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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 199 records · Page 11Linked to original sources

Mechanism and contribution of the pentose phosphate cycle to glucose metabolism in epididymal fat tissue.

1. Glucose 6-phosphate, fructose 6-phosphate and altroheptulose 7-phosphate are the major products formed non-oxidatively from ribose 5-phosphate by rat epididymal fat pad enzymes. 2. Arabinose 5-phosphate was detected among the reaction products and significant activity of the new enzyme of the L-type pentose pathway, D-glycero D-ido octulose 1,8-bisphosphate: D-altroheptulose 7-phosphotransferase was found. 3. The glucose moieties of glucose 1-phosphate, glucose 6-phosphate and glucose 1,6-bisphosphate were degraded and showed that epididymal fat pad enzymes relocate 14C from [2-14C]glucose into C-1, C-2, and C-3 of each hexose-phosphate. 4. The 14C-distribution patterns in the hexose-phosphates revealed that these intermediates were not in isotopic equilibrium and the rate of the transaldolase exchange reaction was relatively small. 5. The 14C-distribution data suggest that glucose 1-phosphate, rather than glucose 6-phosphate, is the first intermediate in the path of glycogen synthesis from glucose in this tissue. 6. The data provide the first proof of the mechanism of the pentose pathway in adipose tissue.

Adipose Tissue↗

Hydroxyproline and passive stiffness of pressure-induced hypertrophied kitten myocardium.

Passive stiffness and hydroxyproline content of myocardium hypertrophied by pressure-loading were determined in kittens 2, 8-16, and 24-52 wk after pulmonary artery banding, which initially elevated right ventricular systolic pressure by 10-15 mm Hg. Right ventricular mass increased by approximately 75%, three-quarters of which occurred during the first 2 wk after banding. Passive stiffness was assessed from resting length-tension relations of isometrically contracting isolated right ventricular papillary muscles. Stiffness constants, alpha and beta were determined from the relationship sigma = alpha (e beta epsilon - 1) where sigma = stress and epsilon = Lagrangian strain. Elastic stiffness (d sigma/d epsilon) was derived from: d sigma/d epsilon = beta sigma + beta alpha. Right ventricular hydroxyproline increased in proportion to muscle mass so that hydroxyproline concentration remained unchanged after banding. Both alpha, beta, and elastic stiffness-stress relations were similar to values in nonbanded controls. Thus, we did not observe an increase in passive stiffness or hydroxyproline concentration of pressure-stiffness or hydroxyproline concentration of pressure-induced hypertrophied myocardium in contrast to most previous studies.

Animals↗

Number and distribution of IgM cells and IgA cells in colonic tissue of conditioned sex- and breed-matched dogs.

Colonic tissue from 3 male and 3 female Beagle dogs was stained for immunoglobulin (Ig)A and IgM cells. The colonic mucosa was divided vertically into 3 zones with an ocular reticule. The mean numbers of IgA and IgM cells and the mean percentages of the total number of the IgA or IgM cells were determined for each zone. (A comparison of IgM cell counts obtained by 2 investigators gave evidence that the results were consistent between different counters.) Comparison of the data from males with data from females showed that there was no difference for IgM cells, but that young, male dogs had more IgA cells that did old, female dogs in that portion of the colonic mucosa that was closest to the colonic lumen. The number and pattern of IgA cells were similar to those found in a previous study of IgA cells which used male, mixed-breed dogs, ie, there were fewer IgA cells in the lamina propria closest to the colonic lumen than in the deeper lamina propria. The distribution of IgM cells showed a similar nonuniform trend. Finally, there were fewer IgM cells than IgA cells in the deeper lamina propria; however, the percentages of the total number of IgA and IgM cells found in each zone were equivalent.

Animals↗

Taenia taeniaeformis (Cestoda) in the rat: ultrastructure of the host-parasite interface on days 1 to 7 postinfection.

