Comparison of serum hepatitis C virus RNA and core antigen concentrations and determination of whether levels are associated with liver histology or affected by specimen storage time

An enzyme immunoassay has recently been developed for the hepatitis C virus (HCV) core antigen. To evaluate the possible association between core antigen and HCV RNA levels with regards to the change in liver histology over time as well as study the effect of duration of storage on viral load results, sequential sera were analyzed from 45 patients with chronic HCV infection who had undergone two or more liver biopsies. A relatively strong association was found between the core antigen and HCV RNA concentrations (r(s) = 0.8), with a core antigen level of 1 pg/ml corresponding to approximately 1,000 IU/ml. All 42 sera with detectable HCV RNA at the time of the second biopsy had core antigen concentrations above 1 pg/ml, and the three sera without detectable HCV RNA had concentrations below 1 pg/ml. No association was found between HCV RNA or core antigen levels and the stage of fibrosis in biopsy samples, progression of fibrosis, necro-inflammatory grade, steatosis, genotype, alanine aminotransferase level, or alcohol consumption. A significant association was demonstrated between the storage time of the samples and both the HCV RNA and core antigen concentrations. The median log HCV RNA concentrations (international units/milliliter) were 3.92 for the sera obtained at the time of the first biopsy (median storage time, 13.0 years) and 4.41 for the sera obtained at the time of the second biopsy (median storage time, 6.6 years) compared to 5.96, the median for 102 different routine clinical patient samples.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Factors affecting frequency of communication about family health history with family members and doctors in a medically underserved population

Objective

Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information.

Methods

1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors.

Results

Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p = .012) and heart disease (p < .001), seek health information frequently in newspapers (p < .001) and in general (p < .001), and be female (p < .001). Patients who talked frequently with doctors about FHH were more likely to report a family history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p < .001) and in general (p < .001), be female (p < .001), and not have experienced racial discrimination in healthcare (p < .001).

Conclusion

Patients with a family history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions.

Practice implications

Interventions are needed to encourage providers to update patients’ family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control.     

A Novel Combination of Methotrexate and Epigallocatechin Attenuates the Overexpression of Pro-inflammatory Cartilage Cytokines and Modulates Antioxidant Status in Adjuvant Arthritic Rats

The present study was designed to evaluate the combinatory effect of methotrexate (MTX) and epigallocatechin (EGCG) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of Freund's complete adjuvant. AA rats were treated with methotrexate (0.3 mg/kg) thrice a week, EGCG (100 mg/kg) daily, and combination of MTX and EGCG thrice a week for a period of 28 days. Paw swelling changes and histopathological and radiographic analysis was assessed to evaluate the antiarthritic effect. Lipid peroxidation and antioxidant enzyme activities in joint tissue homogenate were performed to observe the modulation of antioxidant status along the expression of different pro-inflammatory cartilage cytokines like TNF-α and IL-6. MTX and EGCG combination potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect (SOD, GSH, and catalase) as well as suppression of lipid peroxidation. Combination therapy of MTX and EGCG significantly inhibited the development phase of arthritis, which is supported by histopathological, radiographical, and attenuation of overexpression of cartilage cytokines. EGCG act as potent antioxidant and immunomodulator, suggesting that combined administration of MTX along with EGCG suppressed the development phase of arthritic progression in rats.     

Associations of MTHFR DNMT3b 4977 bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in non-obstructive infertility in Indian men

Methylenetetrahydrofolate (MTHFR) and DNMT3b play imperative roles in DNA synthesis and de novo methylation. GSTM1 is involved in detoxification of carcinogens. Mitochondrial DNA deletion has been associated with lower motility in human sperm. We analysed if polymorphisms in MTHFR (C677T and A1298C) and DNMT3b (C46359T) are associated with non-obstructive male infertility. We also analysed if folate, vitamin B(12), homocysteine (Hcy), 8'-hydroxy-2'-deoxygnanosine (8-OHdG) levels, dietary folate intake and mtDNA deletion (4977 bp) affects fertility, such interactions are modified by deletion and methylation of GSTM1. In this case-control study, we included 179 oligoasthenoteratozoospermia patients and 200 fertile men. Single-nucleotide polymorphism analysis was performed by PCR-restriction fragment length polymorphism. The MTHFR (C677T and A1298C) and DNMT3b (C46359T) frequencies did not differ significantly in two groups. GSTM1 in association with mtDNA 4977 deletion is significantly associated with infertility. Plasma folate and vitamin B(12) levels are decreased and total Hcy is elevated in infertile men. GSTM1 methylation status was investigated by methylation-specific PCR. Methylation is significantly correlated with GSTM1 reduced/loss of expression in infertile men. Infertile men have significantly higher 8-OHdG levels. Dietary folate intake is not linked with GSTM1 methylation. Low folate intake in association with CT + TT genotypes (C677T) has significant protective effect on GSTM1 methylation. Results indicate that micronutrients, 8-OHdG levels, mtDNA deletion and GSTM1 promoter methylation are frequent alterations in infertility.     

Upregulation of KIR expression on murine bone marrow cells by paraformaldehyde fixed tumor cells

We have previously shown that the activation of mouse spleen NK cells by IL2 is markedly boosted if paraformaldehyde fixed tumor target cells are added during the activation phase. In the present study, we have shown that such a boosting effect is not seen if mouse bone marrow (BM) cells are used instead of spleen cells. Addition of fixed tumor cells (1:100 ratio of tumor cells to BM cells) however resulted in a marked increase in the expression of Ly49 molecules on BM cells. The enhancement of Ly49 expression was not seen if fixed allogeneic BM cells were added, suggesting that Ly49 upregulation was tumor specific. Expression of Ly49A as well as Ly49C isotypes were augmented by fixed tumor cells. Moreover, increased Ly49 expression was seen on cell populations expressing TCRbeta as well as NK1.1 markers. These results indicate that exposure to tumor cells may be an important factor regulating KIR expression on NK and T cells. Implications of these results are discussed.     

High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons

Steroidogenic factor 1 (SF-1)-expressing neurons of the ventromedial hypothalamus (VMH) control energy homeostasis, but the role of insulin action in these cells remains undefined. We show that insulin activates phosphatidylinositol-3-OH kinase (PI3K) signaling in SF-1 neurons and reduces firing frequency in these cells through activation of K(ATP) channels. These effects were abrogated in mice with insulin receptor deficiency restricted to SF-1 neurons (SF-1(ΔIR) mice). Whereas body weight and glucose homeostasis remained the same in SF-1(ΔIR) mice as in controls under a normal chow diet, they were protected from diet-induced leptin resistance, weight gain, adiposity and impaired glucose tolerance. High-fat feeding activated PI3K signaling in SF-1 neurons of control mice, and this response was attenuated in the VMH of SF-1(ΔIR) mice. Mimicking diet-induced overactivation of PI3K signaling by disruption of the phosphatidylinositol-3,4,5-trisphosphate phosphatase PTEN led to increased body weight and hyperphagia under a normal chow diet. Collectively, our experiments reveal that high-fat diet-induced, insulin-dependent PI3K activation in VMH neurons contributes to obesity development.