Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction

Objectives. Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied.Methods. Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 μg of subcutaneous recombinant EGF on a daily basis after UUO.Results. Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clusterin gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma.Conclusions. These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.     

A Decade of Change in Obesity Surgery

Background: The International (formerly National) Bariatric Surgery Registry began collecting data in January 1986. The aim of this study was to examine changes in the practice of surgical treatment of severe obesity that occurred during the decade of 1986 through 1995, as observed in the IBSR data. Methods: All data submitted to the IBSR during the decade were transferred to the IBM mainframe computer for analysis. Characteristics of operative type populations were compared over time using analysis of variance (ANOVA) for age, body mass index (BMI), operative weight and Chi-square (χ²) test for gender. Results: There has been a steady increase over the decade in mean patient weight. The operations used have changed from predominantly ‘simple’ operations to more frequent use of ‘complex’ operations. Within the categories of ‘simple’ and ‘complex’, an increase in the variety of operations occurred. As a group, patients with ‘simple’ operations have been heavier, more often male and public pay patients than those who have undergone ‘complex’ operations. One year weight loss was greater for Roux-en-Y gastric bypass (RGB) than vertical banded gastroplasty (VBG), but follow-up rates were too low to study the relative merits of the operations used. The reported incidence of operative mortality and serious complications (leak with peritonitis, abscess and pulmonary embolism) remained low. Conclusions: These observations and their implications can be summarized in three statements which relate to action for improved patient care in the beginning of the new century: (1) increasing weight of candidates for surgical treatment during this decade indicates the need for earlier use of operative treatment before irreversible complications of obesity can develop; (2) low risk of obesity surgery, decreasing postoperative hospital stay, and early weight control support the continued and increased use of surgical treatment; (3) continued widespread use of both ‘simple’ and ‘complex’ operations with increased modifications of standard RGB and VBG procedures emphasizes the need for standardized long-term data and analyses regarding both weight control and postoperative side-effects.     

Recurrent dislocation of the patella and the Goldthwait operation

In this study 17 patients with recurrent dislocation of the patella were followed up 10 years after their Goldthwait operation. The subjective and clinical findings were excellent or good in 70%. X-radiographs indicated osteoarthritis of the femoropatellar joint in 60%. Concerning the aetiopathological factors, we found an increased external torsion of the afflicted extremity (measured by computed tomography).     

Bullous pemphigoid in association with cutaneous lesions specific to a myelodysplastic syndrome

Specific cutaneous lesions are a rare occurrence in myelodysplastic syndromes (MDS). The concurrent association of blistering skin lesions similar to those in bullous pemphigoid (BP), even though a rare event, suggests that BP may be a paraneoplastic syndrome. We report an 86-year-old man who had a refractory anaemia with excess bone marrow blasts in transformation, who developed a generalized pruritic blistering eruption. Immunohistopathological tests showed subepidermal blisters with linear deposits of IgG and C3 along the basement membrane zone of the epidermis surrounding a tumoral dermal infiltrate of CD13+ and CD15+ cells. Immunoblotting studies using epidermal extracts revealed circulating IgG antibodies against three protein bands: a 210–215 kDa band. a 180kDa band which co-migrated with the BP 180 antigen, and a 190kDa band. The tumour infiltrate may have revealed antigenic determinants which led to the onset of BP. The concept of paraneoplastic pemphigoid remains to be either confirmed or invalidated by further epidemiological studies.     

Detection of neutral protease (Periocheck) and BANA hydrolase (Perioscan) compared with traditional clinical methods of diagnosis and monitoring of chronic inflammatory periodontal disease

Abstract Perioscan requires a plaque sample to detect the presence of enzymes capable of degrading N-benzoyl-DL-arginine-2-naphthylamide (BANA) from relatively few anaerobic periodontal pathogens. Periocheck assays the presence of neutral proteases in crevicular fluid. The aim of this study was to compare these test kits with traditional clinical methods of detecting periodontal disease and to monitor the ability of the kits to reflect the response to initial therapy. 19 patients with moderately severe chronic periodontitis were seen before and after a course of oral hygiene and root instrumentation consisting of 4 appointments. Clinical measurements and test assays were collected at 5 diseased sites and 2 healthy sites in each subject. Complete data from 125 sites were available for statistical analysis. At baseline Periocheck had a sensitivity of 88% and a specificity of 61% whereas Perioscan had a sensitivity of 99% and a specificity of 55%, when related to the clinical diagnosis. A composite clinical assessment, based on improvement or deterioration of one whole unit change of the subjective clinical indices and 2mm changes or greater in probing depth or probing attachment level, revealed 75 sites which improved following treatment, whereas 45 sites did not change and 5 sites deteriorated. The probability that the tests agreed with the clinical outcome after treatment, was calculated as 50.4% for Periocheck and 52% for Perioscan. The diagnostic kits did not reliably reflect the clinical assessment of periodontal disease in the cross sectional study, or the outcome following treatment.     

Effects of capsaicin in temporomandibular joint arthritis in rats

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P- (SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.     

Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.