Ockham’s Razor for a Retinal Lesion and Acromegaly and Breaking the Vicious Circle

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. Treatment consists of surgical removal of the primary tumor, cytostatic therapy, “cold” or radioactive somatostatin analogue treatment, and medical therapy for acromegaly, if needed. A 53 year-old female had an ocular lesion noted on a routine optician visit, originally considered to be an ocular melanoma. She had a bronchial carcinoid successfully removed 22 years previously. She had acromegalic features with an enlarged pituitary gland on magnetic resonance imaging and, additionally, metastatic lesions in her bones, liver, and thyroid gland. Elevated GHRH levels (>250× upper limit of normal) suggested a metastatic lung neuroendocrine tumor secreting GHRH. Cold and radioactive somatostatin analogue therapy reduced both GHRH and insulin-like growth factor 1 (IGF-1) levels, but normalization of the biochemical markers of acromegaly was only achieved after pegvisomant was introduced. Complete control of IGF-1 was achieved, and this may have hindered the growth of the metastatic lesions as well, as the patient remains well 13 years after the diagnosis of metastatic disease and 35 years after the original lung operation. A gradual rise in prolactin levels over last 4 years was noted, which is likely due to the prolonged effect of GHRH on prolactin-secreting cells. The diagnosis of this case applied the law of parsimony from the Ockham’s razor principle. We consider that breaking the vicious circle of IGF-1 feeding the metastatic tumor was key for the long-term outcome of this case

Murine CD1d-Restricted T Cell Recognition of Cellular Lipids

AbstractNKT cells are associated with immunological control of autoimmune disease and cancer and can recognize cell surface mCD1d without addition of exogenous antigens. Cellular antigens presented by mCD1d have not been identified, although NKT cells can recognize a synthetic glycolipid, α-GalCer. Here we show that after addition of a lipid extract from a tumor cell line, plate-bound mCD1d molecules stimulated an NKT cell hybridoma. This hybridoma also responded strongly to three purified phospholipids, but failed to recognize α-GalCer. Seven of sixteen other mCD1d restricted hybridomas also showed a response to certain purified phospholipids. These findings suggest NKT cells can recognize cellular antigens distinct from α-GalCer and identify phospholipids as potential self-antigens presented by mCD1d

Electronic and optical properties of new synthesized TTF-based azine derivatives – Experimental and theoretical study

The synthesis and detailed characterization of two tetrathiafulvalene-appended azine derivatives, namely 2-([2,2′-bi(1,3-dithiolylidene)]-4-yl)-6-((2,4-dimethylphenyl)hydrazono) methyl)pyridine (L1) and 5-([2,2′-bi(1,3-dithiolylidene)]-4-yl)-2-((2,4-dimethylphenyl)hydrazono) methyl)pyridine (L2) are described. The crystal structure of ligand L2 indicates that the mentioned molecule is completely planar with the presence of a strong intramolecular N1 [single bond] H1⋯N3 hydrogen bonding. The quantum chemical calculations show that the intermolecular interaction in crystal structure does not affect the HOMO and LUMO orbitals present in isolated molecule. The optical properties of these ligands indicate the presence of intramolecular charge transfer band in the case of ligand L2 while the electrochemical behavior of the two compounds indicates that they are valuable candidates for the construction of crystalline radical cation salts

XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk

Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Poleri, Lucía Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Apoptotic cell clearance in chronic inflammation of lateral neck cysts

The mechanism driving accumulation of large numbers of apoptotic and necrotic neutrophils in inflamed lateral neck cysts (LNC), in the absence of infection, remains obscure. The cellular content of cysts obtained from 17 patients was co-cultured with human macrophages. Phagocytosis levels of cyst-derived neutrophils were determined and compared to the uptake of spontaneously apoptotic neutrophils. Simultaneously, the expression of cytokines in macrophages exposed to cyst contents was measured. In comparison to spontaneously apoptotic neutrophils, the phagocytosis of LNC-derived neutrophils by macrophages was inefficient. An inverse correlation between neutrophil content in LNC and their uptake was observed. Macrophages co-cultured with cyst contents responded with variable expression of IL-6, TNF-α and IL-10. The hindered clearance of apoptotic neutrophils in LNC may lead to secondary necrosis of these cells and stimulation of the inflammatory reaction. Together with local production of anti-inflammatory cytokines, this may fuel chronic inflammation in the cysts

Socio-demographic, lifestyle and health characteristics among snus users and dual tobacco users in Stockholm County, Sweden

<p>Abstract</p> <p>Background</p> <p>Socio-demographic and lifestyle characteristics of snus users have not been systematically described. Such knowledge is pivotal for tobacco control efforts and for the assessment of health effects of snus use.</p> <p>Methods</p> <p>A cross-sectional study was conducted, based on the Stockholm Public Health Survey, including a population-based sample of 34,707 men and women aged 18-84 years. We examined how socio-demographic, lifestyle and health-related characteristics were associated with the prevalence of current daily snus use, smoking and dual tobacco use. Logistic regression was used to calculate odds ratios of prevalence (ORs) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>Low educational level (OR = 1.60, CI = 1.41-1.81 and OR = 1.49, CI = 1.17-1.89, for men and women respectively), as well as occupational class and low income were associated with snus use. Some unfavourable lifestyle characteristics, including risky alcohol consumption (males: OR = 1.81, CI = 1.63-2.02; females: OR = 1.79, CI = 1.45-2.20), binge drinking and low consumption of fruit and vegetables were also associated with snus use. In contrast, physical inactivity and overweight/obesity were not, nor was perceived health. The prevalence of smoking followed steeper gradients for social as well as lifestyle characteristics. Overweight and obese men were however less often smokers. Perceived poor general health and psychological distress were highly related to smoking. Social disadvantage, as well as unhealthy lifestyle and self-reported poor health were strongly associated with dual use. There were limited differences between men and women.</p> <p>Conclusions</p> <p>The social, lifestyle and health profiles of exclusive snus users in Stockholm County are less favourable than those of non-users of tobacco, but more advantageous than those of exclusive smokers. This knowledge should guide tobacco control measures as well as the interpretation of health risks linked to snus use.</p

Expression of TopBP1 in hereditary breast cancer

TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p < 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (p < 0.05 and p < 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (p < 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer