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Objective:Helicobacter pylori infection places a heavy burden on medical and economic resources. Standard diagnosis requires the presence of established H. pylori gastric disease. Study Design and Setting: A multicenter screening trial assessing 2 immunochromatographic H. pylori antigen oral tests was carried out with 201 participants. The analysis also included a urea breath test (UBT), a Campylobacter-like organism test, silver stain, culture, serology, and stool tests. Results: The participants were grouped into UBT positive (UBT+) and UBT negative (UBT-) people, using conventional methods with congruent clusters based on p values from McNemar's paired χ2 analysis and 95% CI estimates. Both oral tests were also positive in 82% of the seropositive UBT- people. However, oral antigen and seroprevalence divided UBT- people into 2 statistically separate CI subgroups: the UBT- symptomatic (highly positive) group and the UBT- asymptomatic (mostly negative) group. 90.5% of all people whose oral tests were both negative were also UBT-. Conclusions: Saliva H. pylori antigen is an important indicator in UBT- asymptomatic patients. Currently, its clinical significance remains uncertain, but saliva may be a reservoir from where H. pylori is transmitted to the stomach. In symptomatic patients, it is strongly associated with stomach infection.

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 ( TGM1 ) gene, which encodes for the epidermal enzyme transglutaminase-1 (TGase-1), are one of the causes of ARCI. Methods: The TGM1 mutation spectrum was characterised and genotype–phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA. Methods: Germline mutations in TGM1 were identified in 55% (57/104) of patients with ARCI. Arginine residues in TGase-1 were mutated in 39% (22/57) of patients overall and 54% (20/37) of those with missense mutations. In total, 55% (12/22) of missense mutations were within CpG dinucleotides and 92% (11/12) of these mutations were C→T or G→A transitions. The genotype–phenotype investigation found that ARCI with TGM1 mutations was significantly associated with presence of collodion membrane at birth (p = 0.006), ectropion (p = 0.001), plate-like scales (p = 0.005) and alopecia (p = 0.001). Patients who had at least one mutation predicted to truncate TGase-1 were more likely to have more severe hypohidrosis (p = 0.001) and overheating (p = 0.0007) at onset of symptoms than were those with exclusively TGM1 missense mutations. A logistic model was developed, which predicted that individuals with collodion membrane, alopecia and/or eye problems are about four times more likely to have TGM1 mutations than patients without these findings. Conclusion: This is the largest investigation of patients with ARCI to date. It expands the TGM1 mutation spectrum and confirms that despite genetic and phenotypic heterogeneity in ARCI, TGM1 is the main causative gene for this disorder. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of CpG dinucleotides.

Functionally gradient materials (FGMs) were prepared by mixing 5 layers comprised of different ratios of (YSZ-20%Al2O3) and 422 stainless (SUS422) powders, followed by hot pressing for densification. Two design concepts were proposed: One as a FGM with a monotonic change of the CTE (coefficient of thermal expansion) for each layer, and is designated as the monotonic mode, and the other was a FGM with a change of CTE that is not monotonic for each layer, and is termed the non-monotonic mode. The FGM with a monotonic CTE mode cracked at the ceramic surface after it was removed from the hot pressing furnace. In contrast, the FGM with a non-monotonic CTE mode survived after hot pressing. Based on ABAQUS simulation results, a non-monotonic change in CTE resulted in a decrease of residual stress on the ceramic side but an increase inside the metal-rich layers of the FGMs. The induced change in the stress distribution inside the FGMs was compromised by the deformation of the metal-rich ingredient (SUS422) in the FGM. Thermal shock tests of FGMs were performed between 25°C and 600°C. The non-monotonic FGM endured up to 100 thermal cycles with only slight bending, and was free of delamination and cracking. The use of composition-adjusted layers to manipulate thermal expansion coefficients of each layer greatly changed the stress contour of the FGM. It is noted that a modified functional-gradient FGM can be fabricated with a hard ceramic surface on one side to resist high temperature, and a ductile metallic surface on the other side to provide toughness.

