An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.     

Micropatterned surfaces for control of cell shape, position, and function

The control of cell position and function is a fundamental focus in the development of applications ranging from cellular biosensors to tissue engineering. Using microcontact printing of self-assembled monolayers (SAMs) of alkanethiolates on gold, we manufactured substrates that contained micrometer-scale islands of extracellular matrix (ECM) separated by nonadhesive regions such that the pattern of islands determined the distribution and position of bovine and human endothelial cells. In addition, the size and geometry of the islands were shown to control cell shape. Traditional approaches to modulate cell shape, either by attaching suspended cells to microbeads of different sizes or by plating cells on substrates coated with different densities of ECM, suggested that cell shape may play an important role in control of apoptosis as well as growth. Data are presented which show how micropatterned substrates were used to definitively test this hypothesis. Progressively restricting bovine and human endothelial cell extension by culturing cells on smaller and smaller micropatterned adhesive islands regulated a transition from growth to apoptosis on a single continuum of cell spreading, thus confirming the central role of cell shape in cell function. The micropatterning technology is therefore essential not only for construction of biosurface devices but also for the investigation of the fundamental biology of cell-ECM interactions.     

An economic evaluation of the use of rare earth screens to reduce the radiation dose from diagnostic X-ray procedures in Israel

In Israel the diffusion of rare earth screen technology has been limited. These screens could halve the radiation dose to the patient from diagnostic X-ray radiography, with little managerial effort and without being detrimental to the quality of the diagnostic image. We estimated the total effective dose from diagnostic film radiography capable of reduction by the use of rare earth screens, based on the number of hospital and ambulatory diagnostic X-ray procedures. This number was multiplied by the computed radiation dose per body site for a series of diagnostic procedures. The annual dose was approximately 0.53 mSv per head, approximately half of which could be averted by the introduction of rare earth screen technology. Based on a fatality risk of 3% Sv-1, it is estimated that the adoption of rare earth screen technology might reduce the annual incidence of cancer by some 93 cases, half of which would be fatal after an average latency period of 18.4 years. The cost of purchasing rare earth screens on a nationwide basis is approximately $3.0 million. This cost is outweighed by a saving of $9.6 million in X-ray tube replacement costs over the period 1997-2006. Government legislation enforcing the use of rare earth screens is essential, because of the lack of prestige associated with acquiring rare earth technology, as well as institutional reluctance to accept the external benefits of reduced morbidity and mortality and/or to extend budgetary time horizons.     

Assessing disability after head injury: improved use of the Glasgow Outcome Scale

OBJECTIVE: The objective of this study was to assess somatic and inherited androgen receptor gene mutations in families with only one affected individual. METHODS: Molecular genetic analysis of the androgen receptor gene in DNA derived from blood leukocytes from 30 families with single-strand conformation analysis, direct sequencing, and restriction fragment analysis was performed. RESULTS: In 22 families the mothers and all investigated grandmothers were heterozygous carriers. However, within the sisters and aunts, both heterozygous carriers and noncarriers were present. In eight families a de novo mutation was characterized. In three of these patients indication for somatic mosaicism was found. CONCLUSIONS: De novo mutations occur at a high rate within the androgen receptor gene (8 of 30 = 26.7%); a high proportion (3 of 8) arise after the zygote stage. Thus only direct analysis of the underlying mutation of the androgen receptor gene in the proband and his or her family can provide the basis for genetic counseling.     

Liposomes containing lipid A serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.     

Health-promoting behaviors of rural adolescent women

A part of a larger study of the health behaviors of adolescent women, this investigation examined health-promoting behaviors and the influence of cognitive, social, and environmental factors on these health-promoting behaviors of rural adolescent women. The sample consisted of 128 rural African-American and white adolescent women. Forty-four percent of the variance in health-promoting behavior of this sample was explained by five variables: self-image, problem solving, mother's education, employment status, and family structure. Self-image was the most salient predictor of health-promoting behavior, explaining 33% of the variance.     

Reflex sympathetic dystrophy: is the immune system involved?

OBJECTIVE: Evaluation of immune system function in patients with reflex sympathetic dystrophy (RSD). DESIGN: Survey on blood samples obtained from RSD patients and from a randomly selected control group. The lymphocyte populations (T, B, NK cells), and the activated T cells (CD25, and HLA-Dr-positive CD4 and CD8 cells) were analyzed by flow cytometry with dual-color direct immunofluorescence after whole-blood lysis. Clinical chemistry parameters were analyzed in additional serum samples. SETTING: Tertiary care center (outpatient rehabilitation clinic). SUBJECTS: Thirteen patients (nine women) with RSD and a control group of 21 healthy individuals. MAIN OUTCOME MEASURES: The results of the flow cytometry analysis of RSD patients were related to those of the control subjects. Means were analyzed, and confidence intervals for differences of the means were calculated. The means of the clinical chemical analysis were related to local reference values. RESULTS: The flow cytometry analysis did not differ between RSD patients and healthy controls. Although in some patients an individual parameter of clinical chemical analysis differed from its reference value, all of the mean values were within reference limits. Stratification on medications with immunomodulatory effects and on probability of a definite diagnosis of RSD had no influence on the results. CONCLUSION: No association between immunologic indices and RSD was found. This finding is relevant, because recent theories stress that it is not the sympathetic nervous system but a local inflammatory reaction that is fundamental in the pathogenesis of RSD. The results of this study do not support this theory.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

The effect of nitric oxide on cytokine-induced release of PGE2 by human cultured astroglial cells

Articles in this issue by A. C. Casiglia, A. LoCoco, and C. Zappulla; D. S. Crystal, H. Watanabe, K. Weinfurt, and C. Wu; M. Keller, N. Edelstein, C. Schmid, F. Fang, and G. Fang; and J. J. Han, M. D. Leichtman, and Q. Wang are discussed according to (a) the extent to which cultural variability can be reconciled with developmental theory and (b) the dimensions of cultural variability that matter most for development. It is argued that (a) cross-cultural research needs to be predicted on a model of how culture interacts with the forces that underlie and guide development and (b) the interpretation of cross-cultural research is severely limited without the direct measurement of the specific culture-related variables and processes that are hypothesized to account for diversity in development. Finally, within-culture variability needs to be studied in conjunction with between-culture variability so that a full model of diversity and development can be constructed.