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Defensins are cysteine-rich peptides involved in the innate immunity of insects and many other organisms. In the present study, two novel defensin-encoding cDNAs and the respective genomic DNAs (def3 and def4) of Triatoma brasiliensis were identified and their tissue-specific and temporal expression was characterized. Both of the deduced mature peptides consisted of 43 amino acid residues and were highly similar to previously identified triatomine defensins (81.4-100%). Semi-quantitative RT-PCR data showed that def3 was constitutively expressed in the fat body and was induced in salivary glands and the small intestine at 5 and 3 days after feeding (daf), respectively. The def4 mRNA level was highly up-regulated in the stomach and fat-body tissues at 5 and 3 daf, respectively. The three-dimensional structures of these defensins were predicted using a homology modeling approach with Def-AAA, the defensin from Anopheles gambiae, as template (62-74% identity). A map of the electrostatic potential of these models revealed that, despite their similar folding patterns, mature Def2 and Def4 have a more cationic structure than is the case for Def1 and Def3. Such differences may orient the antimicrobial profile of these defensins against distinct targets in different organs of the insect.

We report new measurements of inclusive pi production from frozen-spin HD for polarized photon beams covering the Delta(1232) resonance. These provide data simultaneously on both H and D with nearly complete angular distributions of the spin-difference cross sections entering the Gerasimov-Drell-Hearn (GDH) sum rule. Recent results from Mainz and Bonn exceed the GDH prediction for the proton by 22 microb, suggesting as yet unmeasured high-energy components. Our pi0 data reveal a different angular dependence than assumed in Mainz analyses and integrate to a value that is 18 microb lower, suggesting a more rapid convergence. Our results for deuterium are somewhat lower than published data, considerably more precise, and generally lower than available calculations.

Biliary cystadenocarcinoma is a rare tumor that originates from the hepatobiliary epithelium. Although this tumor can affect any portion of the biliary tree, intrahepatic location is more common. It is usually a slow growing tumor and often asymptomatic until it reaches a considerable size. The lesion is most often solitary and large when discovered; multiple lesions or metastases within the liver are very rare. A 63-year-old man was referred to our institute for weight loss, abdominal discomfort, worsening bulky symptoms in the right upper abdominal quadrant, and an increase in serum aminotransferases that had been present for several months. Spiral CT of the abdomen demonstrated two lesions, a larger one and a distant intrahepatic lesion, with a multiloculated cystic aspect, a thin peripheral capsule, multiple solid peripheral portions, and irregular septa enhancing in the portal phase after intravenous administration of iodinated contrast medium. The diagnosis of multifocal cystadenocarcinoma of the liver was confirmed by surgical laparoscopy and biopsy of the lesion. The patient was treated with chemotherapy.

Although CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIP(L) (cFLIP(L)) and PED/PEA-15, two antiapoptotic proteins whose exogenous expression in normal thyrocytes inhibited the death-inducing signaling complex of CD95. Additionally, small interfering RNA FLIP and PED antisense sensitized thyroid cancer cells to CD95-mediated apoptosis. Exposure of normal thyrocytes to IL-4 and IL-10 potently up-regulated cFLIP and PED/PEA-15, suggesting that these cytokines are responsible for thyroid cancer cell resistance to CD95 stimulation. Moreover, treatment with neutralizing antibodies against IL-4 and IL-10 or exogenous expression of suppressor of cytokine signaling-1 of thyroid cancer cells resulted in cFLIP and PED/PEA-15 down-regulation and CD95 sensitization. More importantly, prolonged IL-4 and IL-10 neutralization induced cancer cell growth inhibition and apoptosis, which were prevented by blocking antibodies against CD95 ligand. Altogether, autocrine production of IL-4 and IL-10 neutralizes CD95-generated signals and allows survival and growth of thyroid cancer cells. Thus, IL-4 and IL-10 may represent key targets for the treatment of thyroid cancer.

The 1964 US Surgeon General's report was the first from the medical profession to document tobacco as a cause of cancers and other serious illnesses. Over the next 40 years, numerous health care groups have worked to decrease tobacco use and lower the associated morbidity and mortality. Registered nurses are the largest group of health care providers and have one of the highest rates of smoking among health care professionals. As such, registered nurses are an important population to target and treat for nicotine addiction. Hospital-based tobacco control programs can provide nurses and other health care professionals with convenient on-site treatment. The chronic care model provides a useful framework for enhancing tobacco control activities and improving outcomes.

