Biomedical subjects
Publications and source records attributed to D J Williams.
A uric acid bladder stone is described. This stone was unusual in that it had formed on a foreign body, namely surgical suture material. This phenomenon does not appear to have been described previously.
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Three quinoline bases may be found in greyhound urine. 2-aminomethylquinoline is excreted in fresh urine and two others, quinaldine and 2-hydroxymethylquinoline, are formed as the urine decays. Radiolabelling was employed to demonstrate that these bases are derived from the amino acid tryptophan.
Routine screening of compounds for inhibition of collagen-induced platelet aggregation in vitro revealed 4,5-bis-(4-methoxyphenyl)-1,2,3-thiadiazole (2) was active and it represents the first example of a 1,2,3-thiadiazole with possible antithrombotic activity. In order to develop a structure-activity relationship for this heterocycle, a number of new 4(5)-mono- and -disubstituted 1,2,3-thiadiazoles were synthesized. These were tested in our screen and a number of additional active compounds were found. The most active compounds (2, 5a, 5b, and 6c) were those in which the heterocycle was substituted with benzene rings possessing para electron-donating groups.
Factors associated with fat necrosis in cows and tall-fescue summer toxicosis in steers were studied. In the cow study, fescue pastures were fertilized, using 3 rates of N: high N (703 to 483 kg and 0 kg of N/ha/year from broiler litter in 1972 to 1974 and 1975, respectively), moderate N, and low N (224 and 74 kg of N/ha/yr from NH4NO3, 1972 to 1975, respectively). Bermuda grass pastures were fertilized at 2 rates of N: moderate N and low N (280 and 20 kg of N/ha/year from NH4NO3, 1972 to 1975, respectively). Fat necrosis developed only in cows grazing tall fescue, with an occurrence of 60%, 8%, and 3% for high-N, moderate-N, and low-N pastures, respectively. Cows grazing the high-N fescue, and to some extent those grazing the moderate-N fescue, had clinical signs of summer fescue toxicosis. Plasma cholesterol concentrations were lowest in cattle grazing the high-N fescue, averaging 114 mg/dl, followed by 134 and 127 mg/dl in cattle grazing the moderate-N and low-N fescue, respectively. In the steer grazing study, 24 paddocks of 0.49 ha each were seeded with tall-fescue lines G1-307 or G1-306 or with tall-fescue cultivars, KY-31 or Kenhy. All paddocks were fertilized with 170 kg of N/ha/year. Serum cholesterol concentrations were lower in steers grazing on G1-307 than in steers grazing on G1-306 or cultivars. Serum total lipids followed a similar trend, with a positive correlation (r = 0.49) between cholesterol and total lipids.(ABSTRACT TRUNCATED AT 250 WORDS)
Preliminary results of an extended X-ray absorption fine structure (e.x.a.f.s.) and X-ray absorption near edge structure study of jack bean urease have recently been reported [Hasnain & Piggott (1983) Biochem. Biophys. Res. Commun. 112, 279]. These results indicate that the environment of the nickel ion in the enzyme is similar to that in the model compounds Ni(L)2(L')1(ClO4)1 (where L is 1-n-propyl-2-alpha-hydroxybenzylbenzimidazole and L' is the deprotonated form) and Ni(HMB)3(Br)2 (where HMB is 2-hydroxymethylbenzimidazole), the closest similarity being with Ni(L)2-(L')1(ClO4)1. A detailed e.x.a.f.s. analysis has now been carried out and the crystal structures of the two model compounds solved. These results are reported here.
The major plasma membrane proteins of rabbit neutrophils were characterized by SDS-PAGE, surface iodination, 125I-concanavalin A binding, and detergent extraction. Neutrophil membranes were prepared which lacked significant intracellular contamination with good retention of protease-sensitive proteins. The major protein and predominant Con A-binding protein was as surface exposed, 140,000 D (gp 140) protein which was solubilized by nonionic detergents but not low ionic strength. Actin and myosin but not other cytosol proteins were prominently associated with the isolated membrane particularly in a Triton-insoluble form. Membranes were also prepared from surface-iodinated neutrophils previously stimulated with a chemotactic peptide or degranulated. The granule membrane enzyme alkaline phosphatase was incorporated into the plasma membrane fraction of degranulated neutrophils. However, the membrane proteins in the different membrane preparations were identical on SDS-PAGE and autoradiography. Therefore, using these techniques, no major alterations in protein composition of the plasma membrane could be detected following stimulation or degranulation of rabbit neutrophils.
The functional abilities of 9.5-, 10.5-, 11.5-, and 12.5-day-old chick embryos to respond to exogenous thyrotrophin-releasing hormone (TRH) were evaluated by means of changes in plasma total thyroxine (T4). T4 concentrations were determined 3.0, 6.0, 12.0, and 24.0 hr after TRH treatment. The data of the present investigation show that chick embryo adenohypophyseal sensitivity to exogenous TRH, as evidenced by changes in plasma T4 levels, increase during the 10.5- to 12.5-day incubation interval; however, the pattern and magnitude of plasma T4 response to administered TRH change markedly between Days 10.5 and 11.5 of development. This modification of the adenohypophyseal response pattern corresponds in embryonic time with the previously reported increases in immunocytochemically demonstrable TSH cells within the adenohypophysis(R. C. Thommes, J. B. Martens, W. E. Hopkins, D. A. Griesbach, D. J. Williams, M. J. Sorrentino, P. Wernke, and J. E. Woods, 1981, In 'Ninth International Symposium of Comparative Endocrinology"; R. C. Thommes, J. B. Martens, W. E. Hopkins, M. J. Sorrentino, J. C. Caliendo, and J. E. Woods, 1983, Gen. Comp. Endocrinol. 51, 434-443).
