Streptozotocin induced diabetic nephropathy and renal tumors in the rat

Summary Adult Wistar rats rendered diabetic by a single dose of streptozotocin develop renal morphological changes which show subtle differences compared to those seen in human diabetic renal disease. The early tubular degeneration is sited in the distal rather than the proximal convoluted tubule and subsequent glomerular lesion shows linear deposits of IgG and albumin in the basement membrane rather than in the mesangium. The carcinogenicity of streptozotocin in the rat is reconfirmed.Acknowledgements. We wish to thank Mr S.G. Watkins and Mrs D. Greening for technical assistance.     

Solubilization and characterization of a ouabain-sensitive protein from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) in cat cardiac muscle

A new glycoprotein of 31,500 dalton, which has a high affinity for ouabain, and is independent of (Na+-K+)-ATPase, was solubilized from transverse tubule membrane and junctional sarcoplasmic reticulum complexes (TTM-JSR) of cat cardiac muscle. This protein could be extracted only in small amounts from sarcolemma-plasma membrane (SLM-PL) fragments, suggesting that it indeed originates from the TTM-JSR.     

Effect of nerve stimulation on rat skeletal muscle. A study of plasma membrane

Summary The gastrocnemius muscle of the rat showed no morphological, histometric or plasma membrane changes, after sciatic nerve stimulation with a 5 mA current for 30 to 60 min, 10 mA for 30 min and 15 mA for 5 min. However, 10 mA for 60 and 200 min gave rise to mitochondrial and plasma membrane abnormalities. These changes were absent after a rest period. The results indicated the sciatic nerve stimulation at 10 mA for 60 and 200 min caused reversible changes in the rat skeletal muscle mitochondria and plasma membrane.     

Solubilization and characterization of a ouabain-sensitive protein from transverse tubule membranejunctional sarcoplasmic reticulum complexes (TTM-JSR) in cat cardiac muscle

Summary A new glycoprotein of 31,500 dalton, which has a high affinity for ouabain, and is independent of (Na⁺–K⁺)-ATPase, was solubilized from transverse tubule membrane and junctional sarcoplasmic reticulum complexes (TTM-JSR) of cat cardiac muscle. This protein could be extracted only in small amounts from sarcolemmaplasma membrane (SLM-PL) fragments, suggesting that it indeed originates from the TTM-JSR.     

Experimenteller Beitrag zur Frage der Mitochondrienfunktion

Summary In the phase microscope it can be seen that cloudy swelling is the consequence of an enlargement of the mitochondria, whereby the membrane of the mitochondria is detached from the body of the mitochondrion. An increased water intake seems to be the reason of this phenomenon.The intraperitoneal injection of hen egg albumen is followed after several hours by an accumulation of hyaline droplets in the protoplasma of the renal tubule cells. The PM reveals that this foreign protein is stored within the mitochondria, which are converted into brilliant granules. The same is true for the accumulation of vital dyes in kidney tubule cells, but in this case there is a combination of the dye with protein deriving from a slight lesion of the cells.     

Interaction of salicylate and noise results in mortality of rats

Summary Survival as a function of salicylate dose and the intensity of environmental noise was investigated in 150 adult female pigmented rats. Rats were assigned to groups (n=6/group) defined by combinations of salicylate levels from 0- (saline) to 300 mg/kg, injected subcutaneously, and noise levels from ambient noise to 98 dB SPL, presented daily for 10-h periods for up to 17 days. Mortality occurred in groups exposed to the higher combinations of salicylate and noise.     

Polypeptide translocation machinery of the yeast endoplasmic reticulum

Proteins enter the secretory pathway by two general routes. In one, the complete polypeptide is made in the cytoplasm and held in an incompletely folded state by chaperoning adenosine triphosphatases (ATPases) such as hsp70. InSaccharomyces cerevisiae, fully synthesized secretory precursors engage the endoplasmic reticulum (ER) membrane by interaction with a set of Sec proteins comprising the polypeptide translocation apparatus (Sec61p, Sec62p, Sec63p, Sec71p, Sec72p). Productive interaction requires displacement of hsp70 from the precursor, a reaction that is facilitated by Ydj1p, a homologue of theEscherichia coli DnaJ protein. Both DnaJ and Ydj1p regulate chaperone activity by stimulating the ATPase activity of their respective hsp70 partners (E. coli DnaK andS. cerevisiae Ssa1p, resepectively). In the ER lumen, another hsp70 chaperone, BiP, binds ATP and interacts with the ER membrane via its contact with a peptide loop of Sec63p. This loop represents yet another DnaJ homologue in that it contains a region of 70 residue similarity to the J box, the most conserved region of the DnaJ family of proteins. In the presence of ATP, under conditions in which BiP can bind to Sec63p, the secretory precursor passes from the cytosol into the lumen through a membrane channel formed by Sec61 p. A second route to the membrane pore that is used by many other secretory precursors, particularly in mammalian cells, requires that the polypeptide engage the ER membrane as the nascent chain emerges from the ribosome. Such cotranslational translocation bypasses the need for certain Sec proteins, instead utilizing an alternate set of cytosolic and membrane factors that allows the nascent chain to be inserted directly into the Sec61p channel.     

