Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Plant growth substances produced by microorganisms of the rhizosphere and the soil

Microorganisms isolated from the soil and the rhizosphere of wheat plants produce growth regulating substances with effects similar to gibberellins when grown in submerse cultures. Bioassays and thin layer chromatography were used for characterization. Different plant growth regulating substances and variations in their quantity were observed among microorganisms. The amounts of gibberellin-like substances found in culture filtrates varied, in a range from 0.01 to 1.0 mg GA₃ equivalents per liter.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Measurement of functional ability and health status in the arthritic patient

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or ‘instrument’, high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-)effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.     

Membranes of the adrenal medulla: A comparison of membranes of chromaffin granules with those of the endoplasmic reticulum

The protein and lipid composition of the membrane of the chromaffin granule has been compared with that of an endoplasmic reticulum fraction isolated from bovine adrenal medulla. The endoplasmic reticulum was purified by centrifugation of a microsomal fraction in sucrose and Ficoll density gradients. Only insignificant amounts of chromomembrin B, dopamine β-hydroxylase and cytochrome b₅₅₉, which are characteristic protein components of the chromaffin granule membrane, were present in the endoplasmic reticulum fraction; whereas glucose-6-phosphatase and galactosyltransferase, marker enzymes of membranes of endoplasmic reticulum and Golgi complex respectively, were absent from the membranes of chromaffin granules. The lipid composition of the two types of membranes varies in the relative amounts of lysolecithin, lecithin and sphingomyelin and in the molar ratio of cholesterol to phospholipid. Lysolecithin, which is a major phospholipid of the chromaffin granule membrane, is virtually absent from membranes of the endoplasmic reticulum. Different protein patterns were obtained when these two membrane fractions were solubilized with detergent and subjected to polyacrylamide gel electrophoresis.It is concluded that membranes of the endoplasmic reticulum and those of the chromaffin granules are basically different and therefore that the transport of secretory proteins from their site of synthesis to their site of storage occurs, in the chromaffin cell, by a mechanism that does not involve a mixing of the participating membranes.     

Energy dependence of contraction band formation in perfused hearts and isolated adult myocytes.

Aggregation of sarcomeres into contraction bands is a prominent feature of the oxygen paradox, the calcium paradox, and caffeine injury to calcium-free perfused hearts. For investigation of the mechanism of contraction banding, it was necessary to devise a method of evaluating the degree of sarcomere contraction and to define objectively a contraction band. Hearts with mechanical detachment of cells caused by hypocalcemic perfusion and isolated myocytes both allow unrestrained contracture of cells and permit direct optical measurements to quantitate the degree of cell contracture. With the use of the calcium paradox as a model of contraction band necrosis, it was found that cells with lengths of less than 37.3 mu could be considered as containing contraction bands. It was found that the mitochondrial inhibitors cyanide and amytal, as well as the uncoupler 2,4-dinitrophenol, allowed cell contracture but inhibited hypercontracture of sarcomeres into contraction bands during both the calcium paradox and caffeine injury to perfused hearts. However, when 2mM adenosine triphosphate (ATP) was included in the perfusion media, contraction band formation occurred despite the continued presence of cyanide or amytal. In isolated myocyte preparations the addition of the glycolytic inhibitor iodoacetate (IAA, 5 mM) and the mitochondrial inhibitor amytal (3 mM) caused relaxed rod-shaped cells (length/width ratio greater than 3:1) to contract into a stable population of square-shaped forms (length/width ratio less than 3:1), indicating an abrupt and severe decline in cellular ATP levels. Removal of amytal from the incubation medium in the presence of IAA produced a significant conversion of square-shaped cells into round-shaped cells containing contraction bands. Either IAA alone or amytal alone resulted in a mixed population of square and round cells. The results indicate that ATP is required for the formation of contraction bands in intact hearts and for the rounding of isolated myocytes. Formation of contraction bands appears to be an energy-dependent process requiring ATP.     

The effect of sodium lauryl sulphate and triclosan on hamster cheek pouch mucosa

It has recently been shown that triclosan protects the human skin from the inflammation that may be caused by exposure to sodium lauryl sulphate (SLS). The aim of the present study was to examine whether triclosan can protect the hamster cheek pouch mucosa from the irritation caused by exposure to SLS. After four daily applications of a paste containing SLS, the epithelium of the hamster cheek pouch showed consistently prominent structural changes, especially basal hyperplasia, acanthosis, hypergranulosis, and hyperkeratosis. Identical morphological changes were also observed after applications of a paste containing SLS together with triclosan. In contrast, after applications of a paste containing triclosan alone, the cheek pouch mucosa revealed a histological structure essentially similar to the non-treated control mucosa. From these results, we may conclude that SLS, but not triclosan, irritates the hamster cheek pouch epithelium. Moreover, triclosan does not protect the cheek pouch mucosa against structural changes induced by SLS. It must be taken into account that triclosan does not always offer protection against the side-effects of SLS.     

Increased sharing of maternal HLA haplotypes among children exposed to diphenylhydantoin during pregnancy.

During investigation of HLA types among children exposed to diphenylhydantoin (DPH) in utero, we found no evidence of a distortion in haplotype sharing among affected sib pairs. Unexpectedly, however, we found a marked increase in the proportion of all sib pairs (not just affected ones) sharing maternal haplotypes. Among 14 two child families, 12 shared the maternal haplotype (expected would be seven); among families with more than two children the distortion was also pronounced. This finding, if verified in future studies, could indicate that something in the mothers, whether DPH use during pregnancy, or some genetic factor associated with seizures, or some effect of the seizures themselves, may be leading to non-random segregation of HLA haplotypes in their offspring.