Spontaneous and alloantigen-induced cytotoxicity by human T-lymphocyte subpopulations

Freshly isolated human T lymphocytes were separated into two subpopulations on the basis of their ability to form E rosettes after treatment with the phosphodiesterase inhibitor, theophylline. T cells that retained the ability to form E rosettes (T-res cells) and those that failed to form E rosettes (T-sens cells) were assayed for natural killer (NK) cell activity against 51Cr-labeled K562 tumor cells and for the ability to proliferate and kill allogeneic cells in mixed-lymphocyte culture (MLC). T-sens cells were highly enriched for NK activity. In contrast, T-res cells exhibited much less activity than either T-sens or unseparated T cells (T-sens greater than unseparated T cells approximately equal to unseparated PBL approximately equal to non-T cells greater than T-res cells). T-sens cells were poorly responsive to allogeneic cells in proliferation assays and demonstrated greater levels of cytotoxicity against allogeneic cells than T-res cells. T cells stimulated with allogeneic lymphocytes for 7 days were cytotoxic for K562 targets while comparably stimulated non-T cells and T cells cultured with medium were not cytotoxic. Cold target inhibition experiments suggested that within the T-sens subset there are overlapping populations which mediate cytotoxicity against K562 and allogeneic cells. These studies demonstrate that freshly isolated human T cells are composed of heterogeneous populations which differ in their ability to mediate NK and to generate cytotoxic T lymphocytes in culture.     

Testing the Habituation-Based Model of Exposures for Child and Adolescent Anxiety

Exposure has been identified as key to effective treatment of youth anxiety. However, the precise theoretical mechanisms of exposure are a matter of debate. Emotional processing theory emphasizes the need for fear activation during exposure and its habituation both within and across exposures. Despite the popularity of the theory to explain exposure, it has not been tested with anxious youth. To determine whether emotional processing theory parameters predict anxiety severity, coping abilities, and global functioning after cognitive-behavioral treatment. The present study examined 72 youth (M_age = 10.50 years; 45% female; 87.5% non-Hispanic Caucasian) diagnosed with an anxiety disorder and who received family or individual CBT. Three exposure habituation variables—initial fear activation (peak anxiety), within-session habituation, and between-session habituation—were assessed using Subjective Units of Distress and examined as predictors of outcome at posttreatment and at 1-year follow-up. Outcomes were measured using the Coping Questionnaire, Multidimensional Anxiety Scale for Children, Revised Children’s Manifest Anxiety Scale, Children’s Global Assessment Scale, and clinician severity ratings on the Anxiety Disorder Interview Schedule. Emotional processing theory variables did not predict any anxiety outcomes at posttreatment or follow-up with one exception: Initial fear activation predicted less anxiety at follow-up among youth without GAD. In addition, within- and between-session habituation were not associated with one another. Between-session habituation was not associated with initial fear activation. These findings suggest a limited role of habituation within cognitive-behavioral therapy for anxiety in youth. An alternative to emotional processing theory, inhibitory learning theory, is discussed.     

Towards a Neurotransmitter-Based Retinal Prosthesis Using an Inkjet Print-head

Electronic chips that provide a patterned stimulus to cells in the retina may provide a viable treatment for age-related macular degeneration. A surrogate MEMS device, in the form of a print-head from a desktop printer, has been used to eject a pattern of neurotransmitters (bradykinin) onto living rat pheochromocytoma (PC12) cells. Fluorescent calcium imaging was used to measure the patterned stimulation of individual cells. The chemical stimulation of cells by directed microfluidic delivery may have applications in retinal prosthetic devices, and in other prosthetic implants in the nervous system.     

The treatment of difficult proximal femoral fractures with the Russell-Taylor reconstruction nail

The outcome of 30 proximal femoral fractures and pathological lesions in 29 patients treated with the Russell-Taylor reconstruction nail are reported. Four patients had fractures involving both the femoral neck and shaft (segmental). Fifteen patients had extensive comminuted fractures of the proximal femur and ten patients underwent nailing because of pathological fractures (one bilateral). In nineteen operations there were technical difficulties, nail insertion and proximal interlocking being the commonest. In the elderly there was a high post-operative complication rate. Three nails needed to be revised for failure of fixation. On review, all patients under sixty years of age regained full mobility and returned to their pre-fracture level of activities. Patients with per-trochanteric fractures over the age of sixty had less favourable results. No cancer patient returned to their prefracture mobility level. The Russell-Taylor reconstruction nail proved to be useful in the treatment of segmented and, in a lesser degree, pathological fractures. However, the surgical technique is demanding and there is a high incidence of post-operative complications in the patients over the age of sixty.     

The social ecology of syphilis.

