Changes in irisin levels in patients with hyperemesis gravidarum.

PURPOSE: The aim of this study was to compare levels of serum irisin in hyperemesis gravidarum (HG) patients to healthy gravidas. MATERIALS AND METHODS: Twenty pregnant women with hyperemesis gravidarum (Group 1) and 20 healthy pregnant women (Group 2) all of similar ages, body mass index, and all at similar pregnancy development comprised the study cohort. Fasting serum samples were obtained and measured for irisin levels. Comparisons between groups were done by Mann Whitney U (MWU) test and p < 0.05 was considered as statistically significant. RESULTS: All the patients in groups 1 and 2 were primigravid and age, gestational week, and body mass index values were similar. No statistically significant difference were present among these parameters (p > 0.05, MWU test). The plasma irisin concentrations in group 1 were significantly higher (irisin (average ±S D): 116.9 ± 32.3 ng/ml vs. 87.7 ± 26.2 ng/ml) compared to the control group. CONCLUSION: This study suggests a possible role of irisin, which might be involved in the pathology of HG.

Cloaking through cancellation of diffusive wave scattering.

A new cloaking mechanism, which makes enclosed objects invisible to diffusive photon density waves, is proposed. First, diffusive scattering from a basic core-shell geometry, which represents the cloaked structure, is studied. The conditions of scattering cancellation in a quasi-static scattering regime are derived. These allow for tailoring the diffusivity constant of the shell enclosing the object so that the fields scattered from the shell and the object cancel each other. This means that the photon flow outside the cloak behaves as if the cloaked object were not present. Diffusive light invisibility may have potential applications in hiding hot spots in infrared thermography or tissue imaging.

Thermal invisibility based on scattering cancellation and mantle cloaking.

We theoretically and numerically analyze thermal invisibility based on the concept of scattering cancellation and mantle cloaking. We show that a small object can be made completely invisible to heat diffusion waves, by tailoring the heat conductivity of the spherical shell enclosing the object. This means that the thermal scattering from the object is suppressed, and the heat flow outside the object and the cloak made of these spherical shells behaves as if the object is not present. Thermal invisibility may open new vistas in hiding hot spots in infrared thermography, military furtivity, and electronics heating reduction.

Impaired cell death and mammary gland involution in the absence of Dock1 and Rac1 signaling.

Throughout life, the tight equilibrium between cell death and the prompt clearance of dead corpses is required to maintain a proper tissue homeostasis and prevent inflammation. Following lactation, mammary gland involution is triggered and results in the death of excessive epithelial cells that are rapidly cleared by phagocytes to ensure that the gland returns to its prepregnant state. Orthologs of Dock1 (dedicator of cytokinesis 1), Elmo and Rac1 (ras-related C3 botulinum toxin substrate 1) in Caenorhabditis elegans are part of a signaling module in phagocytes that is linking apoptotic cell recognition to cytoskeletal reorganization required for engulfment. In mammals, Elmo1 was shown to interact with the phosphatidylserine receptor Bai1 and relay signals to promote phagocytosis of apoptotic cells. Still, the role of the RacGEF Dock1 in the clearance of dying cells in mammals was never directly addressed. We generated two mouse models with conditional inactivation of Dock1 and Rac1 and revealed that the expression of these genes is not essential in the mammary gland during puberty, pregnancy and lactation. We induced mammary gland involution in these mice to investigate the role of Dock1/Rac1 signaling in the engulfment of cell corpses. Unpredictably, activation of Stat3 (signal transducer and activator of transcription 3), a key regulator of mammary gland involution, was impaired in the absence of Rac1 and Dock1 expression. Likewise, failure to activate properly Stat3 was coinciding with a significant delay in the initiation and progression of mammary gland involution in mutant animals. By using an in vitro phagocytosis assay, we observed that Dock1 and Rac1 are essential to mediate engulfment in epithelial phagocytes. In vivo, cell corpses accumulated at late time points of involution in Dock1 and Rac1 mutant mammary glands. Overall, our study demonstrated an unsuspected role for Dock1/Rac1 signaling in the initiation of mammary gland involution, and also suggested a role for this pathway in the clearance of dead cells by epithelial phagocytes.

Platonic scattering cancellation for bending waves in a thin plate.

