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Biomedical subjects

D Crowe

Publications and source records attributed to D Crowe.

At least 19 recordsLinked to original sources
PubMed2000

Expression of myogenic regulatory factors during the development of mouse tongue striated muscle.

While the role of myogenic regulatory factors (MRFs) in skeletal myogenesis has been well evaluated in limb and trunk muscles, very little is known about their role in tongue myogenesis. Here the expression of MRF mRNA in mouse tongue muscle was examined during development from embryonic day (E)11 to birth and compared them with that in hind-limb muscle. Desmin, muscle creatine kinase and troponin C mRNAs were used as markers for myoblast determination, myotubule formation and myofibre maturation, respectively. The mRNA quantities were determined by competitive reverse transcriptase-polymerase chain reaction. The expression profile of desmin mRNA indicated that myoblast determination occurred before E11 in both the tongue and hind-limb muscles; the profile of muscle creatine kinase and troponin C mRNAs indicated that myotubule formation and myofibre maturation began between E11 and 13 in both tongue and hind-limb muscles, but ended 2 days earlier in the tongue than in the hind limb. Expression of myoD and myogenin mRNAs began at E11, increased, and showed peak values earlier in the tongue muscle (E13) than in the hind-limb muscle (E15). Expression of MRF4 mRNA appeared earlier in the tongue (E13) than in the hind-limb muscle (E15) and increased in both muscles after that. These results suggest that myotubule formation and myofibre maturation in the tongue muscle progress faster than in the hind-limb muscle, a result of earlier expression of myoD, myogenin, and MRF4 in response to earlier functional demands such as suckling immediately after birth.

Animals↗
PubMed1998

N epsilon,N epsilon-dimethyl-lysine cytochrome c as an NMR probe for lysine involvement in protein-protein complex formation.

The reductively dimethylated derivatives of horse and yeast iso-1-ferricytochromes c have been prepared and characterized for use as NMR probes of the complexes formed by cytochrome c with bovine liver cytochrome b5 and yeast cytochrome c peroxidase. The electrostatic properties and structures of the derivatized cytochromes are not significantly perturbed by the modifications; neither are the electrostatics of protein-protein complex formation or rates of interprotein electron transfer. Two-dimensional 1H-13C NMR spectroscopy of the complexes formed by the derivatized cytochromes with cytochrome b5 and cytochrome c peroxidase has been used to investigate the number and identity of lysine residues of cytochrome c that are involved in interprotein interactions of cytochrome c. The NMR data are incompatible with simple static models proposed previously for the complexes formed by these proteins, but are consistent with the presence of multiple, interconverting complexes of comparable stability, consistent with studies employing Brownian dynamics to model the complexes. The NMR characteristics of the Nepsilon,Nepsilon-dimethyl-lysine groups, their chemical shift dispersion, oxidation state and temperature dependences and the possibility of chemical exchange phenomena are discussed with relevance to the utility of Nepsilon, Nepsilon-dimethyl-lysine's being a generally useful derivative for characterizing protein-protein complexes.

Animals↗
PubMed1998

A model of bridging angiogenesis in the rat.

A model of angiogenesis has been developed in the rat. The epigastric vascular pedicle was exposed in the groin, a 7 mm segment of epigastric artery was excised leaving the vein intact and, after a variable period of time for angiogenesis to occur between the ends of the artery, a skin flap was elevated on the epigastric vascular pedicle so that it depended completely for its blood supply on bridging angiogenesis across the created gap. Skin flap survival and vessel counts were measured as indices of the angiogenic response. In this model we observed a spontaneous increase in vessel counts between the ends of the artery, and a corresponding increase in skin flap tissue survival until day 10 after which time vessel counts plateaued whilst tissue survival continued to increase until day 14. In the angiogenic pedicle, a time-dependent development of granulation tissue containing numerous macrophages and mast cells, and capillary sprouting were documented. When flap elevation was performed 7 days after arterial excision skin flap survival was 42%. Thus, in this model, 7 days is a suitable interval for the future evaluation of the effects of either pro- or anti-angiogenic agents.