Ultrastructural observation were made on the host-parasite interface from 1 to 7 days postinfection (DPI) with Taenia taeniaeformis in the rat. Over this period the organism developed from a multicellular oncospheral mass, equivalent in size to a host hepatocyte, into a fluid-filled, grossly visible vesicle, the walls of which showed the arrangement of syncytial tegument, cytoplasmic bridges and subtegumental cell bodies typical of older cestodes. Microvilli, often branched, extended from the free, tegumental surface of the parasite from 1 DPI onwards. Fragments of the microvilli were pinched off distally, and became segmented and distended. Some were seen in intercellular spaces as far as 40 micrometers from the free tegumental surface; others were ingested by nearby host phagocytic cells, and appeared to swell and rupture within phagosomes. Microvillar branching was less frequent after 4 DPI and the microvilli became progressively shorter. By 7 DPI the tegumental surface had become irregular and the microvillar bases were broad and knoblike. Electron-dense deposits were present on the outer membrane of microvilli, the tips of which had become truncated or globular. Although phagocytic host cells were seen in migratory tracks and in contact with some organisms as early as 1 DPI, they caused no detectable damage to the parasites. However, many host cells, including hepatocytes and endothelial cells, were injured or destroyed; their contents contributed to the debris surrounding the parasite at all stages. Inclusions, probably lipid, appeared within the tegument and subtegumental cell bodies from 3 DPI onwards, and similar droplets were seen in adjacent host cells. The great increase in surface area of postoncospheral forms over the first week of infection, augmented by the display of multiple, microvillar projections, may provide not only or the absorption of nutrients required for growth, but also for the enhanced release of factors that affect survival of host cells and stimulate immunological defense mechanisms.

Animals↗

Effect of quinidine on positive inotropic action of digoxin.

To determine whether digoxin-quinidine interaction alters the inotropic effect of the glycoside, the response of peak isometric force and maximal rate of force development (dF/dt) in isolated feline right ventricular papillary muscles to digoxin and quinidine alone, and in various combinations, was examined. The administration of 1.3 or 2.6 x 10(-5) M of quinidine after 2 x 10(-7) M of digoxin resulted in an increase in contractile performance in each animal. Although 1.3 x 10(-5) M of quinidine alone produced a positive inotropic effect, 2.6 x 10(-5) M of quinidine produced no such effect. Because myocardial digoxin content has been reported to decline after administration of quinidine these results suggest that the increase in contractile performance when quinidine was administered after digoxin is due to displacement of digoxin from less to more active myocardial sites. The administration of 2 or 4 x 10(-7) M of digoxin after 2.6 x 10(-5) M of quinidine resulted in a minimal increase in force and rate of force development. A similar inhibition of the inotropic effect of digoxin was found in rabbit papillary muscles pretreated with quinidine. Inhibition was not limited to digoxin because pretreatment of muscles with quinidine also inhibited the inotropic effect of acetylstrophanthidin. Thus, quinidine has diametrically opposite effects on digitalis-induced inotropy dependent on the sequence with which the drugs are administered.

Animals↗

Depression of hepatic mixed-function oxidase activity by B. pertussis in splenectomized and athymic nude mice.

Administration of Bordetella pertussis (B. pertussis), Corynebacterium parvum (C. parvum), and several other immunoactive substances is known to cause a marked decrease in the activity of the hepatic microsomal mixed-function oxidase system. The effect of C parvum has been reported to involve the reticuloendothelial system. In the present study, the effect of B. pertussis administration to decrease hepatic microsomal drug metabolism was studied in unoperated, sham-operated, and splenectomized mice as well as in athymic nude (nu/nu) mice and their phenotypically heterozygous (+/nu) littermates. Administration of B. pertussis to the splenectomized, sham-operated, and unoperated mice resulted in a decrease in the activity of the microsomal enzyme system that was approximately the same for each of the three groups of animals. Administration of B. pertussis to nu/nu mice and the +/nu mice also decreased the microsomal enzyme activity measured 24 hr after injection. However, at 7 days after B. pertussis administration, the hepatic drug-metabolizing activity of the nu/nu mice was not significantly different from control values, whereas the activity of the +/nu mice was still significantly depressed. The failure of splenectomy to prevent the decrease in microsomal mixed-function oxidase activity caused by B. pertussis indicated that the effect of this agent differs from that of C. parvum, whose effect was prevented by splenectomy. Indeed, the results obtained with the athymic nude mouse suggests that the depression of hepatic mixed-function oxidase activity by B. pertussis may involve T-cell dependent responses.