We propose an ultra-thin elastic cloak to control the scattering of bending waves in isotropic heterogeneous thin plates. The cloak design makes use of the scattering cancellation technique applied, for the first time, to the biharmonic operator describing the propagation of bending waves in thin plates. We first analyze scattering from hard and soft cylindrical objects in the quasistatic limit, then we prove that the scattering of bending waves from an object in the near and far-field regions can be suppressed significantly by covering it with a suitably designed coating. Beyond camouflaging, these findings may have potential applications in protection of buildings from earthquakes and isolating structures from vibrations in the motor vehicle industry.

Homozygous feature of isolated triphalangeal thumb-preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes.

Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.

Periodontal disease in patients with familial Mediterranean fever: from inflammation to amyloidosis.

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever stimulates a very intense acute-phase reactants response and if left untreated eventually leads to amyloidosis. The aim of this study was to determine the prevalence of periodontal disease among patients with familial Mediterranean fever in the Black Sea region in Turkey and to evaluate whether periodontitis is related to amyloidosis in patients with familial Mediterranean fever. MATERIAL AND METHODS: One-hundred and thirty three patients with familial Mediterranean fever and 50 healthy subjects were included in this study. Periodontal health and disease were evaluated using the gingival index, papillary bleeding index, plaque index and periodontal disease index. The concentrations of serum acute-phase reactants were measured at baseline and at 4-6 wk after completion of the nonsurgical periodontal therapy. Genetic testing for familial Mediterranean fever was performed using the familial Mediterranean fever StripAssay. Kidney biopsy was carried out on all proteinuric patients. RESULTS: The prevalence of moderate to severe periodontitis in familial Mediterranean fever patients with amyloidosis (80.6%) was significantly greater (p < 0.01) than in familial Mediterranean fever patients without amyloidosis (38%) and in controls (20%). Serum levels of acute-phase reactants in familial Mediterranean fever patients were reduced significantly following nonsurgical periodontal therapy (p < 0.01). CONCLUSION: Periodontal therapy seems to reduce the serum levels of acute-phase reactants in patients with familial Mediterranean fever. Therefore, treating periodontitis might help to alleviate the disease burden in patients with familial Mediterranean fever.

Spinal reflexes in normal and sulfite oxidase deficient rats: effect of sulfite exposure.

Sulfites, which are commonly used as food preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). Although sulfite treatment has been reported to increase the excitability of some neurons in vitro, the possible effects of sulfite on neuronal excitability in vivo remain unclear. The aim of this study was to investigate the possible effects of sulfite treatment on spinal reflexes in anesthetized SOX competent and deficient rats. For this purpose, male albino rats used in this study were divided into four groups such as control group (C), sulfite group (CS), SOX deficient group (D), and SOX deficient + sulfite group (DS). Rats in SOX deficient groups were made deficient in SOX by the administration of low molybdenum (Mo) diet (AIN 76, Research Dyets Inc., USA) with concurrent addition of 200-ppm tungsten (W) to their drinking water in the form of sodium tungstate (NaWO4). Sulfite in the form of sodium metabisulfite (Na2O5S2, 70 mg/kg) was given orally by adding to drinking water to the S and DS groups. Monosynaptic reflex potentials were recorded from the ipsilateral L5 ventral root. SOX deficient rats had an approximately 15-fold decrease in hepatic SOX activity compared with normal rats. This makes SOX activity of SOXD rats in the range of human SOX activity. The results of this study show that sulfite treatment significantly increases the amplitude of the monosynaptic reflex response in both S and DS groups with respect to their respective control groups (C and D). SOX deficient rats also had enhanced spinal reflexes when compared with control rats. In conclusion, sulfite has increasing effects on the excitability of spinal reflexes and we speculate that this compound may exhibit its effects on nervous system by affecting sodium channels.

Lack of association between leptin G2548A gene polymorphism and Behçet's disease.

