Biomedical subjects
Publications and source records attributed to D S Jackson.
Polyorchidism is rare. We report a recent case and review the literature. A simple classification based on anatomic and functional arrangements of the testes and their drainage systems is described. Combining this classification with a knowledge of potential complications, we propose a management strategy.
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Cefadroxil has been used for the treatment of acute osteomyelitis. However, its pharmacokinetics and pharmacodynamics have not been studied in these patients. We evaluated the kinetics and dynamics of cefadroxil in a pediatric patient with osteomyelitis caused by Staphylococcus aureus. After initial clinical improvement on intravenous nafcillin, the patient received oral cefadroxil, 60 mg/kg every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, 8 and 12 h; bactericidal titers were determined at 2 and 12 h. Cefadroxil was measured by an HPLC method. The peak and trough serum concentration of cefadroxil was 35.4 and 0.5 micrograms/ml, respectively. The oral clearance and elimination half-life were 11.5 ml/min/kg and 2.4 h, respectively. The peak bactericidal titer was 1:4 and the trough titer was less than 1:2 for the infecting organism. The child's finger appeared worse with an increase in swelling and erythema after 2 days of cefadroxil therapy. Cefadroxil was discontinued and the patient was treated successfully with intravenous nafcillin. The apparent failure of cefadroxil therapy can be explained by lower than recommended peak (greater than or equal to 1:8) and trough (greater than or equal to 1:2) titers for therapeutic success. Thus, an alternative dosage regimen of cefadroxil should be considered in the future studies.
Whereas psoas abscess secondary to many local intra- and extra-peritoneal septic processes is well recognised, primary psoas abscess is much less common and the diagnosis is often delayed, leading to significant morbidity and mortality. A case of primary psoas abscess is described and the role of ultrasound in the investigation and management is discussed.
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Embryonic-chick tendon poly(A)-containing RNA was translated in the wheat-germ and mRNA-dependent rabbit reticulocyte-lysate systems. The ability of each system to synthesize polypeptides similar to pro-alpha chains of collagen was tested on the bases of electrophoretic mobility and susceptibility to highly purified bacterial collagenase. Very small amounts of polypeptides in the size range of pro-alpha chains were synthesized in the wheat-germ system, whereas efficient synthesis of two polypeptides similar to pro-alpha1 and pro-alpha2 chains was achieved in the reticulocyte lysate. The collagenous nature of the major high-molecular-weight products synthesized was demonstrated by their susceptibility to collagenase and ability to act as a substrate for purified collagen proline hydroxylase. Determinations of the relative amounts of these translation products suggest that the 2:1 ratio of pro-alpha1 and pro-alpha2 chains found in type I procollagen is reflected in proportional amounts of translatable mRNA for pro-alpha1 and pro-alpha2 chains. Comparisons of the electrophoretic mobilities of hydroxylated and unhydroxylated reticulocyte-lysate translation products were made with appropriate standards of hydroxylated and unhydroxylated procollagen polypeptides. The results suggest that, in common with a number of secreted proteins, procollagen is synthesized as pre-pro molecules consistent with the ;Signal Hypothesis'.
A re-examination of the subcellular fractions obtained from matrix-free chick tendon and cartilage cells has been made since the discovery that three out of four of the micrographs of chick tendon microsomal fractions published in an earlier paper from this laboratory were not authentic. The present studies demonstrate that by using the procedures previously reported it is possible to isolate microsomal and submicrosomal fractions from tendon and cartilage cells which exhibit typical morphology when examined by electron microscopy. These observations are consistent with our original biochemical characterization of subcellular fractions, which we know to be valid. Other publications from this laboratory in which these fractionation procedures have been applied to studies of collagen biosynthesis are in no way compromised, and indeed, most of our data have been confirmed by several other laboratories.
This paper reviews some of the biochemical modifications involved in fibrous tissue formation and discusses possible ways of controlling fibrosis in clinical conditions. The lathyritic agents, beta-aminoproprionitrile (BAPN) and penicillamine, appear in certain situations to be able to control fibrosis by blocking the biosynthesis of collagen. There are no compounds that are yet known which are capable of reversing pre-existing fibrosis and future research may perhaps be more profitably directed towards the stimulation of collagen catabolism rather than the inhibition of its synthesis.
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Cell cultures derived from foetal bovine ligamentum nuchae accumulate extracellular fibrils morphologically identical with elastic-tissue microfibrils. Two glycoproteins synthesized by the ligament cells are closely related to the matrix microfibrils as assessed by immunological and chemical extraction techniques.
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1. Confluent human skin fibroblasts maintained in a chemically defined medium incorporate l-[1-(3)H]fucose in a linear manner with time into non-diffusible macromolecules for up to 48h. Chromatographic analysis demonstrated that virtually all the macromolecule-associated (3)H was present as [(3)H]fucose. 2. Equilibrium CsCl-density-gradient centrifugation established that [(3)H]fucose-labelled macromolecules released into the medium were predominantly glycoproteins. Confirmation of this finding was provided by molecular-size analyses of the [(3)H]fucose-labelled material before and after trypsin digestion. 3. The [(3)H]fucose-labelled glycoproteins released into fibroblast culture medium were analysed by gel-filtration chromatography and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. These techniques demonstrated that the major fucosylated glycoprotein had an apparent mol.wt. of 230000-250000; several minor labelled species were also detected. 4. Dual-labelling experiments with [(3)H]fucose and (14)C-labelled amino acids indicated that the major fucosylated glycoprotein was synthesized de novo by cultured fibroblasts. The non-collagenous nature of this glycoprotein was established by three independent methods. 5. Gel-filtration analysis before and after reduction with dithiothreitol showed that the major glycoprotein occurs as a disulphide-bonded dimer when analysed under denaturing conditions. Further experiments demonstrated that this glycoprotein was the predominant labelled species released into the medium when fibroblasts were incubated with [(35)S]cysteine. 6. The relationship between the major fucosylated glycoprotein and a glycoprotein, or group of glycoproteins, variously known as fibronectin, LETS protein, cell-surface protein etc., is discussed.