Animals↗
PubMed1996

CD11b+CD28-CD4+ human T cells: activation requirements and association with HLA-DR alleles.

Engagement of CD28 induces a major costimulatory pathway required by many CD4+ T cells in addition to activation via the TCR. In the absence of signals provided by CD28, ligation of the TCR alone can induce anergy or apoptosis in CD28+ cells. However, we report here characterization of a distinct subset of CD4+ T cells that are CD28-. Three autoreactive CD4+ human T cell clones that could be activated to produce IL-2 and proliferate by anti-CD3 alone were found to lack expression of CD28. CD28- clones that were activated with anti-CD3 alone were not anergic to restimulation via CD3. The presence of CD28-CD4+ T cells was verified in peripheral blood, and their frequency ranged from 0% to >22% of CD4+ T cells in different individuals. The percentage of CD28-CD4+ T cells in the peripheral blood of 57 individuals was significantly correlated with specific class II MHC alleles. Persons with HLA-DRB1*0401 and DR1 alleles had significantly higher numbers of CD28- T cells, while individuals with HLA-DR2(15) had significantly fewer CD28-CD4+ T cells than the mean. Like the CD28- clones, CD28-CD4+ T cells isolated from peripheral blood proliferated upon CD3 cross-linking in the absence of costimulation. The finding that CD28-CD4+ T cells resist induction of anergy following engagement of the TCR in the absence of conventional costimulation demonstrates one mechanism by which autoreactive T cells can escape processes that censor self-reactivity. The MHC associations observed suggest a relationship with autoimmunity and loss of self-tolerance.

Alleles↗
PubMed1995

Morphologic change in rabbit femoral arteries induced by storage at four degrees Celsius and by subsequent reperfusion.

PURPOSE: Cold-stored arteries function well as microvascular autografts, but little is known of the morphologic changes that occur in them during cold storage or of further changes during reperfusion. METHODS: In part A of the study, rabbit femoral arteries were stored at 4 degrees C for up to 6 months. In part B rabbit femoral arteries were stored at 4 degrees C for up to 6 months, inserted as end-to-end autografts into contralateral femoral arteries, and reperfused for 24 hours. Tissue was examined by histologic study, transmission and scanning electron microscopy, histochemical study, immunohistochemical study, and tissue culture. RESULTS: Cell viability declined gradually at 4 degrees C, so that by 4 weeks no viable cells remained. However, the extracellular framework and elastic lamellae remain intact. If cold-stored arteries are reinserted as autografts for 24 hours, this accelerates breakdown of necrotic cells and reduces the thickness of the medial wall and internal elastic lamina but does not alter the extracellular framework. CONCLUSIONS: Cold storage results in acellular vascular grafts with intact extracellular frameworks. After 24 hours reperfusion there is no major change to the extracellular framework.

Actins↗
PubMed1994

Acute inflammation in foetal and adult sheep: the response to subcutaneous injection of turpentine and carrageenan.

Because of the small number of inflammatory cells found in skin wounds, it has been considered that foetal sheep are incapable of an adequate inflammatory response. The present study shows that subcutaneous injection of turpentine or carrageenan into foetal sheep consistently excites a severe cellular inflammatory reaction. At 75 days gestation the inflammatory cells are all macrophages. As the foetus develops, polymorphs play an increasing role in the early response to turpentine. By 120 days inflammatory cells are almost all polymorphs as in adult sheep. However the response to carrageenan remains macrophage in type. At all stages of gestation the acute cellular response is followed by development of scar tissue, more pronounced with turpentine than carrageenan. Any proposed intrauterine surgery must allow for the pronounced and prolonged inflammatory response and scar tissue formation caused by persistent inflammatory stimuli in foetal animals.

Animals↗
PubMed1994

Management of severe spasticity with intrathecal baclofen delivered by a manually operated pump.