Involution of the mesonephros and differentiation of the epididymis in chickens: immunohistological study]

By means of purified rabbit anti-adult chicken kidney antibodies two types of antigens have been identified in the mesonephros: one, localised in the cells of the proximal segment of the secretory tubules, the other characteristic of the collecting segments derived from the Wolffian duct. During the transformation of certain mesonephric tubules into ductuli efferentes and conjugentes of the epididymis the collecting tubule antigen disappears whereas the proximal secretory tubule antigen not only persists but can also be detected in the parietal layer of Bowman's capsules as they transform before connecting with the rete testis.     

Monoaminoguanidine prevents sorbitol accumulation, nonenzymatic protein glycosylation and development of kidney lesions in diabetic rats

Monoaminoguanidine administration (25 mg/kg b.wt, i.p. for 14 weeks) to alloxan diabetic rats (blood glucose greater than or equal to 250 mg/dl) decreased the nonenzymatic protein glycosylation and sorbitol levels. It prevented development of Armanni-Ebstein tubular lesions, pathological changes in the glomerular capillary tufts and glomerular basement membrane thickening in the kidney.     

Tetraspanins and cell membrane tubular structures

Tetraspanins regulate a variety of cellular functions. However, the general cellular mechanisms by which tetraspanins regulate these functions remain poorly understood. In this article we collected the observations that tetraspanins regulate the formation and/or development of various tubular structures of cell membrane. Because tetraspanins and their associated proteins (1) are localized at the tubular structures, such as the microvilli, adhesion zipper, foot processes, and penetration peg, and/or (2) regulate the morphogenesis of these membrane tubular structures, tetraspanins probably modulate various cellular functions through these membrane tubular structures. Some tetraspanins inhibit membrane tubule formation and/or extension, while others promote them. We predict that tetraspanins regulate the formation and/or development of various membrane tubular structures: (1) microvilli or nanovilli at the plasma membranes free of cell and matrix contacts, (2) membrane tubules at the plasma membrane of cell-matrix and cell-cell interfaces, and (3) membrane tubules at the intracellular membrane compartments. These different membrane tubular structures likely share a common morphogenetic mechanism that involves tetraspanins. Tetraspanins probably regulate the morphogenesis of membrane tubular structures by altering (1) the biophysical properties of the cell membrane such as curvature and/or (2) the membrane connections of cytoskeleton. Since membrane tubular structures are associated with cell functions such as adhesion, migration, and intercellular communication, in all of which tetraspanins are involved, the differential effects of tetraspanins on membrane tubular structures likely lead to the functional difference of tetraspanins.     

Alleviation of mortality induced by salicylate and stress

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2×2×4 factorial design, rats were assigned to groups defined by:A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution;B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements;C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.     

Monoaminoguanidine prevents sorbitol accumulation,nonenzymatic protein glycosylation and development of kidney lesions in diabetic rats

Summary Monoaminoguanidine administration (25 mg/kg b.wt, i.p. for 14 weeks) to alloxan diabetic rats (blood glucose 250 mg/dl) decreased the nonenzymatic protein glycosylation and sorbitol levels. It prevented development of Armanni-Ebstein tubular lesions, pathological changes in the glomerular capillary tufts and glomerular basement membrane thickening in the kidney.CDRI Communication no. 4694.     

The effects of salicylate and aspirin on the activity of phosphorylase a in perfused hearts of rats

Summary Sodium salicylate and aspirin are known to have a glycogenolytic effect as judged by either the glycogen level or lactate production in perfused hearts of rats. In this work it was possible to demonstrate that phosphorylase a level was increased in the hearts subjected to the action of these drugs.     

