Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: structural requirements differ from those for responses to lipopolysaccharide

The purpose of this study was to identify the functional significance of the binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to compare the structural requirements of sCD14 for the binding to PGN and lipopolysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS-induced cell responses. sCD14 did not facilitate the responses of membrane CD14 (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the responses of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells to PGN. sCD14 enhanced mCD14-mediated cell activation by both PGN and LPS, but only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein. Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region of sCD14 were needed for binding to both PGN and LPS and for enhancement of cell activation by both PGN and LPS. However, deletions of individual sequences had different effects on the ability of sCD14 to bind to PGN and to LPS and on the ability to enhance the responses to PGN and to LPS. Thus, there are different structural requirements of sCD14 for binding to PGN and to LPS and for the enhancement of PGN- and LPS-induced cell activation.     

Effect of High Doses of Radiation on Human Neutrophil Chemotaxis, Phagocytosis and Morphology

Human neutrophils were exposed to varying amounts of ionizing radiation up to 1,000,000 rad and evaluated as to their ability to respond to chemotactic stimuli and phagocytize and kill bacteria. Striking morphologic and functional resistance to radiation was apparent. At doses up to 5,000 rad there was little or no impairment of chemotaxis. As the dosage increased to 50,000 rad, chemotaxis decreased to approximately 50% of nonirradiated control values. At very high doses of radiation (250,000 to 1,000,000 rad) neutrophils failed to respond significantly to chemotactic stimuli. Effects of radiation as measured by phagocytosis and the degree of ultrastructural change paralleled the chemotaxis results.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

An Upsurge in early childhood mortality in Kenya: A search for explanations

This study seeks to document recent trends in early childhood mortality in the country and to offer some plausible explanations for the upsurge in the trends. Data and information from various sources are used in this paper to achieve this purpose. The results obtained show that infant, child and under-five mortality rates had declined in the 1960s and 1970s but were taking an upward trend since early 1990s. This situation is attributable to a combination of factors, including increased poverty, adverse effects of economic hardships and cost recovery programs associated with structural adjustment programs, increased childhood malnutrition, decreased use of certain maternity care services, decline in the coverage of child immunisations, inability of the public health system to provide services, and the HIV / AIDS epidemic and the recent ethnic clashes that rocked some parts of the Rift Valley, Coast, Nyanza and Western province. In order to reverse the upward trend in mortality, there is an urgent need to intensify efforts to reduce poverty, to enable most people to have adequate food supply, improve the public health sector so that it can deliver health care to all people; to make greater efforts to raise the living standards of rural populations and improve the quality of housing, sanitary and sewerage conditions in urban slums. In addition, concerted efforts must continue to be made to contain the spread of HIV/AIDS, to assist Aids orphans and to eliminate completely and to avoid recurrence of ethnic clashes and cattle rustling.     

Psychiatric genetics: Research challenges and pathways forward

Lessons from past psychiatric genetic research, together with key issues in psychiatry requiring genetic investigation, are reviewed in order to consider the implications for the ways forward. It is argued that traditional quantitative genetics needs to use a combination of twin, adoptee, and family strategies, to examine continuities and discontinuities in psychopathology between childhood and adult life, to compare dimensions and categories, to employ adequate conceptualization and measurement of disorders, to use statistical techniques based on latent constructs, to use biological trait indicators where possible, to examine risk factors as well as diseases, to include good measures of postulated environmental risk variables, to study the interplay between genes and environment, and to study the key assumptions underlying genetic strategies. Molecular cytogenetics needs to consider both the general and specific psychopathological risks associated with chromosome abnormalities and to examine the mechanism involved, to examine the role of submicroscopic chromosomal deletions and of mitochondrial disorders, and to investigate the mechanisms involved in trinucleotide repeat amplifications that take place during intergenerational transmission. Molecular genetics needs to make greater use of smaller pedigrees in view of the concerns over phenotypic definition and genetic heterogeneity in very large extended dense pedigrees, to use sib-pair designs in view of the likelihood that most psychiatric disorder will prove to be multifactorial, to combine association strategies with linkage analyses, to pay careful attention to the definition of phenotypes in probands, to remain in close touch with other branches of biological psychiatry, and to make effective use of collaboration between centers. To date, transgenic models have had a rather limited application in psychiatry but, despite their difficulties, they are likely to provide an underpinning for gene therapy in disorders where that seems feasible. © 1994 Wiley-Liss, Inc.     

