Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia

To examine the possible role of gap junctions in mouse skin tumor progression, we generated a panel of mouse skin tissue samples exhibiting normal, hyperplastic, or neoplastic changes and characterized the expression of the gap-junction genes connexin 43 (Cx43) and connexin 26 (Cx26) by in situ hybridization and immunohistochemical analyses. In normal skin, these two gap junction genes were differentially expressed; Cx43 was found predominantly in the less differentiated lower spinous layers, whereas Cx26 was found in terminally differentiating upper spinous and granular layers. In hyperplastic epidermis exhibiting an expansion of the differentiated upper layer, i.e., epidermis with a thickened granular layer or in which the granular layer was replaced with keratinocytes exhibiting tricholemmal differentiation, expression of Cx43 and Cx26 remained segregated in the lower and upper spinous layers, respectively. However, in papillomas, Cx26 was localized in the lower but not upper spinous layer, an expression pattern identical to that of Cx43. In addition, the overall expression levels of both Cx43 and Cx26 appeared to be greatly elevated in the papillomas. It is interesting that such marked alteration in the pattern of Cx26 expression occurred within the context of hyperplastic changes histologically identical to those seen in the nonpapillomous hyperplasias. Interestingly, in neoplastic skin lesions containing a squamous cell carcinoma, Cx43 and Cx26 expression was extinguished. Moreover, expression of Cx43 was also significantly reduced in adjacent apparently nonneoplastic tissues. Overall, these observations show that perturbations in gap-junction gene expression are associated with skin hyperplasia and neoplasia. Such findings suggest a possible role for gap junctions in the malignant conversion of mouse epidermal cells.     

Glycine agonists: what can they teach us about schizophrenia?

Plantar fibromatosis is a rare, benign lesion involving the plantar aponeurosis. Eleven patients (13 feet) underwent 24 operations, including local excision, wide excision, or complete plantar fasciectomy. Clinical results were evaluated retrospectively. There were no differences among the subgroups in postoperative complications. Two primary fasciectomies did not recur. Three of six revised fasciectomies, seven of nine wide excisions, and six of seven local excisions recurred. Our results indicate that recurrence of plantar fibromatosis after surgical resection can be reduced by aggressive initial surgical resection.     

Developing a culture of lifelong learning in a library environment

Between 1995 and 1996, the Annette and Irwin Eskind Biomedical Library (EBL) at Vanderbilt University Medical Center (VUMC) radically revised the model of service it provides to the VUMC community. An in-depth training program was developed for librarians, who began to migrate to clinical settings and establish clinical librarianship and information brokerage services beyond the library's walls. To ensure that excellent service would continue within the library, EBL's training program was adapted for library assistants, providing them with access to information about a wide variety of work roles and processes over a four to eight-month training period. Concurrently, customer service areas were reorganized so that any question--whether reference or circulation--could be answered at any of four service points, eliminating the practice of passing customers from person to person between the reference and circulation desks. To provide an incentive for highly trained library assistants to remain at EBL, management and library assistants worked together to redesign the career pathway based on defined stages of achievement, self-directed participation in library-wide projects, and demonstrated commitment to lifelong learning. Education and training were the fundamental principles at the center of all this activity.     

Histamine immunoreactive axons in the macaque retina

PURPOSE: The goal of these experiments was to identify the neurotransmitter in centrifugal axons of the macaque retina. METHODS: Macaca mulatta retinas and optic nerves were fixed overnight in carbodiimide and labeled with an antiserum to histamine with the use of an immunofluorescence technique. RESULTS: Several large histamine-immunoreactive axons ran from the optic nerve head to the peripheral retina, where they branched extensively and terminated in the inner plexiform layer, occasionally alongside retinal blood vessels. Other axons that emerged from the optic nerve head ran in the optic fiber layer to the central retina, circled the fovea, and then returned to the optic disc. These may be the source of histamine-immunoreactive axons that have been observed in central visual areas. No labeled cell bodies were present in the retina. Because perikarya in the posterior hypothalamus are the only known source of histamine in the primate central nervous system and because neurons there can be retrogradely labeled from the cut optic nerve, the histamine-immunoreactive axons must have originated there. CONCLUSIONS: Centrifugal axons in the macaque retina are part of the system of axons containing histamine that originate in the hypothalamus and project throughout the brain. Because the activity of these neurons is highest during the morning, histamine might play a role in preparing the retina to operate in daylight. The contacts of histamine-immunoreactive axons with blood vessels suggest that histamine may also play a role in regulating the retinal microvasculature.     

Transrectal ultrasound applicator for prostate heating monitored using MRI thermometry

PURPOSE: For potential localized hyperthermia treatment of tumors within the prostate, an ultrasound applicator consisting entirely of nonmagnetic materials for use with magnetic resonance imaging (MRI) has been developed and tested on muscle tissue ex vivo and in vivo. METHODS AND MATERIALS: A partial-cylindrical intracavitary transducer consisting of 16 elements in a 4 x 4 pattern was constructed. It produced a radially propagating acoustic pressure field. Each element of this array (1.5 x 0.75 cm), operating at 1.5 MHz, could be separately powered to produce a desired energy deposition pattern within a target volume. Spatial and temporal temperature elevations were determined using the temperature-dependent proton resonant frequency (PRF) shift and phase subtraction of MR images acquired during ultrasonic heating. Four rabbits were exposed to the ultrasound to raise the local tissue temperature to 45 degrees C for 25 minutes. Six experiments compared thermocouple temperature results to PRF shift temperature results. RESULTS: The tests showed that the multi-element ultrasound applicator was MRI-compatible and allowed imaging during sonication. The induced temperature distribution could be controlled by monitoring the RF power to each transducer element. Therapeutic temperature elevations were easily achieved in vivo at power levels that were about 16% of the maximum system power. From the six thermocouple experiments, comparison between the thermocouple temperature and the PRF temperature yielded an average error of 0.34+/-0.36 degrees C. CONCLUSIONS: The MRI-compatible intracavitary applicator and driving system was able to control the ultrasound field and temperature pattern in vivo. MRI thermometry using the PRF shift can provide adequate temperature accuracy and stability for controlling the temperature distribution.     

The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster

The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira (mor) and its molecular characterization. mor encodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.     

Factor structure of a measure of anxiety sensitivity in children

Anxiety sensitivity (i.e., the disposition to react to autonomic arousal with fear) has taken a central role in recent conceptualizations of anxiety. However, questions regarding the dimensional nature of anxiety sensitivity remain. In particular, the factor structure of anxiety sensitivity is unexplored in nonadult populations. The factor structure of the Anxiety Sensitivity Index for Children (ASIC) was examined in three studies. Study 1 (N = 95) used a sample of school children in Grades 4-8 to investigate the reliability of items and factor structure. Items with weak psychometric properties were eliminated, and subsequent analyses revealed that the ASIC was best viewed as a hierarchical scale with a higher order factor (Anxiety Sensitivity) and two first-order factors (Fear of Physiological Arousal and Fear of Mental Catastrophe). Study 2 (N = 112) and Study 3 (N = 144) used more distressed samples of youngsters, and they also found the ASIC to be a hierarchical scale. These findings add a developmental perspective to the Anxiety Sensitivity Index factor analytic discussion and are highly consistent with emergent thinking in the adult anxiety sensitivity literature.     

Silicon and aluminium interactions in haemodialysis patients

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.