Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo–epidermal junction

Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo–epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo–epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6‐month‐old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short‐term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.     

Progress and pitfalls in underrepresented minority recruitment: perspectives from the medical schools

PURPOSE: To assess current initiatives at U.S. medical schools to recruit underrepresented minorities (URM) and to identify perceived barriers to enrollment of URM students. METHODS: We developed a survey that was mailed to the dean of Student Affairs of all U.S. allopathic and osteopathic medical schools in 2002. Respondents were asked to list their schools' URM recruitment programs and rate the effectiveness of these programs. They were also asked to indicate barriers to URM recruitment from a list of 37 potential barriers and rate their overall success with URM recruitment. RESULTS: The study had a 59% response rate. All schools reported a wide variety of initiatives for URM recruitment with > or =50% of all schools using each of the 11 strategies. The three most commonly listed barriers to URM recruitment were MCAT scores of applicants (90%), lack of minority faculty (71%) and lack of minority role models (71%). Most schools rated their recruitment efforts highly; on a scale of 1 to 10 (10 being very successful), the average score was an 8. CONCLUSION: While schools continue to invest tremendous efforts in recruiting minority applicants, admissions criteria, lack of URM faculty and the need for external evaluation remain important barriers to achieving a diverse physician workforce.     

Distinct effects of altered allopeptide analogs on a human self-restricted T cell clone

Alloreactive T cells involved in indirect recognition play a key role in initiating and sustaining graft rejection. One of the most promising approaches to achieve specific immunosuppression of indirect allorecognition resides in the use of chemically modified allopeptides. In order to design and test such peptide analogs, we have defined the dominant immunogenic peptide of the HLA-DRB1^*0101 antigen recognized by DRB1^*1101 responders. Next we engineered structural variants of this peptide (DRB1^*0101/residues 22-35), carrying single amino acid substitutions at postulated MHC and TCR contact residues. These analogs were tested for: (i) binding affinity to recombinant HLA-DRB1^*1101 protein (rDR11), and (ii) stimulatory activity exerted on a human anti-DR1/22-35 self-restricted T cell clone. The binding affinity of the analogs carrying non-homologous substitutions at putative anchor positions (24V/E and 29R/A) was significantly decreased, while little or no effect was observed in either peptide-binding or T cell proliferation assays for conserved substitution (24V/Y and 29R/K). This indicates that positions 24 and 29 are primarily involved in contacting the HLA-DR11 molecule. In contrast, single amino acid substitutions at positions 25 through 28 strongly affected the proliferative response of the clone, even when binding affinity to rDR11 was not altered. This finding suggests that positions 25 through 28 are TCR contact residues. Two peptide analogs (26L/I and 27L/V) displayed a higher stimulatory activity than the wild-type peptide and induced high-zone tolerance. Two other peptides (25R/A and 28E/Q), while binding to rDR11, did not exhibit any stimulatory activity and blocked the presentation and recognition of the wild-type peptide. Our data underscore the therapeutic potential of allopeptide analogs, as well as their value in dissecting the fine antigenic structure of a peptide determinant.     

Maternal and umbilical cord serum leptin concentrations in small-for-gestational-age and in appropriate-for-gestational-age neonates: a maternal,fetal, or placental contribution?

Leptin is secreted during pregnancy by the placenta and by the maternal and fetal adipose tissues. The leptin levels mainly reflect the amount of fat stored and thus are indicative of the energy balance, i.e., small-for-gestational-age (SGA) neonates represent the negative metabolic balance of in utero starved babies. We chose to compare maternal and umbilical cord leptin levels in pregnancies complicated by asymmetrical SGA versus those with appropriate-for-gestational-age (AGA) neonates as well as a model of multifetal growth concordant gestations in order to establish through the 'leptin link' the relative contributions of mother, fetus, and placenta to fetal weight. We found that the maternal leptin levels at delivery correlated poorly with the maternal weight gain/body mass index and with neonatal birth weight. Furthermore, the umbilical cord leptin levels correlated well with neonatal and placental weights in the AGA group but not in the SGA group. As in AGA singleton pregnancies, in multifetal uncomplicated pregnancies, the umbilical cord leptin levels correlated well with the birth weight of individuals, regardless of the status of the twin or triplet in the set. Thus, we speculated that in SGA neonates the birth weight represents the lean body weight and the low adipose tissue content (as opposed to the AGA neonates who have a substantial adipose tissue content) and, therefore, reflects mainly the basic placental contribution.