Obliterative bronchiolitis after lung and heart-lung transplantation

Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.     

EC Directive on the Control of Dangerous Substances (76/464/EEC): Its Impact on the UK Water Industry

This paper discusses the impact on the UK water industry of EC legislation which has been adopted and proposed for the control of dangerous substances discharged to the aquatic environment. The main impact arises from the increased monitoring needs, requiring more sophisticated analytical equipment and skilled staff, together with the increased administrative burden to produce reduction programmes and to set and control consents for dangerous substances. The paper also summarizes recent initiatives which have been taken by the UK towards a more precautionary approach to pollution control, by requiring that 'red-list' substances should be controlled by environmental quality standards and limit values whichever are the more stringent.     

Glutathione S-transferase a major allergen of the house dust mite, Dermatophagoides pteronyssinus

Cutaneous electrogastrography (EGG) allows the measurement of gastric electrical activity. An association of EGG with gastrointestinal motility disorders has been shown. Abnormalities of electrical rate or rhythm are accepted as the most important parameters in EGG. However, the reliability of the magnitude of electrical amplitude in the assessment of motility is discussed controversially. Therefore in a prospective study we investigated the relation between amplitude and antral contractions by means of ultrasonography. 8 healthy volunteers (4 men, 4 women, 24-31 years) ingested 400 ml carbonated mineral water after an overnight fast at two separate study days. Over a period of 10 min preprandial and 10 min postprandial small and intense antral contractions were measured employing sagittal antral planimetry. Simultaneous amplitudes were determined during contractions and at 1 min intervals (average amplitude) by cutaneous electrogastrography. Data were analyzed by Wilcoxon's rank sum test and Spearman rank correlation test. The coefficient of variation of the postprandial/preprandial amplitude ratio was nearly two times greater between subjects than between recordings in the same subject, which reflects a moderate intraindividual reproducibility. We found a significant increase in the average amplitude postprandially (p < 0.05). Although postprandial contractions (n = 243) predominated preprandial contractions (n = 127) significantly (p = 0.02), no significant correlation between the number of contractions and the average amplitude existed (R = 0.1; p = 0.7). Moreover the average amplitude did not differ from amplitudes during intense and small contractions significantly (p = 0.7; p = 0.1). The magnitude of the amplitude measured by EGG does not correlate with the mechanical gastral activity significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct voltammetric observation of redox driven changes in axial coordination and intramolecular rearrangement of the phenylalanine-82-histidine variant of yeast iso-1-cytochrome c

Direct square-wave and cyclic voltammetric electrochemical examination of the yeast iso-1-cytochrome c Phe82His/Cys102Ser variant revealed the intricacies of redox driven changes in axial coordination, concomitant with intramolecular rearrangement. Electrochemical methods are ideally suited for such a redox study, since they provide a direct and quantitative visualization of specific dynamic events. For the iso-1-cytochrome c Phe82His/Cys102Ser variant, square-wave voltammetry showed that the primary species in the reduced state is the Met80-Fe2+-His18 coordination form, while in the oxidized state the His82-Fe3+-His18 form predominates. The addition or removal of an electron to the appropriate form of this variant serves as a switch to a new molecular form of the cytochrome. Using the 2 x 2 electrochemical mechanism, simulations were done for the cyclic voltammetry experiments at different scan rates. These, in turn, provided relative rate constants for the intramolecular rearrangement/ligand exchange and the equilibrium redox potentials of the participating coordination forms: kb,AC = 17 s-1 for Met80-Fe3+-His18 --> His82-Fe3+-His18 and kf,BD > 10 s-1 for His82-Fe2+-His18 --> Met80-Fe2+-His18; E0' = 247 mV for Met80-Fe3+/2+-His18 couple, E0' = 47 mV for His82-Fe3+/2+-His18 couple, and E0' = 176 mV for the cross-reaction couple, His82-Fe3+-His18 + e- --> Met80-Fe2+-His18. Thermodynamic parameters, including the entropy of reaction, DeltaS0'Rxn, were determined for the net reduction/rearrangement reaction, His82-Fe3+-His18 + e- --> Met80-Fe2+-His18, and compared to those for wild-type cytochrome, Met80-Fe3+-His18 + e- --> Met80-Fe2+-His18. For the Phe82His variant mixed redox couple, DeltaS0'Rxn = -80 J/mol.K compared to DeltaS0'Rxn = -52 J/mol.K for the wild-type cyt c couple without rearrangement. Comparison of these entropies indicates that the oxidized His82-Fe3+-His18 form is highly disordered. It is proposed that this high level of disorder facilitates rapid rearrangement to Met80-Fe2+-His18 upon reduction.     

