and reverse transcriptase-PCR. To determine whether hCG directly modulated these uterine responses, we treated ovariectomized baboons sequentially with estradiol and progesterone to mimic the hormonal profile of the normal menstrual cycle. Infusion of hCG into the oviduct of steroid-hormone-treated ovariectomized baboons induced the expression of alphaSMA in the stromal cells and glycodelin in the glandular epithelium. The epithelial plaque reaction, however, was not readily evident. These studies demonstrate a physiological effect of CG on the uterine endometrium in vivo and suggest that the primate blastocyst signal, like the blastocyst signals of other species, modulates the uterine environment prior to implantation.

Actins↗
PubMed1999

Seeking muscle stem cells.

Skeletal muscle development requires the formation of myoblasts that can fuse with each other to form multinucleate myofibers. Distinct primary and secondary, slow and fast, populations of myofibers form by the time of birth. At embryonic, fetal, and perinatal stages of development, temporally distinct lineages of myogenic cells arise and contribute to the formation of these multiple types of myofibers. In addition, spatially distinct lineages of myogenic cells arise and form the anterior head muscles, limb (hypaxial) muscles, and dorsal (epaxial) muscles. There is strong evidence that myoblasts are produced from muscle stem cells, which are self-renewing cells that do not themselves terminally differentiate but produce progeny that are capable of becoming myoblasts and myofibers. Muscle stem cells, which may be multipotent, appear to be distinguishable from myoblasts by a number of indirect and direct criteria. Muscle stem cells arise either in unsegmented paraxial mesoderm (anterior head muscle progenitors) or in segmented mesoderm of the somites (epaxial and hypaxial muscle progenitors). These initial stages of myogenesis are regulated by positive and negative signals, including Wnt, BMP, and Shh family members, from nearby notochord, neural tube, ectoderm, and lateral mesoderm tissues. The formation of skeletal muscles, therefore, depends on the generation of spatially and temporally distinct lineages of myogenic cells. Myogenic cell lineages begin with muscle stem cells which produce the myoblasts that fuse to form myofibers.

Animals↗
PubMed1998

Bcl-2 expression identifies an early stage of myogenesis and promotes clonal expansion of muscle cells.

We show that Bcl-2 expression in skeletal muscle cells identifies an early stage of the myogenic pathway, inhibits apoptosis, and promotes clonal expansion. Bcl-2 expression was limited to a small proportion of the mononucleate cells in muscle cell cultures, ranging from approximately 1-4% of neonatal and adult mouse muscle cells to approximately 5-15% of the cells from the C2C12 muscle cell line. In rapidly growing cultures, some of the Bcl-2-positive cells coexpressed markers of early stages of myogenesis, including desmin, MyoD, and Myf-5. In contrast, Bcl-2 was not expressed in multinucleate myotubes or in those mononucleate myoblasts that expressed markers of middle or late stages of myogenesis, such as myogenin, muscle regulatory factor 4 (MRF4), and myosin. The small subset of Bcl-2-positive C2C12 cells appeared to resist staurosporine-induced apoptosis. Furthermore, though myogenic cells from genetically Bcl-2-null mice formed myotubes normally, the muscle colonies produced by cloned Bcl-2-null cells contained only about half as many cells as the colonies produced by cells from wild-type mice. This result suggests that, during clonal expansion from a muscle progenitor cell, the number of progeny obtained is greater when Bcl-2 is expressed.

Animals↗
PubMed1998

The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial.

Dehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.

Animals↗
PubMed1998

Surface and gradiometer coils near a conducting body: the lift-off effect.

The use of surface coils in magnetic resonance is widespread. Examples include MRI, detection of subsurface aquifers by NMR, and, more recently, landmine detection by nuclear quadrupole resonance. In many of these cases a finite-sized sample to be examined is contained within a larger medium that is a poor electrical conductor, and eddy currents induced by the RF fields provide a loss mechanism that reduces the effective quality factor Q of the transmitter and receiver coils. Here the losses induced in a circular surface coil (a horizontal loop antenna) separated a distance from a dissipative medium are calculated and compared to measurements. It is shown that often the overall efficiency of the coil for magnetic resonance can be improved by displacing the coil away from the conducting medium a prescribed "lift-off" distance. The use of a gradiometer as a surface coil is also examined, and it is shown by theory and experiment that in certain circumstances such a gradiometer can be more efficient than a conventional surface coil for inspection of conducting media.

Magnetic Resonance Spectroscopy↗
PubMed1998

Sialic acid concentration of brain gangliosides: variation among eight mammalian species.