Reducing disparities in asthma care: priorities for research--National Heart, Lung, and Blood Institute workshop report

Minority groups with diverse racial and ethnic heritages and persons living in poverty are much more likely to die of asthma and to require emergency care for exacerbations of asthma than white persons not living in poverty. The National Heart, Lung, and Blood Institute convened a multidisciplinary group of expert scientists and clinicians to review current research aimed at understanding risk factors for these disparities in asthma health outcomes, to describe key barriers to improving asthma outcomes, and to establish priorities for future research. Education programs for asthma and other chronic diseases were reviewed. Successful elements of clinic and community-based programs were identified. Factors potentially involved in producing disparities include gene-environment interaction, psychologic and social factors, and socioeconomic status. Stress potentially contributes to asthma morbidity at both the individual and community level. Recommendations are made to stimulate research to understand risk factors for disparities and their mechanisms (e.g., gene-by-environment interactions and the role of stress), to define appropriate research designs and methods for evaluating behavioral and community interventions, and to examine how differential access to care contributes to morbidity. Research is encouraged to identify strategies that improve cultural adaptation and adoption of proven programs in a variety of populations.     

Allergic cross-reactions between cat and pig serum albumin

After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross-reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti-albumin IgE titrations and cross-inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat-allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross-sensitization not only to porcine serum albumin but also to other mammalian serum albumins.     

Patient access to records: expectations of hospital doctors and experiences of cancer patients.

The aim of this study was to examine cancer patients' reactions to the offer of access to their medical records, hospital doctors' preconceptions of patient access to medical records and the reality of access to records for both parties. Semistructured interviews were conducted with 32 patients and 21 hospital doctors. Hospital doctors were also shown letters from their department to the general practitioner and asked about any changes they would have made as a result of knowing about patient access to records. The results showed that most patients were able to judge for themselves if they wanted access or not and that patients who chose to look at their records found access to their records helpful and reassuring even if the news was bad. Doctors expected access to records to be harmful to patients but would not have wished to amend many of the letters they had written. Patient access to records can be a safe and useful adjunct to good patient care.     

Isolation and characterization of BK virus-transformed hamster cells.

BK virus (BKV) was used to transform baby hamster kidney (HK) and hamster embryo fibroblast (HE) cells in culture. Six clones of each of the BKV-transformed HK and HE cells were isolated and characterized with respect to a number of biological properties. None of the cloned lines was found to produce infectious BKV, and all 12 lines were shown to contain BKVT antigen, to have a lower serum dependency for growth and to grow to higher saturation densities than the corresponding untransformed cells, to have higher plating efficiencies than control cells, to have acquired the ability to produce colonies in soft agar, and to produce progressively growing tumors when injected subcutaneously into weanling hamsters. Differences were found to exist among the cell lines of each group with respect to these parameters, and, in general, transformed HK cells have a lower serum dependency, grow to higher saturation densities, and have higher plating efficiencies and a greater capacity to produce colonies in soft agar than do the transformed HE cells. Infection of secondary cultures of HE cells with various input multiplicities of BKV showed that transformation is a multiplicity-dependent phenomenon and can be achieved with an input multiplicity as low as 3 PFU/cell.     

Saliva-binding region of Streptococcus mutans surface protein antigen.

