Early epidermal destruction with subsequent epidermal hyperplasia is a unique feature of the papilloma-independent squamous cell carcinoma phenotype in PKCepsilon overexpressing transgenic mice

Protein kinase C epsilon (PKCepsilon) overexpressing transgenic (PKCepsilon Tg) mice develop papilloma-independent squamous cell carcinomas (SCC) elicited by 7,12-dimethylbenz[a]anthracene (DMBA) tumor initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) tumor promotion. We examined whether epidermal cell turnover kinetics was altered during the development of SCC in PKCepsilon Tg mice. Dorsal skin samples were fixed for histological examination. A single application of TPA resulted in extensive infiltration of polymorphonuclear neutrophils (PMNs) into the epidermis at 24 h after TPA treatment in PKCepsilon Tg mice while wild-type (WT) mouse skin showed focal infiltration by PMNs. Complete epidermal necrosis was observed at 48 h in PKCepsilon Tg mice only; at 72 h, epidermal cell regeneration beginning from hair follicles was observed in PKCepsilon Tg mice. Since the first TPA treatment to DMBA-initiated PKCepsilon Tg mouse skin led to epidermal destruction analogous to skin abrasion, we propose the papilloma-independent phenotype may be explained by death of initiated interfollicular cells originally destined to become papillomas. Epidermal destruction did not occur after multiple doses of TPA, presumably reflecting adaptation of epidermis to chronic TPA treatment. Prolonged hyperplasia in the hair follicle may result in the early neoplastic lesions originally described by Jansen et al. (2001) by expanding initiated cells in the hair follicles resulting in the subsequent development of SCC.     

Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins

Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling.     

Effect of danazol in immune thrombocytopenic purpura

Danazol and vinblastine are effective in many patients with chronic immune thrombocytopenic purpura (ITP). To evaluate the mechanism of action of these drugs, we studied six consecutive patients with chronic ITP treated with danazol and one treated with vinblastine. All the patients responded clinically without a notable change in the level of platelet-associated IgG. Instead, the clinical response to therapy was associated with a decrease in the number of monocyte binding sites for monomeric IgG (Fc receptors). In one patient, clinical relapse was associated with a spontaneous 2.7-fold increase in the number of monocyte Fc (IgG) receptors, without a change in the level of platelet-associated immunoglobulin. A decrease in the number of monocyte Fc (IgG) receptors following vinblastine infusion was associated with a clinical remission. We conclude that the clinical course of ITP may be influenced by the expression of monocyte or macrophage Fc (IgG) receptors. Danazol and vinblastine may mediate their clinical effect, at least in part, by influencing the number of available Fc (IgG) receptors on phagocytic cells.     

Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides

The ability of five purified amphibian antimicrobial peptides (dermaseptin-1, temporin A, magainin I, and II, PGLa), crude peptide fractions isolated from the skin of Rana pipiens and R. catesbeiana, and four antimicrobial peptides (AMPs) from hybrid striped bass (piscidin-1N, -1H, -2, and -3) were examined for their ability to reduce the infectivity of channel catfish virus (CCV) and frog virus 3 (FV3). All compounds, with the exception of magainin I, markedly reduced the infectivity of CCV. In contrast to CCV, FV3 was 2- to 4-fold less sensitive to these agents. Similar to an earlier study employing two other amphibian peptides, the agents used here acted rapidly and over a wide, physiologically relevant, temperature range to reduce virus infectivity. These results extend our previous findings and strongly suggest that various amphibian and piscine AMPs may play important roles in protecting fish and amphibians from pathogenic viruses.     

Clinical features and risk factors for mortality in Aeromonas bacteremic adults with hematologic malignancies.

BACKGROUND AND PURPOSE: Aeromonas spp. often cause infections in immunocompromised patients. To specifically understand the clinical features of Aeromonas bacteremic adults with hematologic malignancies, we investigated the demographic, clinical and microbiologic characteristics of Aeromonas bacteremia in this patient population. METHODS: Retrospective study performed in a tertiary medical center in southern Taiwan, in which adults with hematologic malignancies suffered from Aeromonas bacteremia admitted between 1995 and 2003 were included for study. RESULTS: There were 45 episodes of Aeromonas bacteremia in 41 adults with hematologic malignancies. Episodes of Aeromonas bacteremia which occurred at least 2 months apart were counted as separate cases in the analysis. A total of 30 men and 15 women (mean age: 53.2 years), with 4 patients experiencing 2 episodes, was included. The 3 leading underlying hematologic malignancies were acute myelogenous leukemia (37.8%), myelodysplastic syndrome (26.7%) and non-Hodgkin's lymphoma (17.8%). No cluster of Aeromonas bacteremia was found during the study period. Twenty nine (64.4%) of the 31 patients with nosocomial Aeromonas bacteremia had received recent antineoplastic chemotherapy. The 3 leading clinical manifestations were fever (88.9%), septic shock (40%), and altered consciousness (26.7%). Eleven (24.4%) episodes of bacteremia were polymicrobial. Sixteen (35.6%) patients died within 14 days of onset of bacteremia. The mean duration from sampling blood for culture to death was 3.81 days. Altered consciousness (odds ratio, 8.999; 95% confidence interval, 1.787-45.33; p=0.008) was the only independent prognostic factor for mortality. High resistance rates (11.1% to piperacillin and 35.6% to imipenem) among Aeromonas isolates were also noted. CONCLUSION: In febrile patients with hematologic malignancies and suspected Aeromonas infections, particular attention to the development of alteration of consciousness is needed as it is an independent risk factor for mortality.     