Sialic acid is a vital component of brain gangliosides which play an essential role in the transmission and storage of information in the brain. The concentration of bound sialic acid in gangliosides and free sialic acid in the brain cortex of eight different mammals [human, chimpanzee (Pan troglodytes), rat (Rattus norvegicus), mouse (Mus musculus), rabbit (Oryctolagus cuniculus), sheep (Ovis aries), cow (Bos indicus) and pig (Sus scrofa)] were compared. Total sialic acid concentration (890+/-103 microg/g wet weight tissue, mean+/-SE, n = 6) was 2-4 times higher in the human brain compared with the other species studied (0.001 < p < 0.05). There was no significant difference between human males and females. The rank order of adult brain sialic acid after humans (in microg/g) was rat (493+/-23, n = 12), mouse (445+/-29, n = 16), rabbit (380+/-18, n = 6), sheep (323+/-43, n = 6), cow (304+/-14, n = 6) and pig (252+/-14, n = 6). Apart from the cow vs the sheep, the differences between species were statistically significant (p < 0.05). In the mouse, cow and sheep, total sialic acid concentration increased during maturation by 18-32% (p < 0.05). In a 2-year-old chimpanzee, the sialic acid concentration in the left lobe of the brain cortex was 25% higher than that of right lobe at 6 weeks of age (p < 0.05). Free sialic acid was higher in the human brain cortex (41+/-3 microg/g) than that of the rat and mouse (32+/-3 and 25+/-5 microg/g respectively) and absent from other species. Variation in brain sialic acid concentration among different animals has implications for the evolution of the brain and may affect learning ability in animals.

Aging↗
PubMed1997

MRF4 can substitute for myogenin during early stages of myogenesis.

MRF4, myogenin, MyoD, and Myf-5 are the four members of the basic helix-loop-helix family of muscle-specific regulatory factors (MRFs). We examined whether MRF4 could substitute for myogenin in vivo by determining if the myofiber- and MRF4-deficient phenotype of myogenin (-/-) mice could be rescued by a myogenin promoter-MRF4 transgene. When the transgene was expressed at a physiological level in myogenin-deficient fetuses, we found that expression of the endogenous MRF4 gene was restored to normal levels, whereas MyoD levels were unchanged. Thus, MRF4 can participate in a positive autoregulatory loop and can substitute for myogenin to activate its own promoter. Myogenin-deficient fetuses that expressed the transgene also had more myosin, more and larger myofibers, and a more normal ribcage morphology than myogenin-deficient littermates without the transgene. The transgene failed, however, to restore normal numbers of myofibers or viability to myogenin-deficient mice, because the approximately 1.6 kb myogenin promoter fragment was not expressed in most late-forming myofibers. These results demonstrate that MRF4 is able to substitute for myogenin to activate MRF4 expression and promote myofiber formation during the early stages of myogenesis.

Animals↗
PubMed1997

Clinic nurses: confronting campus alcohol use on the frontline.

Alcohol use is common on college campuses. Nurses in the student health clinic, in collaboration with other health professionals, have a responsibility and an opportunity to assess, intervene, and prevent problems related to the use of alcohol and other drugs. In this article, the author suggests how college health nurses, in everyday practice, can seize opportunities for helping students face their alcohol-related problems.

Adolescent↗
PubMed1997

Human milk oligosaccharides: only the breast.

Over 100 years ago it was first deduced that a major component of human milk must be an unidentified carbohydrate that was not found in cows milk. At first this was thought to be a form of lactose and was called gynolactose. We now know that this was not a single carbohydrate but a complex mixture of approximately 130 different oligosaccharides. Although small amounts of a few oligosaccharides have been found in the milk of other mammals, this rich diversity of sugars is unique to human milk. The oligosaccharide content of human milk varies with the infant's gestation, the duration of lactation, diurnally and with the genetic makeup of the mother. Milk oligosaccharides have a number of functions that may protect the health of the breast fed infant. As they are not digested in the small intestine, they form the 'soluble' fibre of breast milk and their intact structure is available to act as competitive ligands protecting the breast-fed infant from pathogens. There is a growing list of pathogens for which a specific oligosaccharide ligand has been described in human milk. They are likely to form the model for future therapeutic and prophylactic anti-microbials. They provide substrates for bacteria in the infant colon and thereby contribute to the difference in faecal pH and faecal flora between breast and formula-fed infants. They may also be important as a source of sialic acid, essential for brain development.

Female↗
PubMed1996

Isolation and characterization of an avian slow myosin heavy chain gene expressed during embryonic skeletal muscle fiber formation.