Factors affecting the transmission of syphilis can be categorized into those acting at the level of individuals (e.g., number of sex partners) and others at the level of the sociophysical environment (e.g., availability of treatment services for curable infections). In a prior study, we identified several sociophysical factors correlated with the ten-year mean syphilis rate in a regression analysis of United States counties. In the present study we used qualitative methods to investigate additional aspects of some factors in the regression, as well as to identify entirely new factors. Twelve counties with populations less than 100,000 and ten-year mean syphilis rates that were greater or less than expected by the regression model were selected for a three to five day visit. The case study protocol included observations, unstructured interviews with care providers and county residents, and a standardized questionnaire completed by state and local sexually transmitted disease control personnel pertaining to characteristics and practices of the local health department. Comparisons of the field notes and questionnaires revealed patterns of factors of the sociophysical environment that potentially affect county syphilis rates. These included access to the health department STD clinic, race relations, employment opportunities for minorities, interagency coordination, STD outreach activities, the social acceptability of discussing STDs, and intercommunity dynamics. In addition we noted the disproportionate influence of particular individuals on these factors. Some of the factors identified are readily quantifiable and could enhance the predictive power of multivariable models of county syphilis rates. The hypotheses generated by this study may also lead to a better measurement and understanding of potentially important environmental determinants of community syphilis rates, and the development of new or enhanced prevention strategies.     

Contaminated sediments from tributaries of the Great Lakes: Chemical characterization and carcinogenic effects in medaka (Oryzias latipes)

Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with organic solvents to produce a crude extract, which was separated on alumina into two fractions: predominantly polycyclic aromatic hydrocarbons; and predominantly nitrogencontaining polycyclic aromatic compounds. Crude extracts were redissolved in acetone and analyzed by gas chromatography and gas chromatography-mass spectrometry. The acetone-redissolved crude extracts from the four industrialized sites contained 5.6–313.3 g total polycyclic aromatic compounds/g sediment and 3.0–36.4 g other compounds/g sediment. In addition to the typical EPA priority pollutants, a substantial amount (228.7 g/g sediment) of alkyl-polycyclic-aromatic compounds was detected in sediments from one of the industrialized sites. Extracts from the reference site contained 1.55 g total polycyclic aromatic compounds/ g sediment. Medaka (Oryzias latipes) were exposed to multiple pulse doses of acetone-redissolved extracts and fractions. Medaka were also exposed to a known carcinogen, methylazoxymethanol acetate, to verify that chemicals produced tumors in the test fish. Acetone-redissolved extracts and fractions from contaminated sediments were toxic to medaka. Fin erosion and non-neoplastic liver abnormalities were more prevalent in medaka after exposure to acetoneredissolved extracts and fractions from contaminated sediments. Neoplasms previously associated with chemical exposure in wild fishes were induced in medaka exposed to acetone-redissolved extracts and fractions from two of the contaminated sites, but not from the reference site or controls. These findings further support the hypothesis that chemical contaminants in sediments are involved in epizootics of neoplasms in wild fishes at contaminated sites.     

The effect of timing of maternal tetanus,diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels – A prospective study

Background

The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27–36 weeks.

Aim

To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn.

Methods

This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n = 61).

Results

The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks (n = 21) compared with 31–36 weeks (n = 30) and >36 weeks (n = 7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29–87.30) vs. 8.69 IU/mL (95% CI, 3.66–20.63) and 21.12 IU/mL (95% CI, 7.93–56.22), p < 0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks compared with 31–36 weeks and >36 weeks, 225.86 IU/mL (95% CI, 182.34–279.76) vs. 178.31 IU/mL (95% CI, 134.59–237.03) and 138.03 IU/mL (95% CI, 97.61–195.16), p < 0.02, respectively.

Conclusions

Immunization of pregnant women with Tdap between 27–30⁺⁶ weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.     

Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium

Objective. To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM-3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-1), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1). Methods. We performed immunohistochemical analyses of frozen sections of normal and rheumatoid synovial tissue using monoclonal antibodies to the molecules examined. Results. ICAM-1 staining was detectable on the vascular endothelium and the synovial lining cells of both normal and rheumatoid synovial membranes. A variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM-1. ICAM-2 staining was demonstrable in the vascular endothelium of both normal and inflamed tissues, the latter demonstrating a significantly higher proportion of positive vessels. ELAM-1 staining was not detectable in normal synovial membranes but was seen on the endothelium of a limited number of rheumatoid synovial vessels, usually close to the synovial lining cell layer. VCAM-1 staining was intense in both normal and rheumatoid synovial lining cells, but vascular staining was weak in both. In contrast, ICAM-R staining was not detected in association with any synovial blood vessels, but was widely expressed by lymphocytes and macrophages. Cells of the lining layer did not stain for ICAM-R. Conclusion. Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels. Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation.