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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 307 records · Page 17Linked to original sources
PubMed1985

Isolation and characterization of clonal cell lines from a transplantable metastasizing rat mammary tumor, TR2CL.

The metastasizing rat mammary cell strain from the Ludwig Institute for Cancer Research (London Branch) which was originally developed from a benign rat mammary tumor induced by N-methyl-N-nitrosourea (CAS: 684-93-5), yielded single-cell-cloned lines of isometric epithelial cells [rat mammary (Rama) 600-Rama 621] and one line of elongated cells (Rama 622); the former had a higher estrogen receptor content than the latter. All the representative epithelial cell lines tested (Rama 600, 603, and 617) failed to convert to elongated, myoepithelial-like cells or droplet cell/doming, alveolar-like cells in vitro. All representative cell lines tested induced tumors in syngeneic F344/N rats and CBA nu/nu mice, but only the epithelial lines metastasized to lungs and local lymph nodes in rats and to lungs in nude mice. The involved lungs and lymph nodes contained mainly intravascular thrombi and deposits in the subcapsular sinus, respectively. Tumors and metastases from the representative epithelial cell lines contained acinar and glandular structures together with an elongated cellular component. The Rama 622 tumors contained mainly spindle cells. Antisera to rat milk fat globule membranes and human keratins stained some of the epithelial and elongated cells in the Rama 600 tumors; less staining was observed in the Rama 622 tumors. None of the tumor cells stained with antiserum to myosin. Anti-laminin serum delineated a fragmented basement membrane in glandular elements and stained weakly the cytoplasm of the more elongated tumor cells. Ultrastructural analysis confirmed the identity of epithelial cells in the Rama 600 tumors, but no well-differentiated myoepithelial cells were seen in either type of tumor. Since nonmetastasizing epithelial cells isolated directly from carcinogen-induced benign rat mammary tumors can differentiate to myoepithelial-like cells in vitro or when growing as tumors in animals, it is suggested that the development of the malignant phenotype is associated with a loss of this differentiating ability.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Binding characteristics of swine erythrocyte insulin receptors.

Crossbred gilts (controls; n = 7) had 8.8 +/- 1.1% (mean +/- SEM) maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows (n = 5) had a significant increase (P less than 0.01) in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet (n = 3) and a low-fiber diet (n = 4) did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.

Animals↗
PubMed1985

The endocrine glands in Pompe's disease. Report of two cases.

Pompe's disease (type II glycogenosis), an infantile form of generalized glycogenosis, is characterized biochemically by deficiency of lysosomal acid alpha-1,4-glucosidase and morphologically by intralysosomal glycogen storage in multiple organs, notably the central nervous system, heart, liver, and skeletal muscles. The endocrine system has not been described in detail in the literature. In two infants with Pompe's disease, intralysosomal glycogen was identified in the adrenal cortex and medulla, thyroid gland, parathyroid glands, pancreatic islets, and pituitary gland. Of special interest is the severe glycogen accumulation in the zona fasciculata of the adrenal glands.

Adrenal Glands↗
PubMed1985

Efficacy of the tris-salt of 2 [(methoxycarbonylamino)-[2-nitro-5-(n-propylthio) phenylimimo] methylamino] ethane sulfonic acid against inhibited larvae of Ostertagia ostertagi.

The tris-salt of 2-[(methoxy-carbonylamino) - [2-nitro-5-(n-propylthio) phenylimimo] methylamino] ethane sulfonic acid (MCA) was evaluated against naturally acquired gastrointestinal parasitism in cattle during spring in Louisiana to determine efficacy of the compound against inhibited early 4th-stage larvae (EL4) of Ostertagia ostertagi. Forty-three crossbred yearling beef heifers were grazed together on contaminated pastures between Mar 1 and Apr 18, 1984. On April 17, 3 of the 43 heifers were slaughtered. Analysis of worm population characteristics in the 3 cattle indicated sufficient numbers of O ostertagi EL4 and other worm genera and species in these cattle to pursue a valid evaluation of the anthelmintic efficacy of MCA. The remaining 40 heifers were removed from pasture on April 18. On April 24, they were allotted into 4 treatment groups (10/group) based on an equal distribution of body weights and on whether they were spring- or autumn-born cattle. On April 25, the cattle were treated as follows: group 1, nontreated controls; group 2, treated with MCA at 7.5 mg/kg of body weight by oral drench; group 3, treated with MCA at 15.0 mg/kg by oral drench; and group 4, treated with MCA at 20.0 mg/kg by oral drench. The cattle were then confined in drylot pens until May 7. Similar numbers of cattle from each group were killed over a 3-day period from May 8 to May 10 (13 to 15 days after treatment). Mean numbers of O ostertagi recovered from nontreated controls were: adults, 8,279; developing 4th-stage larvae, 2,806; and inhibited EL4, 12,070.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗
PubMed1985

Synergistic influence of Ostertagia ostertagi and Trichostrongylus axei on Ostertagia ostertagi larval inhibition and abomasal lesions in cattle.

