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G H Cope

Publications and source records attributed to G H Cope.

At least 19 recordsLinked to original sources
PubMed1992

Electron microscopic immunocytochemical localization of proline-rich proteins in normal mouse parotid salivary glands.

Rabbit polyclonal antibodies against isoproterenol-induced mouse proline-rich proteins (PRPs) were used to localize PRPs in the parotid salivary glands of normal adult BALB/c mice. The antibodies recognized both acidic-type and basic-type PRPs. Immunoblotting experiments revealed that the glands contained an acidic-type and a basic-type PRP. Parotid gland tissue was fixed with Karnosky's fixative and embedded in Lowicryl resin at low temperature. PRPs were localized at the electron microscope level using an indirect post-embedding staining technique with protein A-gold. The secretion granules of the acinar cells were strongly labelled. Pre-absorption of the antibody with purified acidic-type and basic-type PRPs indicated that the basic-type PRP is mainly located at the periphery of the granules but that the acidic-type PRP is more evenly distributed within the granules. Pre-absorption of the antibody with alpha-amylase did not affect the staining pattern, suggesting minimal cross-reactivity. PRPs were also detected within the rough endoplasmic reticulum and the Golgi apparatus of acinar cells, within the granules of the proacinar cells and in the lumena of the ducts, but not within the intercalated or striated duct cell granules.

Animals↗
PubMed1992

Effect of diatrizoate on the function of the isolated perfused rat kidney.

The mechanism of the nephrotoxicity of water-soluble contrast media (WSCM) remains ill defined. We have studied the effect of diatrizoate on the isolated perfused rat kidney (IPRK). Emphasis was on the effect of low- and high-dose diatrizoate on glomerular filtration rate (GFR), renal perfusate flow (RPF), fractional excretion of albumin (FE Alb) and fractional reabsorption of sodium (FR Na). The addition of diatrizoate to the IPRK led to a dose-dependent biphasic change in RPF and GFR characterized by an initial transient increase followed by a marked and sustained decrease. Diatrizoate induced a diuresis and a parallel increase in urinary sodium excretion (fall of FR Na). Fe Alb was also increased in kidneys exposed to diatrizoate. Electron microscopy of a control kidney showed preservation of cellular architecture, which contrasted with the observed cytoplasmic vacuolation of proximal tubular cells after perfusion with diatrizoate. This study confirms a direct effect of WSCM on the function of the IPRK. In this experimental model, diatrizoate reproduces the effects observed in vivo on GFR and renal perfusion.

Animals↗
PubMed1992

Peritoneal ultrafiltration after chronic exposure to dialysis fluid.

Eleven rats were given twice-daily intraperitoneal injections of 20 mL of dialysis fluid containing 4.5% glucose for 6 weeks. The peritoneal ultrafiltration capacity of this group was compared with that of a control group of 10 rats that had received no injections by measuring the volume and glucose concentration of the dialysate remaining in the peritoneal cavity 2 hours after injection. Animals that had received injections of dialysis fluid showed significant loss of peritoneal ultrafiltration: volume of dialysate remaining in the control group was 31 (13-35) mL, and in the experimental group was 25 (11-45) mL, with p less than 0.02 (Mann-Whitney). This was associated with enhanced glucose absorption: glucose absorbed by the control group was 382 (312-706) mg, and 595 (435-738) mg in the experimental group (p less than 0.002, Mann-Whitney).

Animals↗
PubMed1991

Role of growth hormone in the development of experimental renal scarring.

Recent experimental data has implicated growth hormone in the development of glomerular sclerosis. In this study, we have examined the development and progression of glomerular and tubulointerstitial scarring in Wistar and Dwarf rats, selectively growth hormone-deficient, following subtotal nephrectomy. Wistar rats showed progressive proteinuria, hypertension and renal failure as well as severe renal scarring 120 days after subtotal nephrectomy. In contrast, growth hormone-deficient Dwarf rats had minimal proteinuria, mild renal functional impairment and moderate renal histological scarring. The difference in these functional and structural parameters between the two strains is highly significant, although both experimental groups had comparable food consumption and systemic blood pressure. The significantly smaller glomeruli and limited kidney hypertrophy over 120 days observed in Dwarf rats may account for some of the protection against glomerular sclerosis and tubulointerstitial scarring observed in that strain.

