Biomedical subjects
Publications and source records attributed to J Hickman.
A pigmented lesion of the soft palate was excised to exclude melanoma. The histology suggested an amalgam tattoo which was confirmed on energy dispersive X-ray analysis by the detection of silver and copper. This represents a very rare mimic of melanoma of the soft palate.
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Pretreatment of the osteogenic sarcoma cell line UMR-106-01 with insulin results in sensitization to both parathyroid hormone (PTH) and isoproterenol. In insulin-pretreated cells, the two hormones cause a significantly greater cyclic AMP (cAMP) accumulation than in noninsulin-treated cells. In the presence of cholera toxin, which enhances cAMP production by these cells in both the basal and PTH-stimulated state, the effect of insulin is maintained. In the presence of pertussis toxin, which has no effect on basal cAMP accumulation but enhances both PTH and isoproterenol stimulation, insulin sensitization for both hormones is abolished. These data suggest that insulin sensitizes these cells to subsequent hormone stimulation by lessening the action of an inhibitory guanine nucleotide regulatory protein, possibly Gi.
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Propionibacterium acnes as the single cause of intracranial infections has rarely been described. We present four patients in whom the infection arose as a result of a breach of skin tegument, and postulate that P. acnes is an under-recognised pathogen.
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The rat osteogenic sarcoma subclone UMR-106-01 is a cell type with osteoblast-like properties. This cell line has been shown to process specific receptors for insulin and insulin-like growth factor I (IGF-I), but not IGF-II. Insulin at physiological concentrations (1-5 ng/ml) in serum-free medium can maintain cell growth, as assessed by protein accumulation, thymidine uptake, and an increase in cell number. IGF-I is less potent than insulin, but, based on relative binding affinities for the insulin receptor, possibly acts via its own receptor. Insulin also enhances PTH-stimulated cAMP accumulation in these cells both by increasing cell number and an effect independent of cell number. Insulin may have a role in bone homeostasis.
The chemotactic peptide formylmethionylleucylphenylalanine rapidly elevated the intracellular calcium concentration, in a concentration-dependent manner, of human leukemic (HL-60) cells which had been differentiated to polymorphonuclear leukocyte-like cells by pretreatment with dimethyl sulfoxide (1.3%). Preincubation of the cells with phorbol 12-myristate 13-acetate, a protein kinase C-activating phorbol ester, inhibited the formylmethionylleucylphenylalanine-induced rise in intracellular calcium in a time- and concentration-dependent manner. 4 alpha-Phorbol 12,13-didecanoate, which does not activate protein kinase C, was inactive in this capacity. The use of calcium-free medium suggested that the elevation of intracellular calcium by formylmethionylleucylphenylalanine consisted of rapid intracellular release followed by calcium influx. Phorbol 12-myristate 13-acetate (10(-7) M) inhibited both components of the elevation of intracellular calcium, whereas 10(-8) M phorbol 12-myristate 13-acetate inhibited only the calcium influx. The influx of calcium was not prevented by verapamil, which blocks the voltage-dependent calcium channels. These data suggest that, in differentiated HL-60 cells, 12-O-tetradecanoylphorbol-13-acetate rapidly inhibits both the intracellular release of calcium and calcium influx through non-voltage-dependent calcium channels in response to formylmethionylleucylphenylalanine.
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The incorporation of autogenous cancellous bone graft was studied in eight yearling ponies. The site for the defect to be grafted was chosen so that the effect on the graft, of both the host cortical and trabecular bone, could be assessed. To obtain information concerning the vitality of the graft and the dynamic aspects of the modelling and remodelling processes of graft incorporation, a double and treble tetracycline intravital labelling technique was used. Radiographs of the graft and host tissues of all ponies were obtained regularly, but were of little assistance in assessing graft incorporation. The ponies were destroyed humanely at regular intervals between nine and 241 days after installation of the graft, followed by histological examination of undecalcified sections. The study revealed that all installed graft trabeculae showed signs of non-vitality at nine days after installation and gradually disintegrated. Two processes of new bone formation were observed. First, finger-like projections of immature new trabeculae were found to originate from the graft/host interfaces. Second, a gradual process of accretion of osteoid and woven bone upon disintegrating graft trabeculae occurred uniformly throughout the graft. The graft adapted to the structure of opposing host bone by corticalisation and trabecularisation. The present study confirmed clinical observations relating to convalescence time following grafting of large osseous defects in horses and indicated that equine bone reacts to autogenous bone grafts in a similar manner to other mammals.
