Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.     

Methicillin-resistant Staphylococcus aureus: investigation of a hospital outbreak using a case-control study

A retrospective case-control study of 50 MRSA-positive patients was carried out during an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at an acute general hospital in London. Controls were randomly selected from MRSA-negative patients admitted during the outbreak period. Risk factors investigated included length of admission prior to screening, number of ward changes, main diagnosis, extent of staff contact, pressure sores, surgical and other invasive procedures and antibiotic treatment. Outcome variables examined were rates of infection (versus colonization) with MRSA and mortality. Patients with MRSA were in hospital longer before microbiological specimens were taken and moved wards more often than controls. In a logistic regression analysis, length of stay in hospital, pressure sores, physiotherapy and surgical procedures were associated with a significantly increased risk of acquiring MRSA. Odds ratios (and 95% confidence intervals) for having acquired MRSA were: 8·3 (1·02−71·43) if a patient had pressure sores; 3·7 (1·10−12·5) if they received physiotherapy; and 3·2 (1·82−10·0) if they underwent surgical procedures. The rate of clinical infection amongst patients with this strain of MRSA was 26% and included life-threatening infections such as septicaemia, underlining the potential virulence of MRSA. Surgery and physiotherapy may have been markers of debility. Physiotherapy was probably a marker of increased rates of contact with all hospital staff, and high standards of hand hygiene should be promoted amongst all staff as the most important factor in controlling an outbreak of MRSA. Good bed management is essential for hospital infection control.     

Access to primary health care for Australian young people: service provider perspectives.

BACKGROUND: To adequately address the complex health needs of young people, their access to services, and the quality of services received, must be improved. AIMS: To explore the barriers to service provision for young people and to identify the training needs of primary healthcare service providers in New South Wales (NSW), Australia. DESIGN OF STUDY: A cross-sectional, qualitative study of the perspectives of a range of health service providers. SETTING: A range of primary healthcare organisations across NSW. METHODS: Samples of general practitioners (GPs), youth health workers, youth health coordinators, and community health centre staff were drawn from urban and rural clusters across NSW. Focus groups and interviews were used to identify barriers to service provision and the training needs of service providers. Data were tape recorded, transcribed, and analysed. RESULTS: Barriers to service provision among GPs and community health centre staff included inadequate time, flexibility, skills, and confidence in working with young people, and poor linkages with other relevant services. Training needs included better knowledge of and skills in adolescent health requirements, working with adolescents, and working with other services. Barriers to service provision for youth health workers and coordinators included lack of financial resources and infrastructure. There were few linkages between groups of service providers. CONCLUSION: Models of service provision that allow stronger linkages between service providers, sufficient time for consultation with young people, adequate training and support of health professionals, and flexibility of service provision, including outreach, should be explored and evaluated.     

Error analysis by simulation studies in renography deconvolution

The renogram, defined as the time-activity curve obtained from measurements with a gamma detector over the kidneys after a prior injection of a radioactive tracer, can be quantified using the deconvolution method. Essentially all the inherent information in the renogram, the estimated relative renal uptake function and transit time spectrum through the kidney, can be derived from the computed renal retention function. This study shows how statistical and physiological noise and different backgrounds affect the accuracy of the derived parameters. Confidence intervals for the estimated relative renal function and mean transit time (MTT) are presented. The principal source of error in relative renal function was due to extrarenal background. It was found that the error in mean transit time due to statistical noise was proportional to MTT, that the presence of extrarenal background strongly affected the accuracy of the MTT, whereas the vascular background in the renogram was of minor importance. Physiological noise, interpreted as periodic changes in transit times does, strictly speaking, invalidate the deconvolution principle, but it was possible to calculate a valid mean value of the different actual transit times. The transit time spectrum, measured by differentiation of the computed retention function, was found to be of no practical value with use of the unconstrained matrix method. The signal to noise ratio and consequently the need for smoothing can be estimated from the sum of the squared second derivatives of the renogram itself. The plateau levels in the renal retention function provide a more reliable estimate for the relative function ratio than the relative amplitude of a renogram in which extrarenal background only has been subtracted.