Phosphorylation of receptors and ion channels and their interaction with structural proteins

The death rate from pneumonia in Singapore has increased steadily over the past decade. The emerging respiratory pathogens may have contributed to this increased mortality. New challenges have arisen from changes in the characteristics of the host and the susceptibilities of the various pathogens to antibiotics. There has been a 60-fold increase in the incidence of penicillin resistance in Streptococcus pneumoniae, the major pathogen for community-acquired pneumonia (CAP). Gram-negative bacilli are the major pathogens in severe CAP with Klebsiella pneumonia being the most frequently isolated organism. There has been a small increase in the number of cases of Legionnaire's disease and a marked increase in the incidence of melioidosis. While the overall incidence of tuberculosis has been unchanged, the number of non-residents with tuberculosis has doubled in the past 5 years. The rising prevalence of human immunodeficiency Virus infection is reflected in an increasing number of apparently healthy young men who present with CAP caused by Pneumocystis carinii. There is increasing resistance to antibiotics among gram-negative bacilli and Staphylococcus aureus, the dominant pathogens in hospital-acquired pneumonia. New strategies are urgently needed to prevent the emergence of pathogens in the hospital environment which may be resistant to all known antibiotics.     

Comparison of IL-10 levels in chronic venous insufficiency ulcers and autologous donor tissue

In previous immunohistochemical studies, chronic venous insufficiency (CVI) ulcers have been shown to display positive staining for interleukin-10 (IL-10), while other wounds (including autologous donor wound tissue) show a reduced staining level. IL-10 inhibits the synthesis of many proinflammatory cytokines, while also inhibiting antigen presentation by antigen-presenting cells. It is possible that abnormally high amounts of IL-10 in chronic wounds may be related to the failure of these wounds to progress to final wound healing. The purpose of this study was to quantify the levels of IL-10 in CVI ulcers and autologous donor tissue using Western blotting. Extracts were prepared from frozen wound tissue samples and equal amounts of protein were concentrated by immune-precipitation for Western blot analysis. Densitometric analysis was performed on nonsaturated chemilumigraphs and normalized to an IL-10 standard run on each gel. The quantity of IL-10 in CVI ulcers was found to be 490% of the quantity in autologous donor tissue. This study provides confirmatory quantitative data which supports previous immunohistochemical findings showing elevated levels of IL-10 in CVI ulcers.     

Laparoscopic evaluation for a contralateral patent processus vaginalis: part III

OBJECTIVES: Between May 1, 1992 and August 1, 1996, 759 consecutive children younger than 10 years of age were evaluated and treated for known inguinal hernia. These children were participating in a prospective investigation of the potential role of diagnostic laparoscopy in the evaluation of the contralateral inguinal anatomy. The initial two series of data (parts I and II of this three-part series) were previously presented at the 1993 and 1995 American Academy of Pediatrics meetings. METHODS: Of 759 patients, 100 children were diagnosed with bilateral inguinal hernias and therefore did not undergo laparoscopy. Thirty-two patients did not undergo laparoscopic evaluation due to technical difficulties or complicated clinical situations. The patient's contralateral inguinal region was carefully examined under anesthesia, and predictions were made regarding the likelihood of contralateral patent processus vaginalis (CPPV). Six hundred twenty-seven children underwent diagnostic laparoscopy to confirm the presence or absence of CPPV. Laparoscopy was initially exclusively performed through the umbilicus prior to repair of the known hernia, but over the last 26 months, 250 children successfully underwent laparoscopy through the ipsilateral hernia sac. RESULTS: Of patients younger than 1 year of age, 114 were diagnosed with both a known unilateral hernia and CPPV, whereas 132 had a unilateral hernia only (46% versus 54%). Among children older than 1 year of age, 148 (39%) were diagnosed with unilateral hernia and CPPV, and 233 (61%) were diagnosed with a unilateral hernia alone. After examination under anesthesia, 233 of the 627 patients were suspected of having a CPPV, and 107 were confirmed at laparoscopy (46%). The remaining 394 patients were not believed to have a CPPV. Normal inguinal anatomy was confirmed in 234 patients (59%), but 160 patients were found at laparoscopy to have a CPPV (41%). CONCLUSIONS: A contralateral patent processus vaginalis may be present in a surprising number of young patients being evaluated for a known inguinal hernia. Laparoscopy can be performed without a separate incision when the ipsilateral hernia sac is of sufficient width to allow passage of the scope. Laparoscopy is the best method for evaluating the contralateral inguinal region, particularly in younger children, as it prevents unnecessary inguinal exploration and it decreases the risk that the child will later present with a clinical contralateral hernia.     

Report of the first workshop on the genetic map of bovine chromosome 1

Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and cytokines were measured in supernatants from cultures of peripheral blood mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with asthma, and healthy individuals. All cultures for the three subject groups were studied in the presence and absence of two purified Af antigens (the 35-kD antigen and heat shock protein 1). We found that increased in vitro levels of IgE in unstimulated PBMC culture supernatants correlated significantly with serum IgE concentrations in ABPA patients. We measured a decrease in IgE levels of up to 75% of baseline values in supernatants from PBMC cultured with Af antigens. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in the three subject groups. An inverse relation was noted between the changes in IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser extent in purified eosinophils from healthy subjects. These results show that the 35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of inducing eosinophilia in ABPA. Further studies could result in the characterization of epitopes leading to these disparate effects. An identification of the IgE-down-regulating epitopes in Af antigens might have therapeutic significance.     

