In vitro action of testosterone in potentiating gonadotropin-releasing hormone-stimulated gonadotropin-II secretion in goldfish pituitary cells: involvement of protein kinase C, calcium, and testosterone metabolites

Overnight preincubation of goldfish pituitary cell culture with testosterone (T) enhanced the gonadotropin (GTH)-II responses to GTH-releasing hormone (GnRH). In this study, the involvement of GnRH signal transduction components and the requirement for T metabolism in mediating this direct, pituitary cell action of T were examined using cultured pituitary cells from both male and female goldfish. Each sets of related experiments were done in at least two different stages of the gonadal reproductive cycle and similar effects were observed. Overnight treatment with 10 nM T increased GTH-II responses to maximal stimulatory doses (100 nM) of either salmon (s)GnRH or chicken (c)GnRH-II, but not the total cellular GTH-II contents measured prior to and after a 2-h GnRH challenge. T increased the efficacy and sensitivity of the GTH-II response to stimulation by a protein kinase C (PKC) activator, tetradecanoyl phorbol acetate (TPA) without altering the ED50 of the dose-response curve. In T-treated cells, addition of a PKC inhibitor attenuated GTH-II responses to 100 nM doses of sGnRH, cGnRH-II, or TPA. T did not affect the GTH-II release stimulated by high concentrations of the Ca2+ ionophore ionomycin (100 microM) and the voltage-sensitive Ca2+ channel (VSCC) agonist Bay K 8644 (10 microM); similarly, the sensitivity of the GTH-II response to ionomycin and Bay K 8644 was also unaltered. Taken together, these data suggest that T potentiates GnRH-stimulated GTH-II release by enhancing the effectiveness of PKC-dependent pathways, but not by increasing the total Ca2+-sensitive GTH-II pool, the sensitivity of the release response to increases in intracellular Ca2+, or the amount of available GTH-II. However, the VSCC agonist nifedipine reduced sGnRH- and cGnRH-II-elicited GTH-II release in T-treated as well as in non-T-treated cells, suggesting that VSCC dependence is still present in the GnRH-induced response following exposure to T. Since total cGnRH-II binding to pituitary cells was not increased by T, increases in GnRH receptor capacity are unlikely following T treatment. The ability of T to increase GnRH-stimulated GTH-II secretion was not mimicked by 11-ketotestosterone or dihydrotestosterone, but was abolished by coincubation with an aromatase inhibitor. When viewed together, these observations suggest that aromatization of T may be required for the pituitary action of T on GnRH-induced GTH-II release.     

Thermally stimulated current study on flexible siloxane-modified epoxy sheets

Copolymers prepared from the epoxy resin of ALBIFLEX and PMPS oligomer were evaluated with IR, ¹H-and ¹³C NMRs for structural determinations. The flexible epoxy resin as a model compound was examined by TSC with variations on the operational parameters t_p and V_p. Transitions denoted as T_g,δ, T_g,γ, T_g,β, T_g,α and T_g,ρ in increasing order of temperature were observed for these copolymers. As an example, ESAF-7430 copolymer showed these transitions at −138, −84, 26, 87, and 110 °C, respectively. Each transition except the T_g,ρ at 110 °C, has been correlated to a segment in the copolymeric structure. The result indicates that TSC provides clear molecular transitions at the temperature of the transition. The molecular transition of the grafted PMPS-siloxane segment in an epoxy matrix appeared at the −45 °C region as a broad, nearly flat peak as it filled the concave part of the TSC curve of the unmodified resin. The flexibility that the modified copolymers retained may be attributed to these sub-T_g transitions as observed in the TSC spectrum.     

Diseases of the skull in pre-Columbian South American mummies

OBJECTIVE: The majority of paleopathological investigations focus on the study of the skull. This is because the skull is the most frequently preserved part of the human body recovered from archaeological excavations. From studying the skull, a variety of information can be obtained regarding the individual, such as sex, age, nutritional status, and other disease processes, if present. METHODS: This study represents the examination of more than 700 human skulls recovered from archaeological excavations from the Andean region of southern Peru and northern Chile and dating back more than 8000 years. RESULTS: A variety of skull abnormalities were encountered. The nonmetric variables of Huschke's foramina and palatine tori were common. Cranial deformation was observed in more than 85% of the cases. There were two cases of sagittal synostosis. Iron deficiency anemia resulting in porotic hyperostosis of the skull was evident in certain cultures. Exostoses of the external auditory canal resulting from chronic otitis was evident only among coastal populations. One skull demonstrated a periostitis consistent with Treponema infection. Trephination was encountered only in the skulls from Peru. Fifty-four cases of skull fractures were observed, half of which showed evidence of healing. Finally, only two cases of neoplastic skull lesions were encountered. CONCLUSION: The study of the human skull alone provides a large amount of information regarding the health and diseases of ancient populations.     

