Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

Adenovirus 5‐ and 35‐based immunotherapy enhances the strength but not breadth or quality of immunity during chronic SIV infection

Heterologous adenovirus‐based vectors hold promise as preventative HIV vaccines but their capacity to induce effective T‐cell immunity in established infection has not been explored. We vaccinated rhesus macaques chronically infected with SIVmac251 and undergoing antiretroviral therapy (ART) with human adenovirus serotype 5‐based vectors expressing SIV Gag, Env, and Nef with and without IL‐15 and evaluated vaccine immunogenicity. Vaccination increased Ag‐specific T cells 20‐fold but did not expand the breadth of epitopes recognized or the quality of response, as the majority of CD8⁺ and CD4⁺ T cells produced only one cytokine irrespective of vaccination. Immunization transiently restored blood CD4⁺ central memory T cells (Tcm) and boosted CD4⁺ and CD8⁺ Tcm and effector cell responses but did not prevent virus rebound upon cessation of ART. Boosting with human adenovirus serotype 35‐based vectors during a second ART cycle increased Ag‐specific T cells to 50‐fold above pre‐vaccination levels and boosted CD4⁺ Tcm numbers but did not expand the breadth or quality of immunity or control virus levels following drug discontinuation. The number of blood CD4⁺ Tcm correlated positively with complexity of T‐cell responses and negatively with virus load, suggesting that more complete restoration of this subset through vaccination would be beneficial.     

Physician‐Assisted Suicide Attitudes of Older Mexican‐American and Non‐Hispanic White Adults: Does Ethnicity Make a Difference?

Little is known about attitudes toward physician‐assisted suicide (PAS) in various ethnic groups. This study compares attitudes held by older Mexican Americans and non‐Hispanic whites and examines subject characteristics that may influence their responses. A convenience sample of 100 older Mexican Americans and 108 non‐Hispanic whites (n=208) aged 60 to 89 were recruited from four primary care community‐based practice sites in San Antonio, Texas. Interview items measured attitudes toward PAS, cognitive status, functional status, and religiosity. Older Mexican Americans (52.7%) reported stronger agreement than non‐Hispanic whites (33.7%) with PAS. Male sex (odds ratio (OR)=2.62, 95% confidence interval (CI)=1.09–6.35) predicted agreement with legalization in Mexican Americans, whereas lower religiosity scores (OR=0.84, 95% CI=0.75–0.94) were predictive of agreement in older non‐Hispanic whites. This study is the first to find positive attitudes among community‐dwelling older Mexican Americans toward PAS that are higher than those of older non‐Hispanic white adults. Sex and religious views were important determinants of positive attitudes toward PAS. Larger, more‐generalizable studies should be conducted to confirm the attitudinal patterns that have been identified in this study.     

Leitlinienkonforme Versorgung

Background

Whereas the Scottish guidelines are audited annually, nobody evaluates guideline compliance in Germany. Thus, can external quality assurance data pursuant to section 137 of the German Social Code Book V be suitable for auditing guideline compliance?

Materials and methods

From North Rhine Westphalia, a total of 48,831 cases of femoral fractures near the hip joint were evaluated. Compliance with the guidelines was determined based on preoperative hospital stay, thrombosis, and antibiotic prophylaxis. Guideline rationale was reviewed in terms of mortality and thromboembolism rate.

Results

Sixty-four percent of the interventions were performed in a timely manner. Thrombosis prophylaxis was given in 99% of cases. Antibiotics were given as a single shot. There was no connection between mortality and thromboembolism rates or time to surgery.

Conclusion[Überschrift]

Guideline compliance is similar in German and Scotland. The external quality assurance data are suitable for evaluating guideline compliance. The literature recommends a short time to surgery. Given the short observation period, it was not possible to demonstrate any improvement in outcomes.     

Gene promoter hypermethylation in ductal lavage fluid from healthy <Emphasis Type="Italic">BRCA</Emphasis>gene mutation carriers and mutation-negative controls

Introduction  

Female germline BRCA gene mutation carriers are at increased risk for developing breast cancer. The purpose of our study was to establish whether healthy BRCA mutation carriers demonstrate an increased frequency of aberrant gene promoter hypermethylation in ductal lavage (DL) fluid, compared with predictive genetic test negative controls, that might serve as a surrogate marker of BRCA1/2 mutation status and/or breast cancer risk.     

Influence des facteurs psychosociaux sur l’apparition de douleurs post-tumorectomie Une étude prospective auprès de cinquante femmes opérées d’un cancer du sein

Objective

To study the influence of psychological factors in predicting the onset of postmastectomy pain syndrome (PMPS). The objective was to evaluate the possible role of factors, such as depression and anxiety, in the appearance of PMPS.

Patients and methods

We carried out an exploratory study of fifty breast cancer patients who underwent lumpectomy, including axillary node dissection, by the same technique in the gynaecology department of CHR Orléans. These patients were evaluated before and one month after the surgical procedure. We measured depression using the Montgomery-Asberg depression rating scale, and anxiety using the Hamilton anxiety scale. At the time of the second evaluation of pain, a pain management specialist assessed the patients to establish a diagnosis of PMPS.

Results

The results showed a statistically significant difference in the preoperative level of depression and anxiety between the patients who later develop PMPS and those who do not. One month after surgery, patients experiencing pain are always more depressed and have more intense psychological and somatic anxiety compared to the others.

Conclusion

Psychological factors, such as depression and anxiety, are possible predictive factors in the onset of PMPS. Moreover, we demonstrated the role of depression and anxiety in the appearance and maintenance of pain, as previously described in the literature.