The effect of nonablative laser energy on the ultrastructure of joint capsular collagen

This study was designed to evaluate the effect of laser energy at nonablative levels on the ultrastructure of joint capsular collagen. The femoropatellar joint capsules of six mature New Zealand white rabbits were harvested immediately after death. Specimens were divided into three treatment groups (5, 10, and 15 watts) and one control group. Laser energy was applied using a holmium: YAG laser. Transmission electron microscopy showed significant ultrastructural alterations in collagenous architecture for all laser treatment groups, with increased fibril cross-sectional diameter for each of the treated groups. The fibrils began to lose their distinct edges and their periodical cross-striations at subsequently higher energy densities. A morphometric analysis showed that each subsequently higher laser energy caused a significant increase in collagen fibril diameter. Ultrastructural alteration of collagen fibril architecture caused by the thermal effect of laser energy is probably the dominant mechanism of laser-induced tissue shrinkage.     

Bilateral brachial plexus neuritis following parvovirus B19 and cytomegalovirus infection

A man, 23 years of age, had a typical erythema infectiosum, complicated by a severe bilateral brachial plexus neuritis. Motor function recovered slowly and only partially after 6 months. An infection by human parvovirus B19 was demonstrated, with strongly positive and gradually declining IgM antibodies and viral DNA detectable in serum for more than 3 months. There was also clear evidence of a recent infection by cytomegalovirus. The interaction between these two viruses could be responsible for this rare and severe complication of common infections in this patient.     

Effect of mebendazole on free amino acid composition of cyst wall and cyst fluid of Echinococcus granulosus harbored in mice

Eighteen and 23 FAA components were detected in the cyst wall and cyst fluid of E granulosus, respectively, by using automatic amino acid analyzer. The concentrations of most of the determined FAA were higher in the cyst fluid than those in the cyst wall, especially the taurine was 5-fold higher. Mebendazole treatment resulted in an increase in the concentration of alanine, valine, lysine, and taurine in both cyst wall and cyst fluid, the most notable being the alanine in the cyst wall. The results are interpreted as a coupling of glycolysis and amino acid metabolism, suggesting an involvement of FAA metabolism in the mechanism of Meb action.     

Differences in self reported morbidity by educational level: a comparison of 11 western European countries

Raman and infrared spectra were examined for guanosine 5'-diphosphate (GDP) and guanosine 5'-triphosphate (GTP) in aqueous solution. The vibrational modes were assigned on the basis of isotopic frequency shifts and relative intensities in the Raman and infrared spectra. The observed frequency shifts on 18O isotope labeling made it possible to identify the bands from each phosphate group (alpha, beta, gamma). Frequency shifts were observed as Mg2+ complexes with GDP and GTP. The results suggested that Mg2+ binds to GDP in a bidentate manner to the alpha, beta P[symbol: see text]O bonds and in a tridentate manner to the alpha, beta and gamma P[symbol: see text]O bonds of Mg.GTP. The results indicate that structure of Mg2+ coordinated to GTP in aqueous solution differs somewhat to that found for Mg.ATP.     

Gelatinase A (MMP-2) and cysteine proteinases are essential for the degradation of collagen in soft connective tissue

Epidermal growth factor (EGF) is a potent mitogen for normal mouse mammary epithelial cells grown in primary culture. EGF activation of the EGF-receptor (EGF-R) induces intrinsic tyrosine kinase activity which results in EGF-R autophosphorylation and tyrosine phosphorylation of other intracellular substrates involved in EGF-R signal transduction. Genistein and erbstatin are anticancer agents which have been shown to be potent tyrosine kinase inhibitors. However, the effects of these compounds in modulating EGF-dependent normal mammary epithelial cell proliferation is presently unknown. Therefore, studies were conducted to determine the effects of genistein and erbstatin on EGF-dependent proliferation, and EGF-R levels and autophosphorylation in normal mouse mammary epithelial cells grown in primary culture and maintained in serum-free media. Chronic treatment with 6.25-100 microM genistein or 1-16 microM erbstatin significantly decreased EGF-dependent mammary epithelial cell proliferation in a dose-responsive manner. However, the highest doses of genistein (100 microM) and erbstatin (16 microM) were found to be cytotoxic. Additional studies showed that acute treatment with 6.25-400 microM genistein did not affect EGF-R levels or EGF-induced EGF-R autophosphorylation, while acute treatment with 1-64 microM erbstatin caused a slight reduction in EGF-R levels, but had no effect on EGF-dependent EGF-R autophosphorylation in these cells. In contrast, chronic treatment with similar doses of genistein or erbstatin resulted in a large dose-responsive decrease in EGF-R levels, and a corresponding decrease in total cellular EGF-R autophosphorylation intensity. These results demonstrate that the inhibitory effects of chronic genistein and erbstatin treatment on EGF-dependent mammary epithelial cell proliferation is not due to a direct inhibition of EGF-R tyrosine kinase activity, but results primarily from a down-regulation in EGF-R levels and subsequent decrease in mammary epithelial cell mitogenic-responsiveness to EGF stimulation.     