From Manchester Docks to Salford Quays: Ten Years of Environmental Improvements in the Mersey Basin Campaign

The decline of the former Manchester Docks and its resurgence as Salford Quays is described. The isolation of water within the Quays from the Manchester Ship Canal was a principal proposal of the development plan, and the water-treatment system which was installed has been highly successful in creating a thriving aquatic ecosystem and enabling water-based recreation activities to take place. Whilst the water quality within the Quays is excellent, outside in the Manchester Ship Canal it remains grossly polluted. Under the auspices of the Mersey Basin campaign, the various partners are involved in a major project to clean up the canal. The Lowry Centre, a Millennium Fund bid, is giving an added impetus to this work. The conclusions identify the involvement of the local council as being critical to the success of the project, and that a respect for quality has been essential, as has a long-term commitment to an overall vision.     

Awareness during anesthesia and posttraumatic stress disorder

The prevalence of tarsal coalition is probably 1% or less. The two sites most commonly affected are the calcaneonavicular joint and the middle facet of the talocalcaneal joint. Diagnosis should be suspected in the preteen or teenage patient with insidious or sudden onset of pain in the midfoot to hindfoot associated with a lack of motion in the subtalar joint. Initial treatment with immobilization or an orthosis may relieve symptoms, but most patients will have persistent symptoms that warrant surgical correction. Long-term results indicate that excision of the coalition is moderately successful in relieving symptoms in the calcaneonavicular bar. Long-term success with excision of subtalar bars is less clear, although early relief of symptoms is usually possible.     

Living with mental illness: the family as caregiver

1. Families of persons with severe mental illness are often anguished because of stressors and are unprepared to be caregivers. Their needs must be addressed by mental health professionals. 2. Family members may experience grief, guilt, anger, powerlessness, and fear. 3. Education and peer groups may be most helpful to family members in dealing with their distress and becoming better prepared caregivers.     

The isolation and characteristics of the green monkey lentivirus

We characterized the simian immunodeficiency virus isolated from Cercopithecus aethiops (subspecies C. a. pygerythrus) originating from Kenya. SIV was isolated and continuously produced with the MOLT4 clone 8 cell line and was designated as SIV-SU1. SIV-SU1 isolate replicated with high efficiency in MOLT4 clone 8, MT-2 with moderate efficiency in CEM x 174 and with poor efficiency in HUT-78, U937, C8166. The infection of MT-2, C8166 and HUT-78 resulted in extensive cell killing. Western blotting of purified preparations of SIV-SU1 revealed viral proteins of 130, 68, 55, 41, 24, 17 kDa. Cross-reactivity of SIV-SU1 proteins with HIV-1, HIV-2, SIVmac, SIVsm, SIVmnd was studied by radioimmunoprecipitation assay. The most extensive cross-reactivity was observed with SIVmac. Total cellular DNA from chronically infected cells was hybridized to SIVagm266 DNA probes. Detection of cross-hybridizing DNA sequences required very low stringency, and the restriction endonuclease fragmentation pattern of SIV-SU1 differed from other SIVs.     

Harlequin ichthyosis. Variability in expression and hypothesis for disease mechanism

BACKGROUND: Harlequin ichthyosis is an inherited skin disorder that usually results in death shortly after birth. Although the clinical features of this disorder are well described, the underlying molecular basis is not understood. In this article, we discuss the results of the latest histologic, immunochemical, and Western immunoblotting studies done in our laboratory and propose a hypothesis for molecular basis of this disorder. OBSERVATIONS: Previous experiments done in our laboratory show suggestive evidence for defective lipid synthesis and protein dephosphorylation in harlequin ichthyosis. Our latest study shows that the catalytic subunit of one of the most prevalent protein phosphatase, type 2A protein phosphatase, appears to be altered in some cases of type 2 harlequin ichthyosis. CONCLUSIONS: Based on these observations and the known functions of protein phosphatase in keratinocytes, we hypothesize that the underlying molecular basis of harlequin ichthyosis may be related to mutations affecting protein dephosphorylation. We further describe approaches by which this hypothesis can be tested.