Heat shock protein 27: developmental regulation and expression after peripheral nerve injury

The heat shock protein (HSP) 27 is constitutively expressed at low levels in medium-sized lumbar dorsal root ganglion (DRG) cells in adult rats. Transection of the sciatic nerve results in a ninefold upregulation of HSP27 mRNA and protein in axotomized neurons in the ipsilateral DRG at 48 hr, without equivalent changes in the mRNAs encoding HSP56, HSP60, HSP70, and HSP90. Dorsal rhizotomy, injuring the central axon of the DRG neuron, does not upregulate HSP27 mRNA levels. After peripheral axotomy, HSP27 mRNA and protein are present in small, medium, and large DRG neurons, and HSP27 protein is transported anterogradely, accumulating in the dorsal horn and dorsal columns of the spinal cord, where it persists for several months. Axotomized motor neurons also upregulate HSP27. Only a minority of cultured adult DRG neurons are HSP27-immunoreactive soon after dissociation, but all express HSP27 after 24 hr in culture with prominent label throughout the neuron, including the growth cone. HSP27 differs from most axonal injury-regulated and growth-associated genes, which are typically present at high levels in early development and downregulated on innervation of their targets, in that its mRNA is first detectable in the DRG late in development and only approaches adult levels by postnatal day 21. In non-neuronal cells, HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefore, its upregulation after adult peripheral nerve injury may both promote survival of the injured neurons and contribute to alterations in the cytoskeleton associated with axonal growth.     

Clinical, physiological, and radiological study of a new purpose-designed artificial bowel sphincter

BACKGROUND: Studies of the use of artificial urinary sphincters for faecal incontinence have led to refinement and adaptation of such sphincters to the anatomy of the anal region. We aimed to test this new device. METHODS: Six women, median age 53 (range 32-58) years, who were unsuitable for sphincter repair, had an artificial bowel sphincter implanted as a one-stage procedure without colostomy cover. Clinical assessment, physiological testing, and endosonography were done before and after the operation. Plain radiography, three-dimensional endosonography, and magnetic-resonance imaging were done after the operation, to define its anatomical location. RESULTS: Median follow-up was 10 (range 5-13) months and the device was functional in five patients. In one patient, the device was removed after ulceration through the skin. Of the patients with intact devices, Wexner incontinence scores improved from a median of 19 (18-20) of 20 before the operation, to 3 (0-6) of 20 after the operation. Median anal pressure at rest significantly increased from 60 (range 30-80) cm H2O to 110 (100-120) cm H2O. Functional anal-canal length varied after the operation from 3.3 cm to 3.8 cm. There was no significant change in the maximum tolerated volume of the rectum (140 [80-230] vs 100 [75-250] mL), or rectal compliance (2.9 [2.8-6.0] cm H2O/mL vs 3.5 [2.3-7.3] cm H2O/mL). All the imaging techniques accurately located the implant relative to the anal canal and pelvic floor in each patient. INTERPRETATION: The new artificial bowel sphincter provided a good functional result in five of the six patients, the surgical procedure was straightforward, and the maximum resting anal pressure rose without affecting rectal function. The ease of visualisation of such implants in situ should aid simple management of complications, should they arise.     

Directional stimulus-response compatibility: a test of three alternative principles

The basis of directional stimulus-response compatibility was studied using a task in which 128 participants moved a cursor into targets with a joystick, resembling the operation of certain industrial and construction equipment. Compatible and incompatible versions of three alternative compatibility principles were compared in all combinations. Visual Field (VF) compatibility was present if cursor and controlling limb movement were in the same direction in the visual field, Control Display (CD) compatibility meant that the control motion was in the same direction as, and parallel to, cursor motion, and Muscle Synergy (MS) compatibility was defined as use of the muscle synergy normally associated with the required direction as seen in the visual field. VF-compatible conditions had significantly shorter reaction, movement and homing times, and fewer reversal errors, for males and females, in two testing sites. These advantages were maintained over practice. VF compatibility was confirmed as a robust spatial compatibility principle that is affected by neither the orientation of the operator's limb or head nor the muscle synergy used in executing the task. It offers not only more rapid performance, but also a markedly reduced rate of potentially dangerous directional errors. The relationship between this finding and theoretical aspects of stimulus-response compatibility is discussed.     

