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Biomedical subjects

J T White

Publications and source records attributed to J T White.

At least 19 recordsLinked to original sources
PubMed2001

Support for the multigenic hypothesis of amyloidosis: the binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influences transthyretin amyloidogenicity in vitro.

The amyloidoses are a large group of protein misfolding diseases. Genetic and biochemical evidence support the hypothesis that amyloid formation from wild-type or 1 of 80 sequence variants of transthyretin causes the human amyloid diseases senile systemic amyloidosis or familial amyloid polyneuropathy, respectively. The late onset and variable penetrance of these diseases has led to their designation as multigenic--implying that the expression levels and alleles of multiple gene products influence the course of pathology. Here we show that the binding stoichiometry of three interacting molecules, retinol-binding protein, vitamin A, and L-thyroxine, notably influenced transthyretin amyloidogenicity in vitro. At least 70 genes control retinol-binding protein, vitamin A, and L-thyroxine levels in plasma and have the potential to modulate the course of senile systemic amyloidosis or familial amyloid polyneuropathy.

Amyloidosis↗
PubMed2001

An engineered transthyretin monomer that is nonamyloidogenic, unless it is partially denatured.

Transthyretin (TTR) is a soluble human plasma protein that can be converted into amyloid by acid-mediated dissociation of the homotetramer into monomers. The pH required for disassembly also results in tertiary structural changes within the monomeric subunits. To understand whether these tertiary structural changes are required for amyloidogenicity, we created the Phe87Met/Leu110Met TTR variant (M-TTR) that is monomeric according to analytical ultracentrifugation and gel filtration analyses and nonamyloidogenic at neutral pH. Results from far- and near-UV circular dichroism spectroscopy, one-dimensional proton NMR spectroscopy, and X-ray crystallography, as well as the ability of M-TTR to form a complex with retinol binding protein, indicate that M-TTR forms a tertiary structure at pH 7 that is very similar if not identical to that found within the tetramer. Reducing the pH results in tertiary structural changes within the M-TTR monomer, rendering it amyloidogenic, demonstrating the requirement for partial denaturation. M-TTR exhibits stability toward acid and urea denaturation that is nearly identical to that characterizing wild-type (WT) TTR at low concentrations (0.01-0.1 mg/mL), where monomeric WT TTR is significantly populated at intermediate urea concentrations prior to the tertiary structural transition. However, the kinetics of denaturation and fibril formation are much faster for M-TTR than for tetrameric WT TTR, particularly at near-physiological concentrations, because of the barrier associated with the tetramer to folded monomer preequilibrium. These results demonstrate that the tetramer to folded monomer transition is insufficient for fibril formation; further tertiary structural changes within the monomer are required.

Amino Acid Substitution↗
PubMed2001

Prostate short-chain dehydrogenase reductase 1 (PSDR1): a new member of the short-chain steroid dehydrogenase/reductase family highly expressed in normal and neoplastic prostate epithelium.

Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma. We used cDNA microarrays comprised of prostate-derived cDNAs to profile transcripts regulated by androgens in prostate cancer cells. This study identified a novel gene that we have designated prostate short-chain dehydrogenase/reductase 1 (PSDR1), that exhibits increased expression on exposure to androgens in the LNCaP prostate cancer cell line. Northern analysis demonstrated that PSDR1 is highly expressed in the prostate gland relative to other normal human tissues. The PSDR1 cDNA and putative protein exhibit homology to the family of short-chain dehydrogenase/reductase enzymes and thus identify a new member of this family. Cloning and analysis of the putative PSDR1 promoter region identified a potential androgen-response element. We used a radiation-hybrid panel to map the PSDR1 gene to chromosome 14q23-24.3. In situ hybridization localizes PSDR1 expression to normal and neoplastic prostate epithelium. These results identify a new gene involved in the androgen receptor-regulated gene network of the human prostate that may play a role in the pathogenesis of prostate carcinoma.

