Search PubMed⌕ Search

Biomedical subjects

M D Bentley

Publications and source records attributed to M D Bentley.

At least 37 records · Page 2Linked to original sources

Comparison of the effects of calcium antagonists and converting enzyme inhibitors on renal function under normal and hypertensive conditions.

Calcium antagonists decrease the ability of the kidney to autoregulate renal blood flow (RBF) and glomerular filtration rate (GFR). Therefore, when afferent renovascular resistance is elevated, as in essential hypertension, there is a resultant increase in RBF and GFR with the administration of calcium antagonists. These agents also induce a marked natriuresis because of direct tubular action through unknown mechanisms. The natriuresis can be dissociated from renal and systemic hemodynamic actions, indicating that the decreased sodium reabsorption could override other compensatory mechanisms explaining the absence of sodium retention during the treatment. The renal effects of converting enzyme inhibitors (CEIs) can be explained by the reduction of intrarenal formation in angiotensin II. Because the activation of the renin-angiotensin system is mainly responsible for inducing sodium retention during a decrease in systemic blood pressure, CEIs could have a protecting effect without disturbing other homeostatic mechanisms. CEIs decrease efferent glomerular resistance, reducing capillary pressure and thereby reducing GFR. This effect is not translated in sodium retention because the reduction of GFR is mild during captopril administration in kidneys with normal or increased renal perfusion pressure. At low renal perfusion pressure, the reduced glomerular afferent vasoconstriction can compromise GFR, leading to renal insufficiency. Although these situations are not likely to be encountered during the treatment of uncomplicated essential hypertension, in severe hypertension with hypertrophy of pre-glomerular vessels, glomerular perfusion may decrease. Combination therapy of calcium antagonists and CEIs has been reported to be an effective treatment of severe hypertension. Currently, little information is available on the manner in which renal function is affected by simultaneous administration of both drugs.

Angiotensin II↗

Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor.

The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation.

Animals↗

Estimation of tissue volume from serial tomographic sections. A statistical random marking method.

Computer operator-interactive planimetric methods that have been employed to measure volume of a selected tissue in serial computed tomographic sections are time consuming, and the accuracy of the measurement is limited by the operator's skill in outlining the tissue. We introduce an alternate method that is 5 to 6 times faster than planimetry and is independent of the operator's outlining dexterity. This method involves the random marking of voxels in a three-dimensional array of known size and subsequent identification of the proportion of those voxels that are within the tissue of interest. Tissue of the kidney and left ventricular myocardium were imaged in situ with a high speed, volume scanning, computerized x-ray tomographic imaging system. Volumetric measurements made by the random marking method correlated highly (r = 0.99) with measurements made by planimetry and with postmortem weight. These data indicate that the random marking method provides a rapid and accurate means of estimating tissue volume in serial tomographic sections.

Animals↗

Possible modulatory role of angiotensin II on atrial peptide-induced natriuresis.

Studies showing that atrial natriuretic peptides (ANP) induce a suppression of the renin-angiotensin system suggest that there might be a modulatory influence of angiotensin II (ANG II) on the natriuretic effect of the ANP system. To evaluate this possibility we assessed, in anesthetized dogs, the net increments in fractional excretion of sodium (FENa) and lithium (FELi) produced by ANP and by the inhibition of ANG II formation with captopril. These agents were infused at separate time periods into the renal artery at a maximal level that has been shown not to alter glomerular filtration rate (GFR). ANP caused an increment in FENa of 4.0 +/- 0.2, whereas captopril caused a much smaller increase of 0.2 +/- 0.04, indicating that most of the natriuretic effect of ANP is unlikely to be solely accounted for by inhibition of ANG II. The administration of both ANP and captopril produced increases in the FELi used as a marker for proximal tubular reabsorption. An infusion of ANG II superimposed on the infusion of captopril reduced the FENa from 1.5 +/- 0.3 to 0.8 +/- 0.1. Under these conditions the administration of ANP produced an increment of 2.7 +/- 0.4 in the FENa. This increase in FENa is 32.5% less than the net increase obtained when ANP was given in the absence of ANG II, whereas under these conditions FELi remained statistically unchanged. These results suggest that the modulatory activity of ANG II on the natriuretic affect of ANP could be negligible under normal conditions.

Angiotensin II↗

Contraction of isolated canine renal arteries induced by the radiocontrast medium sodium diatrizoate and meglumine diatrizoate.

