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Biomedical subjects

A J Cox

Publications and source records attributed to A J Cox.

At least 55 records · Page 3Linked to original sources

Delineation of atypical insulin receptors from classical insulin and type I insulin-like growth factor receptors in human placenta.

Insulin-like growth factor (IGF)-binding sites copurifying with human placental insulin receptors during insulin-affinity chromatography consist of two immunologically distinct populations. One reacts with monoclonal antibody alpha IR-3, but not with antibodies to the insulin receptor, and represents Type I IGF receptors; the other reacts only with antibodies to the insulin receptor and is precipitated with a polyclonal receptor antibody (B-10) after labelling with 125I-multiplication-stimulating activity (MSA, rat IGF-II). The latter is a unique sub-population of atypical insulin receptors which differ from classical insulin receptors by their unusually high affinity for MSA (Ka = 2 x 10(9) M-1 compared with 5 x 10(7) M-1) and relative potencies for insulin, MSA and IGF-I (40:5:1 compared with 150:4:1). They represent 10-20% of the total insulin receptor population and account for 25-50% of the 125I-MSA binding activity in Triton-solubilized placental membranes. Although atypical and classical insulin receptors are distinct, their immunological properties are very similar, as are their binding properties in response to dithiothreitol, storage at -20 degrees C and neuraminidase digestion. We conclude that atypical insulin receptors with moderately high affinity for IGFs co-exist with classical insulin receptors and Type I IGF receptors in human placenta. They provide an explanation for the unusual IGF-II binding properties of human placental membranes and may have a specific role in placental growth and/or function.

Antibodies, Monoclonal↗

Infection of catheterised patients: bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy.

The surfaces of 32 encrusted urinary catheters were examined by scanning electron microscopy to investigate the association of bacteria with the encrusting deposits. Deposits consisted of struvite crystals surrounded by aggregates of very small crystallites of hydroxyapatite. Underneath these minerals there was a layer of closely packed bacteria. Impressions of bacteria were also observed in hydroxyapatite. Crystals were often engulfed by the bacterial layer, which thus appeared to bind the crystals to each other and to the catheter surface. This thick layer of bacteria associated with crystals may protect both the bacteria from antibiotics and the crystals from acidic bladder washout solutions intended to dissolve them. Furthermore, the existence of this sessile population explains why urease-producing bacteria are not invariably detected in the urine of patients with encrusted catheters. The observation of this bacterial layer (or "biofilm") by scanning electron microscopy provided direct evidence for infection being implicated in catheter encrustation.

Bacterial Adhesion↗

Resistance of catheters coated with a modified hydrogel to encrustation during an in vitro test.

Mid-shaft specimens were cut from latex catheters coated with a modified hydrogel, latex catheters coated with silicone elastomer, and 100% silicone catheters. These specimens were subjected to controlled in vitro encrustation conditions. During a test period of 11 weeks, there was no significant difference in the quantities of encrusting deposits formed on the three materials.

Catheters, Indwelling↗

Calcium environment in encrusting deposits from urinary catheters investigated by interpretation of EXAFS spectra.

Extended x-ray absorption fine structure (EXAFS) spectra were recorded, above the K absorption edge of Ca, from 10 encrusted urinary (Foley) catheters obtained from 10 different patients. The presence of poorly crystalline apatite was demonstrated in all the deposits, even though this phase could not be detected in the x-ray powder diffraction patterns of most samples because of the obscuring effect of struvite, which was also present. Furthermore, the EXAFS spectra could be interpreted to yield quantitative information on the average short-range structure surrounding the Ca2+ ions in the poorly crystalline apatite.

Calcium↗

Morphology of mineral deposits on encrusted urinary catheters investigated by scanning electron microscopy.

Struvite and hydroxyapatite were precipitated from artificial urine onto the surfaces of catheter materials by the controlled addition of urease. They were precipitated both together and separately (by omitting components of the artificial urine), and with and without the inclusion of albumin (which was intended to mimic the proteinaceous debris found in infected urine). Precipitates were identified by X-ray powder diffraction and the artificially encrusted surfaces examined by scanning electron microscopy. In the presence of protein, hydroxyapatite was precipitated as a poorly crystalline form which aggregated to form a crust. Struvite crystals could be easily identified under the scanning electron microscope by their relatively large size and characteristic appearance. Fifteen encrusted catheters from patients were also examined by scanning electron microscopy, and a further six using X-ray microanalysis. Their appearance was very similar to that of the materials encrusted in vitro. Encrustation involves the formation of hydroxyapatite and the growth of struvite crystals, intimately associated with bacteria.

Durapatite↗

Resistance of conformable indwelling urinary catheters to encrustation.

Conformable and conventional indwelling urinary catheters, made of latex coated with Teflon and of the same nominal size, were encrusted in vitro. The extent of encrustation was quantified by dissolving the deposits, determining the concentrations of calcium and magnesium in the resulting solutions (by atomic adsorption spectroscopy), and calculating the surface densities of calcium and magnesium. Surface densities of both elements were significantly less on the conformable than on the conventional catheters. This result can be explained by the pulsed flow of urine through the conformable catheter tending to dislodge deposits adhering to its inner surface. A similar action is expected to occur in vivo.

Calcium↗

Effect of a hydrogel coating on the surface topography of latex-based urinary catheters: an SEM study.