A 190-kDa surface protein antigen (PAc) of Streptococcus mutans binds to human salivary components. For detection of specific binding of the PAc protein to human salivary components, a simple sandwich assay was used. Microtiter plates precoated with recombinant PAc (rPAc), PAc fragments, or S. mutans whole cells were allowed to react with human whole saliva and then were incubated with biotinylated rPAc. The biotinylated rPAc bound to salivary components was detected by use of alkaline phosphatase-conjugated streptavidin and p-nitrophenylphosphate. In this assay, the binding of whole cells of S. mutans and purified rPAc to salivary components was confirmed. For determination of a saliva-binding region of the PAc molecule, 14 truncated PAc fragments were constructed by use of the polymerase chain reaction and an expression vector, pAX4a+. The binding of these truncated PAc fragments to human salivary components was determined by the sandwich assay. Among the truncated PAc fragments, fragments corresponding to residues 39 to 864 and residues 39 to 1000 of PAc showed a high ability to bind to salivary components. Shorter recombinant fragments corresponding to residues 39 to 217, residues 200 to 481, residues 470 to 749, and residues 688 to 864 did not exhibit any binding ability. The fragment that corresponds to a proline-rich repeating region (residues 828 to 1000) bound directly to the PAc protein. These results suggest that residues 39 864 of the PAc molecule are important in the binding of the surface protein to human salivary components, and the proline-rich repeating region of the PAc protein may contribute to spontaneous self-aggregation of the PAc protein.     

To What Does the Terminal Orienting Response Respond?

Previous authors suggested that the electrodermal orienting response to stimulus onset (OR) reflects cognitive processes related to the content of a stimulus while responses to stimulus offset (TOR) reflect processes related to stimulus duration. Experiment 1 tested the hypothesis that the OR and TOR are special cases of Ss responding to whatever part of the stimulus contains information necessary to make the requested judgment. The results clearly supported this alternative hypothesis. The Ss responded to stimulus onset when asked to judge the pitch (content) of a constant tone and to stimulus offset when asked to judge the terminal pitch of a varying tone. They responded to both the onset and offset of a stimulus when asked to compare the onset and offset pitch and when asked to judge stimulus duration. Experiment 2 partially replicated Experiment 1 in an attempt to assess the OR-TOR phenomenon in a second sensory modality (vision) and with a second dependent measure. The patterns of both electrodermal and heart rate responses were similar to those of Experiment 1 and to those observed by other authors.     

Effect of the Aldehyde Dehydrogenase Inhibitor, Cyanamide, on the Ex Vivo Sensitivity of Murine Multipotent and Committed Hematopoietic Progenitor Cells to Mafosfamide (Asta Z 7557)

The ex vivo sensitivity of murine multipotent (CFU-GEMM) and committed (CFU-Mk, CFU-GM, BFU-E and CFU-E) hematopoietic progenitor cells to mafosfamide was quantified with and without concurrent exposure to cyanamide, an inhibitor of aldehyde dehydrogenase activity. In the absence of cyanamide, CFU-GEMM, CFU-Mk and CFU-GM were approximately equisensitive to mafosfamide while the erythroid progenitors were more sensitive to the drug. Cyanamide potentiated the cytotoxicity of mafosfamide toward CFU-GEMM and CFU-Mk, but not toward CFU-GM, BFU-E and CFU-E. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophos-phamide/aldophosphamide, the major intermediate in cyclophosphamide and mafosfamide activation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that 1) murine CFU-GEMM contain the relevant aldehyde dehydrogenase activity, and 2) the relevant aldehyde dehydrogenase activity is retained upon differentiation to progenitors committed to the megakaryocytoid lineage, but lost upon differentiation to progenitors committed to the granulocytoid/monocytoid and erythroid lineages. The relative insensitivity of CFU-GM to mafosfamide is apparently due to a cellular determinant that influences their sensitivity to all cross-Unking agents since CFU-GM were found to be relatively insensitive to non-oxazaphosphorine cross-linking agents as well.     

Skin test reactivity to histamine from infancy to old age

The skin test reactivity to allergen and histamine differs according to the age of the patients, but complete data from infancy to old age are still lacking. Three hundred sixty-five subjects (1 to 85 years of age, 33.9% atopic, and 50.1% male patients) were prick tested with threefold dilutions of histamine hydrochloride (1 to 243 mg/ml). There was a significant (p less than 0.0001; F test) main effect of age on the skin reactivity to histamine. Age groups were defined and statistical analysis were performed by means of parallel line bioassay. All dose-response curves were linear and parallel. There is a significant increase in the mean wheal size between 4 to 5 and 6 to 9 years of age, 10 to 14 and 15 to 20 years. There was almost no difference between 15 to 20 and 21 to 50 years. No difference was observed between 21 to 30, 31 to 40, and 41 to 50 years, and then, the mean wheal sizes decreased significantly to reach a plateau after the age of 60 years. There was no sex difference, and skin tests with histamine were similar in atopic and nonatopic individuals.     