We have isolated and begun characterization of the quail slow myosin heavy chain (MyHC) 3 gene, the first reported avian slow MyHC gene. Expression of slow MyHC 3 in skeletal muscle is restricted to the embryonic period of development, when the fiber pattern of future fast and slow muscle is established. In embryonic hindlimb development, slow MyHC 3 gene expression coincides with slow muscle fiber formation as distinguished by slow MyHC-specific antibody staining. In addition to expression in embryonic appendicular muscle, slow MyHC 3 is expressed continuously in the atria. Transfection of slow MyHC 3 promoter-reporter constructs into embryonic myoblasts that form slow MyHC-expressing fibers identified two regions regulating expression of this gene in skeletal muscle. The proximal promoter, containing potential muscle-specific regulatory motifs, permits expression of a reporter gene in embryonic slow muscle fibers, while a distal element, located greater than 2600 base pairs upstream, further enhances expression 3-fold. The slow muscle fiber-restricted expression of slow MyHC 3 during embryonic development, and expression of slow MyHC 3 promoter-reporter constructs in embryonic muscle fibers in vitro, makes this gene a useful marker to study the mechanism establishing the slow fiber lineage in the embryo.

Amino Acid Sequence↗
PubMed1996

Differential expression of PTP1D, a protein tyrosine phosphatase with two SH2 domains, in a slow and fast skeletal muscle fibers.

We show that PTP1D, a protein tyrosine phosphatase that contains two SH2 domains, is preferentially expressed in slow skeletal muscle fibers. Immunohistochemical staining using polyclonal antibodies against PTP1D demonstrated that PTP1D was expressed in a subpopulation of rodent muscle fibers. These fibers were identified as slow Type I fibers based on histochemical ATPase assays and slow myosin heavy chain expression. Northern and Western analyses showed that PTP1D levels were higher in predominantly slow muscles than in predominantly fast muscles. This differential expression of PTP1D in slow muscle fibers appeared by birth. In cultures of mouse myogenic cells, PTP1D was expressed after MyoD and myogenin and appeared in myotubes derived from embryonic, fetal, and postnatal myoblasts. Remarkably, PTP1D was organized into sarcomeres in a pattern coincident with myosin heavy chain, suggesting that PTP1D associates with a component of the thick filament. These results show that PTP1D is preferentially expressed in slow muscle fibers. We speculate that PTP1D may play a role in slow muscle fiber function and differentiation.

Animals↗
PubMed1996

Acceleration of somitic myogenesis in embryos of myogenin promoter-MRF4 transgenic mice.

The four muscle regulatory factors (MRFs) of the MyoD family are expressed in distinct temporal and spatial patterns in developing somites. To examine MRF function and regulation in somites, we generated myogenin promoter-MRF4 transgenic mice in which MRF4 was expressed in rostral somites about a half day earlier than normal. We found that the transgene, which was expressed at about the same level as endogenous MRFs, did not noticeably alter developing or adult mice, whereas the rostral somites of transgenic embryos showed accelerated myocyte formation, as well as precocious expression of the endogenous MRF4 gene. In an individual transgenic somite, MRF4 was expressed in both presumptive myotomal (mesenchymal) and dermatomal (epithelial) cells. Transgenic dermatomal cells also contained myogenin, which is expressed early in myogenesis, but did not contain myosin, which is expressed late in myogenesis. In transgenic myotomal cells, in contrast, precocious expression of MRF4 accelerated late events in myogenesis, including myosin expression and striated myofibril formation. MRF function, therefore, appears to be differentially regulated in dermatomal and myotomal cells.

Animals↗
PubMed1996

POU homeodomain genes and myogenesis.

We show that members of the POU homeodomain family are among the transcription factors expressed in developing mouse skeletal muscle. From a cDNA library prepared from fetal muscle mRNA, we cloned a cDNA identical to that of Brn-4, a POU class II gene previously cloned from neural tissues. In limb muscle, we found that Brn-4 mRNA expression was highest at embryonic days 15-18, declined-after birth, and was undetectable in adults. The mRNAs of two additional POU genes, Emb (POU class VI) and Oct-1 (POU class II), were also expressed in developing muscle and, unlike Brn-4, continued to be expressed in postnatal and adult muscles. In skeletal muscle, expression of Brn-4 is myogenin-dependent, because muscles from myogenin-deficient fetuses contained much less Brn-4 mRNA than muscles from myogenin-expressing littermates. In contrast, expression of Emb was the same in the presence or absence of myogenin. The distinct pattern of Brn-4 mRNA expression and its dependence on a myogenic regulatory factor suggest that Brn-4 is part of the network of interacting transcription factors that control muscle-specific gene expression during mammalian myogenesis.

3T3 Cells↗