The contractile effects of a commonly used radiographic contrast medium, sodium diatrizoate and meglumine diatrizoate, were examined on isolated canine renal arteries. Rings of renal artery, with and without endothelium, were mounted in organ chambers filled with Krebs-Ringer bicarbonate solution to record isometric tension. Both preparations contracted comparably to increasing concentrations (10(-9) to 10(-4) mol/L) of norepinephrine, and only rings with endothelium relaxed with the application of acetylcholine. The contractile responses of the rings to increasing concentrations of either contrast medium or osmotically matched solutions of glucose were similar, suggesting that the primary factor for contraction was the osmolality of the bathing solution. No significant differences were observed between the responses of rings with and without endothelium, suggesting that the endothelium did not influence the contractile response. After exposure to the hyperosmotic solutions, rings were again tested for relaxation with acetylcholine. Rings that were prepared with endothelium relaxed with the application of acetylcholine, suggesting that functional properties of the endothelium were not affected by the hyperosmotic media. The results of this study indicate that the vasoconstrictor effects of radiographic contrast media such as meglumine/sodium diatrizoate are related to increased osmolality and are not influenced by the presence of endothelium.

Animals↗

Isolation and identification of the principal siderophore of the dermatophyte Microsporum gypseum.

The dermatophyte Microsporum gypseum has been shown to produce two siderophores under conditions of low-iron stress. These compounds have been separated as Fe(III) complexes on silica gel, and the principal siderophore has been identified as ferricrocin using the methods of amino acid analysis, comparative thin-layer chromatography, partial sequencing by gas chromatography-mass spectrometry, ultraviolet spectroscopy, and proton nuclear magnetic resonance spectroscopy of the Al(III) complex.

Amino Acids↗

The vasopressin-sensitive adenylate cyclase in collecting tubules and in thick ascending limb of Henle's loop of human and canine kidney.

The major tubular effects of [8-Arg]vasopressin (AVP) in regulation of renal water excretion are initiated by stimulation of adenylate cyclase (AdC) coupled with V2 receptors. We explored whether the AVP-sensitive AdC is present in both collecting tubules and the thick ascending limb of Henle's loop of human and canine kidney. In cortical collecting tubule (CCT) and medullary collecting tubules (MCT) of human kidney, AdC was markedly stimulated by AVP [maximum change from basal level (delta), +2700%] and the the nonhormonal stimulatory agent forskolin (delta, +2000%). In human CCT, the effects of both compounds were synergistic. In contrast, AVP had no effect on AdC in either the medullary (MAL) or cortical (CAL) segment of the thick ascending limb of Henle's loop of human kidney; AVP also did not stimulate AdC in CAL or MAL in the presence of forskolin. Similar to that in the human kidney, in the canine kidney, AdC in CCT and MCT was markedly stimulated by AVP and forskolin (delta, +1000%), but AVP had no effect on AdC in CAL and MAL of the canine kidney. In intact tubules dissected from dog kidney and incubated in vitro, AVP markedly increased cAMP accumulation in MCT. AVP also elicited a small but detectable increase in cAMP accumulation in MAL. From these observations, we conclude that AVP-sensitive AdC is well developed in collecting tubules, but that AVP-sensitive AdC is absent in MAL and CAL of human kidney. Likewise, in canine nephron, the AVP-sensitive AdC of MAL and CAL is rudimentary or very labile. These findings suggest that the unresponsiveness of the AdC-cAMP system to AVP in segments of the thick ascending limb of Henle's loop may be a factor that accounts for a relatively low maximum osmotic concentration of urine which can be achieved by human or canine kidneys.

Adenylyl Cyclases↗

The relationship of epithelial cell types in the ventral prostate glands of castrated mice treated with testosterone.

The purpose of this study was to determine the relationship of epithelial cell types in the ventral prostate glands of castrated mice treated with testosterone during the period of maximum DNA synthesis, mitosis, and restitution of the epithelium. Of 33 adult mice, ten were used as normal controls, six were used as castrated controls at day zero of treatment, and 17 castrates were treated with testosterone for 1 through 8 days. Selected normals, castrates, and treated mice were injected with 3H-thymidine prior to their sacrifice. Tissue samples from each mouse were processed for electron microscopy and autoradiography. The epithelium of the ventral prostate glands after testosterone treatment had four cell types: basal, intermediate, mitotic, and columnar. Intermediate and mitotic cells were most frequent during the second, third, and fourth day of androgen treatments. Basal and columnar cells were observed in normal, castrates, and androgen-treated mice. The restitution of the epithelium included an initial phase of cell growth which was essentially complete by the fifth day of hormone treatment. During the growth phase many basal and columnar cells synthesized DNA and became mitotic. Columnar cells increased their cell height and showed variable amounts of organelles and inclusions. The growth phase was followed by the secretory phase in which columnar cells contained abundant supranuclear organelles and inclusions and appeared as secretory cells much as those observed in normal prostate. The restitution process of the prostate glands of castrates was completed by the eighth day of hormone treatment.

Animals↗

Production and isolation of siderophores from the soil fungus Epicoccum purpurascens.

A large number of iron transport agents, siderophores, which stimulated the growth of Arthrobacter flavescens JG-9, were isolated during a study of the antitumor activity associated with the metabolic products of the fungus Epicoccum purpurascens. The production of the siderophores was significantly enhanced in a variety of media by culture of the fungus in the near absence of ferric iron. A novel method of purification involving a carboxylic ion-exchange resin separated the siderophores into four subgroups. The first subgroup, which contained the majority of the activity, was subsequently resolved in a similar manner with the carboxylic resin into seven individual siderophores. Of these, two were characterized as ferricrocin and coprogen whereas the others appeared to represent new compounds. One of the latter was given the name triornicin and exhibited slight antitumor activity in mice injected with Ehrlich ascites tumor cells.

