Deviation of the alloimmune response toward tolerance by chimeric class I MHC molecules

Class I major histocompatibility complex (MHC) molecules induce either accelerated rejection or prolonged survival of allografts, presumably because of the presence of immunogenic or tolerogenic epitopes, respectively. To explore the molecular basis of this phenomenon, three chimeric class I molecules were constructed by substituting the rat class I RT1.A$\sp{\rm a}$ sequences with the N-terminus of HLA-A2.1 (N$\sp{\rm HLA-A2.1}$-RT1.A$\sp{\rm a}$), the $\alpha\sb1$ helix (h) with $\rm\alpha\sb{1h}\sp{u}$ sequences ( ($\rm\alpha\sb{1h}\sp{u}$) -RT1.A$\sp{\rm a}$) or the entire $\alpha\sb2$ domain (d) with $\rm\alpha\sb{2d}\sp{u}$ sequences ( ($\rm\alpha\sb{2d}\sp{u}$) -RT1.A$\sp{\rm a}$). Wild type (WT) and chimeric cDNAs were sequenced prior to transfection into Buffalo (BUF; RT1$\sp{\rm b}$) hepatoma cells. Stable transfectants were injected subcutaneously (s.c.) into different hosts 7 days prior to challenge with a heart allograft. In BUF hosts, chimeric ($\rm\alpha\sb{1h}\sp{u}$) -RT1.A$\sp{\rm a}$ accelerated the rejection of Wistar Furth (WF; RT1$\sp{\rm u}$) heart allografts, but had no effect on the survival of ACI (RT1$\sp{\rm a}$) grafts. In contrast, the ($\rm\alpha\sb{2d}\sp{u}$) -RT1.A$\sp{\rm a}$ (containing $\rm\alpha\sb{1d}\sp{a}$ sequences) immunized BUF recipients toward RT1$\sp{\rm a}$ grafts. In WF hosts, WT-RT1.A$\sp{\rm a}$ was a potent immunogen and accelerated ACI graft rejection, N$\sp{\rm HLA-A2.1}$-RT1.A$\sp{\rm a}$ was less effective and ($\rm\alpha\sb{\rm 1h}\sp{u}\rbrack$-RT1.A$\sp{\rm a}$ was not immunogenic. Thus, dominant and subdominant epitopes inducing in vivo sensitization to cardiac allografts are present in the $\alpha\sb1$ helix and the N-terminus, respectively. The failure of ($\rm\alpha\sb{2d}\sp{u}$) -RT1.A$\sp{\rm a}$ transfectants (containing recipient-type $\alpha\sb{\rm 2d}$ sequences) to sensitize WF hosts toward ACI (RT1$\sp{\rm a}$) grafts, despite the presence of donor-type immunogenic $\alpha\sb{\rm 1d}\sp{\rm a}$, suggests that "self-$\alpha\sb2$" sequences displayed on chimeric antigens interfere with immunogenicity. The ($\rm\alpha\sb{1h}\sp{u}$) -RT1.A$\sp{\rm a}$ transfectants injected s.c. prolonged the survival of WF (RT1$\sp{\rm u}$) hearts in ACI (RT1$\sp{\rm a}$) recipients. Furthermore, intra-portal injection of extracts from ($\rm\alpha\sb{1h}\sp{u}$) -RT1.A$\sp{\rm a}$, but not WT-RT1.A$\sp{\rm a}$ or RT1.A$\sp{\rm u}$, in conjunction with a brief cyclosporine course rendered ACI hosts permanently and specifically tolerant to donor-type WF cardiac allografts. Thus, immunodominant allodeterminants are present in the $\alpha\sb1$, but not the $\alpha\sb2$, domain of rat class I MHC molecules. Furthermore, the $\rm\alpha\sb{1h}\sp{u}$ immunogenic epitopes trigger tolerogenic responses when flanked by host-type N-terminal$\sp{\rm a}$ and $\rm\alpha\sb{2d}\sp{a}$ sequences. ^

A STUDY OF THE RELATIONSHIP BETWEEN SELF-ASSESSMENT AND CLINICAL EVALUATION OF HEARING STATUS

The relationship was explored between a subjective measure of hearing status, derived from a functional self-assessment expressed in terms of ability to hear and understand spoken words, and a comparable objective measure of hearing status, obtained from a speech reception test. The Augmentation Survey of the Health and Nutrition Examination Survey of the National Center for Health Statistics provided the necessary data for a sample of 3059 adults. Using chi-square tests for the subsample with the highest level of objectively assessed hearing status, favorable subjective assessments were found to be significantly associated with higher income, lower age group, higher level of educational attainment, greater psychological adjustment, fewer symptoms of depression, and higher self-ratings of overall health. In a linear regression with self-assessment of hearing status as the dependent variable, less than one-quarter of the variation could be explained by objective status and the six explanatory variables.^

AN INVESTIGATION OF THE POSSIBLE RELATIONSHIP BETWEEN CERTAIN PHYSIOLOGICAL AND PSYCHOLOGICAL MEASURES AND SMOKING CESSATION IN A SELF - SELECTED POPULATION

This study focused on the possible relationship between certain physiological and psychological variables and the cessation of smoking. The population studied was employees enrolled in a multimodality smoking cessation program at the local offices of a major American corporation. In order to be eligible to participate, each individual must have become a non-smoker by the end of the smoking cessation program.^ Three physiological measures were taken on each individual while performing a relaxation exercise; (1) Electromyogram (EMG), (2) Galvanic Skin Response (GSR), and (3) Skin Temperature. The psychological measure consisted of the variable "anxiety" in the Cattell 16-PF personality inventory. Individual's self report of their smoking status was verified through a test for expired carbon monoxide levels.^ For the total population (N-31) no significant relationships were found between the physiological and psychological variable measured and cessation; however, with the removal of two cases discovered during the post-test interview to be influenced by external factors of high caffeine level and a severe family crisis, the measure of EMG, attained significance in discriminating between the successful and unsuccessful in Smoking Cessation. ^

Cross-sectional study examining the role of acculturation in self-reported hypertension among Mexican Americans in Harris County, Texas

The objective of this secondary analysis was to examine the role of acculturation and self-reported hypertension in a Mexican-American cohort from Harris County, Texas. Specifically, we examined the acculturation measures of language-based Bidimensional Acculturation Scale (BAS), nativity, and length of United States (U.S) residency. Of 6,229 participants aged 40 and older, 38.0% self-reported hypertension at baseline. ^ Multiple logistic regression was used to estimate the prevalence odds ratios (pOR) for the association of each acculturation measure and hypertension while controlling for confounding. When adjusted for age, gender, body mass index, number of comorbidities, and family history of hypertension, U.S.-born participants were 1.37 times more likely to report having hypertension compared to Mexico-born participants (95% CI: 1.21, 1.55). Similarly, immigrants residing in the U.S. for more than 20 years had an adjusted pOR of 1.40 (95% CI: 1.16, 1.70) as compared to immigrants living in the U.S. for less than 10 years. ^ In conclusion, individuals who were born in the U.S. or emigrated to the U.S. over 20 years ago were more likely to report having hypertension compared to individuals born in Mexico or compared to those who emigrated more recently to the U.S. This study will contribute to the literature in demonstrating the need for more initiatives in prevention of cardiovascular disease, specifically hypertension, in the acculturating Mexican American population.^