GBV-C/hepatitis G virus in acute nonA-E hepatitis and in acute hepatitis of defined aetiology in Italy

The role of GBV-C/HGV in the aetiology of acute non A-E hepatitis and its impact on the course of acute hepatitis of defined aetiology were investigated by detecting viral RNA by RT-PCR and antibody to the E2 protein of GB virus C (anti-E2) by EIA. Ninety-eight patients with acute nonA-E hepatitis, 35 patients with acute hepatitis A, 63 with acute hepatitis B, 29 with acute hepatitis C and 270 controls were enrolled in this study. The prevalence of GBV-C/HGV RNA was similar among patients with acute nonA-E hepatitis (3.1%), with acute hepatitis A (2.9%), and controls (3.7%), but significantly higher (P < 0.05) among those with hepatitis B or C (19.0% and 48.3%, respectively). Similar figures were obtained considering the total rate of GBV-C/HGV exposure (viral RNA or anti-E2 positivity). The majority (24/30 or 80%) of GBV-C/HGV RNA positive patients reported a parenteral source of exposure whereas the remaining 20% denied having known risk factors. The liver function test values and the rate of chronic hepatitis B and C were similar in patients co-infected and in those not co-infected with GBV-C/HGV. This study excludes a significant role of GBV-C/HGV infection in the aetiology of acute nonA-E hepatitis in Italy. Concomitant GBV-C/HGV and HBV or HCV infection does not worsen the clinical course of illness among patients with acute hepatitis.     

Defining epithelial cell progenitors in the human oxyntic mucosa

In the human stomach, the oxyntic epithelium includes numerous tubular invaginations consisting of short pits opening into long glands. The pit is lined by pit cells, whereas the gland is composed of three regions: the base, containing zymogenic cells; the neck, containing neck cells; and the isthmus, composed of little known immature cells and of parietal cells, which are also scattered through the neck and base. The aim of this study was to examine the ultrastructure of the immature cells and to determine their relation to mature cells. To do so, normal oxyntic mucosal biopsies from subjects ranging from 20-43 years old were fixed in aldehydes and postfixed in reduced osmium for electron microscopy and morphometric analysis. The immature cells were sorted out into four classes, whose roles were clarified by comparison with the thoroughly investigated mouse oxyntic epithelium. The first class was composed of the least differentiated immature cells, which were rare and characterized by minute, dense, or cored secretory granules and were accordingly named mini-granule cells. Their function was not clarified. The second class consisted of pre-pit cells, which were characterized by few dense mucous granules and give rise to pit cells that ascend the pit wall and, after reaching the luminal surface, die or are extruded. Both pre-pit and pit cells underwent continuous renewal and, therefore, together constituted a renewal system referred to as pit cell lineage. The third class, or pre-neck cells, characterized by cored secretory granules, give rise to neck cells that descend toward the base region and differentiate further into pre-zymogenic cells, which finally become zymogenic cells. The latter eventually degenerate and die. Thus pre-neck cells and their progeny constitute a renewing system, designated zymogenic cell lineage. The fourth class, or pre-parietal cells, characterized by long microvilli and few tubulovesicles, differentiate into parietal cells that descend along the neck and base regions and eventually degenerate and die. Pre-parietal and parietal cells represent a renewing system referred to as parietal cell lineage. While the origin of the last three classes of progenitor cells has not been elucidated, it is likely that they arise either from an unidentified multipotential stem cell, possibly the mini-granule cell itself, or from the mitotic activity of pre-pit and pre-neck cells. In conclusion, the human oxyntic epithelium is composed of continually renewing cells organized in distinct cell lineages.     

Effect of age on left ventricular systolic function in humans: a study of systolic isovolumic acceleration rate

The aim of this study was to examine the effect of age on left ventricular (LV) systolic function in normal healthy adults. Eighty consecutive subjects without cardiovascular disease underwent standard and tissue Doppler (TD) echocardiographic imaging. LV systolic function was assessed by load-dependent indices as ejection fraction (EF) and myocardial systolic velocities by TD as well as by the load-independent index, systolic isovolumic acceleration rate (IVA). None of the echocardiographic measurements of systolic function declined with age (mean IVA for the group, 286 +/- 123 cm s(-2); IVA vs. age, r = 0.21, P = 0.1). Likewise, LV end diastolic dimension, wall thickness, mass and left atrial maximum volume were not significantly related to age. On the other hand, as previously reported, echocardiographic indices of diastolic function showed a significant decline with age (P < 0.05). When the group was stratified by gender, isovolumic velocity and acceleration were higher in men than women, but the differences were not significant (P = 0.12 and 0.37, respectively). No significant relation was observed between age and measurements of LV systolic function by regression analysis in women (P > 0.1). However, in men, a positive correlation was noted between average IVA and age (r = 0.63, P = 0.007). In conclusion, age is not associated with a change in cardiac structure and LV systolic function, but is accompanied by a decline in echocardiographic indices of diastolic function. With respect to gender, age does not appear to influence LV systolic function in women, but is associated with an increase in IVA and septal systolic ejection in men.     

Antibody response of humans to the circumsporozoite protein of Plasmodium vivax.

We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax-1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans.     

Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration

Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindness. How the human retina accommodates mis-specified types and numbers of neurons and advances to retinal degeneration are unknown. We studied the retinal organization in vivo of patients with NR2E3 mutations. Early human NR2E3 disease with S cone hyperfunction showed thickened retinal layers within an otherwise normally structured retina. With visual loss, however, lamination was coarse and there was a strikingly thick and bulging appearance to the retina, localized to an annulus encircling the central fovea. This pattern was not found in other retinal degenerations. The abnormal laminar retinal architecture of early NR2E3 disease may be due in part to larger cells with an S cone phenotype in place of rods that failed to differentiate. The later-stage dysplastic appearance suggests a previously unrecognized proliferative response in human retinal degeneration.     

Role of extracellular Ca2+ in gating of CaV1.2 channels

We examined changes in ionic and gating currents in Ca_V1.2 channels when extracellular Ca²⁺ was reduced from 10 m m to 0.1 μ m . Saturating gating currents decreased by two-thirds ( K _D≈ 40 μ m ) and ionic currents increased 5-fold ( K _D≈ 0.5 μ m ) due to increasing Na⁺ conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca²⁺], which appeared to reflect the rapid activation of channels that were not blocked by Ca²⁺ and a slower reversal of Ca²⁺ blockade of the remaining channels. Removal of Ca²⁺ following inactivation of Ca²⁺ currents showed that Na⁺ currents were not affected by Ca²⁺-dependent inactivation. Ca²⁺-dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca²⁺ conductance and Ca²⁺-dependent inactivation depend on extracellular Ca²⁺ and are linked to changes in selectivity.     

Mixed epithelial and stromal tumors of the kidney. A report of 22 cases

Mixed epithelial and stromal tumor of the kidney (MESTK) is a recently described subset of renal neoplasm that tends to occur in middle-aged and older women and is characterized by a distinctive histological appearance. To further characterize this lesion, we report the clinicopathological and immunohistochemical features of 22 additional cases from our institutional files. Grossly, the tumors ranged in size from 1 cm to 14 cm (mean 6.7 cm), were well circumscribed but unencapsulated, and showed a cystic cut surface. The tumors were composed of a spindle cell proliferation that resembled ovarian stroma, as well as an epithelial component lining the cystic structures, which usually consisted of flat to hobnailed cells typical of collecting-duct epithelium. Areas displaying features of Müllerian differentiation were also documented in 6 cases, including epithelium of endometrioid, tubal, clear cell and squamous cell type as well as one case showing an architecture that closely resembled Müllerian adenofibroma and adenosarcoma. Follow-up in 14 patients (average 4.4 years) showed no evidence of recurrence or metastasis. We believe these tumors represent the renal counterpart of similar mixed epithelial and stromal neoplasms occurring in the biliary tract and pancreas, which is also characterized by cystic structures lined by epithelium, admixed with ovarian-type stroma. The differential diagnosis for these tumors includes cystic nephroma and cystic partially differentiated nephroblastoma, which we believe to represent clinically and morphologically distinct entities from MESTK. In particular, the distinction from cystic nephroma in adult male patients is emphasized, and two cases of this entity are included in the study for comparison.     

