Dimensional changes of proximal tubules and cortical capillaries in chronic obstructive renal disease

Summary The study was carried out to determine the proximal tubular length, surface area and length of peritubular capillaries and the nephron numbers in kidneys with chronic nephropathy and varying increase in the cortical interstitial volume. Kidneys of pigs with varying chronic obstructive nephropathy were used for the experiments. Two subgroups of ureterobstructed kidneys were defined arbitrarily according to the volume of cortical interstitium. One subgroup (I) comprised kidneys with a volume fraction of cortical interstitium less than 30% (mean 17.2%; mean of controls 9.7%). The other subgroup (II) consisted of kidneys with severe chronic nephropathy and with a volume fraction of interstitium more than 30% (mean 44.5%). Proximal tubular length and length and surface area of peritubular capillaries were assessed by conventional morphometric techniques on 1 m thick sections of plastic embedded material. Nephron numbers were determined by a stereological method for counting glomeruli.The results demonstrated that proximal tubular length and capillary dimensions were significantly reduced in subgroup II, whereas no significant changes were observed in subgroup I. The mean number of glomeruli was not significantly different from control values in any of the subgroups.The results are in line with observations from previous quantitative analyses of proximal tubular cross-sections indicating that proximal tubular dimensions become reduced mainly at advanced stages of chronic nephropathy. The results also indicate that shortening of individual tubules rather than loss of entire nephrons is responsible for the observed reduction in total length of proximal tubules. Finally, the present observations suggest that reduced dimensions of the cortical capillary network may have pathogenetic significance for ongoing proximal tubular atrophy in chronic renal desease.     

Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis

Objective

Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.

Psychological aspects of Crohn's disease

This is a critical review of 16 studies reporting a relationship between Crohn's disease and psychological variables. The studies reviewed indicate a relationship between the psychological variables of stressful life events, personality characteristics, and psychopathology and the onset and/or exacerbation of Crohn's symptoms. Personality characteristics such as depression, anxiety, and dependency are frequently reported as are the occurrence of stressful life events and the presence of psychopathology. The nature of the relationship is not explained by the research to date; however, the findings summarized in this report indicate that additional investigation into this association is warranted. A plan for such research is suggested.     

Fast-induced changes in plasma glucose, insulin and free fatty acid concentration compared in rats during the night and day

Changes in PG, PI and PFFA were examined and compared in fed rats or after 0 to 12 hours of fasting, during the night or during the day. At night, a progressive decrease in PG and PI and an increase in PFFA were induced by 0 to 12 hours of food deprivation. During the light period a decrease in PG occurred only from the 6th hour of fasting. A slight, progressive increase in PFFA levels was induced from 0 to 12 hours of fasting, while no significant variation of PI levels was observed. The results are discussed in terms of relationships between blood glucose, PFFA levels, and food intake in control rats over the circadian cycle.     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome

Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow-up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae.     

Selection of stereotyped VH81X-{micro}H chains via pre-B cell receptor early in ontogeny and their conservation in adults by marginal zone B cells

The pre-B cell receptor (preBCR) plays critical roles in early B cell differentiation. It has been shown that not all muH chains are capable of pairing with surrogate light (SL) chains to form preBCR. Here, we established a novel system to differentially identify two types of early pre-B cell populations in bone marrow and fetal liver of mice, one producing SL-pairing muH chains and the other producing SL-non-pairing muH chains. The former population accounted for 80% of all the early pre-B cells in adult bone marrow, while it accounted for only 20% of those in fetal liver. Comparison of the two types of pre-B cell populations in fetal liver revealed the structural difference between SL-pairing and -non-pairing muH chains encoded by the V(H)81X segment that was most frequently utilized in fetal liver pre-B cells but rarely expressed by B cells generated in adults. PreBCR played an important role in the positive selection of V(H)81X-muH chains carrying the characteristic sequences of the complementarity-determining region 3 with little or no nibbling or N nucleotide addition, leading to their predominance in neonatal splenic B cells. These fetal-type V(H)81X-muH chains were also detected in adult spleen, but almost exclusively in marginal zone (MZ) B cells in contrast to the adult-type V(H)81X-muH chains. This strongly suggests that neonatally generated and selected B cells expressing the stereotyped V(H)81X-muH chains are maintained in the adult MZ and could function as innate-like lymphocytes.