Amino Acid Sequence↗
PubMed2000

PART-1: a novel human prostate-specific, androgen-regulated gene that maps to chromosome 5q12.

Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma. We used cDNA microarrays containing 1500 prostate-derived cDNAs to profile transcripts regulated by androgens in prostate cancer cells. This study identified a novel gene that we have designated PART-1 (prostate androgen-regulated transcript 1), which exhibited increased expression upon exposure to androgens in the LNCaP prostate cancer cell line. Northern analysis demonstrated that PART-1 is highly expressed in the prostate gland relative to other normal human tissues and is expressed as different transcripts using at least three different polyadenylation signals. The PART-1 cDNA and putative protein are not significantly homologous to any sequences in the nonredundant public sequence databases. Cloning and analysis of the putative PART-1 promoter region identified a potential binding site for the homeobox gene PBX-la, but no consensus androgen response element or sterol-regulatory element binding sites were identified. We used a radiation hybrid panel and fluorescence in situ hybridization to map the PART-1 gene to chromosome 5q12, a region that has been suggested to harbor a prostate tumor suppressor gene. These results identify a new gene involved in the androgen receptor-regulated gene network of the human prostate that may play a role in the etiology of prostate carcinogenesis.

Amino Acid Sequence↗
PubMed1999

Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2.

Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma. We used cDNA microarrays containing 1500 cDNAs to profile transcripts regulated by androgens in prostate cancer cells and identified the serine protease TMPRSS2 as a gene exhibiting increased expression upon exposure to androgens. The TMPRSS2 gene is located on chromosome 21 and contains four distinct domains, including a transmembrane region, indicating that it is expressed on the cell surface. Northern analysis demonstrated that TMPRSS2 is highly expressed in prostate epithelium relative to other normal human tissues. In situ hybridization of normal and malignant prostate tissues localizes TMMPRSS2 expression to prostate basal cells and to prostate carcinoma. These results suggest that TMPRSS2 may play a role in prostate carcinogenesis and should be investigated as a diagnostic or therapeutic target for the management of prostate cancers.

Androgens↗
PubMed1994

Blood-flow mapping of oral tissues by laser Doppler flowmetry.

The purpose of this study was to develop a rapid protocol for noninvasive quantification of blood flow at intraoral sites by laser Doppler flowmetry. For each flow measurement, the lowest flow observed over a 30-s period was recorded. Three flow readings at each site were averaged and recorded. Forehead and dorsal right-hand blood flows measured agreed with previous laser Doppler flow measurements. Flows measured with a hand-held probe were not different from flows measured with a stent-stabilized probe on the attached gingiva and an adhesive-stabilized probe on the dorsal hand. High flows were found in the tongue, buccal mucosa, and buccal vestibule. Medium flows were found in the attached gingivae. The lowest flows were found in the teeth. These results indicate that flow in intraoral tissues varies by site and can be noninvasively quantified with the laser Doppler flowmeter when a rigorous measurement protocol is used.

Adult↗
PubMed1991

Effect of air abrasives on marginal configurations of porcelain-fused-to-metal alloys: an SEM analysis.

Air abrasion of castings for metal ceramic crowns is a routine procedure in ceramics laboratories for cleaning, seating, and preparing casts for porcelain application. This technique can result in damage to the margins of castings. This investigation evaluated the extent and significance of this procedure. Marginal abrasion ranged from 5 to 110 microns. ANOVA, followed by Tukey's post hoc evaluation revealed no difference between abrasives, but significant differences were noted among alloys and margin configurations (p less than 0.05). Marginal loss by alloy was as follows: [Jelenko O] greater than [Olympia = Cameo] greater than [Jelstar] greater than [Genesis II]. Marginal loss by marginal configuration was as follows: [beveled shoulder] greater than [chamfer = shoulder]. Significant marginal damage can occur during air abrasion of dental castings.