Parasite-free 4-month-old calves were inoculated with Ostertagia ostertagi and/or Trichostrongylus axei followed 6 weeks later by increasing doses of O ostertagi for 8 weeks. Clinical signs of parasitism, fecal egg counts, and plasma pepsinogen concentrations were monitored, and gross lesions and parasite burdens were determined postmortem. Clinical signs of parasitism were not observed and weight gains were not affected in experimentally infected calves. In calves infected with O ostertagi, mean plasma pepsinogen concentrations were greater than for control calves and were diagnostically significant 4 weeks after inoculation and during the last 4 weeks of serial inoculations with O ostertagi. In calves that were given O ostertagi and T axei, abomasal pH was significantly increased, and abomasal lesions were more pronounced than in control calves or in calves inoculated with only O ostertagi or T axei. Abomasal lymph nodes were enlarged in all parasitized calves; other lymph nodes in the calves inoculated with both O ostertagi and T axei were usually smaller than in calves inoculated with only O ostertagi or T axei. Numbers of O ostertagi-inhibited larvae were small in all inoculated calves, but the percentage inhibition was significantly greater in calves inoculated with both O ostertagi and T axei. The percentage inhibition was 3.53% for the O ostertagi-inoculated calves and 7.07% for calves inoculated with both O ostertagi and T axei. These percentages indicated a synergistic effect of concurrent abomasal parasitism, whereas a synergistic effect on T axei worm burden was not observed. The low percentage of larval inhibition indicated that factors other than host resistance are involved in naturally occurring pretype II ostertagiosis.

Abomasum↗
PubMed1985

Experimentally induced ostertagiosis in rabbits inoculated with Ostertagia ostertagi of bovine origin.

Weanling specific-pathogen-free rabbits were orally inoculated with 50,000 Ostertagia ostertagi 3rd-stage infective larvae cultured from bovine feces and were killed 42 days after inoculation. Two preliminary trials were done, using conventionally reared weanling rabbits inoculated with 2,500, 5,000, and 50,000 O ostertagi 3rd-stage larvae and dexamathasone in 1 of the trials; the rabbits were killed 14 and 28 days after inoculation. Fecal egg counts were monitored, and worm burdens were determined. The pH of the gastric contents was measured at necropsy. Recoveries of the parasite from the gastric mucosa comprised early 4th-stage larvae and larvae that had developed beyond the early 4th stage. The maximum worm burden established at 42 days after inoculation was 1,668 immature nematodes or 3.34% of the inoculum. Gross and microscopic gastric lesions were present. Gross nodular mucosal elevations, which tended to be confluent in the cardiac region, were observed. Microscopic changes were principally mucosal hyperplasia, focal lymphocyte accumulation with moderate glandular dilation, and slight variable eosinophil and plasma cell accumulation. The pathologic changes had characteristics similar to those in cattle infected with O ostertagi and other conditions characterized by gastric mucosal hyperplasia.

Animals↗
PubMed1985

Enzyme immunoassay for surveillance of Q fever.

An enzyme-linked immunosorbent assay (ELISA) was developed to monitor antibodies against Coxiella burnetii among animal populations used in research and teaching facilities. Various antigenic components of C burnetii prepared from phase I and phase II whole cells and commercially available antigens were evaluated. A trichloroacetic acid extract was selected for routine use. There was a linear relationship between the transformed absorbance readings of the ELISA results and microagglutination (MA) titers. Comparison between positive or negative results of the MA test and ELISA gave 98.6% concordance. Using the MA test as the standard, ELISA results were 97.8% sensitive and 100% specific. The efficacy of ELISA was evaluated by testing ruminants with known histories of C burnetii infection. Antibody prevalence was 0 in 117 sheep with no history of C burnetii infection, 22% in 145 naturally infected sheep used for research, and 53% in 115 sheep used for vaccine field trials. Forty-eight percent of 120 dairy cows and 52% of 79 goats from endemically infected herds were seropositive. These results indicate that ELISA should be the test of choice for mass screening and surveillance of animals when Q fever is a suspected biohazard.