Functionally gradient materials (FGMs) composed of 3YSZ and IN713LC were developed in three different configurations. A linear-mode FGM had its compositions with a monotonic change in coefficient of thermal expansion (CTE). Negative- and positive-deviated FGMs had their compositions with lower and higher CTEs, respectively, on the ceramic sides. Fracture behaviors of these three types of FGMs were evaluated with aids of residual stress analyses. FGMs with a positive CTE deviation demonstrated the best performance in the experiment. The brittle ceramic side was under high compressive stress, and high tensile stresses were primarily initiated in the metal-rich gradient layers.

Background: Birt–Hogg–Dube syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. Objective: To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. Methods: Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. Results: The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. Conclusion: BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families.

Contrast source inversion method (CSIM) is one of robust methods for reconstructing dielectric objects by integral equation approach. The method requires an intensive calculation of volume integrals over imaging domain in the optimization of cost functional and the process is very tedious. In this work, we incorporate a novel meshless scheme with the CSIM to simplify the calculation of volume integrals so that the reconstruction can be accelerated. The meshless scheme changes the volume integrals into boundary integrals through the Green-Gauss theorem when the integrands are regularized by excluding a small cube enclosing the observation node in the imaging domain. Numerical examples for reconstructing two contacting dielectric spheres are presented to illustrate the inversion approach and good results have been obtained.

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus. Objective: To measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines and fibroblast cell lines of individuals with HLRCC and other familial renal cancer syndromes. Methods: FH enzyme activity was determined in the whole cell, cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast cell lines including cell lines from individuals with HLRCC with 16 different mutations. Results: Lymphoblastoid cell lines (n = 20) and fibroblast cell lines (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from normal controls (p

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

Helicobacter pylori infection places a heavy burden on medical and economic resources. Standard diagnosis requires the presence of established H. pylori gastric disease.A multicenter screening trial assessing 2 immunochromatographic H. pylori antigen oral tests was carried out with 201 participants. The analysis also included a urea breath test (UBT), a Campylobacter-like organism test, silver stain, culture, serology, and stool tests.The participants were grouped into UBT positive (UBT+) and UBT negative (UBT-) people, using conventional methods with congruent clusters based on p values from McNemar's paired χ2 analysis and 95% CI estimates. Both oral tests were also positive in 82% of the seropositive UBT- people. However, oral antigen and seroprevalence divided UBT- people into 2 statistically separate CI subgroups: the UBT- symptomatic (highly positive) group and the UBT- asymptomatic (mostly negative) group. 90.5% of all people whose oral tests were both negative were also UBT-.Saliva H. pylori antigen is an important indicator in UBT- asymptomatic patients. Currently, its clinical significance remains uncertain, but saliva may be a reservoir from where H. pylori is transmitted to the stomach. In symptomatic patients, it is strongly associated with stomach infection.

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene ( FH ). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African-American families with HLRCC. Methods: Using direct sequencing analysis we identified FH germline mutations in 100% (21/21) of new families with HLRCC. Results: We identified 14 germline FH mutations (10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense (L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense (S102X), one insertion (111insA), and one splice site (138+1G>C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% (13/21) had renal cancer and 76% (16/21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% (22/22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype-phenotype correlations were identified. Conclusions: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC (20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% (52/56) in families suspected of HLRCC.

A number of genes underlie the molecular bases of intelligence. Among these is probably CALL, a novel member of the L1 gene family of neural cell adhesion molecules. By using the single strand conformation polymorphism (SSCP) protocol, we screened the regions of the CALL gene corresponding to the 5' and 3' untranslated regions (UTRs) of the CALL mRNA, searching for polymorphisms that could be useful in association studies in the field of intelligence. We report the finding of T-to-A and T-to-C single nucleotide polymorphisms (SNPs) in the 3' UTR of CALL. These SNPs have an index of heterozygosity of 0.13 and 0.10, respectively. Research is in progress to understand the association between these variants and high IQ.

