Long-term effects of interferon-based therapy for chronic hepatitis C

Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.     

Kawasaki disease in infants three months of age or younger.

BACKGROUND AND PURPOSE: Kawasaki disease (KD) is rare in infants < or =3 months of age. This study analyzed the features of KD in 25 infants < or =3 months of age treated from February 1994 to December 2004. METHODS: Basic characteristics, clinical, laboratory, echocardiographic, therapeutic, and follow-up data of the infants were obtained from chart records. RESULTS: There were 19 male and 6 female infants in this cohort. The frequency of the 5 principal clinical features was as follows: changes in lips and oral cavity, 84%; bilateral bulbar conjunctival injection without exudates, 80%; polymorphous exanthem, 68%; cervical lymphadenopathy, 28%; and changes in extremities, 24%. Six infants (24%) fulfilled criteria for KD including fever which persists for 5 or more days with at least 4 of the principal clinical criteria, and the remaining infants were classified as having incomplete KD (all of whom showed coronary involvement). Coronary artery dilatation was found in 20 infants (80%). One infant developed a medium-size aneurysm (5.2 mm), while the others had only coronary arterial ectasia or small aneurysms. Coronary artery aneurysms regressed within 1-year follow-up in all but one infant. No fatal or recurrent case was observed during the study period. CONCLUSIONS: Infants < or =3 months of age with KD usually presented with incomplete clinical features. A high proportion of coronary artery involvement was observed in this series. Echocardiography should be considered in very young infants with unexplained prolonged fever who do not present all of the principal clinical features of KD.     

Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes

Bacteria encounter oxidative stress by exposure to reactive oxygen species (ROS) present in the aerobic environment and during immune responses. In Streptococcus pyogenes, Dpr has been identified as a stress protein conferring resistance to hydrogen peroxide and multiple other stresses. The expression of Dpr is under perR (peroxide stress response regulator) control. However, the exact molecular mechanism of PerR regulation of Dpr is not clear. In this study, a perR deletion mutant was constructed by double cross-over mutagenesis. The profile of Dpr expression, performed by Western blot assay, revealed growth-phase dependency under normal culture conditions. Dpr expression decreased under iron-restricted conditions, whereas iron, zinc, nickel, and hydrogen peroxide induced its expression. The perR mutant does not induce Dpr as well when exposed to environmental signals. PerR binds the promoter region of dpr. Increased iron and hydrogen peroxide concentrations decreased PerR binding to the promoter region of dpr, suggesting that regulation of Dpr by environmental signals is mediated by PerR directly.     

Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities

Objective

We present prenatal diagnosis and molecular cytogenetic characterization of 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities.

Prenatal diagnosis of a familial 1q21.1-q21.2 microdeletion in a fetus with polydactyly of left foot on prenatal ultrasound

Objective

We present prenatal diagnosis of a familial 1q21.1-q21.2 microdeletion in a fetus with polydactyly of left foot on prenatal ultrasound.

The Association between the Polymorphisms in a Sodium Channel Gene SCN7A and Essential Hypertension: A Case‐Control Study in the Northern Han Chinese

Na_x, an α‐subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Na_x/SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case‐control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033–1.592]; P = 0.013, OR = 1.203, 95%CI [1.040–1.392]; respectively). The three SNPs were in close pair‐wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G–A–T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G–A–T will be a genetic risk factor for EH in the Northern Han Chinese population.     

Latex agglutination test for detection of antibodies to Toxoplasma gondii.

A resurgence of interest in Toxoplasma gondii has occurred because this coccidian parasite causes lethal infections in immunologically compromised hosts and is responsible for at least 3,000 congenitally infected infants in the United States annually. Thus, rapid, specific, and inexpensive serologic tests are required for routine screening of patients, especially pregnant women. We have developed a latex agglutination test for antibodies to T. gondii which utilizes covalently coupled T. gondii antigens. When compared with an indirect immunofluorescence assay, the latex test had a sensitivity of 94% and specificity of 100%. Compared with an enzyme-linked immunosorbent assay, the latex test had 86% sensitivity and 100% specificity. When testing samples which exhibited nonspecific polar staining by the immunofluorescence assay, the enzyme-linked immunosorbent assay had a 50% false-positive rate, whereas the latex agglutination test yielded no false-positive results. Thus, the latex agglutination test provided an efficacious method for routine serological screening for antibodies to T. gondii.     

Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men

Purposes

To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men.

Methods

This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reactio(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia.

Results

Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls.

Conclusions

There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.