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S Benchimol

Publications and source records attributed to S Benchimol.

86 records · Page 5Linked to original sources
PubMed1979

Metaplastic and mitotic activity of the ischemic (endocrine) kidney in experimental renal hypertension.

Partial ligation of the aorta between the renal arteries in the rat induces malignant hypertension, metaplasia of smooth-muscle cells of arterioles and arteries into juxtaglomerular cells, and a complex series of events in tubular cells at all levels of the ischemic kidney. The tubular cells of the outer cortex, particularly the proximal convoluted cells, show a very rapid and progressive simple atrophy. In contrast, necrosis of individual cells is followed by mitotic activity in atrophic tubular cells of the inner cortex, medulla, and papilla. Subsequently, polyploidy and hyperplasia occur in the inner cortex. At the same time, hypertrophy of the protein-synthesizing apparatus and an increase in protein, DNA, and RNA, followed by a decrease in the protein content, are seen in the tubular cells of the inner cortex. In the medulla and papilla, necrosis of individual cells proceeds side by side with waves of mitotic activity. These events take place, albeit to a lesser degree, even in cases of very mild renal ischemia. While they may by unrelated to hypertension, these changes are probably involved in the increase in hydrolytic enzyme activity characteristic of the ischemic renal cortex.

Animals↗
PubMed1978

Ultrastructural radioautography of the incorporation of tritiated leucine by the rat adrenal medulla in vivo.

Sections of tissues from the adrenal medullae of young rats were subjected to radioautography after a single intravenous injection of L-leucine 4, 5(3)H to identify the sites of synthesis and follow the migration of newly-formed proteins in both adrenaline-storing (A) and noradrenaline-storing (N) cells. As early as 2 min after injection of leucine 3H, the label was highest in the rough endoplasmic reticulum (RER) of A and N cells, suggesting that cisternal ribosomes are sites of protein synthesis. By 5 and 10 min, much of the label had migrated from the RER into the Golgi complex of both cell types. Some label was already present over the secretory granule matrix (chromogranins) by 2 min but the peak was reached at 1 h in both A and N cells. By 4 h, the label over the secretory granules had diminished, indicating a release of newly-synthetized chromogranins outside the cells. The label over the hyaloplasm was relatively high at 2 min but it decreased rapidly to low levels. In contrast, the label over the cell surface continually increased to reach the highest levels among all organelles at 4 h in both cell types. The pattern of increment of the label over the cell surface suggests that the newly-formed proteins of these sites are also synthetized in the RER, pass through the Golgi complex and are transported in the hyaloplasm, before reaching the surface of A and N cells.

Adrenal Medulla↗
PubMed1977

Ultrastructural cytochemistry of the human adrenal medulla.

A cytochemical study of the human adrenal medulla showed that it is made up of two types, the adrenaline (A-) and noradrenaline (N-) storing cells. A-and N-storing granules were argentaphobic when ultra-thin sections of Araldite-embedded medulla were stained according to the periodic acid-thiocarbohydrazide silver proteinate technique of Thiery. A small amount of glycogen (which disappeared after digestion with alpha amylase) in the form of B-particles, as well as lysosomes were, however, visualized by this technique. The entire core of A granules was markedly positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA-) embedded medullae were stained with phosphotungstic acid (PTA) at a low pH (O.3). The N granules, in contrast, were mostly unreactive. PTA stained a large part of the Golgi complex of A cells, whereas it generally had no such effect on that of the N cells. In both cell types, the cell coat, lysosomes and multivesicular bodies reacted to PTA. The periodic acid schiff (PAS) technique showed A but not N granules in semithin sections of GMA-or Araldite-embedded medullae. The PTA and PAS stains were abolished by acetylation, restored by saponification, unchanged by methylation and greatly diminished by sulfation or by digestion with beta glucuronidase after oxidation by perchloric acid. These results indicate that in man the A granules and the Golgi complex of A cells, unlike the same structures in N cells, are rich in glycoproteins.

Adrenal Medulla↗
PubMed1977

On the lysosomal function of juxtaglomerular granules.