The 3p- syndrome results from deletion of a terminal segment of the short arm of one chromosome 3 (3p25--pter), and is characterized by multiple congenital anomalies and mental retardation. Due to its variable expression, it is assumed this disorder is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. In an effort to discover genes contributing to mental defects in 3p- syndrome, we determined whether the CALL gene, mapped to 3p26.1 and coding for a neural recognition molecule, is deleted in a boy with this disorder. We found that the break in this patient is distal to the VHL gene, removing D3S18 and the CALL loci. The deletion of one copy of the CALL gene might be responsible for mental defects in patients with 3p- syndrome. Am. J. Med. Genet. 86:482-485, 1999. Published 1999 Wiley-Liss, Inc.

Using overlapping cosmids representing the vascular endothelial growth factor (VEGF) locus, the VEGF gene was mapped by fluorescence in situ hybridization to chromosome 6p12. This localization permits linkage analysis and the identification of gene interaction in the region, as well as alterations of the VEGF structure or expression in cancer cells with chromosome abnormalities.

Members of a family carrying a constitutional balanced translocation [t(3;8) (p14;q24)] have a high risk of developing multiple, bilateral clear-cell renal carcinomas. Two genetic mechanisms of carcinogenesis for this malignancy have been proposed: (1) disruption of a gene at the translocation breakpoint and (2) mutation of the von Hippel-Lindau tumor-suppressor gene at 3p25. This study further evaluates the role of the von Hippel-Lindau gene in the etiology and pathogenesis of t(3;8)-associated renal carcinomas.Two new t(3;8)-associated renal carcinomas were tested for mutations in the von Hippel-Lindau gene by single-stranded conformational polymorphism analysis followed by direct DNA sequencing, for loss of alleles on chromosomes 3p and 8, and for methylation abnormalities in the first cloned exon of the von Hippel-Lindau gene.A missense mutation in the von Hippel-Lindau gene was found in one of the two t(3;8)-associated renal carcinomas. This mutation would produce a stop codon and a truncated protein. Both tumors showed a loss of alleles on the derivative 8 chromosome. When these results were combined with the results of our previous studies, two of the four t(3;8)-associated renal carcinomas, which were examined for molecular genetic changes, showed different von Hippel-Lindau somatic mutations. All renal tumors from the 3;8 translocation family showed loss of the translocated portion of chromosome 3.These results support a mechanism of tumorigenesis in the chromosome (3;8) translocation family that involves the loss of both copies of the von Hippel-Lindau gene.

Using the human liver cancer DNA transfected NIH/3T3 cell line, the human N-ras oncogene and the over expression of the oncoprotein P21ras was demonstrated, BALB/C mice were immunized. The spleen cells from the immunized mice were fused with SP2/0 myeloma cells. After the HAT medium selection and screening, two hybridoma cell lines, SCI-Oncogema 1 and 2, were established. In the immunoprecipitation test, the molecular weight of the protein reacting to Oncogema 1 was 21,000. This M.W 21,000 protein possessed the capability to bind with GTP, i.e. the character of P21ras. These data indicate that the Oncogema 1 is the monoclonal antibody against P21ras. Using Oncogema 1, specimens from 6 liver cancer patients were studied by immunopathology. With ABC stain, it was observed that the malignant cells in all the samples showed dark staining; the P21ras revealed over expression. Although the staining was heterogeneous, it implied that the ras oncogene was involved in the carcinogenesis of these six samples. No over expression was seen in the normal liver cells even in those around the cancerous lesion. However, dysplastic cells were moderately stained which means that the ras oncogene was activated and P21ras over expressed in these cells. The results suggest that the ras oncogene and P21ras play an important role in the early stage of liver cancer carcinogenesis.