Arthrobacter↗

Structure of triornicin, a new siderophore.

Spectroscopic analysis of the tumor inhibitory factor triornicin produced by epicoccum purpurascens indicated that it was of similar structure to the known siderophore desferricoprogen, which is also produced by the fungus. The 1H and 13C NMR spectra indicated the replacement of an (E)-5-hydroxy-3-methyl-2-pentenoyl moiety of the desferricoprogen structure with an acetyl function. Cleavage of triornicin with basic methanol produced two fragments. The first was identified as a natural siderophore, dimerumic acid, which was also produced by basic cleavage of desferricoprogen. The second compound was identified as N alpha, N delta-diacetyl-N delta-hydroxyornithine. The structure of these fragments serves to define the structure of triornicin as a new siderophore.

Hydroxamic Acids↗

Freeze-fracture, ultrastructural and autoradiographic analysis of the ventral prostate glands in castrated mice.

Ultrastructure of the ventral prostate glands was studied in mice castrated for 1 through 60 days and for 11 and 17 months and in age-matched normals. We have described freeze-fracture and ultrastructural characteristics of acinar epithelial cells in addition to the patterns of thymidine incorporation in the cells of castrates and normal animals. Our study has shown a biphasic pattern of prostatic involution in the long-term castrated mice. In castrates the initial atrophy of prostate glands occurred by sloughing of the apical portions of columnar cells, autophagia of the cytoplasmic organelles as well as by occasional sloughing of the individual cells into the acinar lumen. Concurrent with the initial atrophy, the glands and stroma were infiltrated by neutrophils and lymphocytes. The cell loss by sloughing and leucocyte infiltration of glands became infrequent in 7- to 21-day castrates. However, the cell loss by sloughing increased secondarily in mice castrated for 21 to 37 days along with the increased leucocyte infiltration of the glands. The cell loss became minimal in castrates of 60 days and beyond. Our evidence suggests that the cell loss by sloughing was an active process in the involution of prostate glands which also showed differential sensitivity to castration stimuli in mice.

Animals↗

Freeze-fracture observations on the membranes and junctions in human prostatic carcinoma and benign prostatic hypertrophy.

In human prostatic carcinomatous acini, the columnar cells possessed a loosely organized meshwork of ridges and grooves and many isolated, short, and disorganized strands of tight junctions, unlike those of benign prostatic hypertrophy (BPH), where the tight junctional ridges and grooves were numerous and compact. Desmosomes were more irregular in size, shape and distribution in cancerous cells than in BPH. Our observation indicated that the junctional complexes were altered and defective in cancerous cells and probably facilitated migration of some acinar cells into the stroma. In addition, we have also shown that the membranes including the intramembranous particles of Golgi complexes, mitochondria, secretory granules and vacuoles, lipofuscin granules and nuclei, were essentially similar in cancerous and BPH columar cells.

Adenocarcinoma↗

Qualitative and quantitative studies on human myelin basic protein in situ with respect to time interval between death and autopsy.

Normal human frontal lobe white matter obtained at autopsy was used to determine the extent of in situ post-mortem degradation of myelin basic protein (BP). Effects of the following two factors were studied: 1) time interval between death and autopsy, and 2) freezing and thawing the tissue. Quantitative extraction of BP from the autopsy material showed only minimal loss of BP that could be attributed to the time interval between death and autopsy (up to 48 h). The purified BP from these samples was electrophoresed on acrylamide gels at pH 4.3 and it was found that the electrophoretic patterns were comparable to zero hour bovine BP samples. The BP obtained from the autopsy samples was found to be encephalitogenic in guinea pigs. When tested against rabbit anti-human-BP serum, the purified BP preparations gave a single arc in immunoprecipitin test. BP extracted and purified from tissue that was frozen once and processed before it could thaw showed yields, encephalitogenic activity and acrylamide disc gel electrophoretic patterns that were similar to those of BP from tissue that was never frozen. However, frozen tissue that was thawed and then incubated for 8 h at room temperature before processing yielded only 13-25% of the total extractable protein. This BP also was encephalitogenic and showed acrylamide banding pattern that was similar to BP from tissue that was never frozen. Samples of white matter were examined by electron microscope. Unfrozen autopsy material showed some separation of myelin lamellae. Myelin in sections of frozen and thawed white matter showed separation as well as disruption of the lamellae. Samples that were frozen, thawed and then incubated at room temperature for 8 h showed sporadic loss of dense line material in addition to lamellar separation and disruption. The results a) show that BP is quite resistant to autolytic changes and b) are consistent with the location of BP along the cytoplasmic surface of the myelin membrane.

Aged↗