<Emphasis Type="Italic">IL-1B</Emphasis> −31T>C promoter polymorphism is associated with gastric stump cancer but not with early onset or conventional gastric cancers

It has been reported that interleukin-1beta (IL-1B) genes play a crucial role in the genetic predisposition to gastric cancer although there is no information about their role in different subtypes of gastric cancer. We performed single nucleotide polymorphism analysis of IL-1B in 241 gastric cancers including early onset gastric cancers (EOGC), conventional gastric cancers, and gastric stump cancers (GSCs) as well as 100 control patients, using real-time polymerase chain reaction and sequence analysis. The C allele was present in 60% of EOGCs, 59% of conventional gastric cancers, and 90% of GSCs, compared to 62% in the control group. Interestingly, there was no difference between early onset and conventional gastric cancer with respect to the IL-1B -31T>C polymorphism distribution. A statistically significant difference in the presence of the C allele compared to the control group was found in patients with gastric stump cancer (p = 0.008) with the T allele conferring protection against gastric stump cancer. In summary, we have shown that the IL-1B -31C allele promoter polymorphism is significantly associated with gastric stump cancer compared to the control group. Although several molecular differences have been identified between conventional gastric cancer and early onset gastric cancer, the IL-1B -31 allele distribution is similar between these two groups.     

Association study with Wegener granulomatosis of the human <Emphasis Type="Italic">phospholipase Cγ2</Emphasis> gene

Background  

Wegener Granulomatosis (WG) is a multifactorial disease of yet unknown aetiology characterized by granulomata of the respiratory tract and systemic necrotizing vasculitis. Analyses of candidate genes revealed several associations, e.g. with α(1)-antitrypsin, proteinase 3 and with the HLA-DPB1 locus. A mutation in the abnormal limb mutant 5 (ALI5) mouse in the region coding for the hydrophobic ridge loop 3 (HRL3) of the phospholipaseCγ2 (PLCγ-2) gene, corresponding to human PLCγ-2 exon 27, leads to acute and chronic inflammation and granulomatosis. For that reason, we screened exons 11, 12 and 13 coding for the hydrophobic ridge loop 1 and 2 (HRL1 and 2, respectively) and exon 27 of the PLCγ-2 protein by single strand conformation polymorphism (SSCP), sequencing and PCR/ restriction fragment length polymorphism (RFLP) analyses. In addition, we screened indirectly for disease association via 4 microsatellites with pooled DNA in the PLCγ-2 gene.     

Genetic polymorphisms of IL6 gene –174G > C and –597G > A are associated with the risk of COVID-19 severity

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (–597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having ‘C’ allele of IL6 (–174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.     

Interaction of Afobazole with σ<Subscript>1</Subscript>-Receptors

The capacity of living systems to perceive low-intensity stimuli sometimes inducing protective reactions is still little studied. Incubation of neurons under conditions increasing the content of cAMP and Ca²⁺ increases the amplitude of their responses to lidocaine (10⁻³ M). After cell preconditioning with low concentrations of lidocaine (10⁻¹⁵ M) under these conditions, the protective effects of “ineffective” concentrations were detected, because the response amplitude did not decrease. It was hypothesized that the basic amplitude responses retrieved by lidocaine in a concentration of 10⁻³ M are memory traces about the effects of this compound in subthreshold concentrations. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 43-46, January, 2009     

“C3, C4, C5 keep you alive,” or do they?

Contrary to traditional teaching in anatomy courses, historical data suggest that bilateral loss of phrenic nerve function does not necessarily result in death.     

“Mission Impossible”? Midwives’ experiences counseling pregnant women with gestational diabetes mellitus

Objective

Since not all pregnancy-related complications require hospitalization midwives often provide these women with antenatal care and counseling. This study explored the experiences of midwives providing antenatal care and counseling to pregnant women with gestational diabetes mellitus (GDM).

Methods

Twelve midwives participated in the interview study performed in the three northernmost counties in Sweden. Grounded theory was used for analysis.

Results

The emerging core category was ‘Balancing fear of failure’. The unexpected disease increased the demands and the pressure. Three major conflicting situations were revealed. The midwives believed they were obligated to monitor and control the pregnancy, to initiate and motivate the necessary changes in lifestyle and provide empowering relationships with their patients. The fear of failure with these assignments made the midwives chose different strategies to manage the conflicting situations.

Conclusions and practice implications

The midwives described conflicting encounters providing antenatal care to pregnant women with GDM. The fear of failing to fulfill the assignments caused by the GDM made the midwives chose strategies to handle the conflicting encounters. Similar conflicting situations might be present for other health care professionals promoting lifestyle changes. The challenges might be addressed with an organization focusing on support and coaching sessions.     

