Phagocytosis of erythrocytes by the proximal tubule of the rat kidney

Summary Morphological examination of kidney biopsies from patients with glomerulonephritis and hematuria has revealed the presence of erythrocytes within epithelial cells of the proximal tubule. This observation suggested that the proximal tubule might be capable of phagocytizing morphologically intact erythrocytes. To examine this possibility small quantities of heparinized autologous blood were injected into surface convolutions of proximal tubules of the rat kidney using standard micropuncture techniques. At time intervals ranging from 10 min to 120 h after injection, the kidneys were preserved for light and transmission electron microscopy by drip-fixation with a half-strength Karnovsky's glutaraldehyde-formaldehyde fixative.During the initial 6 h there was a flattening of the brush border and accumulation of electron-dense material representing hemoglobin in apical vacuoles and in lysosome-like structures. From 6 to 15 h after micropuncture, there was progressive loss of the brush border and the simultaneous formation of pseudopodia-like evaginations that extended from the apical plasma membrane and surrounded the individual erythrocytes. By 18 and 24 h, erythrocytes were observed in the proximal tubule cells. At later time intervals, edema, lymphocytic infiltration, and fibrosis were observed in the interstitium. In addition, crystalline structures were present in the lumen and the cells of both proximal and distal tubules. These findings suggest that in addition to their well-established ability to pinocytize hemoglobin and other proteins, the cells of the proximal tubule are capable of phagocytizing morphologically intact autologous erythrocytes. It is possible that phagocytosis by the proximal tubule cells may play a role in the disposal of erythrocytes from the tubular fluid in hematuric conditions.     

Effect of the chemical and physical condition of the soil on Verticillium wilt of antirrhinum

Summary In vitro study showed thatVerticillium dahliae Kleb. grew well in a wide range of acid and alkaline media (viz. pH 3.5 to 10.5). The best growth of the fungus was observed in pH 5.5. Soil pH 3.5 was toxic for growing antirrhinum seedlings. Development of Verticillium wilt of antirrhinum was affected by soil pH. The severity of the disease was greater in alkaline soil conditions compared with acid conditions. Soil of pH 3.5 gave very good control of the symptom expression by the infected plants. Rhizosphere analysis results showed that fungal population with the exception ofPenicillium spp., was drastically reduced in the rhizosphere of the plants grown in acid soil. Although the overall population of fungi was reduced in theV. dahliae infected antirrhinum rhizosphere in acid soil, the population ofPenicillium spp. markedly increased. The antagonistic activity of thePenicillium spp. in the rhizosphere might also have reduced the disease severity. Since the seedlings did not grow properly in very dry and very wet soil, rhizosphere analysis of these soils was not possible. Disease severity was much less in wet soil compared with plants grown in medium moisture level and dry soil, but the plant growth was very poor. Dedicated to the memory of the late Prof. H. K. Baruah from whom I had the inspiration for research     

The tight junctions of renal tubules in the cortex and outer medulla

Summary Quantitative aspects of tight junction morphology were systematically studied in the cortical and outer medullary segments of the distal urinary tubules of rat, hamster, rabbit, cat, dog and the primitve primate Tupaia belangeri.Only minor differences in junctional architecture were found between straight and convoluted portions of the distal tubule. In contrast, the collecting duct in cortex and outer medulla, in all species, exhibits the most elaborate tight junctions observed along the uriniferous tubule.The present and previous findings from this laboratory indicate that increasing tightness of the junctional complexes is apparent along the course of the nephron in all species studied.The proposed relationship between quantitative aspects of the zonula occludens and presently available values for transepithelial electrical resistance was re-examined for the renal tubules. It was found that for the mammalian kidney a satisfactory correlation exists between the tight junction morphology and presently known functional parameters. This relationship is the more evident the more additional dimensional characteristics of the intercellular clefts are taken into consideration.It may therefore be concluded that, at least for the mammalian kidney, the assumption of differences in the molecular organization of the tight junctions is not needed to explain so far unresolved discrepancies between tubular morphology and function.Parts of these findings were presented at the 72nd Meeting of the Anatomical Society, Aachen; April 1977 (see Verh. Anat. Ges. 72:229–234 [1978])Supported by the Deutsche Forschungsgemeinschaft     

Na+-dependent,potential-sensitive l-ascorbate transport across brush border membrane vesicles from kidney cortex

l-Ascorbate is taken up into brush border vesicles from kidney cortex of rat, rabbit and guinea pig by an efficient, Na⁺-dependent and potential-sensitive transport process. This uptake shows saturation ($\text{K}{}_{\mathrm{<mtext>m</mtext><mtext>:0.1–0.3\; mM</mtext>}}$) and is strongly stimulated by low concentrations of N₃^?. Erythorbate (d-isoascorbate) seems to be another, but poorer, substrate of the same transporter.     

Entamoeba histolytica: cytopathogenicity of intact amebae and cell-free extracts; isolation and characterization of an intracellular toxin.

Toxicity assays on cell-free extracts of virulent and nonvirulent strains of Entamoeba histolytica were carried out in microtiter plates. These extracts had a cytopathogenic effect (CPE) on monolayers of baby hamster kidney cells. CPE was inhibited by normal human serum, fetal calf serum, and other sera, probably due to their IgG component. Using gel chromatography the toxic material, a protein, was found in a fraction with molecular weight between 35,000 and 45,000. This fraction contained a strong glycoprotein antigen. CPE caused by this toxin differs in several ways from the earlier described “contact lysis” caused by intact amebae. The possible significance of these two modes of toxicity of Entamoeba histolytica for the pathogenesis of amebiasis is discussed.     