Adjuvants, Immunologic↗

Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth.

A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7-21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27-45%; glycolipid 5-11%; and phospholipid 50-61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.

Animals↗

Passive stiffness of pressure-induced hypertrophied cat myocardium.

The effect of myocardial hypertrophy on passive stiffness was determined from the stress (sigma)-strain relationship of right ventricular papillary muscles from 18 pulmonary artery-banded and 21 non-banded cats. By use of Lagrangian strain, (1-lo)lo is initial muscle length, and instantaneous stress elastic constants beta and alpha were calculated from the equation sigma = alpha(ebeta epsilon - 1). Elastic stiffness (d sigma/d epsilon) was determined from the formula d sigma/d epsilon = beta alpha + alpha beta. Banding produced an average increase in RV mass of 70%. Beta averaged 14.2 +/- 0.9 (SEM) and 16.0 +/- 0.8 in the non-hypertrophied and hypertrophied muscles, respectively (NS). However, elastic stiffness was significantly greater in hypertrophied muscles over the entire stress range. Contractile function varied widely among hypertrophied muscles but was not related to changes in stiffness. Thus, moderate degrees of pressure-induced hypertrophy are associated with a modest increase in the passive stiffness properties of the muscle, independent of changes in contractile function.

Animals↗

A simplified method for staining mast cells with astra blue.

The copper phthalocyanin dye astra blue has been used to stain differentially mast cells of the intestine; however; the procedure has not been used widely because of the difficulty in preparing and using the dye solution. Described here is a simple, reliable, and consistent method for selectively staining mast cells using a dye solution that may be prepared in any laboratory without the aid of sophisticated pH metering equipment. Astra blue is mixed with an alcoholic solution containing MgCl2-6H2O and the pH indicator pararosaniline hydrochloride. Concentrated hydrochloric acid is added dropwise, changing the dye mixture from purple to violet and then to blue. In this low range the weakly ionizing ethanol provides a more stable hydrogen ion concentration than the corresponding aqueous solutions used previously. Alcoholic acid fuchsin is a convenient counterstain, and this simple procedure then provides good contrast between the blue staining mast cell granules and the red tissue background.

Animals↗

Differences in susceptibility of rat strains to experimental infection with Taenia teaniaeformis.

Age-matched, outbred, female, Sprague-Dawley-derived rats from different commercial suppliers were compared for their susceptibility to the establishment and growth of Taenia taeniaeformis. Two of the strains, Spb:[SD] and Kng:[SD], gave very similar results, but the third, Hap:[SD]f, was considerably less receptive. Approximately one in eight of the Hap:[SD]f rats proved refractory to infection, and worm growth was slower and more variable than in Spb:[SD] rats. Male Spb:[SD] rats were not detectably different from females in susceptibility or parasite growth rate. Female rats of four different inbred lines all accepted infection, though the proportion of infective eggs giving rise to hepatic cysts differed. These differences, however, were overshadowed by variations observed in susceptibility of inbred rats of the same strain (Wistar-Lewis) purchased from different commercial suppliers. The results emphasize the need for careful standardization of laboratory procedures and rat strains for experimentation with this host-parasite system. In addition, they illustrate the dangers of extrapolation from the extensive literature of the influence of rat strain and sex on susceptibility to infection with T. taeniaeformis.

Animals↗