Complications of surgery for epiretinal membranes

PURPOSE: Surgery has been successful in removing epiretinal membranes (ERM) from the macula, allowing some improvement in vision in 80-90% of patients; however, complications are relatively frequent. We conducted a retrospective study to evaluate the rate of peri- and postoperative complications and their influence on functional outcome of eyes having been operated on for ERM. MATERIAL AND METHODS: Preoperative findings, intraoperative and postoperative complications as final results of 70 consecutive cases of idiopathic or secondary ERM operated on by the same retina surgeon were analyzed. RESULTS: In all cases the ERMs were successfully removed from the fovea. The mean visual acuity (VA) increased from 0.34 +/- 0.2 to 0.54 +/- 0.31 (P < 0.05) postoperatively. Idiopathic and secondary ERM both showed significant improvement after surgery. Complications included intraoperative hemorrhage and retinal tears and postoperative progressive nuclear sclerosis, retinal tears causing detachments, macular edema and retinal pigmentary epitheliopathy. Final VA was not significantly different from the mean after complications, apart from when retinal detachments involved the macular area. CONCLUSIONS: Performing surgery for ERM is worthwhile in eyes with major decreased VA and in eyes with metamorphopsia but only moderately reduced vision. Postoperative complications are frequent but can usually be managed successfully. Of them, only retinal detachment has a negative effect on the final functional outcome.     

A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages

The aims of the work were (1) to develop statistical tests to identify whether substitution takes place under a covariotide model in sequences used for phylogenetic inference and (2) to determine the influence of covariotide substitution on phylogenetic trees inferred for photosynthetic and other organisms. (Covariotide and covarion models are ones in which sites that are variable in some parts of the underlying tree are invariable in others and vice versa.) Two tests were developed. The first was a contingency test, and the second was an inequality test comparing the expected number of variable sites in two groups with the observed number. Application of these tests to 16S rDNA and tufA sequences from a range of nonphotosynthetic prokaryotes and oxygenic photosynthetic prokaryotes and eukaryotes suggests the occurrence of a covariotide mechanism. The degree of support for partitioning of taxa in reconstructed trees involving these organisms was determined in the presence or absence of sites showing particular substitution patterns. This analysis showed that the support for splits between (1) photosynthetic eukaryotes and prokaryotes and (2) photosynthetic and nonphotosynthetic organisms could be accounted for by patterns arising from covariotide substitution. We show that the additional problem of compositional bias in sequence data needs to be considered in the context of patterns of covariotide/covarion substitution. We argue that while covariotide or covarion substitution may give rise to phylogenetically informative patterns in sequence data, this may not always be so.     

HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens

We have investigated the genetic and molecular basis of immune responsiveness to short ragweed (SRW) (Ambrosia artemisiifolia) extract, and group 5 allergens from short and giant (Ambrosia trifida) ragweed using transgenic mice expressing DQ6 (HLA-DQA1*0103, HLA-DQB1*0601) and DQ8 (HLA-DQA1*0301, HLA-DQB1*0302) genes in class II knockout (A beta0) mice. Panels of overlapping peptides spanning the Amb a 5 and Amb t 5 Ags were synthesized. Mice were immunized with whole SRW extract or individual peptides s.c. and lymph node cells (LNC) were challenged in vitro. Strong T cell responses to SRW extract were measured in both HLA-DQ transgenic mice, while control, HLA-DQ6-/DQ8-/H-2A beta0, mice were unresponsive. IL-5 and IL-10 were the primary cytokines produced by in vitro challenged LNC of SRW-primed transgenic mice. HLA-DQ6-restricted T cell responses were detected to all three peptides of Amb t 5 and two determinants (residues 1-20 and 11-30) on Amb a 5. In contrast, LNC of HLA-DQ8 mice did not recognize peptide 11-30 of Amb t 5 Ag, but recognized several Amb a 5 determinants. The immune response in transgenic mice was dependent upon CD4+ T cells and was HLA-DQ restricted. Primed with purified Amb t 5, both transgenics recognized peptide 21-40, and an additional DQ6-restricted epitope was found within residue 1-20. SRW-immunized HLA-DQ6 mice respond to peptide 11-30 of Amb a 5, while HLA-DQ8 mice strongly recognize peptide 1-20. These results demonstrate the specificity of HLA class II polymorphism in allergen sensitivity and pave the way for developing antagonistic peptides for desensitization.     

