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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 253 records · Page 14Linked to original sources
PubMed1997

Organization of fibrillar collagen in the human and bovine cornea: collagen types V and III.

The localization and fibrillar organization of collagen types V and III in the human and bovine corneal stromas were studied. In the chicken cornea, type V co-assembles with type I collagen as heterotypic fibrils and this interaction is involved in the regulation of fibril diameter necessary for corneal transparency. To determine whether this is a regulatory mechanism common to the corneas of different species the human and bovine corneal stroma were studied. Collagen type V was found in the epithelium and Bowman's membrane in the untreated adult human and bovine cornea using immunofluorescence microscopy. In the absence of any treatment, there was no type V reactivity within the stroma. However, type V collagen was detected homogeneously throughout the corneal stroma after treatments that partially disrupt fibril structure. The reactivity was strongest in the cornea, weaker in the limbus and weakest in the sclera. Fetal corneas showed similar reactivity for type V collagen, but unlike the adult, the stroma was slightly reactive. Immunoelectron microscopy demonstrated that type V collagen was associated with disrupted, but not with intact, fibrils in both human and bovine corneal stroma. Type III collagen reactivity was not detected in the cornea, but was present subepithelially in the limbus and in the scleral stroma. These data indicate that type V collagen is a component of striated collagen fibrils throughout the human and bovine corneal stromas. The interaction of type I and V collagen as heterotypic fibrils masks the helical epitope recognized by the monoclonal antibody against type V collagen. The heterotypic interactions of collagen type V indicate a role in the regulation of fibril diameter analogous to that described in the avian cornea.

Adult↗
PubMed1997

A case of factor V deficiency presenting as menorrhagia.

Factor V deficiency is a rare hereditary disorder. We report a patient with factor V deficiency who presented with menorrhagia and pelvic haematoma. The Haematology Department at the Royal Brisbane Hospital performed the definitive factor assays leading to the diagnosis. The challenges of her management were obtaining adequate supplies of factor V and her socioeconomic circumstances. The main future challenge will be the supervision of her pregnancies.

Adult↗
PubMed1997

Thrombin activity associated with indwelling central venous catheters.

Thrombotic complications are frequent with indwelling central venous catheters and result in catheter dysfunction, vascular obstruction and may also contribute to catheter-associated infections. The pathogenesis of catheter thrombosis is not well characterized but may involve vessel damage, local stasis and catheter-associated thrombin formation. We have, therefore, measured the thrombin activity associated with central venous catheters removed from patients and have also determined the ability of hirudin to inactivate catheter-associated thrombin. We obtained 48 catheters from 46 patients and removed 1 cm portions for study. These were taken from the distal end, 5 cm proximal, and 15 cm proximal from the end. Following washing, thrombin activity was measured with a chromogenic assay. Thrombin was associated with 40 of 48 catheters and with 100 of 144 segments with a mean activity of 132 +/- 27 microU/cm with a range of 0 to 2,160 microU/cm. Incubation in hirudin reduced the activity from a mean of 122 +/- 33 microU/cm to 18 +/- 6 microU/cm (p < .001). Scanning electron microscopy of selected catheters showed that some had areas of fibrin deposition which was not apparent visually. The findings indicate that indwelling central venous catheters frequently have associated thrombin activity which can be inhibited by a direct-acting thrombin inhibitor such as birudin.

Catheterization, Central Venous↗
PubMed1997

500 total extraperitoneal approach laparoscopic herniorrhaphies: a single-institution review.