Polarographic activity of the antitumor drug cis-dichlorodiammineplatinum (II). The effect of hydrolysis and trans-isomerization of the drug

Electrochemical activities of cis-dichlorodiammineplatinum (II) (cis-DDP) and its trans isomer were studied by classical and differential pulse polarography (d.p.p.). It was shown that both isomers yielded a polarographic step or peak at about -1.6 V (vs. Ag/AgCl), which corresponded to electroreduction of the complex and to catalytic hydrogen evolution. This signal was easily measurable with the aid of d.p.p. and was suitable for investigation of the extent of hydrolysis and trans-isomerization of cis-DDP leading to the formation of toxic products. The detection limit for determination of cis-DDP and its trans isomer by d.p.p. was 1 X 10(-6) mol/l.     

Pathological changes in the heterologous phase of antibasement membrane antibody mediated disease in the rat

Summary The immunological and structural changes during the heterologous phase of experimental antibasement membrane antibody mediated disease was sequentially studied in the rat following single i.v. injections of rabbit antibodies to basement membrane antigens prepared from kidney, lung and salivary gland tissues. Although each of the anti-bodies bound strongly to GBM, structural changes were initially subtle accompanied by proteinuria and hematuria. More severe structural changes related to dose and duration of the disease did not appear for several weeks.     

Polarographic activity of the antitumor drug cis-dichlorodiammineplatinum (II). The effect of hydrolysis and trans-isomerization of the drug

Summary Electrochemical activities of cis-dichlorodiammineplatinum(II) (cis-DDP) and its trans isomer were studied by classical and differential pulse polarography (d.p.p.). It was shown that both isomers yielded a polarographic step or peak at about –1.6V (vs. Ag/AgCl), which corresponded to electroreduction of the complex and to catalytic hydrogen evolution. This signal was easily measurable with the aid of d.p.p. and was suitable for investigation of the extent of hydrolysis and trans-isomerization of cis-DDP leading to the formation of toxic products. The detection limit for determination of cis-DDP and its trans isomer by d.p.p. was 1×10^–6 mol/l.Acknowledgment. This work was supported in part by Lachema n.e., Brno (Czechoslovakia).     

Kinetics of chemo-attraction of polymorphonuclear leukocytes towards N-formyl peptide studied with a novel polycarbonate (Nuclepore) membrane in the Boyden chamber

Summary The motile responses of human polymorphonuclear leukocytes (PMN) to N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the Boyden chamber using a new sparse-pore polycarbonate membrane (pores 3 m in diameter and occupying 0.1% of surface area) were compared with those demonstrated by using a standard polycarbonate (Nuclepore) filtration membrane (pores 3 m in diameter and occupying 5% of surface area). Motility of PMN in gradients of FMLP using the new membrane was not influenced by chemokinetic effects of the factor, and the background migration of the cells was minimal. However, motility of PMN in gradients of FMLP using the standard membrane was found to be influenced by chemokinetic effects of the chemotactic factor, and the background or control migration (in the absence of chemotactic factor) of the cells was substantial. Greater directional migration of PMN according to steepness of the gradient of chemotactic factor was demonstrated with the use of the new membrane. The new membrane may be of considerable value in the further study of the chemotactic responses of PMN.     

Translation control of UCP2 synthesis by the upstream open reading frame

Uncoupling protein 2 (UCP2) belongs to a family of transporters of the mitochondrial inner membrane. In vivo low expression of UCP2 contrasts with a high UCP2 mRNA level, and induction of UCP2 expression occurs without change in mRNA level, demonstrating a translational control. The UCP2 mRNA is characterized by a long 5′ untranslated region (5′UTR), in which an upstream open reading frame (uORF) codes for a 36-amino-acid sequence. The 5′UTR and uORF have an inhibitory role in the translation of UCP2. The present study demonstrates that the 3′ region of the uORF is a major determinant for this inhibitory role. In this 3′ region, a single-base substitution that kept the codon sense unchanged significantly modified UCP2 translation, whereas some important amino acid changes had no effect. We discuss our results within the framework of the existing models explaining initiation of translation downstream of a uORF. Received 22 March 2006; received after revision 19 May 2006; accepted 8 June 2006 C. Hurtaud and C. Gelly contributed equally to this work.     

Effect of low dose of 70 kVp X-rays on the intrauterine development of mice

Pregnant Swiss albino mice were exposed to low doses of X-rays (approximately 9 mGy) in the range used for diagnostic exposure, on day 3.5 of gestation (preimplantation period), day 6.5 (early organogenesis period) or day 11.5 (late organogenesis period). The fetuses were examined on the 18th day of gestation. Exposure at 3.5 days post coitus (d.p.c.) resulted in a significant increase in prenatal mortality, and an increased incidence of retarded fetuses was observed after exposure at 3.5 and 6.5 d.p.c. The major effect of exposure at 11.5 d.p.c. was a significant decrease in the fetal head size and brain weight.