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Biomedical subjects

I R Scott

Publications and source records attributed to I R Scott.

At least 19 recordsLinked to original sources

Low doses of repetitive ultraviolet A induce morphologic changes in human skin.

Repetitive exposure of skin to sunlight is known to result in dermatoheliosis, characterized by photoaging and carcinogenesis. It has been demonstrated previously that relatively large amounts of ultraviolet (UV) A can produce photodamage and it is believed that UVB plays a major role in the induction of photodamage and photocarcinogenesis. The study reported here determines the cutaneous effects of minimal erythemal amounts of solar-simulated UV radiation as well as suberythemal and minimal erythemal doses of UVA. Previously non-sunexposed human skin was irradiated twice weekly for 24 weeks. Biopsies were obtained 12, 24 and 36 weeks after the initial irradiation and assessed for both epidermal and dermal alterations. Dermal elastic tissue content was measured via computerized image analysis. All UV treatment regimens produced observable epidermal and dermal changes. These alterations were observed after only 12 weeks of twice-weekly irradiation and were still evident 12 weeks after the final irradiation. Interestingly, UVA irradiation produced a decrease in elastic tissue content whereas solar-simulated UV produced a slight increase. Most notable were the changes produced by the suberythemal dose of UVA. Surprisingly, this relatively low UVA dose produced a reduction in elastic tissue content. The results of this investigation demonstrate that small amounts of UVA or solar-simulated UV are capable of producing cutaneous photodamage. These findings suggest that even suberythemal doses of repetitive UVA may lead to photoaging of the skin and that there is a need for daily broad spectrum UV protection.

Adult

Exchange arthroplasty for infected knee replacements. A new two-stage method.

We report a series of 17 exchange arthroplasties for infected knee prostheses, ten one-stage and seven two-stage procedures. The method proved successful in controlling infection and restoring function. In two-stage exchanges the interval between the stages was managed by using a prosthesis as a spacer, and acrylic cement beads containing the appropriate antibiotic to provide high local concentrations. Three one-stage procedures had recurrence of infection, but were successfully treated by further exchange operations. All patients had satisfactory function and there have been no serious complications. We recommend this modified two-stage technique for the management of infected knee arthroplasties.

Administration, Topical

The use of intravenous cholangiography in teaching hospitals: a survey.

Thirty academic radiology departments active in biliary imaging were surveyed to document how frequently intravenous cholangiography (IVC) was being performed. Over a 10-year period the number of examinations has decreased precipitously from approximately 1728 in 1976 to 8 in 1986. This coincides with the increased availability of alternative procedures. The availability of new contrast agents with improved diagnostic yield and decreased toxicity suggests that its use may have been prematurely abandoned.

Cholangiography

Pacemaker electrode repositioning using the loop-snare technique.

Using a percutaneous femoral vein approach under fluoroscopic control, a malpositioned ventricular pacemaker electrode was released from the right ventricular wall by hooking the lead with a deflecting wire inserted into a RIM catheter. A closed loop was formed by tightening the handle of the wire allowing the electrode to be dislodged and pulled into the inferior vena cava. The electrode was then snared using a loop formed by an exchange wire advanced through an 8 French catheter with a J-curve steamed at its tip. The electrode was advanced to the right ventricular apex and released by advancing one end of the snare wire while pulling the other end to open the loop.

Aged

Evidence for filaggrin as a component of the cell envelope of the newborn rat.

A substrate of transglutaminase, specific to the epidermis, was identified, by fluorescent and radioactive labelling with the lysine analogues dansylcadaverine and [14C]putrescine respectively, in newborn-rat epidermal homogenates and whole-skin organ cultures. The labelled analogues were preferentially incorporated into the stratum-corneum protein filaggrin in a Ca2+-dependent manner in both 'in vitro' systems. When filaggrin was labelled in vivo with [3H]histidine and then incubated with rat epidermal preparations, the label was rendered SDS/thiol-insoluble. Incorporation of [3H]filaggrin into the insoluble envelope fraction was Ca2+-dependent and inhibited by EDTA and exogenous amines. Antisera to newborn-rat filaggrin cross-reacted with purified newborn-rat cell envelopes, and this reaction was blocked by adsorbing the antiserum with purified filaggrin. Quantification of the 'envelope-bound' filaggrin showed it to be a significant component, accounting for approx. 10% of the cell-envelope protein.

Animals

Resectable stage III lung cancer: CT, surgical, and pathologic correlation.

