Prolactin-releasing effect of buspirone in developing and adult male and female rats

The prolactin-releasing effects of buspirone, an azaspirodecanedione anxiolytic drug unrelated to the benzodiazepines in structure and pharmacologic properties, was examined in developing and adult male and female rats. The possibility that effects of this drug on hormone release could be modulated by neonatal brain sexual differentiation was also evaluated. A single injection of buspirone, 2 or 10 mg/kg body wt, increased serum prolactin (PRL) levels in both sexes; the increase was significant from Day 12 onward. The PRL-releasing effect increased with age. No significant sexual differences were observed in younger rats, but in peripubertal and adult animals, the hyperprolactinemic response was higher in the female. Neonatal androgenization of females or orchidectomy of males failed to modify the PRL-releasing action of buspirone. Serum titers of luteinizing hormone and follicle-stimulating hormone were not modified by buspirone at any age. The present results show for the first time the ontogeny of the PRL-releasing effect of buspirone in male and female rats, and provide evidence that the response is higher in the female and that the effect does not depend on brain sexual differentiation.     

Expression of the retinoblastoma (RB) tumor suppressor gene inhibits tumor cell invasion in vitro

To determine if replacement of the retinoblastoma (RB) tumor suppressor gene could inhibit invasion of RB-defective tumor cells, the capacity of tumor cells to migrate or invade was quantitated by the Boyden chamber assay. The studies were done in a diverse group of stable RB-reconstituted human tumor cell lines, including those derived from the osteosarcoma and carcinomas of the lung, breast and bladder. The expression of the exogenous wild-type RB protein in these tumor cell lines was driven by either a constitutively active promoter or an inducible promoter. It was found that significantly more tumor cells from the parental RB-defective cell lines and the RB revertants than from the RB-reconstituted RB+ cell lines penetrated through the Matrigel (P<0.001, two-tailed t-test), although both RB+ and RB- cells migrated at approximately the same rate on uncoated polycarbonate filters in the Boyden chambers. Of note, the inhibition of invasiveness of various RB-defective tumor cells by RB replacement was apparently well correlated with suppression of their tumorigenicity in vivo. In contrast, although either functional RB or p53 re-expression effectively suppressed tumor formation in nude mice of the RB-/p53null osteosarcoma cell line, Saos-2, replacement of the wild-type p53 gene had much less impact on their invasiveness as compared to the RB gene. These studies provided an insight into the broader biological basis of the RB-mediated tumor suppression in RB-defective tumor cells.     

Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP

The Clinical Global Impressions Scale (CGI) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder. Criticisms of the original CGI were addressed by correcting inconsistencies in scaling, identifying time frames for comparison, clarifying definitions of illness severity and change, and separating out assessment of treatment side effects from illness improvement during treatment. A Detailed User's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version (CGI-BP) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania, depression, and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis. Interrater reliability of the scale was demonstrated in preliminary analyses. Thus, the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder.     

Radiofrequency tissue ablation: increased lesion diameter with a perfusion electrode

RATIONALE AND OBJECTIVES: We sought to induce large zones of coagulation necrosis using radiofrequency (RF) with perfusion electrodes and to define optimal parameters for this system. METHODS: We developed RF electrodes with internal cannulas to enable tip perfusion. Lesions were created with monopolar RF in ex vivo and in vivo liver and muscle tissue with and without perfusion of the electrode tip using 0 degree C saline. In separate experiments, wattage, current, procedure duration, tip exposure, and perfused tip temperatures were studied. RESULTS: In ex vivo liver tissue, a maximum lesion diameter of 3.1 cm without charring occurred with perfusion at 12 min and 50 W. In in vivo liver tissue with perfusion (tip temperature = 25-35 degrees C) and a 3-cm tip exposure, 80 W were deposited in muscle tissue and 65 W in liver tissue for 12 min without inducing charring. Lesion diameters were 4.5 cm and 2.4 cm, respectively. By comparison, without perfusion a maximum of 20 W could be deposited into either tissue type, resulting in 1.8-cm muscle lesions and 1.2-cm liver lesions. Tip temperatures between 45 degrees C and 55 degrees C resulted in charring. Smaller but predictable lesion diameters were created with a lower power, a shorter tip exposure, or both. Of all the parameters, diameter correlated best with the current applied. CONCLUSION: Perfusion of RF electrodes with chilled saline allows for increased power deposition without tissue charring, increasing the volume of coagulation necrosis created with a single electrode insertion. Perfusion electrodes therefore might decrease the number of probe insertions required for percutaneous tumor ablation therapy or allow for the treatment of larger lesions.     

Ultrasound backscatter microscope analysis of mouse melanoma progression

The incidence and mortality rate of cutaneous melanoma continue to increase throughout the world, making the study of melanoma biology an important area of current research. While recent breakthroughs in transgenic mouse technology have led to promising mouse skin models of melanoma, there is presently no technique available for quantitatively studying subsurface melanoma progression, in vivo. We demonstrate the first application of an imaging method called ultrasound backscatter microscopy (UBM) for imaging early murine melanomas with spatial resolution of 30 microns axial and 60 microns lateral. Murine B16 F10 melanomas have been imaged from their earliest detection, over several days, until they are 2 to 5 mm in diameter. Melanoma dimensions measured by UBM were found to be in excellent agreement with those determined histopathologically on the excised tumours. The relative rms errors in UBM-determined melanoma height and width were found to be 8.7% and 4.2%, respectively. The mean rate of increase in tumour height of early murine melanoma was found to be 0.37 +/- 0.06 mm/day. Computer-generated volumetric renderings of melanomas have been produced from three-dimensional image data, allowing quantitative comparisons of tumour volumes to be made. Using a priori assumptions of ellipsoid tumour shape, the relative error in UBM-determined volume was shown to be less than 17%. These results should be of considerable interest to investigators studying melanoma biology using mouse skin models, and have implications in the use of high frequency ultrasound imaging for the clinical assessment of cutaneous melanoma.     

Biologic and serologic characterization of the 161A strain of Naegleria fowleri

The 161A strain of Naegleria isolated from the nasal swab of a boy (9) was grown axenically in Nelson's medium. When 10,000 amoebae from the axenic medium were inoculated onto each monkey kidney cell (Vero) culture, characteristic cytopathic effects (CPE) were noticed in 4 to 5 days. The CPE consisted of granulation of the host cell cytoplasm, cell shrinkage, nuclear pycnosis, and discontinuity of cell sheet. When 10,000 amoebae were instilled intranasally into a group of ten 2- to 3-week-old mice, 8 of the 10 mice exhibited characteristic symptoms of primary amoebic meningoencephalitis and died within 10 to 12 days. Histopathology of the brain revealed necrotic tissue and an acute inflammatory reaction in the superficial regions of the brain. In the gel diffusion and immunoelectrophoresis tests the sonically disrupted antigens of 161A amoebae reacted extensively with the hyper-immune sera against 3 strains (CA, CJ, HB-1) of pathogenic N. fowleri and produced patterns very similar to those produced by the homologous systems. Further, anti-HB-1 serum absorbed with the 161A antigens failed to react with the antigens of HB-1, CA, CJ, and 161A strains thus indicating antigenic identity of 161A strain with N. fowleri. In view of these observations it was concluded that the strain 161A is pathogenic and should be reclassified as N. fowleri.