Differential expression of galectin-3 in pituitary tumors

Galectin-3 (Gal-3), a beta-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor beta1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.     

Classification of pituitary adenomas

Angiogenesis is of vital importance for the growth of solid tumors and constitutes a target for anti-cancer therapy. Glioblastomas (GBMs) are histologically characterized by striking microvascular proliferation. The identification of the mechanism of angiogenesis is of major importance for the further development of anti-angiogenic therapy. Tumor angiogenesis might be the result of a combination of local tissue conditions (especially hypoxia) and specific genetic alterations acquired during oncogenesis. In order to investigate the relationship between genetic aberrations and tumor angiogenesis in GBM xenograft lines, the genetic alterations were examined by Comparative Genomic Hybridization (CGH). Two vascular phenotypes of GBM xenografts could be identified: a well vascularized and a poorly vascularized type. In this model, the poorly vascularized type had a larger number of genetic alterations. However, there was no unequivocal correlation between angiogenesis, growth rate and patterns of genetic alterations as detected by CGH.     

Ganglion cells in the posterior pituitary: result of ectopia or transdifferentiation?

Histologic examination revealed large ganglion cells within the posterior pituitary of an 80-year-old woman who died of myocardial infarction. Apparently fully mature, the cells were an incidental finding scattered within hyperplastic foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic examination of the pituitary obtained at autopsy. Immunocytochemistry showed staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of the glycoprotein hormones and beta-endorphin. The presence of these ganglion cells with features similar to those of magnocellular hypothalamic neurons could be considered the result of abnormal migration during the early phase of embryonic life, or differentiation/maturation of neuroblasts, presumed to occur in the embryonic neurohypophysis. Alternatively, transdifferentiation from proliferating PI cells may explain the emergence of neurons; a hypothesis supported by the proximity and shared alpha subunit, and beta-endorphin immunoreactivities of the two cell types. Received: 31 August 1999 / Accepted: 12 October 1999     

Five years of fecal microbiota transplantation——an update of the Israeli experience

AIM To evaluate and describe the efficacy of fecal microbiota transplantation(FMT) for Clostridium difficile infection(CDI) in a national Israeli cohort.METHODS All patients who received FMT for recurrent(recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success(at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT(cessation of diarrhea within 7 d) and recurrence at 6 mo.RESULTS There were 111 FMTs for CDI, with a median age of 70 years [interquartile range(IQR): 53-82], and 42%(47) males. Fifty patients(45%) were treated via the lower gastrointestinal(LGI, represented only by colonoscopy) route, 37(33%) via capsules, and 24(22%) via the upper gastrointestinal(UGI) route. The overall success rate was 87.4%(97 patients), with no significant difference between routes of administration(P = 0.338). In the univariant analysis, FMT success correlated with milder disease(P = 0.01), ambulatory setting(P 0.05) and lower Charlson comorbidity score(P 0.05). In the multivariant analysis, only severe CDI [odd ratio(OR) = 0.14, P 0.05] and inpatient FMT(OR = 0.19, P 0.05) were each independently inversely related to FMT success. There were 35(32%) patients younger than 60 years of age, and 14(40%) of them had a background of inflammatory bowel disease.CONCLUSION FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.     

Physical, morphological, and chemical studies of dusts derived from the machining of composite-epoxy materials

This work (in three parts) inquires into whether respirable dusts derived from the machining of six composite-epoxy materials (e.g., aircraft industry) may pose a health risk to the operators. Dust samples representative of a variety of composites and structural components were aerodynamically sized and fractionated. Bulk and fractionated samples were examined by light and electron microscopy and analyzed chemically by thermogravimetry (TGA), gas chromatography (GC) and mass spectrometry (MS). Relative fractions of respirable to total mass of bulk samples were less than 3%; aerodynamic diameters of fractionated particles ranged from 0.8 to 2.0 microns. By microscopy, bulk particles ranged from 7 to 11 microns in diameter, with mean aspect ratios from 4 to 8:1. Mean diameter of fractionated particles was 2.7 microns. By TGA, weight losses were negligible below 250 degrees C and variable but elevated at temperatures up to 860 degrees C. In assays of vapors released at 250 degrees C, GC/MS indicated a variety of compounds in different amounts for each sample. We conclude that under the present machining protocols, dusts at the tool face contained few particles of respirable size with no evidence of splitting of fibers longitudinally and were of a low volatilizable chemical content. Overall, composites were judged to be well cured and thermally stable.     