The new International Staging System identifies a subset of patients with stage III lung cancer who have improved survival rates after surgical resection. The computed tomographic (CT), surgical, and pathologic findings in 26 patients with completely resected stage IIIa lung cancer were reviewed. Preoperative CT scans accurately demonstrated chest wall invasion in only two of ten patients with chest wall or diaphragmatic invasion. CT demonstrated pericardial involvement in only one of three patients. Tumor extension to within 2 cm of the tracheal carina was seen with CT in one of three patients. Eleven of 26 patients had limited ipsilateral mediastinal (N2) disease; eight of 11 had affected nodes greater then 10 mm on CT scans. As previously shown, CT is of limited value in the assessment of chest wall, mediastinal, pleural, or pericardial tumor extension; however, such extension does not preclude complete resection. Ipsilateral node involvement does not preclude surgery. Familiarity with the new staging system and awareness of what constitutes potentially resectable disease are necessary for an adequate assessment of CT findings.

Adult

Ruptured breast implant: computed tomographic and mammographic findings.

We report the computed tomographic and mammographic findings in a patient with a ruptured breast implant. The diagnosis was made by recognition of alteration in prosthesis contour, collapse of the prosthesis envelope, and the presence of free silicone in the breast and axillary region.

Breast

Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment.

Filaggrin is a specific epidermal protein which is the precursor of the free amino acids, urocanic acid and pyrrolidone carboxylic acid which are largely responsible for the ability of the stratum corneum of the skin to remain hydrated at low environmental humidity. The distribution of filaggrin shown by immunofluorescence in the stratum corneum of the rat changed dramatically during the first hours of postnatal life. During late foetal development, filaggrin accumulated through the entire thickness of the stratum corneum, indicating that there was a block on the subsequent processing of the protein which normally would convert it to free amino acids. Immediately after birth this block was lifted and normal proteolysis of the filaggrin took place in the outer part of the stratum corneum, leaving the normal adult pattern of a thin zone of cells containing filaggrin at the bottom of the stratum corneum. This activation of filaggrin proteolysis was dependent on the drop in external water activity caused by the transition from an aqueous environment in utero to a dryer environment after birth and it could be blocked by maintaining a 100% humidity atmosphere around the newborn rat after birth. In isolated stratum corneum in vitro, filaggrin proteolysis took place only between 80 and 95% relative humidity, both higher and lower relative humidity blocked the proteolysis. Application of occlusive patches to adult rats prevented the normal proteolysis of filaggrin, indicating that this mechanism controls not only the massive filaggrin proteolysis occurring after birth but also the proteolysis occurring during normal stratum corneum maturation. The stratum corneum therefore has the ability to respond to changes in external humidity by altering the level of the stratum corneum where it converts its reserves of filaggrin into water binding amino acids, such that under humid conditions water binding components will be produced in only the most superficial stratum corneum, or even not produced at all.

Aging

Alterations in the metabolism of filaggrin in the skin after chemical- and ultraviolet-induced erythema.

We have investigated the effect on the normal synthesis and metabolism of filaggrin of treatment of guinea pig skin with a chemical irritant, hexadecane, or with erythemal doses of UV radiation. Examination of the skin by immunofluorescence with an antiserum against filaggrin demonstrates 3 phases of the response. The first phase is an apparent stabilization of the filaggrin present at the time of treatment. Thus, a zone of stratum corneum is produced which moves up toward the skin surface over the days following treatment, without the loss of immunoreactivity which normally results from the metabolism of filaggrin to free amino acids. The second phase of the reaction, which occurs during the first day after treatment, is a loss of immunoreactive material from the upper viable epidermis, which results over the next day in the formation of a zone of filaggrin-deficient stratum corneum. The third phase, 2-3 days after the treatment, is the reestablishment of immunoreactivity in the newly re-formed granular layer, followed by the formation of an immunoreactive zone at the bottom of the stratum corneum. This zone remains very thin despite the rapid passage of cells through it. This shows that the filaggrin being formed during this phase of the reaction is being broken down normally as the stratum corneum matures. Investigations of the kinetics of filaggrin synthesis and breakdown using a [3H]histidine pulse/chase method, confirm the impression gained from immunofluorescence studies that the time between formation and breakdown of the filaggrin is much reduced in the hyperplastic epidermis resulting from the irritation. Thus, although the hyperplasia is reflected in a thickening of malpighian and granular layers of the epidermis, it does not result in any thickening of the filaggrin-positive zone at the bottom of the stratum corneum. This suggests the action of a control mechanism designed to prevent the extension of this filaggrin-positive zone into the upper stratum corneum.

Alkanes

Late paraplegia as a consequence of intraaortic balloon pump support.

There have been several reports of paraplegia after intraaortic balloon counterpulsation in the surgical literature. In each instance, the paraplegia occurred during the period of counterpulsation support. We describe a patient in whom late paraplegia occurred three days after the removal of an intraaortic balloon catheter.