Incorporation of 3H-thymidine in the nephron of Gasterosteus aculeatus L. and its stimulation by methyltestosterone

Summary The rate of ³H-thymidine incorporation into different parts of the renal proximal tubule of female sticklebacks treated with methyltestosterone was investigated using high-speed scintillation autoradiography. The results are compared with those from normal males before or after mucous transformation of the kidney. Labelled cells are observed in all parts of the proximal tubule, with marked variations from one segment to another. They are numerous in part 2 of the proximal tubule, particularly in the distal region. Male sex hormones affect the labelling rate in all parts of the nephron, especially in the distal region of part 2 of the proximal tubule. In that particular area, new tubule formation by budding is observed in some individuals, but this process does not appear to be a general one. Correlation between the frequency of these figures and the time of treatment could not be established. Comparing the action of sex hormones in females with that in males reveals a difference in reactivity in the proximal zone of part 2 of the proximal tubule, where methyltestosterone has a strong action in females; in contrast, in mature and immature males, only a few labelled cells are present in this region.It is concluded that kidney enlargement during the breeding season does not result only from a swelling of cells belonging to part 2 of the proximal tubule, as was generally believed, but also from a lengthening or even a proliferation of the proximal tubules, induced by an increase in mitotic activity controlled by male sex hormones.

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Résumé L'incorporation de thymidine tritiée dans les tubules proximaux du rein est étudiée par autoradiographie rapide chez des Epinoches femelles préalablement traitées par la méthyltestostérone. Les résultats sont comparés avec ceux obtenus chez des mâles normaux ayant ou non développé un rein muqueux. Des cellules marquées sont présentes à tous les niveaux des tubules proximaux, mais leur nombre varie considérablement d'un segment à l'autre. Elles sont les plus nombreuses dans la seconde partie du tubule proximal, particulièrement dans sa région distale. Le taux de marquage est modifié dans toutes les régions du néphron, mais les variations sont les plus intenses dans la région distale de la seconde partie du tubule proximal, où l'on observe parfois la formation de nouveaux tubules par bourgeonnement. La comparaison des résultats obtenus dans les deux sexes fait apparaître une différence de réactivité au niveau de la zone proximale de la seconde partie du tubule proximal, où la méthyltestostérone agit fortement chez les femelles, alors qu'elle n'exerce pas d'effet notable chez les mâles.L'augmentation de volume du rein chez le mâle lors de la période de reproduction ne résulte donc pas uniquement d'un gonflement des cellules de la seconde partie du tubule proximal, comme on le pensait généralement. Des phénomènes mitotiques interviennent également dans ce processus, sous l'influence des hormones sexuelles mâles, qui conduisent à un allongement, voire à une multiplication des tubules proximaux.

     

Cell junctions in the epithelium of Bowman's capsule

Summary The intercellular connections between the epithelial cells of Bowman's capsule were investigated. It could be demonstrated that typical zonulae occludentes (tight junctions) are present in the species (rat, hamster, and Tupaia) studied. Freeze-fracturing shows a network of anastomizing strands; some species variations are described. In the rat two strands are common. In the golden hamster mostly two to four and occasionally five strands occur. In Tupaia regularly three tight junction strands are found and also gap junctions associated with the zonulae occludentes. In thin sections the goniometric analysis confirms the freeze-fracturing results and reveals attachment zones of macular shape, which are classified as intermediate junctions and desmosomes. The functional role of these cell junctions observed in the epithelium of Bowman's capsule is discussed.     

Identification of marker genes in Alzheimer's disease using a machine-learning model

Alzheimer''s Disease (AD) is one of the most common causes of dementia, mostly affecting the elderly population. Currently, there is no proper diagnostic tool or method available for the detection of AD. The present study used two distinct data sets of AD genes, which could be potential biomarkers in the diagnosis. The differentially expressed genes (DEGs) curated from both datasets were used for machine learning classification, tissue expression annotation and co-expression analysis. Further, CNPY3, GPR84, HIST1H2AB, HIST1H2AE, IFNAR1, LMO3, MYO18A, N4BP2L1, PML, SLC4A4, ST8SIA4, TLE1 and N4BP2L1 were identified as highly significant DEGs and exhibited co-expression with other query genes. Moreover, a tissue expression study found that these genes are also expressed in the brain tissue. In addition to the earlier studies for marker gene identification, we have considered a different set of machine learning classifiers to improve the accuracy rate from the analysis. Amongst all the six classification algorithms, J48 emerged as the best classifier, which could be used for differentiating healthy and diseased samples. SMO/SVM and Logit Boost further followed J48 to achieve the classification accuracy.     

An immune response profile model for immunogenicity quantitation

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.     

Spectral imaging for precise surgical intervention in Hirschsprung's Disease

We used advanced spectral imaging for intrasurgical decision making in a preclinical study, on a mouse model of Hirschsprung's Disease. Our imaging device sampled areas from normal and abnormal (aganglionic) colon in these animals. Spectral segmentation and classification of the resulting images showed a clear distinction between the normal and aganglionic regions, as confirmed by pathological analysis and use of mutant mice. We developed a simple algorithm that could distinguish normal from aganglionic colon with high spatial resolution and reproducibility, and the following statistics: sensitivity = 97%, specificity = 94%, positive predictive value = 92%, negative predictive value = 98%. These studies showed translational proof of concept that spectral imaging could be used during operations, in real time, to help surgeons precisely distinguish normal from abnormal tissue without requiring traditional biopsy. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)