Cells were isolated from the major arteries of 17-day chick embryos by digestion of the tissue with collagenase and trypsin. The cells, when examined immediately after isolation, exhibited a high degree of viability and they were shown to synthesize and secrete procollagen at a high and constant rate for several hours when incubated in suspension in modified Krebs medium. Continuous labelling of the cells with [(14)C]proline demonstrated a lag of about 30min between the time at which the synthesis of non-diffusible peptide-bound hydroxy[(14)C]proline became linear and the time at which its secretion into the medium became linear. This lag time compares with that of 18min observed for freshly isolated matrix-free cells from embryonic-chick tendon, which synthesize and secrete the same type of collagen. Gel-filtration chromatography and polyacrylamide-gel electrophoresis indicated that the collagenous polypeptides secreted into the medium were in the precursor form, known as procollagen, and that the constituent pro-alpha-chains were linked by interchain disulphide bonds and were also in a triple-helical conformation. Characterization of the secreted procollagen by gel-filtration chromatography, polyacrylamide-gel electrophoresis, DEAE-agarose chromatography, and polyacrylamide-gel electrophoresis of peptides obtained by CNBr cleavage, indicated that the predominant form was type-I procollagen. This work extends the range of freshly isolated matrix-free cell systems, which have been characterized for use in studies on the biosynthesis and secretion of procollagen, and it indicates differences in the rates of secretion of procollagen in different cell types secreting the same type of procollagen.
1. The molecular weights of chick tendon and cartilage procollagens, and their constituent polypeptides, were determined by gel filtration and gel electrophoresis. The values obtained are in good agreement and indicate that the mol.wts. of the secreted procollagens (types I and II) and their individual pro-alpha-chains are of the order of 405 000-445 000 and 137 000-145 000 respectively.2. Digestion of tendon procollagen with human rheumatoid synovial collagenase gave products consistent with the presence of large non-helical peptide extensions at both N-and C-termini. Electrophoretic analysis gave apparent mol.wts. of 17 500 and 36 000 for the respective N- and C-terminal extensions of pro-alpha1(I)-and pro-alpha2-chains, and inter-chain disulphide bonds were restricted to the C-terminal location. 3. During the biosynthesis of procollagen by tendon and cartilage cells a close correlation was observed between the extent of inter-chain disulphide bonding and the proportion of procollagen polypeptides having a triple-helical conformation. These processes appeared to commence in the rough endoplasmic reticulum and be completed in the smooth endoplasmic reticulum, but the rate at which they occur in cartilage cells is markedly slower than that found in tendon cells. 4. When the intracellular [14C]procollagen polypeptides present in the rough-endoplasmic-reticulum fractions of tendon and cartilage cells were analysed under non-reducing conditions on agarose/polyacrylamide composite gels, no significant pools of dimeric intermediates were detected. 5. In both cell types, inter-chain disulphide-bond formation occurred even when hydroxylation, and hence triple-helix formation, was inhibited. The presence of pro-alpha1- and pro-alpha2-components in a ratio of 2:1 in the disulphide-linked unhydroxylated procollagen isolated from tendon cells demonstrated that correct chain association occurs in the absence of hydroxylation. This observation is consistent with a model for the assembly of pro-gamma112-chains in which the recognition and selection of pro-alpha1-and pro-alpha2-chains in a 2:1 ratio are directed by the non-helical C-terminal extension peptides of tendon procollagen.
Electrophoretic analysis of the proteins synthesized by cultured human skin fibroblasts demonstrated that the major component released into the medium is a high molecular weight fucosylated glycoprotein (MFGP). Gel filtration chromatography under denaturing and reducing conditions indicated that MFGP has a molecular weight of approx. 250,000; but appears to behave as a disulphide-linked dimer when unreduced. MFGP is further distinguished as the major labelled macromolecule in the medium after incubation of fibroblasts with [35S]cysteine. The role of this glycoprotein is unknown but it bears a striking resemblance to a presumptive structural glycoprotein recently shown to be secreted by arterial smooth muscle cells in culture, and may also be related to a group of much studied cell surface glycoproteins.
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Porcine aortae were digested with pepsin and the solubilised collagen molecules separated by differential salt precipitation at pH7.5. The fraction precipitated at 1.71 M NaCl was shown to comprise collagen type III as judged by its elution characteristics from CM-cellulose, its alpha-chain composition on sodium dodeclysulphate polyacrylamide gel electrophoresis, and amino acid analyses. Pepsin-derived type I collagen was recovered by precipitation at 2.56 M NaCl and similarly characterised. cultures of porcine arterial smooth muscle cells have been established and radiolabelling studies with [14Clproline have demonstrated that these cells synthesis and secrete the precursors of collagen types I and III into the culture medium. Ion-exchange chromatography of these secreted collagen molecules and gel filtration of their pepsin-derived alpha-chains have demonstrated that type III is the major collagen species present in the medium.