Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1

BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.     

Sensitization to horse hair, symptoms and lung function in grooms

OBJECTIVE: This study aimed to investigate the rate of occupational sensitization to horse hair in grooms and whether occupational exposure to horse hair increases respiratory and allergic symptoms and affects lung function in grooms or not. METHODS: This is a cross-sectional study. Two hundred grooms were randomly selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One hundred and twenty-five subjects agreed to enter the study. Ninety-two workers who worked in the different parts of this hippodrome enrolled as the control group. A detailed questionnaire including respiratory and allergic symptoms was filled in, physical examination, skin prick tests and pulmonary function tests were performed. RESULTS: Sensitization to horse hair was 12.8% in grooms and 4.3% in controls. The difference was statistically significant (P = 0.0035). Asthma was found in 14.4% of the grooms and 5.4% of the controls, allergic rhinitis in 42.4% of the grooms and 18.4% of the controls, allergic conjunctivitis in 35.2% of the grooms and 15.2% of the controls, and allergic skin diseases in 32.8% of the grooms and 13% of the controls. The differences were statistically significant (P = 0.043, P = 0.0002, P = 0.001 and P = 0.0008, respectively). The means of FEV1, FEV1/FVC and FVC parameters were significantly lower in the groom group (P = 0.006, P = 0.001 and P = 0.003, respectively). In the multivariate analysis, being in the groom group and working years were found to be predictive factors for impairments of lung function (P < 0.001 and P = 0.002, respectively). CONCLUSION: Occupational exposure to horse increases the sensitization to horse hair, induces asthma and allergic symptoms and also impairs lung functions.     

Rapid change in height and body proportions of Maya American children

Maya families from Guatemala migrated to the United States in record numbers from the late 1970s to the early 1990s. Births to Maya immigrant women have created a sizable number of Maya American children. The height and sitting height of 5 to 12 years children (n = 431) were measured in 1999 and 2000. Leg length was estimated and the sitting height ratio was calculated. These data were compared with a sample of Maya children living in Guatemala measured in 1998 (n = 1,347). Maya American children are currently 11.54 cm taller and 6.83 cm longer‐legged, on average, than Maya children living in Guatemala. Consequently, the Maya Americans have a significantly lower average sitting height ratio (i.e., relatively longer legs in proportion to length of the head and trunk) than do the Maya in Guatemala. These results add support to the hypothesis that both the height and body proportions of human populations are sensitive indicators of the quality of the environment for growth. Am. J. Hum. Biol. 14:753–761, 2002. © 2002 Wiley‐Liss, Inc.     

TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black populations.

The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied.     

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

Deep venous thrombosis and pulmonary embolism

All surgical patients are at risk for the development of deep venous thrombosis and subsequent pulmonary embolism or postphlebitic syndrome. The evolution of ultrasonographic imaging has increased the awareness of prevention, diagnosis, and treatment of deep venous thrombosis. Duplex imaging and Doppler color flow imaging have made the diagnosis of deep venous thrombosis relatively simple, painless, inexpensive, and definitive. These procedures have gained acceptance by both patients and physicians. Several risk factors have been identified that increase the chance of the development of deep venous thrombosis. These factors include a history of deep venous thrombosis, presence of a malignant process, increasing age, cigarette smoking, obesity, prolonged bed rest, and general anesthesia. The greater the number of risk factors, the more aggressive prophylaxis should be. Means of prophylaxis have improved, and surgeons now generally agree that some form of prophylaxis is required. Heparin and intermittent compression devices appear to be equally effective in preventing deep venous thrombosis. The addition of venous monitoring in high-risk patients permits immediate identification of the presence of deep venous thrombosis. During the last decade, the treatment of patients with deep venous thrombosis has changed little. Heparin followed by warfarin remains the treatment of choice. A small group of patients receive fibrinolytic therapy for deep venous thrombosis. Although the incidence of postoperative deep venous thrombosis has decreased during the last decade, it remains a significant complication.     

Diabetes mellitus. II: Routine chest radiography.

Chest radiographs of 43 consecutive diabetic patients were evaluated with a view to determine their role as a routine investigation of patients with diabetes mellitus. 22 (51.2%) patients had normal chest radiographs. The remaining 21 patients had 61 abnormalities found in their chest radiographs. 26 (42.6%) of these were significant abnormalities while 35 (57.4%) were non-significant. Of the former, 42.3% were due to cardiomegaly while in the latter group, aortic unfolding was the main finding. Radiological abnormalities were more commonly observed in patients aged 40 years and over, than in those below, with a ratio of 3:1. Chest radiographs corroborated clinical diagnosis in 19 of the 21 cases in whom abnormalities were observed. This study shows that routine chest radiograph in diabetic patients is useful in those with clinical symptoms and in older diabetics above the age of 40 years.     

The contribution of reoxygenation to ischemic brain damage

This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated.