Epidemiologic evidence supports associations between inhalation of fine and ultrafine ambient particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] and increases in cardiovascular/respiratory morbidity and mortality. Less attention has been paid to how the physical and chemical characteristics of these particles may influence their interactions with target cells. Butadiene soot (BDS), produced during combustion of the high-volume petrochemical 1,3-butadiene, is rich in polynuclear aromatic hydrocarbons (PAHs), including known carcinogens. We conducted experiments to characterize BDS with respect to particle size distribution, assembly, PAH composition, elemental content, and interaction with respiratory epithelial cells. Freshly generated, intact BDS is primarily (> 90%) PAH-rich, metals-poor (nickel, chromium, and vanadium concentrations all < 1 ppm) PM2.5, composed of uniformly sized, solid spheres (30–50 nm) in aggregated form. Cells of a human bronchial epithelial cell line (BEAS-2B) exhibit sequential fluorescent responses—a relatively rapid (~ 30 min), bright but diffuse fluorescence followed by the slower (2–4 hr) appearance of punctate cytoplasmic fluorescence—after BDS is added to medium overlying the cells. The fluorescence is associated with PAH localization in the cells. The ultrafine BDS particles move down through the medium to the cell membrane. Fluorescent PAHs are transferred from the particle surface to the cell membrane, cross the membrane into the cytosol, and appear to accumulate in lipid vesicles. There is no evidence that BDS particles pass into the cells. The results demonstrate that uptake of airborne ultrafine particles by target cells is not necessary for transfer of toxicants from the particles to the cells.

Observations were made on eyes from 46 bowhead whales, Balaena mysticetus, taken in the subsistence harvest near Barrow, Point Hope, Savoonga, and Kaktovik, Alaska. Data reported here include palpebral, eyeball, corneal, scleral, pupillary, and lens dimensions. These quantitative data have allowed us to compare structures relative to one another and sometimes to compare them with similar structures in other species. We found, for example, that the cornea is almost three times as thick at its periphery as at its center; that when the ratio of scleral thickness and eyeball size are compared, the ratio, in the bowhead whale, is twice that of any other cetacean for which data were available; and that the corneal and pupillary width to height ratios indicate a less elongated cornea and pupil than has been reported in other cetaceans. We also found a strong correlation between body length and eyeball size indicating that within the species, unlike what is seen between species, larger animals have larger eyes. Novel observations include the presence of three periorbital fatty layers, 112 ciliary processes, the presence of scleral canals, the absence of an obvious fovea or macular region in the retina, a holangiotic pattern of fundic vessels, the presence of zonular fibers and a lens sheath, and the absence of an obvious pupillary operculum. Anatomical features like the wide angle of divergence and the palpebral dimensions suggest the absence of binocular vision while features like the size of the palpebral sac, abundant conjuctival fat, and the prominence of the retractor bulbi muscle suggest mechanisms for the protrusion and retraction of the eyeball.

The objectives of this anatomical study were to (1) determine if significant bone growth occurs in the base of the alveolar bony crypt of the first mandibular molar to move the tooth through the eruption pathway; (2) determine if the osteogenesis in the crypt correlates with the published chronological gene expression of bone morphogenetic protein-2 (BMP-2) in the dental follicle; and (3) determine chronologically and regionally the crypt bone activity. To accomplish this, the alveolar bony crypts of rat mandibular molars from postnatal days 3 to 18 were processed and examined by scanning electron microscopy (SEM). In addition, mandibles and teeth of ages 12-18 were prepared for light microscopy. SEM demonstrated that bone formation occurs in the basal (apical) portion of the alveolar bony crypt at day 3, whereas bone resorption concurrently is ongoing in the coronal region of the crypt. By day 9, the crypt is beginning to be reduced in depth as the result of basal bone formation, and by day 14, the base of the crypt immediately under the tooth is almost completely filled with bone to form the interradicular septum. At day 18, the tooth erupts as bone formation likely elevates the molar. Bone growth in the basal area of the crypt correlates with a previous study showing enhanced BMP-2 expression in the dental follicle. Thus, SEM indicates that the motive force of tooth eruption likely is bone formation at the base of the alveolar crypt and this osteogenesis may relate to BMP-2 production in the dental follicle.

Purpose: Bleomycin electrochemotherapy has been successfully used in preclinical studies and clinical trials for treating squamous cell carcinoma (SCC) and adenocarcinoma; however, it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment. In this study, we explore the coadministration of bleomycin and interleukin-12 (IL-12) followed by electroporation for treating primary and metastatic tumors. Experimental Design: Bleomycin, IL-12 plasmid DNA, or a combination of both were injected into high-grade malignant mammary tumors and SCCVII followed by electroporation. The tumor growth, survival, metastasis in lungs, CTL activity, and vascular density were analyzed.The results were analyzed by the two-sided Student's t test and Gehan's Wilcoxon test. Results: Coadministration of bleomycin and IL-12 via electroporation eradicates preestablished 4T1mammary tumors in up to 60% of mice, inhibits metastatic tumor development, and extends the long-term survival. Likewise, coadministration of bleomycin and IL-12 via electroporation eradicates squamous cell carcinoma (SCCVII) in 100% of mice and prevents tumor redevelopment in 80% of mice. Neither bleomycin nor IL-12 alone is able to achieve the same therapeutic potency. The primary role of bleomycin is to inhibit the tumor vessel development; the primary role of IL-12 is to increase the immune response that extends the survival of treated mice and inhibits the tumor redevelopment.Conclusions: This combination modality has great potential to be translated in a clinical setting for treating high-grade malignancies and for preventing tumor redevelopment.Breast cancer is the second leading cause of cancer deaths in women today and is the most common cancer among women, excluding nonmelanoma skin cancers (The American Cancer Society, 2005). According to WHO, >1.2 million people will be diagnosed with breast cancer this year worldwide. Despite the improvement in early diagnosis and treatment strategies, novel and effective alternatives for treatment, such as electrochemogenetherapy, have not been explored in breast cancer.SCC of the head and neck is the fourth most common malignancy among males. More than 40,000 cases are diagnosed per year in the United States, 60,000 in Europe, and 500,000 worldwide (1, 2). Patients with SCC of the head and neck are afflicted with a disease that profoundly influences the quality of life (3). Surgical treatment may affect essential functions, including breathing, eating, and communication.Many patients are plagued with tumor redevelopment after surgery that proves fatal. Clearly, patients need an effective but less debilitating local control treatment.Electroporation has been used extensively to deliver drugs and genes into cells. The first report of an in vivo application of electric field pulses in combination with chemotherapeutic drugs was published by Okino and Mohri (4). The process of injecting nondiffusing drugs, such as bleomycin, followed by electric pulses to transiently mak...

Skin samples from most body regions of the bowhead whale were examined. The epidermis is 2.7 to 50 times thicker than that reported in other cetaceans with both regional and individual variations in thickness. The thinnest areas examined (1 mm) occur on the eyelid margins and the thickest (25 mm) occur on the lower jaw. A distinctive parakeratotic stratum corneum with a thick underlying stratum spinosum (without a stratum granulosum) extends over the entire body surface. From a few dozen to several hundred epidermal lesions are present on all whales studied. A typical stratum basale of germinative keratinocytes (with melanocytes in pigmented areas) rests upon a well-defined basal lamina. Epidermal rod arrays arise from the basal keratinocytes which cover highly elongated dermal papillae and extend to the epidermal surface through the distal stratum spinosum and the stratum corneum. At least four diatom genera occur on and in the stratum corneum and lesion areas of different whales. The superficial dermis consists of a papillary layer with long (up to 13 mm) dermal papillae interdigitating with the epidermis from a basal area that is 2-4 mm in thickness. The number of dermal papillae per mm2 varies inversely with the thickness of the epidermis. Large diameter, sensory papillae packed with tortuous, highly elongated, encapsulated nerve end organs also interdigitate with the thin epidermal areas of the ventral surface of the rostrum, the upper and lower lip margins, and the upper and lower eyelid margins. Scattered, single, stiff hairs emerge from the skin only in specific, pigmented regions of the head.