Natural variation in a Drosophila clock gene and temperature compensation.

The threonine-glycine (Thr-Gly) encoding repeat within the clock gene period of Drosophila melanogaster is polymorphic in length. The two major variants (Thr-Gly)17 and (Thr-Gly)20 are distributed as a highly significant latitudinal cline in Europe and North Africa. Thr-Gly length variation from both wild-caught and transgenic individuals is related to the flies' ability to maintain a circadian period at different temperatures. This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection.

Development of a new melanoma model in C57BL/6 mice.

In the present study, we induced melanomas in C57BL/6 mice by a single application of 7,12-dimethylbenz(a)anthracene to the scapular region of 4-day-old mice, followed by twice-weekly applications of croton oil. Of 20 mice treated, melanomas arose in two female littermates. The first melanoma (JB/MS) arose 16 weeks after initiation of treatment, and the second melanoma (JB/RH) arose 23 weeks later. The melanomas maintained their melanotic appearance after s.c. transplantation to normal C57BL/6 mice and metastasized spontaneously in the transplant recipients. To our knowledge, these are the first melanomas to have been induced in C57BL/6 mice since the B16 melanoma arose spontaneously in 1954. We feel that the JB/MS and JB/RH melanomas provide an excellent comparative system for studies done with the B16 melanoma. These melanomas of recent origin will also facilitate the investigation of biological, immunological, and biochemical parameters that influence the growth and metastasis of malignant melanomas.

Psychosocial benefits of postmastectomy lymphedema therapy.

The effect of a comprehensive lymphedema management program was assessed in 25 patients in whom moderate to severe lymphedema had developed after surgery and/or radiotherapy for carcinoma of the breast. Intensive treatment (4 weeks) involved massage, compression bandaging, and sequential pneumatic compression, with an adjunct program of education to provide skills in exercise, massage, bandage, and containment garment use. The intensive treatment phase was followed by a self-management phase based on the skills that had been acquired. A significant reduction in limb circumference and volume, with continuing improvement over 12 months of self-management, was observed. There was a decrease in need for physical assistance. Quality of life generally remained high and stable throughout the 12 months. Quality of life specific to lymphedema, however, declined during the intensive phase of treatment, but recovered and surpassed pretreatment levels during the self-management phase of treatment. Perceived comfort and strength in the lymphedematous limb improved, and perceived size decreased. The study confirmed that the combination of multimodal physical therapy and education for self-management reduces lymphedema and its adverse subjective consequences and maintains the improvement thus achieved.

A mosaic cell layer in human pregnancy.

We present evidence for a novel histological and embryological relationship at the human materno-fetal interface. Here an epi- endo- thelium forms an integrated unicellular layer lining the intervillus space in between the anchoring villi that attach the placenta to the uterus. This layer appears to be derived from two different germ layers (mesoderm and ectoderm). The data presented here reveals that when a probe for the Y-chromosome is used to test the gender of placental cells following the birth of male or female babies, the cell-sheet is a genetic mosaic derived from two individuals (mother and baby). The endothelium is maternally derived; the epithelium is fetal derived. This new allo- epi- endothelium model is relevant to theories of germ layer separation in development, reproductive immunology and the endocrinology of implantation and placentation. It demonstrates cooperative intercellular interactions that are fundamental to achieving a major goal of human interstitial implantation the establishment of a blood sinus for haematotrophic nutrition. Poor implantation is a fundamental cause of pregnancy pathology and this knowledge will be useful in development of our understanding of pregnancy diseases.

Post-mastectomy lymphoedema treatment and measurement.

OBJECTIVE: To evaluate multimodal treatment (massage, pneumatic compression, bandaging and education) of post-mastectomy lymphoedema and to review methods of measurement of lymphoedema. DESIGN: Prospective cohort study with 12 months' follow-up. PATIENTS: Twenty-five consecutive women referred for lymphoedema examination after mastectomy to a private day-patient clinic attached to a tertiary referral hospital. INTERVENTION: Patients received multimodal therapy, including education on self-management techniques, for four weeks. MAIN OUTCOME MEASURES: Changes in body weight, limb circumference and volume, and patient reports of self-management (exercise, massage, bandaging and sleeve wearing). RESULTS: Excess limb volume decreased by approximately 40% immediately after treatment and by over 50% at 6 months' follow-up, remaining stable to 12 months' follow-up. Self-management that required assistance (massage and bandage wearing) declined more after treatment than did exercise or compression sleeve wearing. Correlations between body mass and limb volume and self-management and limb volume reduction were non-significant. CONCLUSION: Multimodal therapy reduced lymphoedematous limb volume by at least half in 18 of 25 patients. Patients can maintain these reductions independently through exercise and sleeve wearing and without further treatment. We used a replicable method of measuring lymphoedema, which we recommend for adoption by researchers in this field.

Molecular coevolution within a Drosophila clock gene.

The period (per) gene in Drosophila melanogaster provides an integral component of biological rhythmicity and encodes a protein that includes a repetitive threonine-glycine (Thr-Gly) tract. Similar repeats are found in the frq and wc2 clock genes of Neurospora crassa and in the mammalian per homologues, but their circadian functions are unknown. In Drosophilids, the length of the Thr-Gly repeat varies widely between species, and sequence comparisons have suggested that the repeat length coevolves with the immediately flanking amino acids. A functional test of the coevolution hypothesis was performed by generating several hybrid per transgenes between Drosophila pseudoobscura and D. melanogaster, whose repetitive regions differ in length by about 150 amino acids. The positions of the chimeric junctions were slightly altered in each transgene. Transformants carrying per constructs in which the repeat of one species was juxtaposed next to the flanking region of the other were almost arrhythmic or showed a striking temperature sensitivity of the circadian period. In contrast, transgenes in which the repeat and flanking regions were conspecific gave wild-type levels of circadian rescue. These results support the coevolutionary interpretation of the interspecific sequence changes in this region of the PER molecule and reveal a functional dimension to this process related to the clock's temperature compensation.