Disposition and metabolism of rifapentine, a rifamycin antibiotic, in mice, rats, and monkeys

Mycobacterium avium is an intracellular pathogen that is associated with disseminated infection in acquired immunodeficiency syndrome (AIDS). Patients with AIDS appear to acquire M. avium mainly through the gastrointestinal tract. Previous studies have shown that healthy mice given M. avium orally develop disseminated infection after 2-4 weeks. The chief site of M. avium invasion of the intestinal mucosa is the terminal ileum. To learn more about the pathophysiology of M. avium infection of the intestinal mucosa, C57BL/6 bg+ bg+ mice were infected orally with M. avium strain 101 and groups of six mice were killed each week for 8 weeks. The terminal ileum was then prepared for histopathological studies and electron microscopy. A delayed inflammatory response was observed and influx of neutrophils in the Peyer's patches was the only abnormality seen at 1 week. A severe inflammatory response was seen from week 2 to week 5 and necrosis of intestinal villi was observed 6 weeks after infection. These results indicate that invasion and infection of the normal intestine by M. avium results in a severe inflammatory response with segmental necrosis of the intestinal mucosa.     

Experimental design of a two-layer electromagnetically coupledrectangular patch with a global response surface modeling technique

A new approach, based on global response surface (GRS) modeling techniques, is used to design two-layer electromagnetically coupled rectangular patch antennas. Data from a grid of design points is used to construct a model of the input impedance of the antenna. The model is then optimized to provide the best design geometries for the frequency band of interest. Three examples are presented to validate the method     

Early advanced hepatocellular carcinoma: evaluation of CT and MR appearance with pathologic correlation

PURPOSE: To determine the computed tomographic (CT) and magnetic resonance (MR) imaging appearances of early advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-seven surgically resected cases of early advanced HCC were studied with CT, CT during arterial portography, CT arteriography, and MR imaging. RESULTS: The sensitivity of standard CT (unenhanced, early, and late CT combined) for the detection of early advanced HCC was 81%, while that of standard MR imaging (T1- and T2-weighted MR imaging combined) was 83%. A nodule-in-nodule appearance was identified in approximately one-third to one-half of cases. Signal behavior of early and advanced components of early advanced HCC followed the expected behaviors of isolated early HCC and isolated advanced HCC, respectively. Tumor size was accurately estimated with standard CT and standard MR imaging. CONCLUSION: More research must be performed to ascertain whether any relationship exists between the different types of HCC and the clinical outcome.     

Localization of human cytomegalovirus structural proteins to the nuclear matrix of infected human fibroblasts

The intranuclear assembly of herpesvirus subviral particles remains an incompletely understood process. Previous studies have described the nuclear localization of capsid and tegument proteins as well as intranuclear tegumentation of capsid-like particles. The temporally and spatially regulated replication of viral DNA suggests that assembly may also be regulated by compartmentalization of structural proteins. We have investigated the intranuclear location of several structural and nonstructural proteins of human cytomegalovirus (HCMV). Tegument components including pp65 (ppUL83) and ppUL69 and capsid components including the major capsid protein (pUL86) and the small capsid protein (pUL48/49) were retained within the nuclear matrix (NM), whereas the immediate-early regulatory proteins IE-1 and IE-2 were present in the soluble nuclear fraction. The association of pp65 with the NM resisted washes with 1 M guanidine hydrochloride, and direct binding to the NM could be demonstrated by far-Western blotting. Furthermore, pp65 exhibited accumulation along the nuclear periphery and in far-Western analysis bound to proteins which comigrated with proteins of the size of nuclear lamins. A direct interaction between pp65 and lamins was demonstrated by coprecipitation of lamins in immune complexes containing pp65. Together, our findings provide evidence that major virion structural proteins localized to a nuclear compartment, the NM, during permissive infection of human fibroblasts.     

The neuronal stem cell of the olfactory epithelium

Reviews and evaluates psychosocial treatments for attention deficit hyperactivity disorder (ADHD) in children and adolescents according to Task Force Criteria (Lonigan, Elbert, & Johnson, this issue). It is concluded that behavioral parent training and behavioral interventions in the classroom meet criteria for well-established treatments. Cognitive interventions do not meet criteria for well-established or probably efficacious treatments. Issues regarding the evaluative process are discussed and future directions for psychosocial treatment for ADHD are outlined.     

Proliferation and apoptosis of fibroblasts and smooth muscle cells in rat uterine cervix throughout gestation and the effect of the antiprogesterone onapristone

OBJECTIVE: The purpose of this study was to determine the relative percentages of apoptosis and proliferation in fibroblasts and cervical smooth muscles throughout gestation and the effect of an antiprogesterone on these processes. STUDY DESIGN: Rats were studied at days 5, 15, 18, and 21 and immediately postpartum (day 22). Apoptosis and proliferation as detected by specific immunohistochemistry quantitative morphometric analysis was performed. Onapristone, an antiprogesterone, was used to study effects of hormonal change on these processes in 16- and 19-day timed-pregnant rats. RESULTS: Proliferation of fibroblasts and smooth muscle cells was highest in early pregnancy and decreased progressively, whereas apoptosis increased progressively in later pregnancy. Onapristone inhibited apoptosis. CONCLUSION: Changes in cervical cellular turnover are initiated early in gestation and are under hormonal influence. Antiprogesterone inhibits cell death at days 16 and 19 of gestation.