Antimicrobial susceptibility testing of Streptococcus pneumoniae: quality assessment results.

Six strains of Streptococcus pneumoniae were distributed to 405 United Kingdom laboratories who were asked to test the susceptibility of the strains to penicillin, tetracycline, chloramphenicol and erythromycin and to provide details of methodology to test the standards of susceptibility testing. High error rates were seen only in failure to detect moderate resistance to penicillin (12%) and resistance to chloramphenicol (16%). Increased error rates were associated with several methods or practices. These included the use of certain culture media; failure to standardise the inoculum; inoculation by loop rather than by swab; failure to use control organisms; failure to measure zone sizes; the use of discs containing a high content of penicillin to test susceptibility to penicillin, and the use of high content discs for testing erythromycin, tetracycline, and chloramphenicol.     

Ability of Veillonella and Neisseria Species to Attach to Oral Surfaces and Their Proportions Present Indigenously

The present study describes the distribution of Veillonella and Neisseria species in the human oral cavity and indicates that their ability to attach to oral surfaces correlates with their proportions found in various sites of the mouth. The mean percentages of Veillonella and Neisseria of the total flora cultivable on anaerobic blood-agar plates was found to be: plaque, 0.75 and <0.13, respectively; lip, 0.38 and <0.05; cheek, 0.66 and <0.14; tongue dorsum, 9.4 and <0.12; saliva, 5.0 and <0.9. The ability of Veillonella and Neisseria species to attach to tooth surfaces was studied by cleaning the labial surfaces of incisors to render them relatively free of viable bacteria. Samples taken 1 hr later contained <0.27% Veillonella and <0.4% Neisseria, whereas saliva to which these teeth were exposed contained 20-fold higher proportions of Veillonella. These data indicate that Veillonella and Neisseria species possess a feeble ability to attach to cleaned teeth. The ability of these organisms to adhere to other oral surfaces was determined by introducing mixtures of streptomycin-resistant strains into the mouths of volunteers for 5 min. Labeled strains of Streptococcus sanguis and S. salivarius were included for comparative purposes. Analysis of samples obtained from oral surfaces after 45 min indicated that Veillonella and Neisseria adhere very poorly to preformed dental plaque as compared to S. sanguis. In contrast, Veillonella adhered to the tongue dorsum markedly better than Neisseria, S. sanguis, and S. salivarius. The greater ability of Veillonella to adhere to the tongue in relation to the other organisms studied correlates with the high proportions of Veillonella found on this site. The feeble ability of Neisseria to attach to surfaces in the oral cavity is reflected by their low proportions found on these surfaces.     

Assumptions and values of community health psychology

There is a need to widen the practice of health psychologists to include the theories and methods of community psychology and an awareness of contemporary issues in community health. The aim of such a community health psychology would be both to deepen our understanding of the aetiology of health and illness in society and to develop strategies that will contribute to a reduction in human suffering and an improvement in quality of life. The aim of this article is to review the background and assumptions of community health psychology and to consider some values that would underlie such an approach.     