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Recordings of cerebral electrical activity produced by the cerebral function analysing monitor ( CFAM ) were obtained from nine healthy volunteers breathing increasing concentrations of N2O in O2. Concentrations of 30 and 50% N2O produced significant reductions in CFAM trace amplitude. Withdrawal of N2O resulted in an increase in amplitude with an initial increase above the control level. There were no consistent changes in the frequency distribution of the weighted electroencephalographic signal with increasing concentrations of N2O.
IgG1 immunoglobulin purified from sera 3 weeks following primary infection with 400 L3 larvae of Nematospiroides dubius was shown to be protective against challenge infection as assessed by worm recovery and worm length. No evidence was seen of blocking activity either using primary infection sera or IgG1 purified from primary infection sera in a variety of assay systems both in vivo and in vitro. In addition, immune complexes precipitated from primary infection sera by polyethylene glycol failed to inhibit the capacity of immune mesenteric lymph node cells to transfer immunity. It is concluded that an explanation for the prolonged survival of Nematospiroides dubius must be sought in mechanisms other than circulating blocking factors.
Platelet aggregation was measured in rat and human platelet-rich plasma (PRP) after the addition of various amounts of arachidonic acid (AA), prostaglandin H2 (PGH2), adenosine diphosphate (ADP), or collagen. AA but not PGH2 caused rat platelets to aggregate in citrated or heparinized PRP. Both AA and PGH2 produced significant amounts of thromboxane A2 (TxA2) measured as thromboxane B2 (TxB2). The lack of aggregation of rat platelets with PGH2 was not due to the formation of an inhibitor of aggregation such as a prostaglandin. Thus, the formation of TxA2 may not be necessary for aggregation of rat platelets. Human platelets were aggregated by PGH2 with the concomitant formation of TxB2.
Twenty-five satisfactory and 25 unsatisfactory potential breeder bulls were examined with a modified Shulman spermagglutination test for the presence of spermagglutinating antibodies in their serum and seminal fluid. This was done to determine whether antibodies to spermatozoa were a contributing factor to classification of the bull as an unsatisfactory potential breeder. No correlation was found between classification as an unsatisfactory potential breeder and the presence of spermagglutinating antibodies. In addition, indirect fluorescent antibody tests were performed to detect antisperm antibodies in the serum and seminal fluid of the bulls. Again, no correlation was found between antisperm antibodies and breeding soundness classification. Finally, there was no correlation between the age of the bulls and occurrences of spermagglutination antibodies in serum or seminal fluid.
Plasma samples from 44 patients with systemic lupus erythematosus (SLE) and 43 with rheumatoid arthritis (RA) were assayed for C3d, a breakdown product of the third component of complement (C3), which was also measured in parallel. Levels of C3d varied in direct proportion with disease activity in RA, whereas C3 showed little change. Although C3d values also increased with worsening clinical condition in SLE, this trend was not considered to be sufficiently clear to be useful and did not provide any advantage over the routinely performed C3 assay.
Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.
The nematode parasite Nematospiroides dubius survives to give a chronic primary infection in mice. However, mice subjected to weekly infections of 125 larvae, interspersed by treatment with an anthelmintic to prevent the accumulation of lethal numbers of adult worms in the intestine, develop host-protective antibodies in their serum. The protective effect of these antibodies was demonstrated by passive transfer to naive recipients or to mice already adoptively immunized with immune mesenteric lymph node cells (IMLNC). Sera were first shown to exhibit protective activity during the third and fourth weeks of the multiple immunizing infection, reaching a peak level by week six beyond which there was no further increase in protective activity. This increase was correlated with a ten-fold, concurrent rise in serum IgG1 levels. None of the other immunoglobulin isotypes underwent comparable changes in concentration nor could they be correlated with the pattern of appearance of host-protective antibodies in the sera of donor mice. This suggested that host protective antibodies were of the IgG1 class. CFLP and C57BL10 mice (the latter is a weak responder strain) both had high levels of host-protective antibodies in their serum. However when the sera from NIH mice (a strong responder strain) were compared, they exhibited far less protective activity on passive transfer to recipient mice, although when given together with IMLNC, serum from multiply-immunized NIH mice enhanced the protective effect of IMLNC synergistically. When primary infection serum was assayed in this passive/adoptive transfer model, no host-protective antibodies could be demonstrated, even with pools of primary infection serum taken 10 and 17 weeks after infection. These results are discussed with respect to the possible mechanisms by which N. dubius evades the host immune system to give rise to long-lasting primary infections in mice.
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Six mechanisms which may produce fracture-separation of the proximal humeral epiphysis are proposed. Four of them are illustrated by case reports. It is suggested that they may be differentiated by examination of the patient and study of the radiographs. In unstable fractures manipulation is indicated and, if performed with an understanding of the mechanism of injury, will produce a stable reduction.