Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings

In the absence of E1B, the 289-amino acid product of human adenovirus type 5 13S E1A induces p53-independent apoptosis by a mechanism that requires viral E4 gene products (Marcellus, R.C., J.C. Teodoro, T. Wu, D.E. Brough, G. Ketner, G.C. Shore, and P.E. Branton. 1996. J. Virol. 70:6207-6215) and involves a mechanism that includes activation of caspases (Boulakia, C.A., G. Chen, F.W. Ng, J. G. Teodoro, P.E. Branton, D.W. Nicholson, G.G. Poirier, and G.C. Shore. 1996. Oncogene. 12:529-535). Here, we show that one of the E4 products, E4orf4, is highly toxic upon expression in rodent cells regardless of the p53 status, and that this cytotoxicity is significantly overcome by coexpression with either Bcl-2 or Bcl-XL. Conditional expression of E4orf4 induces a cell death process that is characterized by apoptotic hallmark features, such as externalization of phosphatidylserine, loss of mitochondrial membrane potential, cytoplasmic vacuolation, condensation of chromatin, and internucleosomal DNA degradation. However, the wide-spectrum inhibitor of caspases, tetrapeptide zVAD-fmk, does not affect any of these apoptogenic manifestations, and does not alter the kinetics of E4orf4-induced cell death. Moreover, E4orf4 expression does not result in activation of the downstream effector caspase common to most apoptosis-inducing events, caspase-3 (CPP32). We conclude, therefore, that in the absence of E1A, E4orf4 is sufficient by itself to trigger a p53-independent apoptosis pathway that may operate independently of the known zVAD-inhibitable caspases, and that may involve an as yet uncharacterized mechanism.     

Prevalence of multiple cardiovascular disease risk factors among women in the United States, 1992 and 1995: the Behavioral Risk Factor Surveillance System

We sought to examine the prevalence of self-reported multiple cardiovascular disease (CVD) risk factors (hypertension, high blood cholesterol, diabetes, overweight, and current smoking) among women in 1992 and 1995 in the United States using data from the Behavioral Risk Factor Surveillance System. In 1992, 37.5%, 34.4%, and 28.1% of women had zero, one, and two or more of the five risk factors, respectively. In 1995, the respective estimates were 35.5%, 34.3%, and 30%. In both years, the prevalence of two or more risk factors increased with age, decreased with educational level, was higher among black women (lowest among Hispanic women and women of other ethnic groups), and higher among women reporting cost as a barrier to healthcare. The percentage of women with two or more risk factors was higher in 1995 than in 1992 for 35 of 48 states, being statistically significant for 7 states. The percentage of women with at least two risk factors was not significantly lower in 1995 than in 1992 for any state. A higher percentage of women reported having multiple CVD risk factors in 1995 compared with 1992. A multifactorial approach to primary prevention and risk factor reduction should be encouraged to help reduce the prevalence and burden of CVD among women.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.     

Plasticity of Na,K-ATPase isoform expression in cultures of flat astrocytes: species differences in gene expression

The sella and parasellar region may be affected by a variety of disease states. Diseases of this region often result in visual disturbances because of the proximity of the sella to the optic pathways and cranial nerves. Knowledge of the pathological conditions affecting the sella and surrounding structures is important for the orbital imager.     

Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin

Human peripheral blood monocytes were examined for migration across an endothelial cell monolayer in an in vitro vessel wall construct. Few monocytes invaded in the absence of a chemotactic gradient, despite significant adhesion to the endothelial monolayer. However, the addition of zymosan-activated human plasma to the lower compartment, to create a chemotactic gradient across the vessel wall, resulted in significantly enhanced monocyte migration. Pretreatment of the monocytes with monoclonal antibodies to thrombospondin (TSP) dramatically inhibited monocyte diapedesis into the vessel wall. The same treatment inhibited monocyte adhesion to endothelial cells in two-dimensional monolayer cultures as well as in vessel wall constructs (no chemotactic gradient). Of interest, however, the monoclonal antibodies had no inhibitory effect on monocyte migration into collagen gels devoid of endothelial cells in response to the same chemotactic gradient, suggesting the importance of TSP in monocyte-endothelial cell interactions. Monoclonal antibodies to fibronectin and normal mouse immunoglobulin G did not inhibit migration in this model of a vessel wall. Furthermore, monoclonal antibodies to TSP showed no inhibition of human peripheral blood neutrophil migration. Previous studies have shown that monocytes synthesize TSP and express this moiety on their surface. The present data suggest that monocytes may utilize TSP to interact with endothelial cells lining the vessel wall during diapedesis.     

Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression

Two cases of cavitary lung cancer with pulmonary aspergillosis were experienced. Case 1 was a 45-year-old male. Chest X-ray and Chest CT revealed a round shadow in the thin-wall cavity of the upper lobe of the right lung. Upper lobectomy of the right lung was performed. Histologically large cell carcinoma was found to invade the entire cavity wall, and aspergillus was not detected in the intracavitary space. Case 2 was a 75-year-old male. Chest X-ray and Chest CT revealed a round shadow in the thin-wall cavity of the upper lobe S1 + 2 of the left lung. As a result of upper lobectomy of the left lung and S6 partial resection, large cell carcinoma was found to invade the entire cavity wall, and aspergillus was not detected in the intracavitary space. Only 19 cases including ours are reported about cases of lung cancer complicated by pulmonary aspergillosis at the same site in Japan. The mechanism of aspergillus infection had not been clarified in the discussions of the reported literature and nothing characteristic could be pointed out in our cases except for the assumption that the presence of cancer was a factor triggering Aspergillus implantation.     

Use of computed radiography in the study of an historic painting

The authors demonstrate the use of radiography in the investigation of an historic painting and describe the potential benefits of computed radiography compared with conventional screen-film radiography. The subject for the comparison was a 16 x 19-foot oil-on-canvas painting, Scipio Africanus Freeing Massiva, by Giovanni Battista Tiepolo. Radiographs of the painting were obtained by using a portable, industrial radiographic unit and both conventional screen-film and photostimulable phosphor plate cassettes. For this investigation, computed radiography had a number of advantages over screen-film radiography, largely due to its wider dynamic range and its capabilities for enhancing the digital images with image processing tools such as magnification, edge enhancement, colorization, and airbrushing. The ability to electronically combine images from the large painting into a single composite image file was extremely valuable, as this technique was much less cumbersome and resulted in much higher quality composite images than could be achieved with conventional radiography. An additional advantage of computed radiography includes the capability to easily archive and transmit these images in a digital format for subsequent review.