Effect of gastrin-17 on lower esophageal sphincter characteristics in man

We studied the effect of gastrin-17 on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in two experiments performed in random order during continuous infusion of saline (control) or gastrin-17 (15 pmol/kg/hr). LES pressure (LESP) and transient lower esophageal sphincter relaxations (TLESR), as most the important reflux mechanism, were measured with intraesophageal sleeve manometry combined with pH metry. Infusion of gastrin-17 resulted in plasma gastrin levels comparable to those reached after a mixed meal. During continuous gastrin infusion, LESP decreased significantly (P < 0.05) compared to control. The rate and duration of TLESR was not influenced by gastrin-17. Gastroesophageal reflux and the number of TLESR associated with reflux were significantly (P < 0.05) increased during gastrin infusion. These results suggest that in humans gastrin at physiological postprandial plasma concentrations decreases LESP, does not influence TLESR, but increases the percentage of TLESR associated with reflux.     

Suppressors of an Arabidopsis thaliana phyB mutation identify genes that control light signaling and hypocotyl elongation

Ambient light controls the development and physiology of plants. The Arabidopsis thaliana photoreceptor phytochrome B (PHYB) regulates developmental light responses at both seedling and adult stages. To identify genes that mediate control of development by light, we screened for suppressors of the long hypocotyl phenotype caused by a phyB mutation. Genetic analyses show that the shy (short hypocotyl) mutations we have isolated fall in several loci. Phenotypes of the mutants suggest that some of the genes identified have functions in control of light responses. Other loci specifically affect cell elongation or expansion.     

Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD

Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). Second, the expansion of CD8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of FasL on CD8+ cells was found in patients with aGVHD (P < 0.01). In summary, an increase in the percentage of CD8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD.     

Characterization of emissions of dioxins and furans from ethylene dichloride (EDC), vinyl chloride (VCM) and polyvinylchloride (PVC) manufacturing facilities in the United States. I. Resin, treated wastewater, and ethylene dichloride

Under the auspices of its Dioxin Characterization Program, members of The Vinyl Institute (VI), have analyzed for potential polychlorinated dibenzodioxin/furan (PCDD/F) concentrations in polyvinylchloride (PVC) resins, treated wastewater effluent and ethylene dichloride (EDC) product at EDC, vinyl chloride monomer (VCM) and PVC manufacturing facilities in the U.S. and Canada. No 2,3,7,8-tetrachlorodibenzodioxin (TCDD) was detected in any sample analyzed under the program to date. Trace concentrations (low pg/g) of PCDD/F were detected in only a few samples of PVC resins and EDC product. Treated wastewater contained low ppq concentrations of PCDD/F. All concentrations are expressed as Toxic Equivalents (TEQ). Extrapolation of these data shows that the contribution of EDC/VCM/PVC manufacturing via these media constitutes substantially less than 1 percent of the estimated annual U.S. dioxin releases to the environment.     

Nontumorous arterioportal shunt mimicking hypervascular tumor in cirrhotic liver: two-phase spiral CT findings

PURPOSE: To determine the two-phase (hepatic arterial phase [HAP] and portal venous phase [PVP]) spiral computed tomographic (CT) findings of a nontumorous arterioportal shunt in the cirrhotic liver that can mimic a hypervascular tumor. MATERIALS AND METHODS: For 14 months, 803 patients with known or suspected hepatocellular carcinoma were referred for initial or repeated transcatheter arterial chemoembolization (TACE). Twenty-nine hyperattenuating lesions on HAP CT images obtained in 25 patients (23 men, two women; age range, 39-70 years) were regarded as nontumorous arterioportal shunts and were included in this study. The diagnosis of nontumorous arterioportal shunt was established by four radiologists who reviewed the two-phase spiral CT images and hepatic angiograms. RESULTS: The longest dimension of the lesion was 1.0-7.9 cm (mean dimension, 2.9 cm). The morphology at HAP CT was wedge-shaped in 25 (86%), geographic (ie, focal area with irregular outline) in two (7%), and nodular in two (7%) lesions. All lesions were homogeneous in attenuation. Hyperattenuating linear branching structures that represented early opacification of portal veins were demonstrated during the HAP in nine (31%) lesions. PVP CT images showed these lesions as isoattenuating (n = 20 [69%]) or slightly hyperattenuating (n = 9 [31%]). Iodized oil CT images showed faint or no accumulation of iodized oil in all lesions. CONCLUSION: In cirrhotic liver, nontumorous arterioportal shunts can be a cause of pseudolesions that mimic hypervascular tumors at two-phase spiral CT. Lesions that have the typical wedge-shaped and homogeneous appearance with or without internal linear branching structures during the HAP and that are isoattenuating or slightly hyperattenuating during the PVP can suggest this unusual condition.