Aged

Markers of epidermal differentiation expressed by rat keratinocytes cultured by a modified feeder layer technique.

A broad range of analytical methods has been used to investigate the expression of key differentiation markers in keratinocytes cultured by a modified feeder layer technique. Cultures were stratified and showed many of the features characteristic of epidermal differentiation in vivo including tonofilaments, desmosomes, loss of organelles and thickening of the plasma membrane to form the cornified envelope. Profilaggrin synthesis was detected by 32P-incorporation and the presence of filaggrin suggested that it was broken down by the normal route. Staining with the lectin from Ulex europeus revealed the presence of a fucose-containing cell-surface glycoprotein. Keratin synthesis was shown by 3H-leucine incorporation and keratins were analysed by two-dimensional gel electrophoresis in comparison with those from different levels of the epidermis. Quantitative and qualitative differences were found between in vivo and in vitro epidermal differentiation. In particular, cornified envelope numbers were low, in keeping with the observation by electron microscopy of only one layer of cells with this structure. The absence of a true stratum corneum in vitro was also indicated by the virtual absence of histidase activity and stratum corneum keratins. The keratin species present in vitro most closely resembled those of the basal cells of the epidermis, although even in this case differences were observed. The evidence as a whole is consistent with the belief that epidermal cells do synthesise in vitro many of the important proteins involved in differentiation, but that they nevertheless do not develop a true keratinised stratum corneum.

Animals

Histidine-rich proteins (filaggrins): structural and functional heterogeneity during epidermal differentiation.

The urea-soluble protein profiles of guinea pig, rat, mouse and human epidermis have been compared by non-equilibrium pH gradient/sodium dodecyl sulphate two-dimensional gel electrophoresis. The histidine-rich proteins (filaggrins) were identified firstly by their characteristic specificity and kinetics of labelling with [3H]histidine and [32P]phosphate, and secondly by their ability in vitro to aggregate keratin filaments specifically into bundles. In all species the phosphorylated filaggrin precursor, profilaggrin, is resolved as a single or doublet band with an apparent molecular weight greater than 300,000 and a neutral or slightly acidic iso-electric point. In striking contrast, the strongly basic filaggrins produced from similar profilaggrins form molecular weight families that are clearly species specific. In rat and man there is a single, principal molecular weight form of filaggrin (Mr 45,000 and 38,000, respectively), while mouse and guinea pig have heterogeneous families, including high molecular weight variants (Mr greater than 200,000). Even filaggrins of a particular molecular weight are not homogeneous proteins, but consist of a number of iso-electric variants, some of which are considerably less basic than the bulk of the filaggrins. Incorporation studies using [3H]arginine and [32P]phosphate indicate that the iso-electric variance is not due to residual phosphate, following profilaggrin breakdown, but rather to a conversion of basic arginine residues into neutral citrulline residues. Filaggrins of all the molecular weights from all the species studied share the ability to aggregate keratin filaments into large, insoluble macrofibrils. However, the more acidic iso-electric variants have lower affinities for keratin, particularly in man and guinea pig where the most acidic filaggrins have completely lost the ability to aggregate keratins. We discuss the possibility that a loss of keratin binding ability, resulting in a loosening of the keratin fibre/filaggrin matrix is necessary before the normal complete proteolysis of the filaggrins can occur.

Amino Acids

Fluorography--limitations on its use for the quantitative detection of 3H- and 14C-labeled proteins in polyacrylamide gels.

The suitability of fluorography for the detection of 3H- and 14C-labeled proteins on polyacrylamide gradient gels has been investigated. It was found that the absorbance of the fluorographic film image produced by a given level of radioactivity decreased as the acrylamide concentration in the gel increased. The use of Coomassie brilliant blue protein dyes to stain the gel prior to fluorography reduced the absorbance of the fluorographic image. It is concluded that quantitative fluorography can only be applied to unstained gels of a uniform acrylamide concentration.

Animals

Pyrrolidone carboxylic acid synthesis in guinea pig epidermis.

To establish the in vivo mechanism of synthesis and accumulation of epidermal pyrrolidone carboxylic acid (PCA), enzymes potentially capable of PCA synthesis have been quantified and located within the guinea pig epidermis. Intermediates in the synthesis of [3H]PCA from a pulse of [3H]glutamine have been identified and quantified to determine which of the several possible metabolic routes occurs in vivo. PCA appears to be synthesized from substrate derived from the breakdown within the stratum corneum of protein synthesized several days earlier. The predominant route is probably via the nonenzymic cyclization of free glutamine liberated from this protein. In view of the high activity of gamma-glutamyl cyclotransferase in the stratum corneum, a minor contribution to PCA formation by the action of the enzyme on gamma-glutamyl peptides cannot be excluded.

Animals