The presence of acid phosphatase, beta-glucuronidase and aryl sulfatase in juxtaglomerular cell granules (JGG) as well as the uptake and concentration of certain low molecular weight dyes by these granules have repeatedly suggested that they are akin to lysosomes. In the present experiments, rats were injected with three substances of widely different molecular weight and physicochemical properties--sucrose, iron sorbitol-citric acid complex (Jectofer) and horseradish peroxidase--that are well known to selectively concentrate in renal tubular cell lysosomes. None of these substances was found to enter the JGG to any significant degree, although both sucrose and Jectofer were evident in juxtaglomerular cells. Contrary to previous reports, thorium dioxide (Thorotrast) particles were not detected in the JGG after parenteral injection. These results indicate that JGG do not possess any significant lysosomal function and raise the question of the role of hydrolytic enzymes in the physiology of these granules.

Acid Phosphatase↗
PubMed1977

Metaplasia of smooth muscle cells into juxtaglomerular cells in the juxtaglomerular apparatus, arteries, and arterioles of the ischemic (endocrine) kidney. An ultrastructural-cytochemical and autoradiographic study.

Partial ligation of the aorta between the renal arteries induces marked atrophy of the cortical tubules of the left (endocrine) kidney with a remarkable increase in the number and granularity of hypersecretory juxtaglomerular cells (JGC), which are found not only at the glomerular pole of arterioles but also in the walls of arteries and arterioles far removed from the glomerulus. Typical vascular smooth muscle cells (SMC), in which secretory granules appear, show a concomitant development of their Golgi complex and rough endoplasmic reticulum, with a gradual decrease in the number of their filaments. Microtubules also appear in the Golgi area. Thiery's periodic acid-thiocarbohydrazide-silver proteinate technique demonstrates that in these "intermediate" cells, as in mature JGC, the amount of glycogen is greater than in SMC. The newly-developed secretory granules of intermediate cells are stained by phosphotungstic acid at a low pH, as are the mature granules of JGC, an indication that both types contain glycoproteins. Light and electron microscopic autoradiography reveal that both JGC and "intermediate" cells of the vascular wall do not incorporate radioactive thymidine (injected during the 10-day observation period). Thus, they develop by metaplasia of preexistent SMC. In control kidneys, radioactive thymidine is practically never incorporated into the nuclei of SMC but is found in a few glomerular and tubular cells of all zones except the papilla.The endocrine kidney shows virtually no reactive nuclei in vascular SMC, glomeruli, or tubular cells of the outer cortex. Thymidine is incorporated into practically all nuclei of the straight portion of proximal tubules and into about half the nuclei of all medullary tubular cells including the papilla.

Animals↗
PubMed1975

Localization and characterization of carbohydrates in adrenal medullary cells.

The localization and characterization of carbohydrates in adrenal medullary cells were studied by histochemical and cytochemical methods. Adrenaline (A)-and noradrenaline (N)-storing granules were argentaphobic when ultrathin sections of Araldite-embedded medullae were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. A small amount of glycogen in the form of single beta-particles as well as lysosomes were, however, visualized by this technique. The entire core of the A granules was markedly positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA)-embedded medullae were stained with phosphotungstic acid (PTA) at low pH (0.3). The N granules, in contrast, were mostly unreactive. In the A cells, PTA stained a large part of the Golgi complex, whereas in the N cells the Golgi complex was mostly unstained. In both cell types, the cell coat, lysosomes, and multivesticular bodies reacted to PTA. The periodic acid-Schiff (PAS) technique showed A but not N granules in semithin sections of GMA- or Araldite-embedded medullae. The PTA and PAS stains were abolished by acetylation, restored by saponification, unchanged by methylation, and greatly diminished by sulfation. In ultrathin sections of GMA- or Araldite-embedded medullae incubated with colloidal iron according to various techniques, the cell coat and lysosomes of both cell types were stained, unlike all the other cytoplasmic organelles. These results indicate that A granules and the Golgi complex of A cells, unlike the same structures in N cells, are rich in glycoproteins which are probably not acidic.

Adrenal Medulla↗
PubMed1975

Comparative ultrastructural cytochemistry of juxtaglomerular cell granules and renal tubular cell lysosomes.