In this work, Sicilian cultivars of prickly pear (Opuntia ficus indica) were partially characterized from a chemical point of view, and the possibility of long-term storage of their juice was investigated. The acidity of the prickly pear juice turned out to be very low (0.02%) and the pH very high (6.4-6.5) if compared with values found in other common fruit juices. In the perspective of processing and storage conditions according to Italian law, the acidity has been corrected by adding the proper amount of tartaric and/or phosphoric acid. The sugar content (mainly glucose and fructose) is very high (11-12%), and also L-ascorbic acid is present in considerable amount (31-38 mg/100 g). Among the transition metals, a high content of manganese(II) (1.7-2.9 ppm) and good amounts of iron(III) (0.6-1.2 ppm) and zinc(II) (0.3-0.4 ppm) were found. In particular, such ions appear to be present mainly in the thick skin of the fruit or "trapped" inside the pulp. Pectin methylesterase (PME) seems to be present in very small amount and/or is not highly active. Furthermore, PME activity decreases considerably after the necessary adjustment of the pH and the thermal treatment requested for long-term storage. After approximately 2 months, none of the juices prepared was affected by noticeable sedimentation of the pulp. Finally, different samples of prickly pear juice were sensorially analyzed, employing descriptors such as color, aroma, viscosity, acidity, sweetness, and off-flavors. The results obtained can be considered very satisfactory, and the juice has been widely appreciated when compared with other products commonly available on the market such as pear and peach juices.

A patient is described with a specific deficit for arithmetical procedures. Unlike in previously described cases, where the observed problems could be attributed to the systematic application of disturbed algorithms, this patient's difficulty seems to stem from an inability to monitor the sequence of operations that calculation procedures specify. Criteria are provided for distinguishing impairments in written calculation due to the application of defective knowledge of the procedures from those determined by lack of monitoring. The role of monitoring and control processes in different calculation components is also discussed.

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.

Sera from patients with aplastic anemia and amegakaryocytic thrombocytopenia contain an activity that stimulates megakaryocyte colony formation in vitro. We have assayed this megakaryocyte colony-stimulating activity (Meg-CSA) in sera of four patients receiving intensive antileukemic chemotherapy to determine whether the appearance of Meg-CSA is a physiologic response to the suppression of megakaryocytopoiesis. Three of the four patients were receiving consolidation or late intensification therapy for acute myoblastic leukemia (AML) in remission. The fourth was receiving induction therapy for de novo AML. During all or part of four chemotherapeutic cycles, serial Meg-CSA levels were assessed and correlated with the corresponding peripheral platelet counts. All courses of cytotoxic chemotherapy resulted in increases in serum Meg-CSA comparable to activity levels present in sera from patients with aplastic anemia. Two of the three patients studied during the early postchemotherapy interval manifested initial serum Meg-CSA elevations seven days before their thrombocytopenic nadirs when platelet counts were still between 100,000/mm3 and 140,000/mm3. Bone marrow recovery from chemotherapy was characterized by a decrease in serum Meg-CSA to pretherapy levels that occurred concurrently with the rise in platelet count to normal. These observations support the hypothesis that Meg-CSA is a physiologic humoral regulator of megakaryocytopoiesis elaborated in response to the depletion of either bone marrow megakaryocytes or megakaryocyte progenitor cells.

Promyelocytic leukemia HL-60 cells induced to differentiate along the granulocytic and monocytic pathways respond to stimulation with phorbol myristate acetate by producing superoxide radicals. The amount of superoxide radical generation can be monitored by spectrophotometric measurement of cytochrome c reduction. We have developed a microtiter assay that assesses differentiation of HL-60 cells on the basis of cytochrome c reduction. HL-60 cells were incubated with known standards or unknown samples, including crude fermentation broths, for 6 days; then cytochrome c reduction was quantified as a function of increasing absorbance at 550 nm on a microtiter plate reader. HL-60 cells induced to differentiate showed up to a 10-fold increase in absorbance over that of control cells. Differentiation was confirmed by morphological assessment and by flow cytometric analysis of the DNA cell-cycle distribution and the cell-surface transferrin receptor. Analysis of 198 crude fermentation broth samples confirmed the feasibility of using this assay for large-scale drug screening.