Differences Between Treatment Seekers in an Obese Population: Medical Intervention vs. Dietary Restriction

This study examined two groups of people who were pursuing treatment for obesity: either medical intervention (a hospital group; N = 20) or support for dietary restriction (a community group; N = 18). This study addressed four questions: (1) Were there differences between the two groups in terms of their psychological distress (as measured by the Symptom Checklist)? (2) Does binge eating moderate psychological distress? (3) Do feelings of ineffectiveness moderate psychological distress? and (4) Which variables best accounted for group membership (i.e., type of treatment sought)? Results suggested that the hospital group was significantly more distressed than the community group. However, there were no differences between the two groups with respect to binge eating or feelings of ineffectiveness. These findings suggest that it is the effects of morbid obesity that are most likely to moderate psychological distress.     

Visual field maps and stimulus selectivity in human ventral occipital cortex

Human visual cortex is organized into distinct visual field maps whose locations and properties provide important information about visual computations. There are two conflicting models of the organization and computational role of ventral occipital visual field maps. We report new functional MRI measurements that test these models. We also present the first coordinated measurements of visual field maps and stimulus responsivity to color, objects and faces in ventral occipital cortex. These measurements support a model that includes a hemifield map, hV4, adjacent to the central field representation of ventral V3. In addition, the measurements demonstrate a cluster of visual field maps in ventral occipital cortex (VO cluster) anterior to hV4. We describe the organization and stimulus responsivity of two new hemifield maps, VO-1 and VO-2, within this cluster. The maps and stimulus responsivity support a general organization of visual cortex based on clusters of maps that serve distinct computational functions.     

A Strain Device Imposing Dynamic and Uniform Equi-Biaxial Strain to Cultured Cells

The objective of this study is to design a new apparatus to allow the control of the magnitude and frequency of dynamic stretch applied uniformly to cells cultured on a silicon elastic membrane. The apparatus is designed to produce equi-biaxial dynamic stretches with area changes ranging from 0% to 55% and frequencies ranging from 0 to 2 Hz. Homogeneous finite strain analysis using triangles of markers was performed to compute the symmetric two-dimensional Lagrangian strain tensor on the membrane. Measurements of strain in both static and dynamic conditions showed that the shear component of the strain tensor (E_rc) was near zero, and that there was no significant difference between radial (E_rr) and circumferential (E_cc) components, indicating the attainment of equi-biaxial strain. Bovine aortic endothelial cells were transiently transfected with a chimeric construct in which the luciferase reporter is driven by TPA-responsive elements (TRE). The transfected cells cultured on the membrane were stretched. The luciferase activity increased significantly only when the cells were stretched by 15% or more in area. Cells in different locations of the membrane showed similar induction of luciferase activities, confirming that strain is uniform and equi-biaxial across the membrane. © 1998 Biomedical Engineering Society. PAC98: 8780+s, 8745-k, 8722-q     

Determinations of blood flow and shunting of 9- and 15-micrometer spheres in regional beds.

In 17 pentobarbitalized dogs, the shunting of 15-micrometer and 9-micrometer microspheres was studied in the brain, myocardium, kidney, intestine, and lung. The veins of these organs were catheterized for constant blood withdrawal for 2 min by direct venipuncture. The ratio of microsphere radioactivity in the venous blood to that in the arterial blood gave the shunting of microspheres by the venous sampling technique. The 15-micrometer microspheres showed 2% or less shunting for all organs studied, whereas the 9-micrometer microspheres had shunting ranging from 3% in the coronary sinus to 24% in the portal vein. The shunting of 9-micrometer microspheres was also calculated from direct tissue counting, where the 15-micrometer spheres were considered to be completely entrapped. The results of direct tissue counting indicate that the 2-min venous sampling underestimates microsphere shunting. CO2 administration increased significantly the shunting of 9-micrometer spheres, whereas the shunting of 15-micrometer spheres determined by venous sampling remained less than 2%. Consideration of shunting indicates that the 15-micrometer microspheres might be more appropriate for regional organ blood flow measurements, including the myocardium.