Intrathecal baclofen abolishes spasticity in many patients with neurological diseases but there are few studies on its long-term effectiveness. Since 1986 a manually operated subcutaneous pump has been used to deliver baclofen intrathecally in 21 patients with a follow up of at least one year. Most patients had multiple sclerosis and all were wheelchair-bound. Sixteen patients had a complete and sustained benefit. In four other patients the treatment was effective in the short term but not in the long term. In the remaining patient the pump never worked. Complications included meningitis, pump failure, erosion through the skin, and baclofen overdose. Nevertheless, only three patients have asked to discontinue the treatment. We conclude that intrathecal baclofen, delivered by a manually operated implanted pump, is an effective treatment for severe spasticity in most patients.

Adult↗
PubMed1990

Synthesis and antiinflammatory activity of novel 12 beta-substituted analogues of betamethasone.

A series of 9 alpha-halo-12 beta-hydroxy and 12 beta-acyloxy analogues of betamethasone 17,21-dipropionate were synthesized and tested for topical antiinflammatory potency in the croton oil ear assay. The compounds were assayed for systemic absorption in the contralateral ear assay, in which it was found that 12 beta-hydroxy analogues 9, 13, and 15 were all absorbed but the corresponding 12 beta-esters 11a-e, 14, and 16 were not. On repeated high-dose applications to the mouse ear, there was no evidence of systemic absorption of any 12 beta-propionate ester as gauged by thymus weights (thymic involution) and plasma cortisol levels (adrenal suppression). Results of limited SAR studies showed that topical antiinflammatory activity and systemic absorption were not greatly influenced by the 9 alpha-halogen but were largely dependent on the polarity and size of the 12 substituent. While the optimal compounds 14 and 16 were less topically active than the controls beta- and beclomethasone dipropionate, unlike the controls, they displayed no systemic effects, even after repeated high-dose applications. Surprisingly, propionate 14 was devoid of atrophogenic activity.

Animals↗
PubMed1984

Gamma interferon induction depresses murine hepatic promutagen/procarcinogen activation.

In vivo induction of gamma interferon (IFN-gamma) by sensitization of mice with Mycobacterium bovis strain BCG and subsequent challenge with tuberculin depressed the ability of liver homogenates from treated animals to metabolically activate promutagens. The Ames Salmonella typhimurium revertant assay was used for analyses of metabolic conversion of promutagens by liver homogenates. Relative to the mutant frequencies determined with control liver homogenates, induction of IFN-gamma depressed the abilities of homogenates from treated animals to activate N-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and benzo[a]pyrene (BP) by 55%, 44% and 95%, respectively. Within 18-24 h of Aroclor 1254 treatment, liver P-450 content had increased 43%, and the relative mutant yields per unit protein for all three promutagens had approximately doubled. In vivo induction of IFN-gamma suppressed the Aroclor 1254-dependent increases in mutagenesis by AAF (63%), AFB1 (90%), and BP (reduced to a level 23% below non-Aroclor 1254 treatment). In all cases, the levels of depression of promutagen activation qualitatively correlated with cytochrome P-450 content and the induction of IFN-gamma.

Animals↗
PubMed1984

Effects of 5-halopyrimidinones with antiviral and antineoplastic activity on murine cytochrome P-450.

Several 5-halopyrimidinones have been shown to have many different biological activities. These include interferon induction, antitumor effects, modulation of immune responses, and polyclonal B-cell activation. The present study was carried out to determine the effects of treatment of mice with two 5-halopyrimidinones, 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and 2-amino-5-iodo-6-phenyl-4(3H)-pyrimidinone (AIPP), on the murine cytochrome P-450 system. Administration of ABPP or AIPP to mice by a dosage regimen similar to that resulting in interferon induction by these chemicals resulted in a significant depression in liver cytochrome P-450 levels. These results suggest that 5-halopyrimidinones can depress cytochrome P-450 levels and that this depression may affect the metabolism of other drugs by cytochrome P-450.

Animals↗