Animals↗
PubMed1984

Colon carcinoma and diabetes mellitus.

A significantly increased occurrence of overt diabetes mellitus was found among colon or rectal carcinoma patients by comparison with that found among lung carcinoma or hip fracture populations in two hospitals.

Adolescent↗
PubMed1984

Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate.

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.

Brain↗
PubMed1984

Glutamyl ribose 5-phosphate storage disease. A hereditary defect in the degradation of poly(ADP-ribosylated) proteins.

A patient with a lysosomal storage disease, progressive neurologic degeneration, and renal failure was found to have accumulated a low molecular weight ninhydrin and phenol-H2SO4 reactive compound. Amino acid analysis and gas chromatography-mass spectrometry identified a glutamic acid moiety. Direct insertion mass spectrometry proved the carbohydrate portion to be a sugar phosphate. NaB3H4 reduction and borate electrophoresis, paper chromatography, and enzymatic digestion indicated the presence of ribose 5-phosphate. Quantitative analysis of the intact compound indicated a 1:1:1 ratio for glutamic acid: ribose:phosphate. Brain was found to contain 0.96 mumol/g, wet weight, and kidney 0.60 mumol/g, wet weight, of glutamyl ribose 5-phosphate. This substance is the linkage region in ADP-ribosylation of histones and other proteins. It is suggested that the primary defect in this patient is a genetic abnormality of ADP-ribose protein hydrolase (Okayama, H., Honda, M., and Hayaishi, O. (1978) Proc. Natl. Acad. Sci. U. S .A. 75, 2254-2257).

Amino Acids↗
PubMed1984

On the mechanism of histamine-induced bronchodilation in conscious guinea-pigs.

The bronchodilatory effect of histamine was evaluated in a conscious guinea-pig model of cholinergically mediated bronchoconstriction. The H1, bronchoconstrictor, property of histamine was masked using high doses of the H1-antagonist chlorpheniramine (30 mg/kg), and the bronchodilatory activity evaluated by observing the increase in latency to collapse induced by aerosol methacholine. Under these conditions, histamine (1.0, 3.0 or 10.0 mg/kg, i.p.) delayed methacholine-induced collapse in a dose-dependent manner. Cimetidine, an H2-receptor antagonist (10 to 100 mg/kg), did not delay collapse either in the presence or absence of an H1-antagonist. However, when cimetidine was administered prior to histamine, the bronchodilatory activity of histamine was abolished. A similar abolition of histamine bronchodilation was observed if propranolol, a beta-adrenoceptor antagonist, was administered prior to histamine. Propranolol alone had no effect on methacholine-induced bronchospasm. These data suggest that the major bronchodilatory property of histamine may be mediated indirectly via catecholamine release through an H2-receptor mechanism.

Aerosols↗
PubMed1984

Primary structure of the L subunit of the reaction center from Rhodopseudomonas sphaeroides.

The reaction center is an integral membrane protein that, together with several cofactors, mediates the primary photochemical events in bacterial photosynthesis. The amino-terminal sequences of the three subunits, L, M, and H, of the reaction center protein and the sequence of the structural gene encoding the M subunit have been reported previously. In the present study, we found that the 3' end of the structural gene encoding the L subunit overlaps by eight bases the 5' end of the gene encoding the M subunit. The primary structure of the L subunit has been determined from the nucleotide sequence of the gene and from analyses of the amino and carboxyl termini of the protein. The sequences of a number of tryptic and chymotryptic peptides were used to corroborate the nucleotide sequence. The L subunit was found to be composed of 281 amino acids (Mr 31,319) and to contain five hydrophobic segments. It is homologous to the M subunit and to a plant thylakoid protein referred to as the QB or Mr 32,000 protein.

Amino Acid Sequence↗
PubMed1984

Monoclonal antibodies distinguish phase variants of Coxiella burnetii.

