Concentrations of endometrial protein PP 14 and CA-125 in uterine flushings performed in natural and stimulated cycles

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be attributed to abnormal endometrial development. This study compared concentrations of endometrial proteins in uterine flushings of infertile patients between natural and stimulated cycles. METHODS: Patients received a standard regimen of ovarian stimulation. Seven days after the LH surge in natural cycles or the hCG injection in stimulated cycles, uterine flushings were performed by slowly injecting and aspirating normal saline through a paediatric Foley catheter. Natural cycles were considered as group A whereas stimulated cycles with serum E(2) <20 000 pmol/l and serum E(2) >20 000 pmol/l were classified as groups B and C respectively. PP 14 and CA-125 in uterine flushings were measured and expressed per total protein content. RESULTS: Concentrations of the total protein, PP 14 and CA-125 in the uterine flushings were similar among the three groups. PP 14 per total protein in the uterine flushings was significantly correlated with serum E(2) on the day of hCG (r = 0.459; P = 0.009) in natural cycles only but not in stimulated cycles. CONCLUSION: There was no significant difference between natural and stimulated cycles in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal phase.     

Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.     

Isolation and characterization of proteins from Rous sarcoma virus

When the Bryan high-titer strain of Rous sarcoma virus RSV (RAV-1) labeled with a mixture of ¹⁴C amino acids was dissociated with a neutral detergent (Brij 35), mercaptoethanol, and urea and analyzed by isoelectric focusing in urea, seven radioactive peaks with pIs between 3.5 and 9.9 were found. The peaks were further analyzed by polyacrylamide gel electrophoresis in SDS to determine the number and molecular weight of the individual protein components in each peak. A total of eight amino acid-¹⁴C-labeled proteins were identified in RSV (RAV-1) with molecular weights between 14,000 and 96,000 daltons. When ³H-glucosamine labeled RSV (RAV-1) was dissociated with SDS and the viral components separated by SDS-gel electrophoresis, four radioactive components were observed. Analysis of glucosamine-³H-labeled virus together with amino acid-¹⁴C-labeled virus by dissociation with Brij 35, urea, and mercaptoethanol and separation of components by isoelectric focusing followed by electrophoresis in SDS-containing gels revealed that three of the glucosamine labeled components were glycoproteins corresponding to the three largest amino acid-labeled proteins. The fourth glucosamine-labeled component did did not contain radioactive amino acids suggesting that it was protein-free carbohydrate. Separation of virion components on Bio-Gel columns revealed that the glycoproteins were released from virus with Brij 35, urea, and mercaptoethanol in a large complex which was further dissociated into smaller units by SDS. Two of the eight protein components had high complement fixation titers and formed crossing precipitin lines in agar gel diffusion with hamster antiserum to the avian tumor virus group-specific antigen.     

Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.     

A vaccine against coccidioidomycosis is justified and attainable.

Coccidioides is a fungal pathogen of humans which can cause a life-threatening respiratory disease in immunocompetent individuals. Recurrent epidemics of coccidioidal infections in Southwestern United States has raised the specter of awareness of this soil-borne microbe, particularly among residents of Arizona and Southern California, and has galvanized research efforts to develop a human vaccine against coccidioidomycosis. In this review, we discuss the rationale for such a vaccine, examine the features of host innate and acquired immune response to Coccidioides infection, describe strategies used to identify and evaluate vaccine candidates, and provide an update on progress toward development of a vaccine against this endemic pathogen.     

A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.     

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study

Objectives

Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.