The hydrated surface of a hydrogel-coated latex urinary catheter has been examined using low temperature SEM, and its appearance compared with those of some other catheter surfaces. The effect of the coating is to smooth over most of the ripples and fissures of the underlying latex. On hydration the hydrogel surface becomes even smoother, with shallower furrows. The surface topography compares favourably with that of 100% silicone, which has a uniformly rippled yet smooth appearance.

Catheters, Indwelling↗

Calcium phosphate in catheter encrustation.

Encrusted catheters from nine female patients were the source of samples of deposits which were examined by X-ray diffraction, atomic absorption spectroscopy, infra-red spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. In eight samples the only crystalline phase which could be clearly distinguished by X-ray diffraction was ammonium magnesium orthophosphate hexahydrate, NH4MgPO4 X 6H2O, which occurs naturally as the mineral struvite. However, atomic absorption spectroscopy revealed an appreciable concentration of calcium in all samples. Calcium phosphates have previously been detected in catheter deposits. Infra-red and EXAFS spectra were consistent with the calcium phosphate being present as a poorly crystalline hydroxyapatite. Thus the deposits appear to consist of a mixture of crystalline struvite and a form of hydroxyapatite which is not fully crystalline.

Catheters, Indwelling↗

Immunohistologic patterns of congenital nevocellular nevi.

To establish sensitive histologic criteria for small congenital nevi (SCN), we examined 29 biopsy specimens of SCN from patients younger than age 1 year by serial sectioning and S100 immunoperoxidase staining. The depth of papillary and reticular dermal infiltration was variable; only the results of six biopsy specimens contained nevomelanocytes in the lower third of reticular dermis. However, all cases had focal nevomelanocytic involvement of adnexa at the midreticular dermis or below (26 of 29 cases in eccrine and 15 of 29 in pilosebaceous structures). Follow-up specimens in ten patients were obtained (mean interval, 10.25 years), and no difference in histologic pattern or cytology was observed. There were variable size increases in the surface area of SCN, ranging from no increase to a maximal ninefold increase.

Biopsy↗

The occurrence of vitiligo after psoralens and ultraviolet a therapy.

The ability of photochemotherapy with 8-methoxypsoralen in conjunction with high-intensity long-wave ultraviolet light (PUVA) to stimulate melanogenesis is well known. This effect on the pigmentary system is evidenced by the diffuse tanning of clinically normal skin in PUVA-treated patients with psoriasis and other disorders, as well as by the repigmentation of lesions in vitiligo. It is now recognized that there may be additional pigmentary effects, resulting in clinical lesions such as PUVA mottling, PUVA lentigines, and localized hypopigmentation. We have documented the occurrence of yet another association with PUVA therapy--the paradoxical appearance of widespread hypopigmentation consistent with vitiligo in three PUVA-treated patients, one with psoriasis and two with mycosis fungoides. Histologic and ultrastructural findings are presented.

Aged↗

Long-term risks of psoralen and UV-A therapy for psoriasis.

It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A [PUVA]) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurely induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.

Animals↗

Epidermal dystrophy and actinic keratoses in psoriasis patients following oral psoralen photochemotherapy (PUVA). Follow-up study.

Focal dystrophy of epidermal cells, which was initially reported in 19 of 37 patients with psoriasis who had been treated with psoralen and ultraviolet A (PUVA), has now been observed in more than half of 70 patients 1 year or more following onset of PUVA therapy. These dystrophic changes, which are similar to those found in actinic keratoses, were present in clinically uninvolved skin of sunlight-protected and sunlight-exposed areas. Control biopsies obtained prior to PUVA therapy of non-sun-exposed skin in 62 patients and sun-exposed skin of 22 of these revealed no such changes. The presence of epidermal dystrophic changes in 9 patients who had a several-month interruption in PUVA therapy indicates that these changes cannot all be attributed to acute effects of PUVA. In 104 PUVA-treated patients returning for dermatologic follow-up after the first year of therapy, 17 (16.3%) developed actinic keratoses during the course of, or following the cessation of, treatment with PUVA. Careful examination of these patients prior to PUVA therapy had revealed no such lesions. In the majority of patients, keratoses were multiple; they occurred in sun-exposed areas, suggesting a possible acceleration or promotion by PUVA of actinically induced lesions.

Biopsy↗

Cultured human epidermal cells do not synthesize HLA-DR.

All nucleated cells express HLA-A, B, and C antigens. However, only a few cells, including epidermal cells, demonstrate HLA-DR antigens which are potent transplantation immunogens in man. The current study was undertaken to determine if epidermal cell continue to synthesize and/or express HLA-DR antigens after prolonged in vitro culture. Epidermal cells cultured for 7 days or more no longer stimulated allogeneic lymphocytes in the epidermal cell-lymphocyte reaction. Indirect immunofluorescence light microscopy of cultured cells using mouse monoclonal antibody to HLA-DR antigen confirmed that these cells do not express HLA-DR antigens whereas they retain beta 2-microglobulin. Detergent extracts of 12-day cultured epidermal cells biosynthetically labeled with 35 S-methionine were immunoprecipitated with monoclonal anti-DR antibody and analyzed by the method of two-dimensional polyacrylamide gel electrophoresis. No radiolabeled proteins were found on these gels in the regions where HLA-DR molecules are known to migrate. These data indicate that HLA-DR antigen is absent from cultured epidermal cells. Finally, we describe a technique for growing epidermal cells on a gelatin membrane which allows subsequent removal of intact cell monolayers from the culture dish. Such monolayers may be useful for purposes of transplantation.

Cells, Cultured↗