Comorbidities and prediction of length of hospital stay

Columnar epithelium-lined esophagus (Barrett's esophagus) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Columnar epithelium resembling intestinal metaplasia (IM) is especially important, since it is considered to be a premalignant condition. The aim of this study was to define the sulfated carbohydrate chain of mucin and its core peptide profile in Barrett's esophagus (BE) and to compare it with the profile in Barrett's adenocarcinoma and lower esophageal adenocarcinoma. The sulfated carbohydrate chain was not expressed in 16 specimens of normal esophageal epithelium, but in BE, it was expressed in 50% (8/16) of the specimens. This chain was detected in 100% (7/7) of esophageal adenocarcinoma specimens, including four cases of Barrett's adenocarcinoma. These data suggest that the sulfated carbohydrate chain may be associated with malignant phenotype of the esophagus. MUC1 core peptide was positive in 87% (13/15) of BE specimens and in 29% (2/7) of the esophageal adenocarcinoma specimens. MUC2 core peptide was present in 57% (8/14) and 43% (3/7) of these specimens, respectively. These data suggest that Barrett's epithelium, which is similar to IM, but not normal esophageal epithelium, expresses the sulfated sugar chain which is known to be present in gastric IM and colonic mucosa. However, there was no significant correlation between the expression of the sulfated sugar chain and the expression of either mucin core peptide MUC1 or MUC2. Thus, this carbohydrate chain may be expressed on as yet unidentified core proteins, other than MUC1 or MUC2 core peptide, in BE and esophageal adenocarcinoma. Identification of these proteins may be very important in helping to detect premalignant status in BE.     

Early operative intervention after thrombolytic therapy for primary subclavian vein thrombosis: an effective treatment approach

PURPOSE: Effective treatment of primary subclavian vein thrombosis focuses on restoration of venous patency, relief of intrinsic stenosis, and decompression of the thoracic inlet. The appropriate method and timing for surgery, however, have not been not well defined. We conducted a study to determine an acceptable treatment approach. METHODS: A retrospective review evaluated 11 patients seen at our institution in an 8-year period. Seven patients were male and four were female, with an average age of 30 years (range 15 to 54 years). Two patients who had symptomatic stenosis without occlusion were omitted from the study. All patients with occlusion received urokinase therapy and underwent surgical decompression within 5 days of thrombolytic therapy. Five percutaneous transluminal angioplasties were attempted before operative intervention. Eleven decompressions were performed, including nine first-rib resections and two scalenectomies. Five operative venous procedures, consisting of thrombectomy with patch closure (n = 3) and bypass (n = 2), and seven venolysis procedures were performed. All patients received coumadin for 3 to 6 months after the operation. RESULTS: Urokinase therapy established wide venous patency in nine of the 11 extremities treated, with the remaining two requiring thrombectomy for residual thrombus at the time of operation. One patient who underwent transluminal angioplasty before the operation had rethrombosis, and the remaining four showed no improvement in venous stenosis after the intervention. Eight of nine extremities treated by first-rib resection and one of two treated by scalenectomy were free of residual symptoms at follow-up. CONCLUSIONS: Preoperative use of percutaneous balloon angioplasty is ineffective and should be avoided in this setting. Surgical intervention within days of thrombolysis obviates the need for interim oral anticoagulation and enables patients to return to normal activity sooner.