Air↗
PubMed1989

Effects of the porcelain firing sequence on the bond strengths of cements.

Bond strengths for the retention of ceramic bonded to metal alloys to the tooth structure involve cavity preparation variables, cement variables and ceramic bonded to metal alloy variables. The aim of this work was to evaluate the retentive strength differences between alloy surfaces, unfired and fired, for porcelain alloys retained with different dental cement compositions. The clinical situation was stimulated by using standardized tooth preparations, extracted teeth and castings cemented with zinc phosphate and polycarboxylate cements, which were debonded on an Instron. Jelenko O, Cameo, Jelstar and Genesis II alloys were compared unfired and fired to simulate porcelain application. Fired Jelenko O casting alloy cemented with polycarboxylate cement produced the greatest bond strengths (6.0 +/- 1.0 MPa). Polycarboxylate cemented castings had greater bond strengths for all alloys whether fired or not. The only effect of firing was an improvement with Jelenko O alloys produced with both cements. All of these differences were statistically significant at the P less than 0.01 level using Tukey's post hoc evaluation. The improvements observed were related to the oxide formation on the internal surfaces of the casting and the ability of polycarboxylate cement to adhere chemically to those layers.

Chromium Alloys↗
PubMed1988

Fabrication of an alloplastic implant for the cranial defect.

This article describes the presurgical fabrication of an inlay/onlay alloplastic cranial implant prosthesis. The technique eliminates the need to modify an artificial stone master cast, thus simplifying the technique and decreasing the laboratory time involved. The final prosthesis replaces lost cranial contours and has a positive seat on the unaltered cranium adjacent to the defect.

Acrylic Resins↗
PubMed1988

Anti-G straining maneuver incompatibility with tactical aircraft oxygen systems.

A spectrum of clinical symptoms consisting of grey-out, black-out, and G-induced loss of consciousness has been identified in pilots of high performance aircraft. The M-1 maneuver used in conjunction with reclined seats and inflated G-suit provides significant protection against these symptoms. Centrifuge-trained United States Navy tactical aircraft pilots have recently reported a decreased ability to perform the M-1 maneuver while using the MBU-12P oxygen mask and CRU-79/P oxygen regulator. This report reviewed the performance specifications of these devices and compared them with published pulmonary flow rates. We found this oxygen system to interfere with the performance of the M-1 and other anti-G maneuvers. Further research is needed to characterize pulmonary flow rates during the performance of the M-1 maneuver in order to make recommendations for breathing system standards aboard high performance aircraft.

Aerospace Medicine↗
PubMed1987

Infection control during elastomeric impressions.

This technique uses an individual applicator per application of an elastomeric adhesive to an acrylic resin tray. To help prevent contamination of the adhesive in the bottle, the Toothette toothbrush should not be dipped into the bottle a second time. A sufficient quantity of adhesive is absorbed with a single immersion into the adhesive to coat an entire tray. The uniformity of the surface application is more easily controlled compared with that of a brush applicator. Because only one immersion is required to coat a tray and the Toothette toothbrush is discarded after one application, cross-contamination of patients is prevented.

Communicable Disease Control↗
PubMed1985

Accuracy of an earpiece face-bow.

The validity of the Hanau ear-bow to transfer an arbitrary hinge axis to a Hanau articulator was clinically compared with a Hanau kinematic face-bow. The study was conducted with 18 randomly selected patients. This investigation demonstrated a significant statistical difference between the arbitrary axis located with an ear-bow and the terminal hinge axis. This discrepancy was significant in the anteroposterior direction but not in the superior-inferior direction. Only 50% of the arbitrary hinge axes were within a 5 mm radius of the terminal hinge axis, while 89% were within a 6 mm radius. Furthermore, the ear-bow method was not repeatable statistically. Additional study is needed to determine the practical value of the arbitrary face-bow and to pursue modifications to improve its accuracy.

Dental Articulators↗