Are Homemade and Commercial Infant Foods Different? A Nutritional Profile and Food Variety Analysis in Spain

Complementary feeding (CF) is an important determinant of early and later life nutrition with great implications for the health status and the development of an adequate growth. Parents can choose between homemade foods (HMFs) and/or commercial infant foods (CIFs). There is no consistent evidence as to whether HMFs provide a better nutritional profile and variety over CIFs. The aim of this study was to compare the nutritional profiles and food variety of HMFs versus CIFs in the Spanish market targeted for infants (6–11 months) and young children (12–18 months). Thirty mothers with their children aged 6 to 18 months were included in this cross-sectional study, following a 3-day weighed food diary of which HMFs were collected and chemically analyzed. HMFs meals for infant provided significantly lower energy, higher protein and higher fiber, for young children provided significantly higher protein and fiber than CIFs meals. HMFs fruit purees for infant shown significantly higher fiber and for young children provided higher energy than CIFs. HMFs meals contained a significantly greater number of different vegetables than CIFs meals (3.7 vs. 3.3), with carrot as the most frequently used in both. However, in CIFs fruit purees shown higher different fruits than HMFs, in both the banana was the fruit most frequently used. There was a predominance of meat and lack of oily fish and legumes in both HMFs and CIFs meals. HMFs and CIFs were equally characterized by a soft texture and yellow-orange colours. Importantly, our findings emphasize the need for clear guidelines for the preparation of HMFs as well as the promotion of food variety (taste and textures) in both HMFs and CIFs to suit infants’ and young children’s nutritional and developmental needs.     

Adiponectin Gene Variant rs3774261, Effects on Lipid Profile and Adiponectin Levels after a High Polyunsaturated Fat Hypocaloric Diet with Mediterranean Pattern

The role of ADIPOQ gene variants on metabolic improvements after weight change secondary to different hypocaloric diets remained unclear. We evaluate the effect of rs3774261 of ADIPOQ gene polymorphism on biochemical improvements and weight change after high polyunsaturated fat hypocaloric diet with a Mediterranean dietary pattern for 12 weeks. A population of 361 obese subjects was enrolled in an intervention trial with a calorie restriction of 500 calories over the usual intake and 45.7% of carbohydrates, 34.4% of fats, and 19.9% of proteins. The percentages of different fats was; 21.8% of monounsaturated fats, 55.5% of saturated fats, and 22.7% of polyunsaturated fats. Before and after intervention, an anthropometric study, an evaluation of nutritional intake and a biochemical evaluation were realized. All patients lost weight regardless of genotype and diet used. After 12 weeks with a similar improvement in weight loss (AA vs. AG vs. GG); total cholesterol (delta: −28.1 ± 2.1 mg/dL vs. −14.2 ± 4.1 mg/dL vs. −11.0 ± 3.9 mg/dL; p = 0.02), LDL cholesterol (delta: −17.1 ± 2.1 mg/dL vs. −6.1 ± 1.9 mg/dL vs. −6.0 ± 2.3 mg/dL; p = 0.01), triglyceride levels (delta: −35.0 ± 3.6 mg/dL vs. 10.1 ± 3.2 mg/dL vs. −9.7 ± 3.1 mg/dL; p = 0.02), C reactive protein (CRP) (delta: −2.3 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL; p = 0.02), serum adiponectin (delta: 11.6 ± 2.9 ng/dL vs. 2.1 ± 1.3 ng/dL vs. 3.3 ± 1.1 ng/dL; p = 0.02) and adiponectin/leptin ratio (delta: 1.5 ± 0.1 ng/dL vs. 0.3 ± 0.2 ng/dL vs. 0.4 ± 0.3 ng/dL; p = 0.03), improved only in AA group. AA genotype of ADIPOQ variant (rs3774261) is related with a significant increase in serum levels of adiponectin and ratio adiponectin/leptin and decrease on lipid profile and C-reactive protein (CRP).