Enhancement of antipsychoticlike properties of raclopride in rats using the selective serotonin2A receptor antagonist MDL 100,907

OBJECTIVE: To study the superior-inferior stabilizing functions of the coracohumeral ligament (CHL) and the rotator interval capsule (RIC) with use of a material testing machine. MATERIAL AND METHODS: The axial translations of the humerus with the superior-inferior translation force of 30 N applied were recorded under the following joint capsule conditions: (1) intact, (2) vented, (3) the CHL sectioned, and (4) the RIC incised in six cadaver shoulders. The order of sectioning was changed for conditions 3 and 4 in six other cadaver shoulders. RESULTS: With the arm in internal and neutral rotations, venting the capsule significantly increased the superior-inferior translation, which was unaffected by further sectioning of the CHL and the RIC. With the arm in external rotation, only the CHL contributed significantly to inferior stability, whereas both this ligament and the RIC contributed to superior stability to a lesser degree. CONCLUSION: The CHL is a stabilizer in superior inferior directions with the arm in external rotation, and the intra-articular pressure that is maintained by the intact RIC is a stabilizer in superior-inferior directions with the arm in internal and neutral rotations. These findings may provide a scientific background to support closure of the interval space to stabilize the shoulder and may explain part of the superior instability observed in shoulders with rotator cuff tears.     

Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-gamma but requires TNF-alpha

CD8+ T cells are effective mediators of immunity against Listeria monocytogenes, but the mechanisms by which they provide antilisterial immunity are poorly understood. CD8+ T cells efficiently lyse target cells in vitro by at least two independent pathways. To test the hypothesis that CD8+ T cell-mediated immunity to L. monocytogenes is dependent on perforin or CD95 (Fas, Apo-1), we used C57BI/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines specific for the L. mono cytogenes-encoded Ag listeriolysin O (LLO). Both lines specifically produce IFN-gamma and TNF-alpha, and mediate target cell lysis in vitro. Cytolysis mediated by the PO-derived CD8+ T cell line is delayed relative to the B6-derived line and is completely inhibited by anti-CD95 Abs. In vivo, PO-derived CD8+ T cells provide specific antilisterial immunity in B6 hosts, CD95-deficient hosts, and IFN-gamma-depleted hosts. However, PO-derived CD8+ T cells fail to provide antilisterial immunity in hosts depleted of TNF-alpha. These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-gamma, but requires TNF-alpha.     

Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice

PURPOSE: To determine the diagnostic accuracy of computed tomography (CT) for pneumonia in patients with adult respiratory distress syndrome (ARDS). MATERIALS AND METHODS: CT scans were obtained within 1 week of bronchoscopic sampling in 31 patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11 patients with pneumonia, five developed symptoms less than 11 days after the onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy was defined by means of the area under the receiver operating characteristic curve, or A2. RESULTS: Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/- 0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive ratings). The generalizability coefficient was good (0.79). No single CT finding was significantly different for the presence of pneumonia. Nondependent opacities predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with early ARDS and 13 (87%) of 15 with late ARDS. CONCLUSION: CT has fair diagnostic accuracy for ventilator-associated pneumonia in patients with ARDS owing primarily to identification of patients without pneumonia. No single CT sign was significantly different for pneumonia, but dependent atelectasis was more common in patients with early ARDS without pneumonia.     

Hepatocyte growth factor/scatter factor has distinct classes of binding site in heparan sulfate from mammary cells

Hepatocyte growth factor/scatter factor (HGF/SF) is a heparan sulfate (HS)-binding growth factor and morphogen for mammary epithelial cells that is produced by mammary stromal fibroblasts. HS chains, purified as peptidoglycans from a panel of cell lines representative of the ductal epithelial cell (Huma 123), the myoepithelial cell (Huma 109), the stromal fibroblast (Rama 27), and malignant mammary epithelial cells (MCF-7 and ZR-75), were used in a biosensor-based assay to identify the classes of HGF/SF-binding sites in the polysaccharide chains. At least three distinct binding sites were identified. One site exhibits fast association and fast dissociation kinetics [kass (1.4-7.7) x 10(6) M-1 s-1; kdiss 0. 0032-0.0096 s-1] and is present on the HS from benign Huma 123 epithelial cells, Huma 109 myoepithelial-like cells, and ZR-75 malignant cells. The second binding site, found on HS from the malignant MCF-7 cells, has slower HGF/SF-binding kinetics (kass 0.20 x 10(6) M-1 s-1; kdiss 0.00055 s-1). The third binding site possesses fast association and slow dissociation kinetics (kass 1.1 x 10(6) M-1 s-1; kdiss 0.00020 s-1) and was found on the HS isolated from the culture medium of the Huma 123 benign epithelial cells. The first and second binding sites have a similar Kd, 1-3 nM, while the third binding site has a considerably higher affinity for HGF/SF (Kd 200 pM). The three binding sites seem to be mutually exclusive, since each sample of HS possessed just one of the sites.     

