Identification of functional elements of p18INK4C essential for binding and inhibition of cyclin-dependent kinase (CDK) 4 and CDK6

An indirect immunofluorescence assay (IFA) was used to identify patients with antibodies reactive to the human granulocytic ehrlichiosis (HGE) agent. Serum samples collected from clinically ill individuals were submitted to the Centers for Disease Control and Prevention by physicians via state health departments from throughout the United States and tested against a panel of ehrlichial and rickettsial pathogens. Antibodies reactive to the HGE agent were detected in 142 (8.9%) of 1,602 individuals tested. There were 19 confirmed and 59 probable (n = 78) cases of HGE as defined by seroconversion or a fourfold or higher titer to the HGE agent than to the Ehrlichia chaffeensis antigens. The average age of patients with HGE was 57 years, and males accounted for 53 (68%) of the patients. Cases of HGE occurred in 21 states; 47 (60%) of the cases occurred in Connecticut (n = 14), New York (n = 18), and Wisconsin (n = 15). Onset of HGE was identified from April through December, with cases peaking in June and July. The earliest confirmed cases of HGE occurred in 1987 in Wisconsin and 1988 in Florida. No fatalities were reported among the 78 patients with confirmed or probable HGE. Reactivity to the HGE agent and to either Coxiella burnetii, Rickettsia rickettsii, or Rickettsia typhi was infrequent; however, 74 (52%) of the 142 individuals who were positive for HGE had at least one serum sample that also reacted to the E. chaffeensis antigen. Thirty-four persons with confirmed or probable human monocytic ehrlichiosis due to E. chaffeensis also had antibodies to the HGE agent in at least one serum sample. The specific etiologic agent for 30 patients was not ascribed because of similarity of titers to both ehrlichial antigens. The use of both antigens may be required to correctly diagnose most cases of human ehrlichiosis, especially in geographic regions where both the HGE agent and E. chaffeensis occur.     

Imaging of the pediatric orbit and visual pathways: computed tomography and magnetic resonance imaging

Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays the diagnosis. Small bowel tumors may be an interesting field of application for enteroscopy, which now can be readily performed with dedicated enteroscopic evaluation in patients with suspected small bowel neoplasia could improve prognosis and treatment. Enteroscopy may also play an important role in the surveillance of inherited polyposis syndromes, as in other precancerous condition of the small bowel. In Peutz-Jeghers syndrome it may reduce polyp-induced complications and improve planning for surgery; in familial adenomatous polyposis it may contribute to preventing upper gastrointestinal tract cancer.     

Heritability of anxiety sensitivity: a twin study

OBJECTIVE: In attempting to explain the familial predisposition to panic disorder, most studies have focused on the heritability of physiologic characteristics (e.g., CO2 sensitivity). A heretofore unexplored possibility is that a psychological characteristic that predisposes to panic-anxiety sensitivity-might be inherited. In this study, the authors examined the heritability of anxiety sensitivity through use of a twin group. METHOD: Scores on the Anxiety Sensitivity Index were examined in a group of 179 monozygotic and 158 dizygotic twin pairs. Biometrical model fitting was conducted through use of standard statistical methods. RESULTS: Broad heritability estimate of the Anxiety Sensitivity Index as a unifactorial construct was 45%. Additive genetic effects and unique environmental effects emerged as the primary influences on anxiety sensitivity. There was no evidence of genetic discontinuity between normal and extreme scores on the Anxiety Sensitivity Index. CONCLUSIONS: This study suggests that one psychological risk factor for the development of panic disorder-anxiety sensitivity-may have a heritable component. As such, anxiety sensitivity should be considered in future research on the heritability of panic disorder.     

Geographic variation in the calls of wild chimpanzees: a reassessment

Male chimpanzees produce a species-typical call, the pant hoot, to communicate to conspecifics over long-distances. Calls given by males from the well-known Gombe and Mahale populations typically consist of four different phases: an introduction, build-up, climax, and let-down. Recent observations suggest that chimpanzees living in the Kibale National Park, Uganda, consistently give calls that lack a build-up and are thus qualitatively distinguishable acoustically from those made by other East African conspecifics. We analyzed additional recordings from Mahale and Kibale to re-examine geographic variation in chimpanzee calls. Results indicate that males from both sites produce pant hoots containing all four parts of the call. Calls made by chimpanzees from the two populations, however, differ in quantitative acoustic measures. Specifically, males at Kibale initiate their calls with significantly longer elements and build-up over briefer periods at slower rates than individuals from Mahale. Kibale males also deliver acoustically less variable calls than chimpanzees at Mahale. Although climax elements do not differ between populations in any single acoustic feature, discriminant function analysis reveals that acoustic variables can be used in combination to assign calls to the correct population at rates higher than that expected by chance. Ecological factors related to differences in habitat acoustics, the sound environment of the local biota, and body size are likely to account for these observed macrogeographic variations in chimpanzee calls.     

Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression

Seckel syndrome has been described as the prototype of the primordial bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60 cases have been reported. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic, endocrine, and central nervous systems. This pleiotropy has implied genetic heterogeneity and prompted reviews of previously reported cases of Seckel syndrome. As a result, the characteristic diagnostic features of Seckel syndrome have been highly debated. Although deletions in chromosome 2q have been described, to date, no genetic defect has been defined. We report three cases of Seckel-like syndrome in siblings from nonconsanguinous Caucasian parents. In addition to the typical Seckel phenotypic features, all three cases were characterized by severe hydrocephalus. We review the literature and propose that there is a spectrum of Seckel conditions that share some common key features, but also demonstrate a wide range of phenotypic features.     

Mechanical transport of rotavirus by the legs and wings of Musca domestica (Diptera: Muscidae)

BACKGROUND: Whether or not tumor response to chemotherapy-sensitized radiation therapy (CTRT) for head and neck cancer leads to an improved outcome is unknown. METHODS: Forty patients who received preoperative cisplatin plus simultaneous radiotherapy for operable stage III and IV head and neck cancer were reviewed retrospectively regarding clinical demographics, staging, and survival status. RESULTS: Twenty-one (57%) patients had a histologic complete response (HCR) and 16 (43%) had a partial (PR) (9) or clinical complete (7) response (CCR). Tumor response of N1 versus N2-3 nodal disease showed 6 (75%) HCR and 4 (25%). Five-year disease-free survival overall was 82% for HCR versus 38% for PR/CCR (P <0.05). Disease-specific 5-year survival was 100% for HCR versus 27% for PR/CCR (P <0.002). CONCLUSIONS: Histologic complete response to CTRT for head and neck cancer is associated with increased survival and encouraging disease-free status. Response to CTRT is inversely proportional to lymphatic tumor load.     

The nitric oxide synthase inhibitor L-NAME (N omega-nitro-L-arginine methyl ester) does not produce discriminative stimulus effects similar to ethanol

Three key aspects of Florence Nightingale remarkable life are examine. First, the influence during her formative years: the education and guidance provided by her father, the resistance by her family when she decided to become a nurse; and the rejection by Nightingale of the societal expectations of a woman in the Victorian era. Secondly, her professional life is examined, in particular how she appears to have been viewed by certain members of society, and how it turn she viewed them. It is anticipated that her position as an early feminist will be postulated and illuminated. Thirdly, an analysis of her personal and professional life indicates a way forward for the nursing profession.     

Binding kinetics of monoclonal antibody using antigen-beta-galactosidase hybrid protein: application to measurement of peptide antigenicity

A simple method for determination of binding kinetics of a solid-phase antibody using antigen-beta-galactosidase hybrid protein was evaluated. To minimize conformational change of the antigen binding site of the antibody when directly binding to a microtiter plate, the microtiter plate was precoated with protein A. The binding and free antigen concentrations were directly obtained from the beta-galactosidase activity. This method can be used for analyses of the equilibrium dissociation constant (KD), and the association (Kass) and dissociation (Kdiss) rate constants. Peptide antigenicity was also analyzed by competitive ELISA using this method. Since both antigen-beta-galactosidase and the peptide used are localized in the fluid-phase, the proper affinity constant (KA) of the peptide can be estimated from the KD value of the antigen-beta-galactosidase-antibody interaction, and from the IC50 value of the peptide.     

Sodium, potassium-activated adenosine triphosphatase activity is impaired in the guinea pig pancreatic duct system in streptozotocin-induced diabetes

In patients with type I diabetes mellitus, clinical studies have demonstrated decreased secretion of pancreatic juice by the pancreatic excretory duct system. The cause of this decrease is unknown, but could involve changes in initial signal transduction pathways or one or more of the electrolyte transport components that subserve regulated fluid secretion. We have compared responsiveness to secretin in pancreatic ducts isolated from healthy and diabetic Hartley guinea pigs and also have compared the expression of CFTR and Na+, K(+)-ATPase in these two groups, as the activities of these two proteins are essential for secretion of pancreatic juice. The increases in cyclic AMP levels evoked by exposure to either 0.1 nM or 0.1 microM secretin were not significantly different in pancreatic ducts isolated from healthy and diabetic guinea pigs nor were levels of CFTR or Na+, K(+)-ATPase expression. By contrast, Na+, K(+)-ATPase activity in pancreatic ducts isolated from diabetic guinea pigs was decreased by 70%, suggesting a change in the enzyme's catalytic properties in the diabetic tissues. The observed decrease would be expected to seriously compromise the production of pancreatic juice.