A human phase-response curve to light.

Using 'classical' experimental protocols, a human phase-response curve (PRC) to a single 3-h bright light pulse has been established. When the light pulse was centred slightly before the time of body temperature minimum, the circadian system delayed, whilst a pulse slightly after the minimum advanced it. Maximum phase shifts were about 2 h. When light pulses over 3 successive cycles were used, larger shifts (4-7 h) were produced. It is concluded that the human PRC does not differ in principle from that found in other species, except with respect to the light intensity required.     

Blepharochalasis.

Blepharochalasis is an uncommon disorder distinguished by recurrent episodes of eyelid oedema in young patients. A hypertrophic form, manifested as fat herniation, and an atrophic form, manifested as fat atrophy, have been described. Ptosis with excellent levator function, laxity of the lateral canthal structures with rounding of the lateral canthal angle, nasal fat pad atrophy, and redundant eyelid skin develop after many episodes of eyelid swelling. Fine wrinkling, atrophy, and telangiectasias characterise the excess eyelid skin. We describe four cases of this syndrome in which external levator aponeurosis tuck, blepharoplasty, lateral canthoplasty, and dermis fat grafts were used to correct atrophic blepharochalasis after the syndrome had run its course.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Murine CD9 is the receptor for pregnancy-specific glycoprotein 17.

Pregnancy-specific glycoproteins (PSGs) are a family of highly similar secreted proteins produced by the placenta. PSG homologs have been identified in primates and rodents. Members of the human and murine PSG family induce secretion of antiinflammatory cytokines in mononuclear phagocytes. For the purpose of cloning the receptor, we screened a RAW 264.7 cell cDNA expression library. The PSG17 receptor was identified as the tetraspanin, CD9. We confirmed binding of PSG17 to CD9 by ELISA, flow cytometry, alkaline phosphatase binding assays, and in situ rosetting. Anti-CD9 monoclonal antibody inhibited binding of PSG17 to CD9-transfected cells and RAW 264.7 cells. Moreover, PSG17 binding to macrophages from CD9-deficient mice was significantly reduced. We then tested whether PSG17 binds to other members of the murine tetraspanin family. PSG17 did not bind to cells transfected with CD53, CD63, CD81, CD82, or CD151, suggesting that PSG17-CD9 binding is a specific interaction. We have identified the first receptor for a murine PSG as well as the first natural ligand for a member of the tetraspanin superfamily.     

Strong association of the rest-activity rhythm with well-being in demented elderly women.

OBJECTIVE: The objective of this study is to investigate the association between actigraphic estimates of the sleep-wake rhythm and a range of functional domains that contribute to well-being in demented elderly patients. METHOD: Eighty-seven women aged 85.5 +/- 5.9 years (mean +/- standard deviation) wore an actigraph for two weeks. Activity profiles were analyzed using nonparametric variables, including dichotomy indices, interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). The associations between these variables and cognitive, functional, behavioral, and emotional states (obtained from standardized neuropsychologic assessments and questionnaires administered to caregivers) were investigated by partial correlations and stepwise regressions. RESULTS: Cognitive, functional, behavioral, and emotional states showed medium to strong correlations with multiple rhythm variables. Partial correlations indicated that this could not be attributed to a uniform worsening with advancing cognitive decline. Stepwise regressions indicated three most distinctive rhythm variables: 1) the interdaily stability of the 24-hour rhythm was most strongly, negatively, related to cognitive decline and depression; 2) the median level of daytime activity was most strongly, negatively, related to impairments of function, of activities of daily living, and of social interaction; and 3) nocturnal restlessness was secondarily, positively, related to impairments of function and social interaction. CONCLUSION: Especially the interdaily stability and median daytime activity level, and secondarily nocturnal restlessness, showed a strong relationship with the functional status and well-being of demented elderly. This raises the possibility that treatments that enhance daytime activity and the stability of the rest-activity rhythm may improve well-being.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.