Animals↗
PubMed1991

Mesothelial hyperplasia in response to peritoneal dialysis fluid: a morphometric study in the rat.

Five rats were given twice daily intraperitoneal injections of hypertonic dialysis fluid for 6 weeks. The structure of the hepatic peritoneum of this group was compared with that of a control group by applying morphometric techniques to transmission electron micrographs. The experimental group showed marked mesothelial hyperplasia with doubling of the number of cells and a significant increase in the length of intercellular junction per unit area of peritoneum. Since cell volumes in the two groups were similar, the increase in cell density in the experimental animals was the result of the cells assuming a more cuboidal shape. Experimental animals also showed an increase in the number of microvilli, pinocytotic vesicles and rough endoplasmic reticulum per unit area of peritoneum. Chronic exposure to dialysis fluid has profound effects on the number, shape and composition of peritoneal mesothelial cells in the rat.

Animals↗
PubMed1991

Beta-adrenergic regulation of beta-actin mRNA abundance in mouse parotid glands by a post-transcriptional mechanism.

In the first 24 h after a single injection of the beta-adrenergic agonist isoprenaline to mice, the level of beta-actin mRNA in the parotid glands increased significantly above that observed in untreated mice. The increase was transient, reaching 11 times the normal level 18 h after treatment and declining thereafter. Repeated daily doses of isoprenaline did not result in any further increase in beta-actin mRNA. Nuclear transcription experiments showed that there was no increase in the transcription rate of the beta-actin gene 8 h after an injection of isoprenaline, although beta-actin mRNA levels were increasing at this time. Immunoblotting revealed an increase in beta-actin protein in parotid gland samples after isoprenaline treatment, although the increase was not to the same extent as the mRNA, perhaps indicating that degradation of beta-actin had also increased. Using immunocytochemistry it was found that beta-actin was located mainly in the apical cortex of the normal acinar cell. There was a significant decrease in cortical beta-actin 24 h after isoprenaline treatment, suggesting that the beta-actin was under the process of redistribution. From these data we propose that isoprenaline caused an increase in beta-actin synthesis by a posttranscriptional mechanism and a redistribution of beta-actin in preparation for the well-known subsequent change in morphology and function of the parotid glands.

Actins↗
PubMed1990

Morphometric studies on the development and sexual dimorphism of the submandibular gland of the mouse.

A light microscopic morphometric analysis of the development of the mouse submandibular gland has been carried out from birth up to the age of 6 weeks. At birth the bulk of the gland consists of approximately equal volume proportions of acinar, terminal tubule and non-secretory cells. The granular convoluted tubule is absent at birth. The neonatal female gland resembles that of the male in many respects. With the regression of the terminal tubule at 2 weeks of age the duct system of the gland is seen to differentiate into excretory, striated and intercalated ducts. The volume proportions of the gland constituents of the female are similar to those of the male at 2 weeks. At this age, the acini occupy 55%, the striated duct 20% and the intercalated duct 15% of the total gland volume. Sexual dimorphism is clearly evident in the gland at 4 weeks of age when the duct system is seen to differentiate to form its granular convoluted tubule component. The granular tubule occupied 19% of the gland volume in the male but only 8% in the female at 4 weeks. The proportions of acini are only 41% in the total gland volume of the male mouse but 62% in the female at 4 weeks. In the male gland the proportions of granular convoluted tubule increase from 13% to 21% between 4 and 6 weeks and the secretory granule content of these cells from 6% to 24%. At 6 weeks of age the volume proportion of granular convoluted tubule in the male is 45% and that in the female is only 12%. At this age the acini occupy a proportion of 30% in the male gland as opposed to 57% in the female gland. At 6 weeks the volume of granular convoluted tubule cells is 40% lower in the female (1842 microns 3) than in the male gland (2995 microns 3).

Animals↗
PubMed1989

The ultrastructure of human abdominal mesothelium.

