Antigen-independent acquisition of MHC class II molecules by human T lymphocytes

We report here that human T lymphocytes have the capacity of acquiring large amounts of MHC class II molecules from various types of antigen-presenting cells (APC) in an antigen-independent manner. The transfer of MHC class II molecules from APC to T cell required direct cell-to-cell contact and appeared to involve the interaction of numerous adhesion molecules between these cells. Depletion of cholesterol from the plasma membrane reduced the amount of MHC class II transferred onto the T cells. Most significantly, the newly acquired MHC class II molecules were capable of efficiently presenting antigen to T helper cells. These results suggest that T cells are able to interact with other T cells to regulate immune responses by presenting MHC peptide complexes that have been snatched away from nearby APC.     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

Developing resources to teach and assess the core competencies: a collaborative approach.

Graduate medical education programs face new challenges as they seek to comply with the mandate from the Accreditation Council on Graduate Medical Education to demonstrate that they are teaching and assessing residents on the six core competencies. The authors describe a project designed as a collaborative venture between the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the Center for Educational Outcomes at Dartmouth College (CEdO) to provide residency programs in allergy/immunology with resources for teaching and assessing the core competencies. The goal was to create a set of learning and assessment resources that maximized the content knowledge expertise provided by the AAAAI and the learning expertise provided by CEdO. A highly interactive, iterative process was used to create a set of Web-based modules. Bilateral communication, buy-in, and active involvement in the process were seen as crucial to the development of resources and their successful implementation. Approximately 18 months after the modules were made available to training program directors, 80% of the directors surveyed were aware of and had accessed the modules. The joint creation process used in this project, designed to be generally applicable across specialties, reveals how the burden of meeting new requirements can be decreased when experts in content knowledge and experts in learning collaborate.     

Identity of BCA200 and c-erbB-2 indicated by reactivity of monoclonal antibodies with recombinant c-erbB-2.

BCA200 has been described as a 200,000 Mr monomeric cell surface glycoprotein associated with human breast cancer. Since the physical properties and cellular distribution of BCA200 resemble those of c-erbB-2, antibodies to BCA200 were tested for the ability to bind a recombinant protein containing the c-erbB-2 extracellular domain (erbB-2 ECD). Three antibodies to distinct epitopes of BCA200 reacted with erbB-2 ECD but not with a control protein expressed in a similar baculovirus lysate. Control myeloma proteins and antibodies to four other antigens did not react with erbB-2 ECD. A protein with the expected molecular weight for erbB-2 ECD was also immunoprecipitated by anti-BCA200 antibody 520C9. We conclude that BCA200 is another synonym for c-erbB-2.     

Genotypic differences in larval olfactory discrimination in twoDrosophila melanogaster strains

Wild-type (+B) and compound chromosome mutant(bB) Drosophila melanogaster larvae were tested in a U-maze. FreshDrosophila food or food and larvae were placed in each of the two goals (+B only in goal 1,bB in goal 2) and served as stimulus. Separate trials were conducted using +B andbB larvae to test for preference in the maze. Significantly more test larvae went to the arm of the maze containing their own strain as stimulus when (1) both goals contained larvae, (2) one goal contained homogenetic larvae and the other fresh food only, and (3) the goals contained biotic residues of stimulus larvae. The strength of the stimulus necessary to elicit the response differed for the two strains, the +B strain apparently being more sensitive. As the density of the stimulus larvae was increased, the choices of the test larvae became statistically nonsignificant and the number of larvae remaining in the starting arm of the maze increased. The data suggested that the strains of larvae utilized here have the capacity for olfactory discrimination.Part of this investigation was supported by National Institutes of Health Award 1 F 32 NS05155-01 CMS from the Institute of Neurological and Communicative Disorders and Stroke to A. P.     

T-antigen expression by peanut agglutinin staining relates to mucosal dysplasia in ulcerative colitis

Staining of 326 rectal mucosal biopsies from ulcerative colitis patients with peanut agglutinin (PNA), which binds to the T-blood group antigen and has been claimed to reflect a cancer-associated mucin alteration, showed highly significant direct associations with mucosal dysplasia (P less than 0.001), disease activity (P less than 0.001), and subsequent development of rectal cancer in a smaller series of patients (P = 0.005). Staining for normal colonic mucin by the Dolichos biflorus (DBA) lectin related significantly and inversely to dysplasia. Intense normal colon mucin staining by DBA related significantly (P less than 0.025) to long disease duration and to subsequent development of cancer (P = 0.02). The latter association is based on a small number of patients only and is not considered conclusive evidence, but may provide a link with goblet-cell hyperplasia. The authors conclude that although T-antigen expression relates to dysplasia, the findings of "false" positive and negative rates of 22 and 33 percent respectively, make it unlikely that staining of biopsy sections for the T-antigen by peanut agglutinin will contribute materially to routine assessment for dysplasia and cancer risk prediction in patients with ulcerative colitis.     

Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

Adherence to Mediterranean Diet and Selected Lifestyle Elements among Young Women with Type 1 Diabetes Mellitus from Northeast Poland: A Case-Control COVID-19 Survey

An appropriate balanced diet and dietary patterns are important at every stage of life, but in the case of young patients with type 1 diabetes mellitus (T1DM), it is especially crucial during the COVID-19 pandemic. The aim of the study was to assess health and nutritional behaviors, mainly adherence to the Mediterranean diet (MD), during the second wave of the COVID-19 pandemic in Poland among women with T1DM, and to compare them with a healthy population. This survey (based on a questionnaire) was conducted in December 2020 and included 219 young women, healthy (n = 106) and with T1DM (n = 113), from northeast Poland. Over 30% of the study group admitted that they did not engage in any physical activity. A large proportion declared that their screen time was 5–7 h a day (48% in control and 40% in T1DM group). High intakes of sweet-beverages, sweets and red meat, but also low intakes of olive oil, fish and nuts were observed. The vast majority of participants (60% vs. 71%) were moderately adherent to the Mediterranean Diet Adherence Screener (MEDAS). The study demonstrated that despite the similarity between the behaviors of healthy people and those with T1DM, negative health and nutritional practices, such as low physical activity, long screen time, medium and high levels of stress and inappropriate eating habits were observed.