At Georgia Baptist Medical Center, a community-based, university-affiliated hospital, we adopted the total extraperitoneal approach (TEPA) to laparoscopic herniorrhaphy due to potential complications in entering the abdominal cavity reported previously with the transabdominal preperitoneal technique (Am Surg 1996;62:69-72). We have also employed regional anesthesia (epidural) in 108 patients in whom the TEPA was utilized. In our institution, the TEPA has compared favorably to the transabdominal preperitoneal technique, with lower complication and recurrence rates. In patients with previous lower abdominal surgery, the TEPA is considered a relative contraindication due to the increased risk of complications (Am Surg 1997, in press). Since June 1993, we have performed 503 laparoscopic herniorrhaphies using the TEPA, with encouraging early results. To date, two recurrences have been reported, one with previous lower abdominal surgery and another whose recurrence was noted to be secondary to incomplete reapproximation of the mesh with staples around the cord structures. Four major complications include two bowel perforations and two cystotomies noted during balloon dissection of the preperitoneal space. Three of these patients had previous lower abdominal surgery. Epidural anesthesia was used in 108 patients, 4 of whom required conversion to general anesthesia due to peritoneal tears and pain associated with pneumoperitoneum. All four of these patients had previous lower abdominal surgery. In summary, the TEPA remains a viable technique for laparoscopic herniorrhaphy with acceptable complication and recurrence rates. Epidural anesthesia is well tolerated by the patients undergoing this particular repair. We feel that lower abdominal surgery may be a mitigating factor in selection of the TEPA. Continued re-evaluation of the procedure is warranted before definitive conclusions can be made.

Adolescent↗
PubMed1997

The design and introduction of videos and leaflets.

This article describes how the staff within the theatre department at Neath General Hospital, Glan-y-Mor NHS Trust, South Wales, developed patient information videos and leaflets for adults and children which will be used to support their pre-operative visiting programme.

Adult↗
PubMed1996

Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44.

Fibrosis results when myofibroblasts invade the wound fibrin provisional matrix. Extracellular matrix receptors on the cell surface mediate cell adhesion, migration, and invasion. Recent work with transformed cells indicates that these cells use the cell surface matrix receptor CD44 for migration and invasion. In this study, we examine whether lung fibroblasts, isolated from patients dying with acute alveolar fibrosis, use CD44 to invade a fibrin matrix. Consistent with a role for CD44 in mediating fibroblast invasion and subsequent tissue fibrosis, immunohistochemical analysis of lung tissue from patients who died from acute alveolar fibrosis after lung injury reveals CD44-expressing mesenchymal cells throughout newly formed fibrotic tissue. PCR, Western, and immunoprecipitation analysis demonstrate that the 85-kD CD44 isoform is expressed by acute lung injury fibroblasts. Consistent with a role in mediating matrix adhesion and migration ultrastructurally, CD44 was found uniformly over the cell surface and was found densely labeling filopodia and lamellipodia, highly motile structures involved in cell migration. To determine if lung injury fibroblasts use CD44 to invade fibrin, a fibrin gel model of fibrosis was used. By blocking the function of CD44 with monoclonal antibodies, fibroblast invasion into a fibrin matrix was inhibited. To examine the mechanism by which CD44 mediates fibroblast invasion, the role of CD44 in fibroblast migration and adhesion was evaluated. Anti-CD44 antibody blocked fibroblast migration on the provisional matrix proteins fibronectin, fibrinogen, and hyaluronic acid. Additionally, fibroblast CD44 mediated adhesion to the provisional matrix proteins fibronectin, fibrin, and hyaluronic acid, but not to laminin, a component of the basement membrane. These findings support the hypothesis that fibroblast CD44 functions as an adhesion receptor for provisional matrix proteins and is capable of mediating fibroblast migration and invasion of the wound provisional matrix resulting in the formation of fibrotic tissue.

Cell Adhesion↗
PubMed1996

A chemical-detecting system based on a cross-reactive optical sensor array.

The vertebrate olfactory system has long been recognized for its extraordinary sensitivity and selectivity for odours. Chemical sensors have been developed recently that are based on analogous distributed sensing properties, but although an association between artificial devices and the olfactory system has been made explicit in some previous studies, none has incorporated comparable mechanisms into the mode of detection. Here we describe a multi-analyte fibre-optic sensor modelled directly on the olfactory system, in the sense that complex, time-dependent signals from an array of sensors provide a 'signature' of each analyte. In our system, polymer-immobilized dye molecules on the fibre tips give different fluorescent response patterns (including spectral shifts, intensity changes, spectral shape variations and temporal responses) on exposure to organic vapours, depending on the physical and chemical nature (for example, polarity, shape and size) of both the vapour and the polymer. We use video images of temporal responses of the multi-fibre tip as the input signals to train a neural network for vapour recognition. The system is able to identify individual vapours at different concentrations with great accuracy. 'Artificial noses' such as this should have wide potential application, most notably in environmental and medical monitoring.

Biosensing Techniques↗
PubMed1996

Four-dimensional imaging: computer visualization of 3D movements in living specimens.

The study of many biological processes requires the analysis of three-dimensional (3D) structures that change over time. Optical sectioning techniques can provide 3D data from living specimens; however, when 3D data are collected over a period of time, the quantity of image information produced leads to difficulties in interpretation. A computer-based system is described that permits the analysis and archiving of 3D image data taken over time. The system allows a user to roam through the full range of time points and focal planes in the data set. The user can animate images as an aid to visualization and can append multicolored labels and text notes to identified structures during data analysis. The system provides a valuable tool for the study of embryogenesis and cytoplasmic movements within cells and has considerable potential as an educational tool.

Animals↗
PubMed1996

Identification and characterization of 1,25-dihydroxyvitamin D3-responsive repressor sequences in the rat parathyroid hormone-related peptide gene.

Parathyroid hormone-related peptide (PTHRP) gene transcription is suppressed by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3. In the present report, we examined 1, 25(OH)2D3-mediated repression of PTHRP expression by transfection of PTHRP promoter/reporter constructs in normal human keratinocytes and by DNA binding. We localized an element conferring 1, 25(OH)2D3-mediated repression in vivo to a 47-base pair (bp) region located -1121 to -1075 from the transcriptional start site. Mobility shift analysis revealed that this vitamin D response element (VDRE) forms DNA-protein complexes. The addition of a monoclonal antibody that recognizes the DNA binding region of the vitamin D receptor (VDR) attenuated binding of the receptor to the 47-bp sequence, whereas the addition of monoclonal antibody raised against the retinoid X receptor (RXR) further retarded the mobility of the protein-DNA complex. Consequently, the PTHRP promoter element binds a VDR.RXR heterodimer. Examination of this VDRE revealed complete sequence homology with a half-site of the human and rat osteocalcin VDRE (GGGTGA). Furthermore, mutation analysis suggests that a 16-bp domain consisting of an almost perfect repeat separated by a 3-base pair "spacer" GGGTGGAGAGGGGTGA is responsible for the DNA-protein interaction within this 47-bp sequence. Our results therefore indicate the existence of an inhibitory VDRE within the PTHRP promoter that is similar in sequence composition and cellular factor requirement to classical up-regulatory VDREs.

Animals↗
PubMed1996

Structure-based design of lipophilic quinazoline inhibitors of thymidylate synthase.

To develop novel lipophilic thymidylate synthase (TS) inhibitors, the X-ray structure of Escherichia coli TS in ternary complex with FdUMP and the inhibitor 10-propargyl-5,8-dideazafolic acid (CB3717) was used as a basis for structure-based design. A total of 31 novel lipophilic TS inhibitors, lacking a glutamate residue, were synthesized; 26 of them had in common a N-((3,4-dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylaniline+ ++ structure in which the aniline was appropriately substituted with simple lipophilic substituents either in position 3 or 4, or in both. Compounds were tested for their inhibition of E. coli TS and human TS and also for their inhibition of the growth in tissue culture of a murine leukemia, a human leukemia, and a thymidine kinase-deficient human adenocarcinoma. The crystal structures of five inhibitors complexed with E. coli TS were determined. Five main conclusions are drawn from this study. (i) A 3-substituent such as CF(3), iodo, or ethynyl enhances binding by up to 1 order of magnitude and in the case of CF(3) was proven to fill a nearby pocket in the enzyme. (ii) A simple strongly electron-withdrawing substituent such as NO(2) or CF(3)SO(2) in the 4-position enhances binding by 2 orders of magnitude; it is hypothesized that the transannular dipole so induced interacts favorably with the protein. (iii) Attempts to combine the enhancements of i and ii in the same molecule were generally unsuccessful (iv) A 4-C(6)H(5)SO(2) substituent provided both electron withdrawal and a van der Waal's interaction of the phenyl group with a hydrophobic surface at the mouth of the active site. The inhibition (K(is) = 12 nM) of human TS by this compound, 7n, showed that C(6)H(5)SO(2) provided virtually as much binding affinity as the CO-glutamate which it had replaced. (v) The series of compounds were poorly water soluble, and also the potent TS inhibition shown by several of them did not translate into good cytotoxicity. Compounds with large cyclic groups linked to position 4 by an SO or SO(2) group did, however, have IC(50)'s in the range 1-5 microM. Of these, 4-(N-((3,4-dihydro-2-methyl-6-quinazolinyl)methyl)-N-prop-2-ynylamino )phenyl phenyl sulfone, 7n, had IC(50)'s of about 1 microM and was chosen for further elaboration.