Prevalence of methicillin resistant Staphylococcus aureus in Karnataka

This study was undertaken to find out the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infection in our hospital and to compare their antibiotic susceptibility pattern with methicillin sensitive Staphylococcus aureus (MSSA). 100 strains of Staphylococcus aureus isolated from various clinical samples were screened for MRSA by disc diffusion method using 1 gm oxacillin disc. Antibiotic sensitivity testing was done by Kirby-Bauer's disc diffusion method. Out of these, 43% were identified as MRSA and the remaining 57% were MSSA. There was a marked difference in antibiotic sensitivity pattern of these M RSA versus the MSSA isolates. None of the MRSA isolate was found to be sensitive to amoxycillin while 36.8% of MSSA were sensitive to this antibiotic. 9.3%, 18.6%, 34.9% and 95.3% of MRSA were sensitive to cotrimoxazole, cloxacillin, ciprofloxacin and chloramphenicol, while 75.4%, 92.9%, 91.2% and 94.7% of MSSA were sensitive to these antibiotics respectively. Sensitivity to macrolide group of antibiotics like erythromycin and roxithromycin were seen in 7% and 14% of MRSA in comparison to 85.9% and 91.2% of MSSA respectively. Amongst the aminoglycosides like gentamicin and amikacin, the sensitivity of MRSA was found to be 18.6% and 46.5% and that of MSSA was 98.2% and 94.7% respectively. Sensitivity to cephalosporins like cephalexin and cefotaxime was seen in 23% and 25.5% of MRSA, whereas 100% of MSSA were sensitive to these antibiotics. All Staphylococcus aureus isolates were found to be uniformly sensitive to vancomycin. Majority of the isolates belonged to phage group III and the common phage types were 54, 54/75 and 54/75/85.     

Retinal transplantation: progress and problems in clinical application

There is currently no real treatment for blinding disorders that stem from the degeneration of cells in the retina and affect at least 50 million individuals worldwide. The excitement that accompanied the first studies showing the potential of retinal cell transplantation to alleviate the progress of blindness in such diseases as retinitis pigmentosa and age-related macular degeneration has lost some of its momentum, as attempts to apply research to the clinic have failed so far to provide effective treatments. What these studies have shown, however, is not that the approach is flawed but rather that the steps that need to be taken to achieve a viable, clinical treatment are many. This review summarizes the course of retinal transplant studies and points to obstacles that still need to be overcome to improve graft survival and efficacy and to develop a protocol that is effective in a clinical setting. Emphasis is given particularly to the consequences of introducing transplants to sites that have been considered immunologically privileged and to the role of the major histocompatibility complex classes I and II molecules in graft survival and rejection.     

The emergence of critical health psychology: can it contribute to promoting public health?

The purpose of this article is twofold: first to provide an overview of the emergence of critical health psychology for those working in the related social and health sciences and as a review of its major developments for health psychology; and second to discuss critically the potential for critical health psychology to contribute to promoting public health with specific reference to the directives espoused by Prilleltensky (2003) and Murray and Campbell (2003). The identification of three philosophical phases of the emergence of critical health psychology is used to examine the directions of the field and the challenges facing critical health psychology in order to contribute to public and global health.     

Immunogenicity of synthetic peptides of Haemophilus influenzae type b outer membrane protein P1.

To identify the B- and T-cell epitopes of P1 of Haemophilus influenzae type b, 13 peptides covering 90% of the protein were chemically synthesized. Mouse, guinea pig, and rabbit antisera raised against purified native P1 were tested for their reactivities against the peptides in peptide-specific enzyme-linked immunosorbent assays (ELISAs). Six immunodominant linear B-cell epitopes were mapped to residues 103 to 137, 189 to 218, 248 to 283, 307 to 331, 384 to 412, and 400 to 437 of the mature P1 protein. When P1 peptides were screened for their reactivities with three human convalescent-phase serum specimens, peptides corresponding to residues 39 to 64, 226 to 253, and 400 to 437 reacted strongly with the antisera. Four regions (residues 39 to 64, 226 to 253, 339 to 370, and 400 to 437) contained murine T-cell epitopes. Rabbit antipeptide antisera were tested for their reactivities with the immunizing peptides and P1 protein by ELISA and immunoblots. All anti-P1 peptide antisera except those raised against peptide HIBP1-8 (residues 279 to 312) or HIBP1-8-keyhole limpet hemocyanin conjugate were shown to be specific for their respective immunizing peptides by ELISA. In addition, rabbit antisera raised against the synthetic peptides corresponding to residues 1 to 29, 39 to 64, 103 to 137, 189 to 218, 226 to 253, 248 to 283, 307 to 331, and 400 to 437 of the mature P1 protein recognized the P1 protein from both typeable and nontypeable isolates. These results suggest that these peptides contain epitopes highly conserved among typeable and nontypeable strains of H. influenzae. However, none of the antipeptide antisera have bactericidal activity, nor were they protective against H. influenzae type b in the infant rat model of bacteremia.