The single nucleotide polymorphism −1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia

The –1131T>C polymorphism in the newly identified apolipoprotein A5 (APOA5) gene has been associated with elevated plasma triglycerides. We determined its incidence in 915 patients attending a lipid outpatient clinic. The frequency of the C allele was significantly higher in patients with triglycerides above the 90th percentile and patients with type III hyperlipidemia compared to those with hypercholesterolemia. The C allele was associated with increased plasma triglycerides and decreased plasma HDL cholesterol, conditions associated with an increased risk of coronary heart disease. The effects on plasma lipids were only observed in overweight (BMI>25) patients and were greater in patients who were also carriers of a least one 4 allele in the APOE gene. Thus additional genetic and/or metabolic factors are required in order for the triglyceride raising and HDL lowering effect of the –1131T>C polymorphism in APOA5 to be expressed.Abbreviations APO Apolipoprotein - BMI Body mass index - DM 2 Diabetes mellitus type 2 - HDL High-density lipoprotein - HLP Hyperlipidemia - LPL Lipoprotein lipase - SNP Single nucleotide polymorphism     

Association study of COX-2 (PTGS2) –765 G/C promoter polymorphism by pyrosequencing in Sicilian patients with Alzheimer's disease

Introduction

Alzheimer''s disease (AD) is characterized by progression of memory problems to a slow global decline of cognitive function. Inflammation when left unregulated becomes a major cofactor in the pathogenesis of AD. PTGS2 is of crucial relevance in the inflammatory response, and it has been shown to play a considerable role in AD pathogenesis.

Material and methods

To assess the possible putative role of a PTGS2 polymorphism (–765 G/C) in AD patients, we examined, by pyrosequencing, its distribution in 84 Sicilian AD patients and in 80 controls.

Results

No significant statistical difference in PTGS2 –765 G/C genotype distribution was found comparing patients with AD and controls. In addition, no significant difference was observed in the distribution of the PTGS2 –765 alleles between AD patients and controls.

Conclusions

These findings suggest that the PTGS2 –765 G/C polymorphism may not be associated with AD in the Sicilian population.     

First‐year growth in children with Noonan syndrome: Associated with feeding problems?

Children with Noonan syndrome show rapid decline of growth in the first year of life and feeding problems are present in over 50%. The aim of this study was to explore whether growth decelerates because of feeding problems or other Noonan syndrome‐related factors. We performed a retrospective, longitudinal cohort study of clinically and genetically diagnosed subjects with Noonan syndrome (n = 143). Questionnaires about the phenotypic–genotypic profile and reported feeding problems were sent to eligible subjects. Data on first‐year growth was obtained from growth charts. Ninety‐one participants were excluded because of different criteria. A total of 52 subjects with Noonan syndrome were included. The largest decline in weight and length standard deviation score (SDS) occurred in the first 2.5 months after birth (−1.93 and −1.15, respectively), with feeding problems causing a decline of 0.57 SDS in the remaining months. At 1 year, children with feeding problems were on average 290 g lighter and 0.8 cm shorter than children without feeding problems. Weight gain was also negatively influenced by having a PTPN11 mutation (n = 39) and a higher gestational age, whereas children of parents with Noonan syndrome and with a higher birth weight gained more weight. Growth in length was reduced by having cardiac surgery and a higher gestational age, but positively influenced by birth length and maternal height. Growth in children with Noonan syndrome is impaired right after birth and only partially associated with feeding problems. In addition, several specific Noonan syndrome‐related factors seem to influence growth in the first year.     

Combination Therapy with Interferon-α and Ribavirin for Hepatitis C

Combination therapy with ribavirin and interferon (IFN)-α for 6 to 12 months is currently the treatment of choice for chronic hepatitis C infection. The overall sustained response rate to treatment, defined as loss of hepatitis C virus (HCV) from serum 6 months after completion of treatment, is 40%. The indications for treatment are serum HCV RNA positivity, abnormal serum transaminases and the presence of portal fibrosis and/or moderate/severe inflammation. Response rates are lower in genotype 1 than in genotype 2 or 3 and in the presence of a high viral load. Anaemia is the most common adverse event and is due to ribavirin; neuropsychiatric adverse effects due to IFNα lead to premature cessation of therapy in 10 to 20% of patients. The current recommended dose of interferon is 3MU given subcutaneously 3 times a week. However, it is likely that longer-acting pegylated interferons, which may be more effective and can be administered once weekly, will in the future replace currently used IFNα.     

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features – “Ependymosarcoma”

By analogy to gliosarcoma, the term “ependymosarcoma” has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5 cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5 cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial–sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical – yet not frankly anaplastic – features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to “ependymosarcoma”.     

Is serum uric acid a predictive factor of response to IFN‐treatment in patients with chronic hepatitis C infection?