Monoclonal antibodies (MAbs) directed against phase I and II variants of Coxiella burnetii were produced by fusing myeloma SP2/O-AG 14 cells with spleen cells from mice immunized with the chloroform-methanol extraction residue of phase I whole cells. Two hybridoma clones which distinguished the phase variants by microimmunofluorescence assay were isolated and characterized. The MAbs showing specificity for phase I cells (MAbI-1, immunoglobulin G, subclass 3 kappa) reacted with the hot phenol-water extract of phase I C. burnetii in immunodiffusion and enzyme-linked immunosorbent assays. MAbI-1 reacted with high-molecular-weight components from phase I phenol-water extract and whole cell in an immunoblot assay. Specificity of MAbI-1 for a carbohydrate epitope in the phenol-water extract was demonstrated by periodic acid inactivation of binding by a competitive enzyme-linked immunosorbent assay. Phase I antigenic sites were apparently well represented on the surface of cells as demonstrated by complete fluorescence and microagglutination. The MAb showing specificity for phase II cells (MAbII-1, immunoglobulin G, subclass 2b kappa) reacted with whole cells in the microimmunofluorescence assay, microagglutination test, complement fixation test, and the enzyme-linked immunosorbent assay. MAbII-1 reacted specifically with a 29,500-dalton surface protein as demonstrated by immunoprecipitation of 125I-surface-labeled cells. Although MAbII-1 reacted with detergent-solubilized protein, it did not react with sodium-dodecyl sulfate-denatured protein by immunoblot assay. This protein was not exposed on the surface of phase I cells, but chloroform-methanol extraction of phase I cells exposed the phase II epitope.

Animals↗
PubMed1984

Biochemical and immunochemical analysis of Rickettsia rickettsii strains of various degrees of virulence.

Six strains of Rickettsia rickettsii from Montana and North Carolina were examined in an effort to identify rickettsial constituents associated with virulence. Fever responses, scrotal reactions, and mortalities of male guinea pigs inoculated intraperitoneally with 1,000 PFU of rickettsial strains revealed that the two Montana patient strains ( Sheila Smith and Norgaard ) and one Montana strain ( Sawtooth female 2) from the wood tick, Dermacentor andersoni, could be placed in the group of highest virulence, the two North Carolina strains (Morgan and Simpson) in the group of lesser virulence, and the Montana strain (HLP) from the rabbit tick, Haemaphysalis leporispalustris , in the group of lowest virulence. The HLP strain was differentiated from the other strains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by staining with Coomassie brilliant blue or with silver. The patient strains could not be differentiated from each other by these procedures. All of the strains apparently had three heat-modifiable proteins. Analysis of proteinase K-digested rickettsial lysates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested that the strains had a complex mixture of polysaccharides. These putative polysaccharides probably were not related to the differences in virulence of the strains, since the patterns for all of the strains were identical. At least five antigens (molecular weights of 128,000, 105,000, 84,000, 30,500, and 20,500) were demonstrated by radioimmune precipitation tests employing extracts from radioiodine-labeled rickettsiae and antibodies from infected guinea pigs. With these same sera a minimum of 14 antigens was detected in these strains by an immunoblotting procedure. The apparent molecular weights of several of the HLP antigens differed from those of the presumed corresponding antigens of the other strains. The electrophoretic techniques utilized in this study were not sufficiently sensitive to demonstrate compositional differences in the patient strains which differed in their virulence for guinea pigs.

Animals↗
PubMed1984

Biochemical and immunological properties of Coxiella burnetii cell wall and peptidoglycan-protein complex fractions.

Coxiella burnetii morphological cell types were fractionated into large-cell variant cell walls, two fractions of small-cell variant cell walls, and one fraction of small-cell variant whole cells. Based on the contents of peptidoglycan (PG)-constituents and the yields of the sodium dodecyl sulfate-insoluble PG-protein complex (PG-PC) from cell walls, the fraction of large-cell variant cell walls contained significantly less PG than did the fraction of small-cell variant cell walls. The yields of PG-PC from the fractions of large-cell variant cell walls and small-cell variant cell walls were 2 and 32%, respectively. These results indicated that the PG of the large-cell variant cell walls may be partially digested by PG-lytic enzymes or incompletely synthesized, whereas the small-cell variant cell walls appeared to have intact PG. Proteins associated with PG-PC were resistant to proteolysis by trypsin, protease VI, and proteinase K. Saturated and unsaturated fatty acids were detected in whole cells and cell walls but not in PG-PC, which contained a 3-deoxy-D-mannooctulosonic acid-like component that is also present in phase I lipopolysaccharide. Immunogenicity of the fractions was tested by measuring the temporal sequence of phase II and phase I antibody responses in vaccinated rabbits. Both phase II and phase I antibody responses were demonstrated with all fractions except the sodium dodecyl sulfate supernatant of the small-cell variant cell walls, whereas PG-PC elicited a pure phase II antibody response up to 29 days postvaccination. The immunogenicity of these fractions may reflect a quantitative difference in antigen concentration or may be due to a qualitative difference in phase II and I determinants.

Agglutination↗