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Biomedical subjects

R A Wagner

Publications and source records attributed to R A Wagner.

14 recordsLinked to original sources
PubMed1995

Evidence for developmentally programmed transdifferentiation in mouse esophageal muscle.

Transdifferentiation is a relatively rare phenomenon in which cells of one differentiated type and function switch to a second discrete identity. In vertebrate embryos, smooth muscle and skeletal muscle are distinct tissues that arise from separate compartments of the mesoderm. The musculature of the mouse esophagus was found to undergo a conversion from smooth muscle in the fetus to skeletal muscle during early postnatal development. The switch from smooth to skeletal muscle features the transitory appearance of individual cells expressing a mixed phenotype, which suggests that this conversion is a result of programmed transdifferentiation.

Actinin↗
PubMed1995

Muscarinic regulation of the cardiac CFTR Cl- current by quaternary ammonium compounds.

In guinea pig ventricle, the protein kinase A-regulated Cl- current (ICl) is conducted by an alternatively spliced isoform of the cystic fibrosis transmembrane conductance regulator. We studied muscarinic regulation of this current using the whole-cell configuration of the patch-clamp technique. Acetylcholine (ACh) antagonized activation of ICl activated by 1 microM isoproterenol (ISO) in a concentration-dependent manner. The concentration of ACh that produced a half-maximal effect (K1/2) was 36 nM, the slope factor was 1.1, and the relative magnitude of the Cl- conductance at maximally effective concentrations of ACh (Gmin) was 21% of that observed in the presence of ISO alone. In the presence of 100 nM atropine, a competitive antagonist at the muscarinic receptor, the K1/2 value for ACh inhibition of ICl was increased to 4.3 microM, but the slope factor and Gmin were not affected, which indicated that the dissociation constant (KB) for atropine was < 1 nM. ACh-induced inhibition of the ISO-activated ICl was also blocked by the quaternary ammonium compound tetraethylammonium (TEA). Like atropine, TEA increased the K1/2 value for ACh inhibition of ICl without affecting the slope factor or Gmin. Schild analysis confirmed that TEA is also a competitive antagonist at the muscarinic receptor, with a KB value of 137 microM. However, tetramethylammonium (TMA), a structurally related compound, acted as an agonist at the muscarinic receptor. TMA inhibited ICl activated by 1 microM ISO with a K1/2 value of 342 microM, a slope factor of 0.87 and a Gmin value of 17%. Increasing the concentration of ISO shifted the K1/2 value for both ACh and TMA inhibition of ICl to higher concentrations and increased Gmin, without significantly affecting the slope factor. These results indicate that muscarinic regulation of ICl depends on the level of beta adrenergic stimulation in a functionally uncompetitive manner. They also suggest that TMA acts like ACh, a full agonist at the muscarinic receptor. Furthermore, we conclude that quaternary ammonium compounds, which are often used as ion substitutes and direct ion channel blockers, should be used with caution because of the significant and diverse effects they exert at muscarinic receptors.

Acetylcholine↗
PubMed1994

Evaluation of serum estradiol concentrations in alopecic ferrets with adrenal gland tumors.

Seventeen ferrets were examined because of progressive bilaterally symmetric alopecia that was nonpruritic. Dermatologic and endocrinologic testing were used to determine the cause of the alopecia. Resting cortisol, testosterone, and thyroxin concentrations and results of ACTH stimulation tests were found to be within reference range limits established for this species. High serum estradiol concentrations were found to be a reliable indicator of adrenal cortical neoplasia in these ferrets.

Adenocarcinoma↗
PubMed1994

Effect of two nonsteroidal antiinflammatory drugs on heterotopic bone formation in a rabbit model.