Primary anastomosis in the treatment of acute disease of the unprepared left colon

Between June 1, 1990 and December 31, 1996, 58 consecutive patients with unprepared colons were urgently explored for nontraumatic disease with intent to proceed with primary left-sided colonic anastomosis. Unprotected anastomoses were not attempted in 15 patients. The causes of exclusion included preoperative and intraoperative shock in three patients, and three patients were on long-term high-dose steroids, four had gross fecal contamination of the peritoneal cavity, four had large pelvic abscesses, and one had ischemic colitis. All 43 patients undergoing anastomosis without protective colostomy had stapled anastomoses. Indications included complicated diverticular disease in 32 cases. There were nine cases of obstruction from colorectal carcinoma and one obstruction due to sigmoid volvulus. There was one case of perforation from pseudomembranous enterocolitis. The most common complications were: atelectasis in nine cases, wound infection in two cases, and prolonged ileus in two cases. Pelvic abscess occurred in one case. There was one wound dehiscence. There was one anastomotic dehiscence, and there was no mortality. Operative time averaged 85 minutes and hospital length of stay 9.7 days. Primary anastomosis of the unprepared left colon is safe in most urgent and emergent situations, thus avoiding the significant morbidity and cost of colostomy closure.     

Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice

Hypertrophic cardiomyopathy (HCM) is a disease of sarcomeric proteins. The mechanism by which mutant sarcomeric proteins cause HCM is unknown. The leading hypothesis proposes that mutant sarcomeric proteins exert a dominant-negative effect on myocyte structure and function. To test this, we produced transgenic mice expressing low levels of normal or mutant human cardiac troponin T (cTnT). We constructed normal (cTnT-Arg92) and mutant (cTnT-Gln92) transgenes, driven by a murine cTnT promoter, and produced three normal and five mutant transgenic lines, which were identified by PCR and Southern blotting. Expression levels of the transgene proteins, detected using a specific antibody, ranged from 1 to 10% of the total cTnT pool. M-mode and Doppler echocardiography showed normal left ventricular dimensions and systolic function, but diastolic dysfunction in the mutant mice evidenced by a 50% reduction in the E/A ratio of mitral inflow velocities. Histological examination showed cardiac myocyte disarray in the mutant mice, which amounted to 1-15% of the total myocardium, and a twofold increase in the myocardial interstitial collagen content. Thus, the mutant cTnT-Gln92, responsible for human HCM, exerted a dominant-negative effect on cardiac structure and function leading to disarray, increased collagen synthesis, and diastolic dysfunction in transgenic mice.     

Plasma patterns of tumor necrosis factor-alpha (TNF) and TNF soluble receptors during acute meningococcal infections and the effect of plasma exchange

In 39 patients with acute meningococcal infections, the plasma concentrations of tumor necrosis factor-alpha (TNF) and its soluble receptors (sRs) TNFsR-p55 and TNFsR-p75 were measured from admission till recovery. At admission, patients with shock had significantly higher TNF, TNFsR-p55, and TNFsR-p75 values than patients without shock. In addition, during the first 24 hours, patients with shock had higher TNFsR-p75 to TNFsR-p55 ratios, indicating that in shock the increase of TNFsR-p75 exceeds that of TNFsR-p55. TNF measured more than 12 hours after admission failed to differentiate between shock and nonshock because TNF concentrations normalized within 12-24 hours. However, because concentrations of TNFsRs remained elevated for 5-6 days, at that time plasma TNFsRs still differentiated between shock and nonshock. Plasma exchange or whole blood exchange (PEBE), performed in 20 patients with shock, accelerated the decrease of plasma TNFsRs. However, because of a rebound after each PEBE session, the overall half-lives of both TNFsRs were not affected by PEBE.     

Sildenafil (Viagra) for the treatment of erectile disorder

Erectile dysfunction is a common but underreported condition. It is to be expected that the number of patients consulting their physician with the complaint of erectile dysfunction will increase considerably with the introduction of sildenafil (Viagra), the first oral drug that enhances penile erection. Sildenafil is an inhibitor of the enzyme phosphodiesterase type 5. It causes erection of the penis by allowing the relaxation of the smooth musculature of the cavernous body to persist. The first clinical results indicate that the treatment with sildenafil is safe and effective in the hands of a sexologically qualified physician. An erection disorder is essentially not more than a symptom which primarily requires causal therapy.     

Mitotic and polytene chromosome analyses in the Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae)

The Queensland fruit fly, Bactrocera tryoni, like the Mediterranean fruit fly, Ceratitis capitata, has a diploid complement of 12 chromosomes, including five pairs of autosomes and a XX/XY sex chromosome pair. Characteristic features of each chromosome are described. Chromosomal homology between B. tryoni and C. capitata has been determined by comparing chromosome banding pattern and in situ hybridisation of cloned genes to polytene chromosomes. Although the evidence indicates that a number of chromosomal inversions have occurred since the separation of the two species, synteny of the chromosomes appears to have been maintained.