Methylation study of a population environmentally exposed to arsenic in drinking water.

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.     

Palm Fruit Bioactive Complex (PFBc), a Source of Polyphenols,Demonstrates Potential Benefits for Inflammaging and Related Cognitive Function

Cognitive function is a key aspect of healthy aging. Inflammation associated with normal aging, also called inflammaging is a primary risk factor for cognitive decline. A diet high in fruits and vegetable and lower in calories, particularly a Mediterranean Diet, may lower the risk of age-related cognitive decline due in part to the associated high intake of antioxidants and polyphenols. A phenolic, Palm Fruit Bioactive complex (PFBc) derived from the extraction process of palm oil from oil palm fruit (Elaeis guineensis), is reported to offset inflammation due to its high antioxidant, especially vitamin E, and polyphenol content. The benefit is thought to be achieved via the influence of antioxidants on gene expression. It is the purpose of this comprehensive review to discuss the etiology, including gene expression, of mild cognitive impairment (MCI) specific to dietary intake of antioxidants and polyphenols and to focus on the potential impact of nutritional interventions specifically PFBc has on MCI. Several in vitro, in vivo and animal studies support multiple benefits of PFBc especially for improving cognitive function via anti-inflammatory and antioxidant mechanisms. While more human studies are needed, those completed thus far support the benefit of consuming PFBc to enhance cognitive function via its anti-inflammatory antioxidant functions.     

Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways

Children's exposure to organophosphorus (OP) pesticides in an agricultural community in central Washington State was determined. Spot urine and hand wipe samples were collected from 109 children 9 months to 6 years of age, as were house dust samples, and wipe samples from various surfaces. Children were categorized based on parental occupation (agricultural vs nonagricultural) and on household proximity to pesticide-treated orchards. Median house dust concentrations of dimethyl OP pesticides in homes of agricultural families were seven times higher than those of reference families (1. 92 vs 0.27 microg/g; P<0.001). Median pesticide metabolite concentrations in agricultural children were five times higher than those in reference children (0.05 vs 0.01 microg/ml; P=0.09). Median pesticide concentrations in housedust (P=0.01) and metabolite concentrations in urine (P=0.01) from agricultural families were significantly higher in the children living near treated orchards (within 200 ft or 60 m) than those living more distant. Ten of 61 agricultural children had detectable OP pesticide levles on their hands, whereas none of the reference children had detectable levels. These findings indicate that children living with parents who work with agricultural pesticides, or who live in proximity to pesticide-treated farmland, have higher exposures than do other children living in the same community Copyright 2000 Academic Press.     

High-dose nicotine patch therapy for smokers with a history of alcohol dependence: 36-week outcomes

This study reports findings from an investigation of the efficacy of high-dose nicotine patch (NP) therapy for heavy smokers with a history of alcohol dependence. One hundred thirty participants were randomly assigned to 42 or 21 mg of transdermal nicotine. Follow-up assessments were conducted at 4, 12, 24, and 36 weeks. Differences between dose conditions were nonsignificant, although, unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine abstinence rates in the 21- and 42-mg NP conditions on Week 36 follow-up were 16.9% and 9.2%, respectively. Patch condition did not interact with severity of nicotine dependence. However, nicotine abstinence at follow-up was related to a longer length of alcohol abstinence. No evidence was found for better outcomes as a function of the percentage of baseline cotinine replaced by NPs. Future research should focus primarily on investigating ways to improve smoking quit rates for smokers in early alcohol recovery.     

Exposure assessment of particulate matter for susceptible populations in Seattle

In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 microm (PM2.5) were similar to the average outdoor PM2.5 concentrations but significantly higher than the average indoor concentrations. Personal PM2.5 exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM2.5, PM10 (PM with aerodynamic diameters < 10 microm), and the ratio of PM2.5 to PM10 were significantly higher during the heating season. The increase in outdoor PM10 in winter was primarily due to an increase in the PM2.5 fraction. A similar seasonal variation was found for personal PM2.5. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM2.5 and PM10 concentrations. Personal PM2.5 exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM2.5 exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM2.5 measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM2.5 exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children.