Several factors, including metabolic profile, are predictive of response to standard antiviral therapy in patients with chronic hepatitis C. In a retrospective study, it was investigated whether uric acid, involved in metabolic syndrome, could be included. A total of 153 patients (56.2% males; mean age 45.7 +/- 11.3 years) treated with pegylated-interferon and ribavirin were included. Eighty-five were infected with hepatitis C virus (HCV) genotype 1 or 4 and 68 with genotype 2 or 3. Viral load was >1,000,000 IU/ml in 101, < or =1,000,000 IU/ml in 35 and unknown in 17 patients. Ishak fibrosis score was < or =4 in 81, >4 in 15 and unknown in 57 patients. Mean serum uric acid was 5.05 +/- 1.3 mg/dl. Sustained virological response (negative serum HCV-RNA 6 months after treatment cessation) was achieved in 102 patients (67%). In the final logistic model, serum uric acid level > or =5.8 mg/dl (OR = 0.46; 95% CI: 0.30-0.62), viral load (OR = 0.29; 95% CI: 0.09-0.92) and HCV genotype (OR = 0.23; 95% CI: 0.09-0.60) were identified as the most important factors independently influencing clinical outcome. The prognostic role of serum uric acid was confirmed on the sub-sample reporting Ishak fibrosis score (OR = 0.49; 95% CI: 0.28-0.85). Serum uric acid level > or =5.8 mg/dl is predictive of poor response to HCV treatment. Prospective studies are needed to clarify the issue.     

Mast cells—Good guys with a bad image?

Mast cells (MCs) are most known because of their prominent role in allergy. In the last years, however, it has become clear that they have pleiotropic functions and a high adaptability to the milieu. This review focuses on negative and positive roles of MCs within the body with particular emphasis on their participation in reproductive processes.     

Neutrophil Function and Apoptosis in Patients with Chronic Hepatitis C Treated with Pegylated Interferon α and Ribavirin

The role of neutrophils in the pathogenesis of chronic hepatitis C as well as the effect of pegylated interferon α (PEG-IFN-α) and ribavirin treatment on neutrophil function is not precisely known. The study included 32 patients with CCH aged between 19 and 58 years (mean 33.5 years). Before and after 12 weeks of treatment with Peg-IFN-α and ribavirin, intracellular reactive oxygen species (ROS) level, expression of adhesion molecules CD11b/MAC-1, CD16, CD18 and CD62L on neutrophils, as well as apoptosis and necrosis of these cells were analyzed with the use of flow cytometry. During antiviral therapy, a statistically significant decrease of mean fluorescence intensity for CD16 high and CD62 and increase for CD11b/MAC-1 along with the increased apoptosis and decreased necrosis of neutrophils were observed. After 12 weeks of treatment, intracellular ROS production by unstimulated neutrophils did not change, but after stimulation with phorbol 12-myristate 13-acetate, statistically significant increase of ROS level was observed. During PEG-IFN-α and ribavirin treatment, activation of neutrophil function and increased ROS production were reported, which possibly resulted in accelerated apoptosis of these cells.     

Evaluation of IFN-γ secretion after stimulation with C. neoformans and C. gattii antigens in individuals with frequent exposure to the fungus

In this study we produced antigenic extracts from prototypical strains of C. neoformans (VNI-VNIV) and C. gattii (VGI-VGIV) and tested IFN-γ secretion by Elispot. Antigens from the eight Cryptococcus molecular types (VNI –VNIV and VGI - VGIV) were obtained after capsule reduction. IFN-γ secretion by Elispot method were stimulated with C. neoformans and C. gattii antigens. Peripheral blood mononuclear cells of fourteen healthy control subjects, being: five ecotourists, two mycologists, three poultry keepers, and four individuals without reports of exposure to the fungus. We observed a significant increase in IFN-γ secretion in the group of ecotourists, mycologists and bird keepers in relation to the group of individuals without reports of occupational exposures to these agents. Our results suggest the significant increase in IFN-γ secretion may be related to the continuous exposure of these groups of individuals to the fungus, as well as to the specific antigen memory immune response developed during exposure to Cryptococcus.     

Association of hepatitis C virus in human sera with β-lipoprotein

Hepatitis C virus (HCV)-RNA in sera of patients with viral hepatitis C is supposed to be included, at least partially, into HCV particles. We found that the density of HCV-RNA-carrying material was variable, as determined by sucrose gradient density centrifugation (1.03–1.20 g/cm³). In some of the sera examined HCV-RNA was restricted to low densities between 1.03 and 1.08 g/cm³. In other sera additional densities of HCV-RNA were found distributed over the whole gradient with peaks at 1.12 and 1.17 and at 1.19–1.20 g/cm³. HCV-RNA banding at low densities could be completely co-precipitated with anti- lipoprotein, whereas HCV-RNA fractions of higher densities were only partially precipitated or not at all. In 8 of 20 sera directly examined, HCV-RNA could be completely and in 9 sera only partially co-precipitated by anti- lipoprotein. In 3 sera no significant precipitation could be observed.