Expressions of hope in cystic fibrosis patients: a comparison with the general population

PURPOSE: Hope was evaluated in Norwegian patients with cystic fibrosis (CF). PARTICIPANTS: The subjects were 87 Norwegian adults with CF and a control group of 1020 from the general population (GP). METHODS: Subjects completed a questionnaires that included the Herth Hope Index and demographic variables. Data on health-related variables were collected for the CF group. RESULTS: The mean age of the CF patients was 29 years (range 18-54). Almost 50% had a forced expiratory volume for one second percent predicted (FEV1%) below 50%, and 21% reported perceiving being in a bad phase of the disease. The CF patients reported lower (poorer) levels of hope than the GP sample, especially for the item scared about the future. However, they scored higher on inner strength and were younger, more often living alone, unmarried, not in paid work, but with similar educational levels. Levels of hope increased with increasing age in the CF patients but decreased for the GP subjects. The health variable that most affected hope in the CF sample was pulmonary function, not the presence of asthma or chronic lung infections. CONCLUSIONS: Persons growing up with CF experience many challenges. CF patients expressed slightly lower levels of hope and were more scared of the future. They scored higher on inner strength than the general population.     

Regulatory T cells and organ transplantation

Empirical studies attempting to explain tolerance to transplanted tissues have demonstrated a regulatory role for CD4+ T-cells. We here propose that regulatory T-cells mediating transplantion tolerance comprise two sets which can functionally complement each other. The CD4+CD25+ "natural regulator" arises in the thymus, and is preoccupied with self-antigens expressed at sites of inflammation. The second, comprising both CD4+CD25+ (FoxP3+) and CD4+CD25- Tr1-like cells are induced by persistent danger-free antigen in the periphery. The role of these cells is to moderate immune responses to prevent tissue destruction while allowing microbial elimination.     

Obesity in adolescence and adulthood and the risk of adult mortality

BACKGROUND There are few long-term follow-up data on the relation between body mass index (BMI) in adolescence and in adulthood, and between adolescent BMI and adult mortality. The present study explores these relations. METHODS: In Norwegian health surveys during 1963-1999, height and weight were measured for 128,121 persons in a standardized way both in adolescence (age 14-19 years) and 10 or more years later. Persons were followed for an average of 9.7 years after the adult measurement. Cox proportional hazard regression models were used to study the association between adolescent and adult BMI and mortality. RESULTS: The odds ratio of obesity (BMI >/=30) in adulthood increased steadily with BMI in adolescence, from 0.2 for low BMI up to 16 for very high BMI. Very high adolescent BMI was associated with 30-40% higher adult mortality compared with medium BMI. Adjusting for adult BMI explained most of the association of adolescent obesity and mortality, especially among men. Adjustment for smoking did not change the results. CONCLUSIONS: Obesity in adolescence tends to persist into adulthood. Adolescent obesity is also connected to excess mortality, but this excess seems to be explained mostly by obesity in adulthood. High BMI in adolescence seems to be predictive of both adult obesity and mortality.     

Relation of height and body mass index to renal cell carcinoma in two million Norwegian men and women

A positive association between body mass index (BMI) and renal cell carcinoma (RCC) has been observed. The association between height and RCC has been less clear. The authors explored these relations in a very large Norwegian cohort. Height and weight were measured in two million Norwegian men and women aged 20-74 years during 1963-2001. During follow-up, 6,453 cases of RCC were registered in the national cancer database. Measurements were also performed in 227,000 adolescents aged 14-19 years, and 154 cases of RCC were registered. Relative risks for RCC were estimated using Cox proportional hazards regression. The risk of RCC increased with increasing BMI among both adults and adolescents. Among adults, the relative risk associated with a one-unit increase in BMI was 1.05 (95% confidence interval (CI): 1.04, 1.06) in both sexes. The relative risk associated with a 10-cm increase in height was 1.19 (95% CI: 1.13, 1.26) in men and 1.17 (95% CI: 1.09, 1.26) in women. In a subgroup analysis, the relation between BMI and RCC was most pronounced in men and women who were never smokers, and the relation between height and RCC was confined to ever smokers. The authors conclude that elevated BMIs are associated with RCC risk in both males and females across a wide age range.     

T cell receptor gamma (TCRG) gene rearrangements in Brazilian children with acute lymphoblastic leukemia: analysis and implications for the study of minimal residual disease

The high frequency of T cell receptor gamma (TCRG) gene rearrangements in both B-lineage and T cell acute lymphoblastic leukemia (ALL), its easy detection and the lower incidence of oligoclonality make this gene one of the main target for the detection of minimal residual disease by PCR in childhood ALL. We analyzed the frequency and type of TCRG rearrangements in DNA samples obtained from the bone marrow of 102 Brazilian children at diagnosis using PCR and automatic sequencing. TCRG rearrangements were found in 69% of patients with B-lineage ALL and in 94% of patients with T cell ALL. In contrast to other studies, rearrangements involving the Vgamma9 segment reported to be uncommon were the most frequent both in B-lineage and T cell ALL and involved 49/109 (45%) of the rearranged alleles. This fact should be considered when standardizing consensus primers for the study of minimal residual disease in different populations.     

Enhanced TGFalpha-EGFR expression and P53 gene alterations contributes to gastric tumors aggressiveness

We determined whether alterations in the expression of p53, p16(INK4) and p21(WAF1/CIP1) influence the invasiveness of a subset of gastric adenocarcinomas co-expressing TGFalpha and EGFR. Immunopositivity for TGFalpha-EGFR (26%) was observed in both early and advanced adenocarcinomas, and 88% of these showed immunoreactivity for p53. SSCP analysis revealed that in 81% of these tumors the p53 gene was mutated in exons 5-8. The intensity of p53 immunoreactivity was significantly higher (P < 0.013) in deeply invasive tumors. p16(INK4) and p21(WAF1/CIP1) immunoreactivity was detected in 93 and 76% of the samples co-expressing TGFalpha-EGFR but the levels were not correlated with those of p53 and other clinico-pathological parameters. We conclude that gastric adenocarcinomas potentially dependent upon the TGFalpha-EGFR autocrine loop for growing exhibit increased aggressiveness in the presence of aberrant p53.     

T-cell sinonasal lymphoma presenting as acute orbit with extraocular muscle infiltration

We describe a rare case of sinonasal T-cell lymphoma in an 11-year-old boy who presented with a right acute orbit characterized by proptosis, eyelid edema and erythema, limitation of eye movements, and excruciating pain on the right side of his face. Orbital computed tomography showed progressive right extraocular muscle enlargement. One biopsy specimen showed extensive tissue necrosis and an infiltrate of atypical cells with pleomorphic nuclei within the walls of blood vessels. Immunohistochemical studies demonstrated that these cells were positive for leucocyte common antigen (CD45), CD3 cytoplasmic, CD45RO, and terminal deoxynucleotidyl transferase and negative for CD20, CD57, CD56, CD99 and Epstein-Barr virus. Chemotherapy for T-cell non-Hodgkin lymphoma was initiated, but the patient's status deteriorated and the child died of respiratory insufficiency, sepsis, and central nervous system infection.     

Clonal evolution as the limiting factor in the detection of minimal residual disease by polymerase chain reaction in children in Brazil with acute lymphoid leukemia

BACKGROUND: The purpose of this investigation was to analyze the incidence of clonal evolution in children in Brazil children with acute lymphoblastic leukemia and its interference with the detection of minimal residual disease by polymerase chain reaction using clone-specific primers. PATIENTS AND METHODS: The authors analyzed DNA samples from 12 children with acute lymphoblastic leukemia at diagnosis and after relapse using polymerase chain reaction and automatic sequencing to determine the presence of T-cell receptor gamma (TCRgamma) gene rearrangements. A clone-specific primer was synthesized based on the sequence obtained at diagnosis for each patient and at relapse for those with clonal evolution for the study of minimal residual disease. RESULTS: A change of the original clone was detected in 3 of 12 patients (25%), involving the same rearrangement detected at diagnosis, suggesting the development of subclones. Minimal residual disease was detected at the end of treatment or before the relapse in all patients who had maintained the same rearrangements detected at diagnosis. Minimal residual disease was investigated at the end of treatment in two of the three patients with clonal evolution and was not detected with the use of clone-specific primers. CONCLUSIONS: These data suggest that clonal evolution for TCRgamma gene rearrangements was not a rare event among children in Brazil and, when present, interfered with the detection of minimal residual disease.     

Nob1p is required for biogenesis of the 26S proteasome and degraded upon its maturation in Saccharomyces cerevisiae

Nob1p is a nuclear protein that forms a complex with the 19S regulatory particle of the 26S proteasome and with uncharacterized nuclear protein Pno1p. Overexpression of NOB1 overrode the defects in maturation of the 20S proteasome of ump1Delta cells, and temperature-sensitive nob1 and pno1 mutants exhibited defects in the processing of the beta subunits and in the assembly of the 20S and the 26S proteasomes. A defect in either NOB1 or PNO1 caused accumulation of newly formed Pre6p in the cytoplasm, whereas Pre6p of the ump1Delta strain accumulated in the nucleus irrespective of the temperature. Here we present a model proposing that (1) Nob1p serves as a chaperone to join the 20S proteasome with the 19S regulatory particle in the nucleus and facilitates the maturation of the 20S proteasome and degradation of Ump1p, and (2) Nob1p is then internalized into the 26S proteasome and degraded to complete 26S proteasome biogenesis.     

Height and body mass index in relation to total mortality

BACKGROUND: The relation between body mass index (BMI) and mortality is not clear in the literature. An inverse relation between height and mortality has been suggested. We explore these relations in a very large cohort in Norway. METHODS: We studied two million men and women, age 20-74 years, who were measured during 1963-2000. These persons were followed for an average of 22.1 years. We used Cox proportional hazard models in the analyses. Also, the optimal BMI (the BMI at the time of measurement that was subsequently related to the lowest mortality) was estimated. RESULTS: Over the study period, 723,000 deaths were registered. The relative risk of death by BMI showed a J- or U-shaped curve, with the lowest rates of death at BMI between 22.5 and 25.0. In men, the optimal BMI increased from 21.6 when measured at age 20-29 to 24.0 when measured at age 70-74. In women, the optimal BMI was consistently higher, increasing from 22.2 to 25.7. Mortality decreased with increased height in men; in women, mortality decreased with height only up to heights of about 160-164 cm and then increased among the tallest women. CONCLUSIONS: The relation between BMI and mortality was J- or U-shaped, with the "optimal" BMI varying by age and sex. Height was inversely related to mortality in men and in women up to a height of 165 cm.