Fresh specimens of human peritoneum collected from heart-beating cadaver organ donors have been examined by transmission electron microscopy. Samples were taken from the anterior abdominal wall and from the surfaces of the liver, stomach and diaphragm. The mesothelium consisted of a single layer of flattened cells generally 2.5 microns to 3 microns thick. These were joined by tight junctions and desmosomes to form a continuous sheet. The cells rested on a prominent basement membrane deep to which was a layer of fibrous connective tissue. This layer was more compact under the mesothelium from the abdominal wall and liver than elsewhere. Long microvilli projected from apical surface of the cells. In many cases these covered the entire surface but sometimes they were more profuse at the edges of the cells near the intercellular junctions. The cells possessed a well-developed cytoskeleton of intermediate filaments which coursed through the cytoplasm in thick bundles. The cells also had a well-developed rough endoplasmic reticulum and Golgi apparatus. Numerous smooth-surfaced and coated vesicles could be seen adjacent to the plasmalemma at all surfaces, providing evidence of considerable pinocytotic activity. There was little regional variation in the structure of the mesothelium. We found no evidence of pores passing through the layer although, on the liver, cisternae were present between the cells and these were often occupied by lymphocytes.

Adolescent↗
PubMed1987

Changes in the size and number of secretion granules in the rat exocrine pancreas induced by feeding or stimulation in vitro. A morphometric study.

The size, number and volume per cell of secretion granules in rat exocrine pancreas have been measured using stereological techniques. The changes which occur as a result of feeding starved animals (90 min) or stimulating lobular fragments in vitro with carbachol are documented. In fasted animals mean acinar cell volume was estimated as 1670 micron 3 and the cells contained an average of around 450 secretion granules with a corrected mean diameter of 0.70 micron. They occupied around 7% of cell volume. After feeding mean cell volume was about 1300 micron 3 and the cells contained an average of about 190 granules per cell with a mean diameter of 0.58 micron. They occupied 3% of cell volume. A shift in the size frequency distribution of granule diameters occurred as a result of feeding. In vitro experiments in which lobules were induced to secrete with carbachol (10 microM, 3 h, 37 degrees C) had a similar effect. Mean cell volume was reduced from around 1760 micron 3 to 1360 micron 3, mean granule number from around 420 per cell to 180 per cell and the volume density of granules was reduced from about 8% to 3% of cell volume. There was no significant change in mean granule diameter or shift in the size-frequency distribution of granule diameters. Incubation of tissues with cycloheximide (1 mM, 3 h, 37 degrees C) did not prevent secretion by carbachol but it prevented replacement of granules. As a consequence, depletion by carbachol was greater in the presence of cycloheximide, the granules being reduced to around 110 per cell and to only 2.5% of cell volume. We conclude that feeding causes a preferential loss of larger granules and that during secretion replacement of granules occurs. Some of these granules are smaller than those evident in the glands of starved animals.

Animals↗
PubMed1984

Effect of glucose on insulin biosynthesis and beta cell ultrastructure in cultured fetal rat pancreas.

Pancreatic rudiments from 14-day fetal rats were cultured whole for 8 days in medium containing 5.5 or 16.5 mmol glucose/l (1G or 3G medium). Rudiments grown in 3G medium (3G cells) contained more DNA and insulin than those grown in 1G medium (1G cells) but there was no alteration in the insulin/DNA ratio or the fractional area of the rudiment occupied by insulin-containing cells. Morphometric analysis of ultrastructure revealed that the beta cells grown in 3G medium were smaller and had smaller nuclei than those grown in 1G medium. The size of exocrine cell nuclei in 1G or 3G medium was similar. Insulin granules occupied a greater proportion of the cytoplasmic volume in rudiments grown in 3G medium although the mean absolute volume of insulin granules per cell grown in 1G and 3G media was similar. Hence the residual cytoplasmic volume (cell--nucleus and granules) of 3G cells was less than that of 1G cells. Insulin granules from 3G cells had smaller granule sacs and cores than those from 1G cells. It is concluded that glucose stimulates the growth of rat fetal pancreas in vitro and has important effects on beta cell ultrastructure.

Animals↗
PubMed1983

Exocrine glands and protein secretion: a stereological viewpoint.

The exocrine pancreas and the parotid salivary gland have been widely used as models for studying the synthesis, intracellular transport and discharge of exportable proteins. This article briefly reviews quantitative morphological (stereological) studies which have been made of these glands and assesses their contribution to our understanding of the secretory process. A general stereological profile of these glands is presented and the way in which their morphology changes during development is outlined. Detailed consideration is given to the granule population of the cells, particularly the way in which granules are formed and discharged as a result of secretory stimuli. The membrane content of secretory cells and membrane dynamics during the secretory cycle are also examined. Throughout, the emphasis is placed on the interpretation of stereological data rather than on the methods themselves.