The quantitative aspects of equine cancellous bone graft incorporation and the possibility of influencing graft incorporation by daily exposure to a pulsed electromagnetic field (PEMF) was studied in eight yearling ponies. In order to be able to quantify formative aspects of graft remodelling, a double and treble tetracycline intravital labelling technique was used. Intravital radiographs were obtained at regular intervals throughout the trial, but were found to be of little assistance in assessing any differences between stimulated and non-stimulated grafts. The ponies were humanely destroyed at regular intervals between nine and 241 days after installation of the graft. Light microscopy and fluorescent light microscopy were used to evaluate quantitative aspects of graft incorporation and to compare PEMF-stimulated grafts with control grafts. There was a small but statistically significant effect of PEMF-stimulation on cancellous bone graft incorporation. In view of this, these observations can only be considered as indicative of a possible trend, but should encourage further studies using different signal modalities.
Lactate 12% lotion was significantly more effective than both its vehicle and a petrolatum-based cream in the treatment of ichthyosis. The treatment regimen was twice-daily application for 4 weeks with evaluations weekly during the treatment period and for 2 weeks after treatment was stopped. Vulgaris, lamellar, sex-linked, Netherton's, and epidermolytic hyperkeratotic forms of ichthyosis were significantly improved by treatment with lactate 12% lotion. This new therapeutic modality expands the scope and extent of ichthyotic conditions that may now be successfully treated.
Four full thickness cartilage defects, two linear and two elliptical, and four subchondral cavity defects were created at the point of weightbearing of the medial femoral condyle in four experimental ponies. This study showed that subchondral bone cysts can develop following full thickness (cartilage only) linear cartilage defects at a weightbearing location. Subchondral bone cysts did not develop following the removal of an elliptical piece of cartilage, exposing the subchondral bone. Primary subchondral defects created in communication with the joint cavity did not heal by replacement with bone over a six-month period. Fibrous and cartilaginous repair occurred which appeared to be unrelated to the size or depth of the subchondral defect. Irrespective of the size of the defects, the surrounding bone showed marked woven bone formation with remodelling of existing and newly formed bone. The resulting osteosclerosis indicated a positive balance and a natural limitation of cavity expansion. The positive balance affected only the surrounding bone and did not lead to re-establishment of the bone within the cavity during the period studied.
The multigene family which codes for the mouse major urinary proteins consists of about 35 genes. Most of these are members of two distinct groups, group 1 and group 2. The group 1 and group 2 genes are organized in head-to-head pairs within 12 to 15 remarkably uniform chromosomal units or domains about 45 kilobase pairs (kb) in size. The 45-kb units are located on chromosome 4, and many of them are adjacent to each other. We propose that the 45-kb unit is a unit both of organization and of evolutionary change. In this study the homologies within the unit were observed by examining, in an electron microscope, heteroduplex and foldback structures made from cloned major urinary protein genes. These show that the 45-kb unit is a gigantic imperfect palindrome. Each arm of the palindrome contains two regions of inverted symmetry of 9.5 and 4.5 kb separated by a 3-kb nonsymmetrical region. We argue that the nonsymmetrical regions arose by a series of deletion events in the two arms of the palindrome. The center of the 45-kb unit is an 8-kb sequence without inverted symmetry flanked by the 9.5-kb regions, which contain the 4-kb genes and their immediate 5' and 3' flanking regions. The junction between adjacent 45-kb units is a 2- to 4-kb sequence without inverted symmetry flanked by the 4.5-kb regions. Some of the 45-kb units are arranged as direct tandem repeats. Others appear to be in inverted orientation with respect to a neighboring unit. Cloned major urinary protein genes show few incidences of the repetitive elements B1, B2, R, and MIF. Two elements, a B1 and an R, may be a constant feature of the 45-kb units. If so, in those cases in which the units are in tandem array, both of these elements will occur with a 45-kb periodicity. A comparison of corresponding parts of different 45-kb units shows that they differ because of a number of deletion or insertion events, particularly in the regions 3' to the genes.
The multigene family which codes for the mouse major urinary proteins (MUPs) consists of approximately 35 genes. Most of these are members of two different groups, Group 1 and Group 2, which can be distinguished by nucleic acid hybridisation. By screening a Charon 4A library of mouse DNA with probes from the 5'-flanking region of a MUP gene, we have isolated clones that contain both a Group 1 and a Group 2 gene, orientated in a divergent fashion, with 15 kb of DNA between the 5' ends of the genes. We show that this pairwise arrangement is the predominant organisation of MUP genes in the BALB/c genome. We argue that the head-to-head gene pair is the unit both of DNA organisation and of evolution. Taking into account the genes themselves, the intervening 15 kb and the homologous 3'-flanking regions, this unit is approximately 45 kb long. We also show that some MUP genes may be linked in a tail-to-tail fashion with 26-28 kb between the 3' ends of two genes. This suggests that the minimum distance between successive 45-kb units is approximately 7 kb.
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The results of surgical treatment of 10 subchondral bone cysts, all located in the medial femoral condyle, are presented. A cancellous bone graft was used in nine cases and a two component acrylic bone cement was used in the case of an extremely large cyst. Eight out of the 10 cases made a satisfactory clinical recovery.