Modulation of the voltage-gated sodium current in rat striatal neurons by DARPP-32, an inhibitor of protein phosphatase

DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methyl-D-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP-32 in striatal neurons. Using a whole cell patch-clamp technique, we have studied the role of DARPP-32 in the regulation of voltage-gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho-DARPP-32, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induced by okadaic acid, with which there was no additivity and by tautomycin. Our results indicate that, in striatal neurons, sodium channels are under dynamic control by phosphorylation/dephosphorylation, and that phospho-DARPP-32 reduces sodium current by stabilizing a phosphorylated state of the channel or an associated regulatory protein. We propose that the DARPP-32-mediated modulation of sodium channels, via inhibition of phosphatase 1, contributes to the regulation of these channels by D1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP-32.     

The immunology of corneal graft rejection

Corneal transplantation is the most successful of organ transplants due to the fact that the eye is an immunologically privileged site, and the cornea is an immunologically privileged tissue. The factors responsible for this include presence of the blood-aqueous barrier, the avascularity of the cornea, the absence of classic antigen-presenting cells (APCs) in the central cornea, inhibitory factors in the aqueous humor, the phenomenon known as anterior chamber-associated immune deviation (ACAID), and the intraocular expression of Fas ligand. Loss of ocular immune privilege can occur with breaching of the blood-ocular barrier, corneal neovascularization, migration of classic APCs to the center of the cornea, loss of inhibitory factors in aqueous humor, abrogation of ACAID, and loss of Fas ligand expression within the anterior chamber. The purpose of this review is to analyze these events and how they relate to corneal graft rejection. A discussion on future research and therapeutic modalities is provided.     

Accuracy of single-photon emission computed tomography myocardial perfusion imaging in patients with stents in native coronary arteries

Strategies to noninvasively evaluate patients after coronary stenting have not been evaluated. To determine the accuracy of single-photon emission computed tomography (SPECT) myocardial perfusion imaging in patients after coronary stenting, 209 patients who had undergone stenting followed by late stress SPECT myocardial perfusion imaging were evaluated. Quantitative coronary angiography was performed in 33 patients following SPECT imaging. SPECT restenosis was defined as a reversible or fixed defect within the stented vascular territory. Angiographic restenosis was examined using 2 definitions: total area narrowing > or =50% or > or =70% of the stent site or stented artery. The SPECT and angiographic findings were concordant in 22 of 33 stented vascular territories using the 50% definition of restenosis and in 29 of 33 stented territories using the 70% definition. Use of the 70% definition of restenosis resulted in improved accuracy of SPECT to detect a significant stenosis in the stented artery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SPECT were 95%, 73%, 88%, 89%, and 88% respectively. In patients with positive SPECT scans, the most significant stenosis in the stented artery was outside the stent site in 50% of cases. SPECT imaging appears to be accurate to predict significant stenosis in the stented artery, although the most severe stenosis is frequently distant from the stent site.     

Controversies in Crohn's disease

Despite recent advances in the medical therapy of Crohn's disease, surgery continues to play a central role in the treatment of the disease. The strategy for surgical management of Crohn's disease continues to evolve. This chapter reviews many of the controversies surrounding surgical palliation of complications of Crohn's disease. Included is a discussion of indications for strictureplasty in treatment of intractable intestinal obstruction. Factors influencing long-term outcome with sphincter-saving resection in the treatment of Crohn's colitis are reviewed. Experience with definitive treatment of anal Crohn's disease and repair of rectovaginal fistulas is examined. Finally, recent experience supporting ileocolic resection when acute Crohn's ileitis is identified during laparotomy for right lower quadrant pain is critically evaluated. These controversial aspects of the surgical treatment of Crohn's disease reflect an improved understanding of the natural history of the disease as well as refinement in surgical techniques and better definition of criteria for surgical intervention.