Because of certain similarities in morphology and function between juxtaglomerular cell granules and renal tubular cell lysosomes, the cytochemistry of both of these structures was compared. Juxtaglomerular cell granules and renal tubular cell lysosomes were found to be argentaphobic when ultrathin sections of Araldite-embedded kidneys were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiéry (Thiéry, J. P. J. Microsc. (Paris) 6: 987, 1967 and J. Microsc. (Paris) 8: 689, 1969). The rim of both structures was moderately positive when ultrathin sections of glutaraldehyde-fixed, glycol methacrylate-embedded kidneys were stained with phosphotungstic acid at a low pH. A reaction was also shown by the cell coats, residual bodies and, in proximal convoluted tubules, by the Golgi complex. In ultrathin sections of either glycol methacrylate- or Vestopal-embedded renal cortex stained by various methods with colloidal iron, juxtaglomerular cell granules were negative whereas renal tublar cell lysosomes were intesely positive. Colloidal iron also stained the cell coats of both justaglomerular and tubular cells. These results indicate that both juxtaglomerular cell granules and renal tubular cell lysosomes contain glycoproteins which are not acidic in the former and are acidic in the latter.

Animals↗
PubMed1975

The chemical nature of human atrial specific granules.

The nature of human auricular specific granules was assessed by a variety of cytochemical and histochemical methods. The specific granules were found to be argentaphobic when ultrathin sections of Araldite-embedded auricular appendages were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. The entire core of these granules was moderately positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA)-embedded auricles were stained with phosphotungstic acid (PTA) at a low pH. A similar reaction was shown by the cell coat, residual bodies (C-granules), lysosomes, Z-discs as well as by a very small portion of the Golgi complex. Analogous results were obtained in semithin sections of GMA-embedded auricles stained by the periodic acid-Schiff (PAS) technique. Incubation of ultrathin sections (fixed in glutaraldehyde and embedded in GMA) with proteolytic enzymes (pronase, pepsin, trypsin, or alpha-chymotrypsin) elicited selective digestion of atrial specific granules and Z-bands and, to a much lesser degree, of the cell coat. It is concluded that human auricular specific granules, as in rat atrial cardiocytes, are composed mostly of proteins. In addition, these granules may contain complex carbohydrates.

Chemical Phenomena↗
PubMedDate not supplied

From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging.

In the cold winter of 1966 Aleksay Olovnikov, a theoretical biologist at the Academy of Sciences in Moscow, was waiting in the subway station where he was hit by the idea that the ends of linear chromosomes can't be replicated fully during each round of replication. In a theoretical paper (Olovnikov, 1971) he proposed that in somatic cells the ends of the chromosomes are not fully replicated during DNA synthesis, resulting in the shortening of linear DNA molecules with each cell division, and that this may be the cause of cell cycle arrest in senescent cells. Almost two decades after this proposal, Calvin Harley and co-workers found that telomeres, the physical ends of human chromosomes, shorten as a function of age in human cells in vitro and in vivo. The telomere hypothesis proposes that critically short telomeres may act as a mitotic clock to signal the cell cycle arrest at senescence (Harley, 1991). Here, we extend the telomere hypothesis and propose a model that incorporates recent advances in tumor suppressors and cell cycle control with several areas of cell aging. We propose that telomere shortening per se is not the direct signal for cell cycle arrest. It is the consequence of telomere loss, which may lead to generation of ds or ss DNA breaks. These breaks activate a p53 dependent or independent DNA-damage pathway that leads to the induction of a family of inhibitors of cyclin dependent kinases (including p21 and p16) and the eventual G1 block of senescence. In agreement with this hypothesis, we demonstrate that the level of p53 protein increases in near senescent cultures of MDFs. This increase may be responsible for induction of p21 (Noda, 1993) and IGF-Bp3 (Goldstein, 1991).

Animals↗
PubMedDate not supplied

Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus.

There is now good evidence that the cellular protein, p53, is involved in the transformation process, although its precise role is unknown. It was reported recently that expression of the p53 gene can immortalize cells and that the p53 gene can replace the myc oncogene in a myc-ras immortalization/transformation assay. We have investigated whether p53 is involved in the progression towards the neoplastic state in vivo and report here that erythroleukaemic cell lines transformed by different isolates of Friend leukaemia virus show altered expression of the cellular p53 gene. High levels of p53 protein are found in certain lines, but the protein is undetectable in others. This heterogeneity in p53 gene expression is associated with heterogeneity in tumorigenicity. We demonstrate that genomic rearrangements are responsible for p53 gene inactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.

Animals↗