Adenocarcinoma↗
PubMed1996

Dibenzoxepinone hydroxylamines and hydroxamic acids: dual inhibitors of cyclooxygenase and 5-lipoxygenase with potent topical antiinflammatory activity.

Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5-lipoxygenase (5-LO) inhibitory properties. Many of these new dual CO/5-LO inhibitors also exhibit potent topical antiinflammatory activity in the arachidonic acid-induced murine ear edema model. On the basis of their promising profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro-11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25, 3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294), were selected as developmental candidates for the topical treatment of inflammatory skin disorders.

3T3 Cells↗
PubMed1996

Distribution within the choroid of cholinergic nerve fibers from the ciliary ganglion in pigeons.

The distribution of the ciliary ganglion (CG) innervation to the pigeon choroid was determined immunohistochemically, using antisera against choline acetyltransferase (CHAT) and a neurofilament-related protein (the 3A10 antigen). Single-labeling revealed that the nerve fibers containing these two antigens were similarly distributed in the pigeon choroid, with the superior and temporal quadrants of the eye containing the most fibers. Both types of fibers surrounded and ramified on choroidal blood vessels. Additionally, CHAT+ varicosities were evident among vessels in the choroid and choriocapillaris. Double-label immunofluorescence revealed that CHAT and the 3A10 antigen were almost completely colocalized in choroidal nerve fibers, but absent from CHAT+ varicosities. Substance P-containing and calcitonin gene-related peptide-containing choroidal nerve fibers were poor in 3A10+ labeling. Transection of the postganglionic fibers of the CG reduced CHAT+ and 3A10+ nerve fibers in the choroid to 3-5% of normal abundance, with most of the residual fibers being located in the nasal and inferior quadrants. The present results suggest that the CG in pigeon preferentially influences choroidal blood flow in the superior and temporal parts of the eye, which are involved in high acuity and binocular vision.

Animals↗
PubMed1996

Synthesis of plasminogen activator inhibitor 1 by bovine mammary epithelial and myoepithelial cell lines.

Conversion of plasminogen to plasmin provides an important source of proteolytic activity in the bovine mammary gland. Plasminogen activator inhibitor 1 (PAI-1) plays a key role in limiting plasminogen activation. The PAI-1 biosynthetic capabilities of various bovine mammary cells were determined. The immortalized epithelial cell lines MAC-T and BME-UV and the myoepithelial cell line BMM-UV were used as model systems. Northern blot analysis indicated that both epithelial and myoepithelial cells contained PAI-1 mRNA. Bovine PAI-1 was encoded by a single mRNA species approximately 3.0 kb long. BME-UV cells contained 2.0-fold (P < 0.01) the PAI-1 mRNA of MAC-T or BMM-UV cells. Reverse zymography indicated that both epithelial and myoepithelial cells synthesized PAI-1 protein with a molecular mass of approximately 50 kDa.

Animals↗