Comparison between true and partial hemifacial hypertrophy.

Hemifacial hypertrophy (HFH) is rare and characterized by unilateral enlargement of the head and teeth. Hemifacial hypertrophy is classified as true HFH (THFH) with unilateral enlargement of the viscerocranium, and partial HFH (PHFH) in which not all structures are enlarged. We present a case of THFH and compare and contrast it with a case of PHFH. Hemifacial hypertrophy may cover a wide spectrum of defects or may involve only muscle or bone. Myohyperplasia, reported previously as a separate syndrome, may actually represent a forme fruste of PHFH or THFH. The PHFH patient lead a healthy, normal life without significant psychosocial problems and was reluctant to accept his deformity. Contrastingly, the THFH patient had significant social stigma and compromised health together with major aesthetic morbidity. Treatment planning in THFH is arduous and involves multiple modalities. Therefore, it is imperative to differentiate THFH and PHFH for better understanding and management of the condition.     

Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer

A randomized clinical trial was performed to compare the efficacy of bilateral oophorectomy with that of tamoxifen at a dose of 10 mg twice daily in premenopausal women with metastatic breast cancer, and to examine the efficacy of each as a crossover treatment. Initial treatment responses were seen in ten of 27 patients (37%) treated with oophorectomy and seven of 26 patients (27%) treated with tamoxifen. The difference was not statistically significant. Crossover responses were seen in five of 15 patients (33%) treated with oophorectomy, including three responses in ten prior tamoxifen nonresponders; and two of 18 patients (11%) treated with tamoxifen. Time to progression distributions were not significantly different during initial treatment, and no significant differences in survival were noted. Thus, there was no overall disadvantage to the use of tamoxifen as opposed to oophorectomy as initial hormonal therapy, and a failure to respond to tamoxifen did not preclude a response to subsequent oophorectomy. Exploratory data analysis within subsets indicated consistent differential treatment effects in the visceral dominant patients. Of the 16 such patients treated with oophorectomy, eight (50%) experienced objective responses but there were no responses in the 14 patients treated with tamoxifen. In the nine visceral dominant crossover patients who had not responded to initial tamoxifen, three (33%) subsequently responded to oophorectomy. Time to progression distributions within the visceral dominant subset appeared to be better for the patients treated initially with oophorectomy. However, one must be very cautious in drawing conclusions from exploratory subset analyses, especially with the small sample size. Further studies would be required to test any hypothesis of differential organ site responsiveness.     

Clinicopathologic correlation of pigmented epiretinal membranes

We performed clinicopathologic correlation on ten surgically removed pigmented epiretinal membranes causing macular pucker. All cases occurred in eyes with existing retinal holes or tears, including eight cases of macular pucker after previous retinal detachment. These cases probably represented a limited form of proliferative vitreoretinopathy. All membranes contained pigment epithelial cells with polarity, basement membrane, and melanosomes. Cytoplasmic melanin granules accounted for the clinical feature of pigmentation in these eyes.     

Lymphogranuloma venereum: biopsy, serology, and molecular biology.

A 21 year old woman presented with painful groin lymphadenopathy and malaise. Lymph node biopsy, to exclude atypical infection and malignancy, suggested the diagnosis of lymphogranuloma venereum. This diagnosis was confirmed by serology and polymerase chain reaction, with the patient subsequently admitting to a casual sexual contact within the United Kingdom. Alternative methods of investigation of this disease are discussed.     

Distinct mechanisms of splicing regulation in vivo by the Drosophila protein Sex-lethal

The protein Sex-lethal (SXL) controls pre-mRNA splicing of two genes involved in Drosophila sex determination: transformer (tra) and the Sxl gene itself. Previous in vitro results indicated that SXL antagonizes the general splicing factor U2AF⁶⁵ to regulate splicing of tra. In this report, we have used transgenic flies expressing chimeric proteins between SXL and the effector domain of U2AF⁶⁵ to study the mechanisms of splicing regulation by SXL in vivo. Conferring U2AF activity to SXL relieves its inhibitory activity on tra splicing but not on Sxl splicing. Therefore, antagonizing U2AF⁶⁵ can explain tra splicing regulation both in vitro and in vivo, but this mechanism cannot explain splicing regulation of Sxl pre-mRNA. These results are a direct proof that Sxl, the master regulatory gene in sex determination, has multiple and separable activities in the regulation of pre-mRNA splicing.     

Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo.

The yeast two-hybrid system and far-Western protein blot analysis were used to demonstrate dimerization of human double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in vivo and in vitro. A catalytically inactive mutant of PKR with a single amino acid substitution (K296R) was found to dimerize in vivo, and a mutant with a deletion of the catalytic domain of PKR retained the ability to dimerize. In contrast, deletion of the two dsRNA-binding motifs in the N-terminal regulatory domain of PKR abolished dimerization. In vitro dimerization of the dsRNA-binding domain required the presence of dsRNA. These results suggest that the binding of dsRNA by PKR is necessary for dimerization. The mammalian dsRNA-binding protein TRBP, originally identified on the basis of its ability to bind the transactivation region (TAR) of human immunodeficiency virus RNA, also dimerized with itself and with PKR in the yeast assay. Taken together, these results suggest that complexes consisting of different combinations of dsRNA-binding proteins may exist in vivo. Such complexes could mediate differential effects on gene expression and control of cell growth.     

Influences on Food Selection of Women on High- and Low-Fat Diets

There is evidence that long-term maintenance of a low-fat diet reduces preference for high-fat foods. Sensory evaluation of the taste of fat, and preference for high and low-fat foods were studied in a group of former participants in a randomized dietary intervention trial aimed at lowering fat consumption. Intervention subjects consuming less than 25% of daily calories as fat and control subjects consuming more than 35% of daily calories as fat agreed to be in a "taste perception" study. In Study 1, subjects tasted 20 dairy solutions containing different levels of fat and sugar. Subjects rated the perceived intensity of fat taste, and of liking, for each of the solutions. In Study 2, subjects were asked to taste and rate 4 high-fat and 4 low-fat snack foods, and were then allowed to freely consume these foods in a preference test. Intervention and control subjects were similar in their sensory evaluation of the taste of fat in Study 1. In Study 2, intervention subjects reported a reduced hedonic rating of the taste of high-fat snack foods compared to control subjects, yet intervention subjects consumed the same amount of high-fat snack foods as control subjects. We conclude that a successful outcome in a dietary intervention may be due to social and cognitive factors, in addition to potential changes in hedonic response to fat.