BACKGROUND: Behçet's disease is a chronic, multisystem, inflammatory disease characterized by the predominance of T-helper 1 cytokines. The disease is also characterized by infiltration of lymphocytes and neutrophils into the affected tissues. Because cytokines are involved in the regulation of lymphocyte and phagocyte functions, they may play an important role in the pathogenesis of Behçet's disease. Leptin, a member of the gp 130 family of cytokines, induces a strong T-helper 1 response and is regarded as a proinflammatory inducer. Recent studies have shown that serum leptin concentration was increased in patients with Behçet's disease and correlated with disease activity. OBJECTIVES: We aimed to investigate the role of G2548A polymorphism of leptin gene in patients with Behçet's disease and compare the results with healthy controls. PATIENTS AND METHODS: A total of 93 subjects with Behçet's disease and 125 healthy controls were included in this study. Analyses of G-2548A polymorphism of the LEP gene were performed using the PCR-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin G2548A) and alleles (G and A of leptin 2548) were scored and the frequency was estimated. The frequencies of the alleles and genotypes in patients and controls were compared. We analysed the correlation between leptin gene polymorphism and the clinical features of BD. RESULTS: Both genotype and allele frequencies were not significantly different between controls and Behçet's disease patients [OR=0.67, 95% CI (0.35-1.29), P=0.197 and OR=0.77, 95% CI (0.52-1.15), P=0.184]. We did not find any significant relationship between leptin gene polymorphism and the clinical features of BD (P>0.05). CONCLUSION: In the present case-control study, we found no evidence of an association between the G-2548A variant of the leptin gene and BD among Turks. Further studies are needed to investigate serum leptin level to explain the mechanisms behind the lack of association between leptin G2548A gene polymorphism and BD.

Detection of LOH of the RB1 gene in bladder cancers by PCR-RFLP.

OBJECTIVES: Retinoblastoma (RB1) gene involves in retinoblastoma, osteosarcoma, bladder, prostate, lung, breast carcinomas, and soft tissue sarcomas. Loss of heterozygosity (LOH) is the most common mutation of the gene. METHODS: Xba I polymorphism in intron 17 of the gene was used to detect LOH in 20 bladder cancer patients. A cystitis and an osteosarcoma were used as control. LOH was investigated in three different kinds of samples (blood, paraffin-embedded tissue and fresh tissue) belonging to the same patients, and 20 blood samples, 20 paraffin-embedded tissue samples and 16 fresh tissue samples were obtained from 20 cancer patients. RESULTS: None of the 20 blood samples showed LOH. Eleven out of 20 paraffin-embedded bladder tissues were amplified, 3 of them homozygous and all 8 informative paraffin-embedded tissues showed LOH. Five out of 16 fresh tumor tissues obtained were amplified, in 1 the fresh tissue was normal, 1 fresh tissue showed LOH and 3 were not digested by Xba I. CONCLUSION: The results of the study have suggested that detection of LOH of the RB1 gene by PCR-RFLP can be a good adjunctive test for evaluation of the bladder cancer.

Nucleotide changes in the gamma-globin promoter and the (AT)xNy(AT)z polymorphic sequence of beta LCRHS-2 region associated with altered levels of HbF.

We have studied 31 beta-thalassaemia intermedia, 30 beta-thalassaemia major patients and 50 normal individuals from Turkey, determining the relationship between the nucleotide variations in beta-globin gene cluster, the altered levels of foetal haemoglobin and the relative ratios of beta- and gamma mRNAs. We have found in beta-thalassaemia intermedia patients with high foetal haemoglobin expression that the three nucleotide variations in the 5' sequences of the gamma globin genes, A-->G at G gamma - 1396, the T-->C at A gamma - 228, and the GA-->AG at A gamma - 603/4, are linked to haplotype II in haplotypic homozygotes and the (AT)8N14(AT)7 motif in beta LCR. Conversely, the three single nucleotide substitutions in the 5' sequences of gamma globin genes, the G-->A at G gamma - 1225, the A-->G at A gamma + 25 and the C-->G at A gamma - 369, which have a strong linkage with haplotype I, V or VI in haplotypic homozygotes and the (AT)10N12(AT)12 and the (AT)9N12(AT)12 motifs in HS-2 of beta LCR are all associated with low foetal haemoglobin levels. The number of nucleotide changes in beta-globin gene cluster implied in our study are not the primary cause of the differences in haemoglobin F levels. They perhaps may contribute to the variations in the clinical severity observed among beta thalassaemia intermedia and major patients with other yet unknown gene conversions.

Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families.

