Innate recognition of bacteria: engagement of multiple receptors

Until recently, consensus was that the mechanism of action of the innate immune system was a simplified one. Current research findings in the field of innate recognition of bacteria suggest that it involves complex associations of receptors depending on cell type and bacterial stimuli, CD14, integrins, Toll-like receptors (TLRs), CD55, ion channels, and activation clusters containing heat shock proteins, chemokine receptor 4 and a plethora of other molecules have been shown to serve as key molecules in bacterial recognition. In this article, we review all the advances in the field and discuss the possibility that the repertoire for recognition of pathogens is defined by the combinational engagement of multiple receptors.     

Managing pain: The Challenge in Underserved Populations: Appropriate Use Versus Abuse and Diversion

ISSUE: Inadequate pain management is a serious public health problem that affects a wide cross-section of Americans. Patients are often denied sufficient medication, because physicians lack training and fear scrutiny from federal and state regulatory agencies. In addition, even the state-financed system of care, Medicaid, has been increasingly denying payment for the best treatment for pain management. These factors are complicated by physician bias about various subgroups and poor physician-patient communication. Comprehensive patient assessment plays a crucial role in determining appropriate treatment and identifying potential abuse problems. Physicians must routinely document medications analgesic effects and screen for potential ill effects and drug abuse. OBJECTIVE: To examine the prevalence of the undertreatment of pain, particularly among African Americans, and to recommend relevant proactive policy and practice changes to aid in eliminating this health problem. CONSENSUS PROCESS: In July 2002, the NMA convened the "Managing Pain: The Challenge in Underserved Populations: Appropriate Use versus Abuse and Diversion" Consensus Meeting in Washington, DC. The country's most renowned experts in the area of pain management and substance abuse reviewed substantial information regarding pain management and substance abuse including the following: --A draft summary paper on pain management and substance abuse that served as briefing material for consensus members; --Annotated bibliographies; --Articles on pain management and substance abuse; and --Key presentations on pain management and substance abuse.     

Rochalimaea henselae sp. nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis.

Nine strains of Rochalimaea spp. that were isolated from patients over a period of 4.5 years were characterized for their enzyme activities, cellular fatty acid compositions, and DNA interrelatedness among Rochalimaea spp., Bartonella bacilliformis, and Afipia felis (cat scratch disease bacillus). All except one isolate, which was Rochalimaea quintana, were determined to belong to a newly proposed species, Rochalimaea henselae sp. nov. After recovery from clinical material, colonies required 5 to 15 days of incubation to become apparent. Cells were small, gram-negative, curved bacilli and displayed twitching motility. Enzyme specificities for amino acid and carbohydrate substrates showed that R. henselae could be distinguished from Rochalimaea vinsonii by L-arginyl-L-arginine and L-lysyl-L-alanine peptidases, but not all strains could be distinguished from R. quintana on the basis of peptidases or carbohydrate utilization. R. henselae also closely resembled R. quintana in cellular fatty acid composition, with both consisting mainly of C18:1, C18:0, and C16:0 fatty acids. However, the strains of R. henselae all contained C18:0 in amounts averaging greater than or equal to 22%, in contrast to R. quintana, which contained this cellular fatty acid in amounts averaging 16 and 18%. DNA hybridization confirmed the identification of one clinical isolate as R. quintana and showed a close interrelatedness (92 to 100%) among the other strains. Under optimal conditions for DNA reassociation, R. henselae showed approximately 70% relatedness to R. quintana and approximately 60% relatedness to R. vinsonii. Relatedness with DNA from B. baciliformis was 43%. R. henselae was unrelated to A. felis. R. henselae is the proposed species of a newly recognized member of the family Rickettsiaceae, which is a pathogen that may be encountered in immunocompromised or immunocompetent patients. Prolonged fever with bacteremia or vascular proliferative lesions are clinical manifestations of the agent.     

Idiotypic relatedness of human monoclonal IgG cryoglobulins.

The serological relatedness of the idiotypic (ID) determinants of one type lambda light chain dimer and fifteen monoclonal IgG cryoglobulins were assayed. Rabbits were immunized with 9/15 IgG cryoglobulins, and twenty-three antisera were obtained and absorbed to render them specific for the ID determinant of the immunizing IgG cryoglobulin. By use of haemagglutination-inhibition, cross-reactivity was detected among five cryoglobulins. This was localized to the Fab region of the IgG, was not related to identity of the variable region subgroups of the heavy and light chains of the cross-reactive cryoglobulins, and was not detected in eighteen non-cryoprecipitable IgG myeloma proteins. The serological relatedness of the ID determinants suggests that a subset of IgG cryoglobulins may possibly have similar variable region structures and/or antigenic specificities.     

Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid.

Vaccination of normal adults with tetanus toxoid induced a two-three-fold rise in the frequency of IgM anti-IgG (rheumatoid factor, RF) B lymphocytes inducible by the polyclonal B cell activator, Epstein-Barr virus. The increase in IgM-RF precursors occurred earlier, was greater in magnitude, and was more sustained than the change in plasma IgM-RF. It was associated with a rise in total IgM levels, and correlated positively with the magnitude of the IgG anti-tetanus antibody response, but not with levels of circulating immune complexes. The ability of apparently innocuous infections and immunizations to increase the frequency of IgM-RF precursor B lymphocytes may be the reason for the previously noted expansion in this autoreactive B cell pool between birth and adulthood.     

Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features

BACKGROUND: This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). METHODS: Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. RESULTS: Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. LIMITATIONS: Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. CONCLUSIONS: Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.     

Laser ablation of discs of agar gel

Discs of agar gel mixed with ink were used to study ablation effects with an argon laser as a light source. Varying amounts of ink were added resulting in a variation of the attenuation coefficient between 0.45 and 6.3 mm-1. For laser beam irradiation horizontally incident on a vertical sample, the average velocity of ablation was found to be approximately constant for thicknesses up to 1.7 mm. When the laser beam was directed vertically on a sample held horizontally, the vaporized debris present in the beam attenuated the incident laser energy to such a degree that the average ablation velocity decreased by a factor of approximately five. Horizontal beam experiments for various attenuation coefficients showed that an attenuation coefficient of about 1.7 mm-1 is optimal for fast penetration of discs thicker than 4 mm. Thus, based upon the optical properties of a given tissue, there may exist an optimum laser wavelength to maximise ablation velocity.     

Effects of temperature, time, and toxin concentration on lesion formation by the Escherichia coli hemolysin.

We performed osmotic protection experiments to test the hypothesis that the Escherichia coli hemolysin forms a discrete-size pore in erythrocyte membranes. The effects of toxin concentration, assay time, temperature, and protectant concentrations were examined. The results we present here raise doubts about the existing model of pore formation by hemolysin. We demonstrate that osmotic protection by various sugars of different sizes is a function of hemolysin concentration and assay time. The data indicate that under various conditions, lesion sizes with a diameter ranging from < 0.6 to > 1.2 nm can be inferred. Quantification of hemolysin permitted the estimation of the number of HlyA structural protein molecules required per erythrocyte for lysis in the presence of each protectant. It appears that hemolysin induces heterogeneous erythrocyte lesions which increase in size over time. Influx experiments utilizing radioactive sugar markers indicated that time-dependent osmotic protection patterns are independent of the diffusion rates of individual protectants. We demonstrate that the rate of the putative growth in the size of hemolysin-mediated lesions is temperature dependent. The erythrocyte membrane lesions formed at 37 degrees C can be stabilized in size when shifted to 4 degrees C. On the basis of these data, new models for the nature of the hemolysin-mediated erythrocyte membrane lesions are presented.     

Acrocentric interconnections and NOR variants in human lymphocytes

Acrocentric interconnections and NOR (nucleolus organizer region) variants are frequently observed in silver-stained metaphase preparations from lymphocytes of phenotypically normal individuals. The types of interconnections and of NOR variants are outlined. It is speculated that the satellite acrocentrics (both normal and variant) are the consequence of breakage and recoiling of these interconnections. Awareness of these two features of the human genome may facilitate understanding of the NOR/nucleolus interaction(s) in such important processes as nucleolus formation and in development and/or diagnosis of disease states (i.e., malignancy).     

Client choice of treatment and client outcomes

Participants in this study suffered from severe mental illness and were homeless at baseline. They were given their choice of five different treatment programs. The current study investigated two major questions: (1) what is the impact of positive expectancies about the efficacy of the chosen program on number of contacts with the chosen program and client outcomes; and (2) what is the impact of positive views about nonchosen programs (alternative choice variables) on contact with the chosen program and client outcomes. Client outcomes assessed were psychotic symptoms, days homeless, and client satisfaction. Positive expectancy variables were the number of reasons for choosing a program and confidence that the program would help. Alternative choice variables were the number of nonchosen programs visited and the attractiveness of a nonchosen program. Only the number of reasons for choosing the program was significantly related to program contact with the chosen program. Both of the positive expectancy variables and program contact were significantly correlated with consumer satisfaction. In general, neither the positive expectancy variables nor the alternative choice variables predicted changes in psychotic symptoms nor days homeless. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 339–348, 2003.