Using the model described by Michelsson, 24 mature New Zealand white rabbits underwent mechanical induction of heterotopic ossification in the quadriceps of the right hind limb. The rabbits were equally divided into four groups: indomethacin-treated, piroxicam-treated, and their respective controls. The effect of drug therapy on the production of heterotopic bone was assessed by analyzing plain radiographs of the femur using the grading system described by Scott. The results demonstrated that, while indomethacin is effective in decreasing the formation of heterotopic bone, piroxicam--when used in the dosage previously demonstrated to have no deleterious effect on healing bone--is not. The analysis of piroxicam blood levels demonstrated that the experimental piroxicam dose is inadequate to produce effective plasma blood levels in the rabbit. Therefore, any potential benefit from using piroxicam, as opposed to other nonsteroidal antiinflammatory drugs regarding fracture healing and bone remodeling, cannot be applied for the prophylactic treatment of heterotopic bone formation.

Animals↗
PubMed1994

Revision total hip arthroplasty in the deficient femur with a proximal load-bearing prosthesis.

The proximal femur is frequently structurally deficient in revision hip arthroplasty, and makes obtaining prosthesis stability more difficult. Between 1984 and 1990, 174 patients were treated with revision total hip arthroplasty, performed by a standardized surgical technique, using cortical onlay strut allografts to restore the structural integrity of the femur, and a calcar replacement proximally porous-coated femoral prosthesis, composed of titanium alloy. The grafts united 98% of the time, and showed evidence of revascularization, and in some cases, complete incorporation. To date, six have been revised for femoral failure. Successful reconstruction of the deficient femur after failed total hip arthroplasty is dependent on several factors: the revision prosthesis must be stable, the deficient femoral bone stock must be augmented, and load must be transferred to the proximal femur so that the future proximal femoral resorption is minimized. The host femur and allograft will respond physiologically to load bearing, and the graft increases bone quantity and quality. The prosthesis must be supported primarily on host bone; the graft may enhance prosthetic support, but can never be used for primary prosthetic support when using uncemented revision prostheses.

Aged↗
PubMed1993

Tetramethylammonium activation of muscarinic receptors in cardiac ventricular myocytes.

Replacement of extracellular Na+ with tetramethylammonium (TMA) reduces the magnitude of the Cl- current activated by beta-adrenergic receptor stimulation in guinea pig ventricular myocytes. However, the effects of replacing Na+ appear to be associated with the presence of TMA, rather than the absence of Na+. Direct addition of TMA to extracellular solutions, without changing the Na+ concentration, was able to inhibit the Cl- current activated by isoproterenol (Iso) in a concentration-dependent manner. The concentration of TMA that caused half-maximal inhibition was 327 microM when the Cl- current was activated by 1 microM Iso and 29 microM when the Cl- current was activated by 0.03 microM Iso. The effect of TMA was also blocked by atropine, suggesting that TMA exerts its effect through stimulation of the muscarinic receptors. Furthermore, TMA inhibited the Iso-activated Ca2+ current, as would be expected for an effect involving muscarinic receptor stimulation. The response to complete Na+ replacement with TMA could not be overcome by increasing the concentration of Iso 1,000-fold, and direct addition of TMA was able to antagonize the Cl- current activated independently of the beta-adrenergic receptor, using forskolin and histamine. These results are consistent with the hypothesis that TMA does not exert its effects through a competitive mechanism at the beta-adrenergic receptor. It is concluded that TMA is able to antagonize adenosine 3',5'-cyclic monophosphate-dependent activation of ion channels in the heart through activation of muscarinic receptors.

Animals↗
PubMed1993

Restoration of femoral bone stock in revision total hip arthroplasty.

The presence of femoral deficiencies in revision total hip arthroplasty may contribute to loosening, subsidence, and fracture. Between 1984 and 1990, 174 patients were treated with revision total hip arthroplasty, preformed by a standardized operative technique using cortical onlay strut allografts to restore the structural integrity of the femur and a calcar deficient proximally porous coated femoral prosthesis, composed of titanium alloy. The grafts united 98% of the time and showed evidence of revascularization and, in some cases, complete incorporation. Cortical onlay strut grafting in conjunction with a proximal load- bearing prosthesis is a viable method of reconstructing the structurally deficient femur in revision total hip arthroplasty.

Aged↗
PubMed1986

Enterococcal bacteremia in two large community teaching hospitals.

This report reviews 55 episodes of enterococcal bacteremia at two large community teaching hospitals. Fifty-eight percent of the patients were older than 60 years, and 84 percent of the patients had some underlying illness. The most common sources of bacteremia were the urinary tract (24 percent), cutaneous wound infection (11 percent), and intra-abdominal infection (11 percent). Five patients had enterococcal endocarditis. Antimicrobial therapy in the week preceding enterococcal bacteremia (42 percent) and polymicrobial bacteremia (38 percent) were common. Despite the institution of appropriate antimicrobial therapy in 75 percent of the patients (41 of 55 patients), the overall mortality rate was 44 percent. Male sex and the presence of a rapidly or ultimately fatal underlying illness were the only factors that showed a statistical tendency toward adversely influencing the mortality risk in enterococcal bacteremia.

Age Factors↗
PubMed1985

Mycotic endophthalmitis caused by Penicillium sp. after parenteral drug abuse.

A 30-year-old man developed endophthalmitis three weeks after an intravenous injection of hydromorphone hydrochloride. Penicillium species was recovered from a vitreous aspirate. Treatment with amphotericin B and flucytosine resulted in documented sterilization of the vitreous. At a six-month follow-up examination, the visual acuity of the involved eye was still limited to light perception.

Adult↗
PubMed1981

Glycosylation is not required for membrane localization or secretion of IgM in a mouse B cell lymphoma.

We have investigated the importance of glycosylation in determining the function of membrane-bound and secreted immunoglobulin M (IgM). Hickman and Kornfeld (1978) previously observed that glycosylation is required for IgM to be secreted by 104E, a mouse plasma cell tumor. In order to determine whether this requirement is a general one for all forms of IgM, we have used WEHI 279.1, a mouse B lymphoma that synthesizes both the membrane and secreted forms of IgM. In the presence of 5 microgram/ml tunicamycin (Tm), glycosylation of both membrane and secreted IgM is at least 90% inhibited, but total protein synthesis is equivalent in control and Tm-treated cells. Despite the absence of carbohydrate, IgM molecules are properly assembled into monomers for membrane localization. Cells whose surfaces have been stripped of membrane IgM by treatment with anti-mu antibody resynthesize the IgM equally well in the presence or absence of Tm. It is more surprising that the assembly of IgM into pentamers and the secretion of these pentamers into the medium are accomplished at the same rate and to about the same levels in control and Tm-treated WEHI 279.1 cells. This is in sharp contrast to the profound inhibition of IgM secretion observed when the plasmacytoma cell 104E is treated with the same concentration of Tm (5 microgram/ml). Although both WEHI 279.1 and 104E cells secrete IgM, the 2 are models for cells at very different points along the B cell differentiation pathway. The difference in the effect of Tm-treatment on IgM secretion may reflect a cellular change that occurs during this differentiation. The unglycosylated IgM is very sensitive to trypsin digestion, whereas the native forms are not. This suggests that the function of glycosylation may be to stabilize the IgM against proteolysis.

Animals↗
PubMed1980

Interactions and survival of enteric viruses in soil materials.

There were marked differences in the abilities of eight different soil materials to remove and retain viruses from settled sewage, but for each soil material the behavior of two different viruses, poliovirus type 1 and reovirus type 3, was often similar. Virus adsorption to soil materials was rapid, the majority occurring within 15 min. Clayey materials efficiently adsorbed both viruses from wastewater over a range of pH and total dissolved solids levels. Sands and organic soil materials were comparatively poor adsorbents, but in some cases their ability to adsorb viruses increased at low pH and with the addition of total dissolved solids or divalent cations. Viruses in suspensions of soil material in settled sewage survived for considerable time periods, despite microbial activity. In some cases virus survival was prolonged in suspensions of soil materials compared to soil-free controls. Although sandy and organic soil materials were poor virus adsorbents when suspended in wastewater, they gave >/=95% virus removal from intermittently applied wastewater as unsaturated, 10-cm-deep columns. However, considerable quantities of the retained viruses were washed from the columns by simulated rainfall. Under the same conditions, clayey soil material removed >/=99.9995% of the viruses from applied wastewater, and none were washed from the columns by simulated rainfall.

Adsorption↗