Hereditary non-polyposis colon cancer (HNPCC) is a common hereditary disease characterized by a predisposition to an early onset of colorectal cancer. The majority of the HNPCC families carry germline mutations of either hMSH2 or hMLH1 genes, whereas germline mutations of hPMS1 and hPMS2 genes have rarely been observed. Almost all of the germline mutations reported so far concern typical HNPCC families. However, there are families that display aggregations of colon cancer even though they do not fulfil all HNPCC criteria (incomplete HNPCC families) as well as sporadic cases of early onset colon cancers that could be related to germline mutations of these genes. Therefore, we screened germline mutations of hMSH2 and hMLH1 genes in 3 groups of patients from France and Turkey: typical HNPCC (n = 3), incomplete HNPCC (n = 9) and young patients without apparent familial history (n = 7). By in vitro synthesis of protein assay, heteroduplex analysis and direct genomic sequencing, we identified 1 family with hMSH2 mutation and 5 families with hMLH1 mutations. Two of the 3 HNPCC families (66%) displayed hMLH1 germline mutations. Interestingly, 4 of 9 families with incomplete HNPCC (44%) also displayed mutations of hMSH2 or hMLH1 genes. In contrast, no germline mutation of these genes was found in 7 young patients. Our results show that germline mutations of hMSH2 and hMLH1 genes contribute to a significant fraction of familial predisposition to colon cancer cases that do not fulfil all diagnostic criteria of HNPCC.

Monoclonal anti-biotin antibodies simulate avidin in the recognition of biotin.

The sequence of the VH gene of a monoclonal anti-biotin antibody was determined. Biotin-binding motifs, similar to those in avidin and streptavidin, were identified in complementary determining regions 2 and 3, suggesting that natural selection of functional motifs may occur in unrelated protein types.

Linkage disequilibrium between glucose-6-phosphate dehydrogenase deficiency and congenital color blindness in Turkish population.

No erythrocyte glucose-6-phosphate dehydrogenase (G6PD)-deficient person was detected among 90 male patients with congenital color blindness (CCB) diagnosed at the Ophthalmology Clinic of our Hospital. Eighteen complete G6PD-deficient subjects had normal color vision. These results suggest that there is a linkage disequilibrium between CCB and G6PD genes.

Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene.

Calpastatin is a widely distributed endogenous inhibitor protein specifically acting on calpain (Ca2+-dependent cysteine endopeptidase). The inhibitor consists of four inhibitory domains (Domains 1-4) with mutually homologous sequences. NH2-terminal Domain L is non-homologous, and all domains have 120-140 residues each. A human calpastatin genomic DNA clone was isolated using a previously obtained human calpastatin cDNA probe. Sequence analysis has revealed that the clone contains Domain 1 and segments of neighboring domains (Domains L and 2). Each of three highly conserved, restricted regions within Domain 1 was located on separate exons, 1A, 1B, and 1C. Exon 2A, corresponding to the first exon of Domain 2, is homologous to Exon 1A and follows Exon 1D of Domain 1. A 27-residue peptide encoded by Exon 1B, including a 12-residue middle conserved sequence, was chemically synthesized and tested for protease inhibitory activities. The synthetic peptide showed strong inhibition against calpain I (low Ca2+-requiring form), and calpain II (high Ca2+-requiring form), but no inhibition against papain or trypsin. These results indicated that Exon 1B forms a self-sufficient functional subdomain of the calpastatin inhibitory domain.

Repair of methyl methane sulfonate-damaged phage by Haemophilus influenzae.

Seven mutants of Haemophilus influenzae strain Rd (mmsA-) have been isolated that are more sensitive to methyl methane sulfonate (mms) than recombination-deficient (recA-) mutants. The mutations cotransformed about 25% with the strA locus while the five studied clustered tightly; they are all probably allelic. The mutants are not sensitive to ultraviolet radiation, X-rays, or nitrous acid. Mms-damaged phage HP1 plated very inefficiently on these mutants, indicating that they lack the first step in the excision repair of the lesion N3-methyladenine (m3A). Incubation of damaged phage at 30 degrees C in the absence of mms resulted in a steady decline of viability when the phage were plated on the wild mmsA+ host but an initial steep rise was seen when it was plated on an mmsA- mutant. The rise is explained by the assumption that m3A lesions hydrolyzed off the DNA giving rise to repairable apurinic sites by both the mmsA+ and mmsA- hosts. No decline in viability was observed when hydroxylamine was present in the medium. This compound is known to prevent or slow down beta-elimination. The delayed decline in viability is therefore explained by assuming that apurinic sites give rise to beta-elimination-induced single strand breaks in the phage DNA that cannot be repaired by either host. Marker rescue experiments indicated that these breaks did not interrupt injection of phage DNA.