Animals↗
PubMed1979

Comparative studies on the nature of purified cytomembranes of the rabbit parotid gland.

Centrifugation procedures have been evolved for isolating purified samples of rough endoplasmic reticulum, Golgi, zymogen granule and plasmalemmal membranes from homogenates of rabbit parotid gland tissue. The purification process was monitored using morphometry and enzyme and chemical marker assays. The membrane preparations were analysed by sodium dodecylsuphate (SDS) polyacrylamide gel electrophoresis, quantitative phospholipid thin layer chromatography and by enrichment studies. The results were used to evaluate various possible general models for the behaviour of membranes during the secretory cycle of parotid acinar cells.

Animals↗
PubMed1978

Stereological analysis of the duct system of the rabbit parotid gland.

The duct system of the rabbit parotid gland constitutes about 5% of gland tissue volume and is divisible into intercalated and striated ducts in a volumetric ratio of about 3:2. The intercalated duct consists of low cuboidal epithelial cells (375 micrometer 2) surrounded by a myoepithlium, and the cells contain a few small secretion granules, particularly at the proximal end of the duct. The cells of the striated duct are larger (531 micrometer 3), columnal in shape, and show a mitochondrial compartment three times that of intercalated duct cells (16.5% of cell volume). These mitochondria are concentrated in a basal and perinuclear position, but they are largely absent from the apical cytoplasm, which is permeated with microfilaments and contains numerous small smooth membraned vesicles, but no clearly recognisable secretion granules. The lateral plasmalemma of these cells is complexly folded, and basal processes interdigitate with those of adjacent cells. This results in an increase in the ratio of apical to lateral/basal plasmalemma from 1:5 in intercalated cells to 1:24 in striated cells. Some slight changes in cell morphology were detected following isoprenaline-induced secretion of the gland in vivo. These included a small increase in the volume fraction of nuclei and mitochondria in intercalated duct cells, and depletion of their secretion granules. Change in striated cells was confirmed to a small increase in the volume of smooth membraned cytoplasmic vesicles. The structure of the duct and changes wrought by isoprenaline are discussed in the context of the role of the duct in the production of saliva.

Animals↗
PubMed1977

Compartmentation of enzymes in the rabbit parotid salivary gland. A study by enzyme histochemical, tissue fractionation and morphometric techniques.

Rabbit parotid gland was chosen as a suitable model tissue for studying the role of membranes in enzyme secretion by acinar cells. The study was initiated using subcellular fractionation techniques. During these experiments the effects of various tissue disruption conditions such as the medium and the duration and vigour of homogenization were explored and the results assessed by enzyme and chemical assays and both quantitatively and qualitatively by electron microscopy. A series of basic fractions was isolated and marker enzyme or chemical assays selected for each of the relevant membrane types (rough endoplasmic reticulum, Golgi apparatus, zymogen granule, plasmalemma). A parallel study was effected using enzyme histochemical methods applied to frozen sections. Interesting comparisons could then be made between histochemical and biochemical methods of enzyme demonstration. These comparisons are discussed. The basic fractions provide the material from which specimens of purified membranes of the four species can be obtained. The isolation and characterization of such purified membranes is the subject of another report.

Acid Phosphatase↗
PubMed1977

Stereological analysis of the mitochondrial compartment of the rabbit parotid gland before and after isoprenaline-induced degranulation.

A stereological analysis of the mitochondrial compartment of the rabbit parotid gland has been carried out before and after isoprenaline-induced degranulation. Normally, mitochondria constitute about 5% of acinar cell volume, 6% of intercalcate duct cell volume and 16% of striated duct cell volume. The ratio of inner electron transport membrane to outer limiting membrane is in the range 2.3:1. Two hours after the induction of secretion by isoprenaline a significant (P less than 0.10) increase in the volume fraction of mitochondria in acinar and intercalated duct cells was noted and this may reflect increased oxidative phosphorylation at this time. Other parameters measured suggest that there is some rounding up of mitochondria Another significant feature was an increase in the number of damaged mitochondrial profiles (+80% to +250%, P less than 0.05) after isoprenaline treatment. This finding is discussed in the context of changes in mitochondrial enzyme levels which have been reported in similar situations.

Animals↗