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Biomedical subjects

P Moy

Publications and source records attributed to P Moy.

At least 19 recordsLinked to original sources

Preliminary report of immediately loaded Altiva Natural Tooth Replacement dental implants.

BACKGROUND: Osseointegration may be described as a direct contact between living bone and an alloplastic implant. It is thought that a period of undisturbed healing is required to ensure osseointegration. The length of the healing period is dependent on a number of factors, such as implant material, surface configuration, site preparation technique, bone quality, healing capacity of the osteotomy, and implant design. Elimination of the healing period offers distinct advantages in terms of cost of therapy and convenience to patients. Recently, a new one-piece implant design was proposed that provides improved stability of the implant to allow immediate support of an interim prosthesis. PURPOSE: This article presents the initial clinical experiences when the Altiva Natural Tooth Replacement one-piece implant was used in a human clinical trial. MATERIALS AND METHODS: This was a prospective multicenter study of the placement and immediate loading of the one-piece implant. A total of 142 implants were placed in the jaws of 93 patients. Implants were placed consecutively and were followed at specified intervals in three private clinical practices. Clinical performance was recorded relative to implant survival and prosthesis support. RESULTS: The implant survival rate was 93.7%, with similar responses in the maxilla (95.0%) and the mandible (92.7%). When implant failure occurred, it was observed as mobility without infection within 3 to 5 weeks of implant insertion. CONCLUSIONS: On the basis of this trial, there is promising evidence that this implant design can succeed at rates similar to other designs that require conventional healing times.

Adult↗

Subfailure injury affects the relaxation behavior of rabbit ACL.

OBJECTIVE: To study changes in viscoelasticity of a ligament due to an incomplete or a subfailure injury. DESIGN: An in vitro study of anterior cruciate ligament preparations. BACKGROUND: The viscoelastic properties are an inherent part of the physical characteristics of a ligament. An injury to a ligament alters both its elastic and viscous properties. Although the effects of several parameters on the mechanical properties of a ligament have been studied, there is no information in the literature concerning the effect of an incomplete or subfailure injury on its viscoelastic behavior. METHODS: Ten pairs of rabbit femur-anterior cruciate ligament-tibia specimens were used. A standardized relaxation (Relax) test was adopted to quantify the viscoelastic behavior, before and after a subfailure injury. One member of the pair was subjected to three sequential tests: Relax 1; Relax 2; and stretch to failure. The other member of the pair was subjected to other three tests: Relax 3; 80% subfailure injury, i.e. stretch of 80% of failure deformation; and Relax 4. RESULTS: We found that the relaxation test by itself (Relax 1 vs Relax 2), did not affect the viscoelasticity of the ligament. On the other hand, the 80% subfailure injury (Relax 3 vs Relax 4) affected the ligament viscoelastic behavior. The force was decreased by about 50% at time zero (10.46 vs 4.79 N, p = 0.014), and at 180 s (8.14 vs 4.11 N, p = 0.018). Fitting a three-element linear viscoelastic solid model to our data, we found the serial spring stiffness to decrease by about 50% (p = 0.01), the parallel spring remained unchanged, and there was a tendency for the dashpot coefficient to decrease (by 57%, p = 0.09). CONCLUSIONS: The 80% subfailure injury decreased the initial stiffness of the ligament, and tended to decrease its viscoelastic property. RELEVANCE: Subfailure or incomplete injuries of ligaments are more common than the complete injuries. The present study describes the effects, on both the elastic and viscous properties, of a ligament subjected to a subfailure injury.

Analysis of Variance↗

Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice.

Despite the potential of type 1 interferons (IFNs) for the treatment of cancer, clinical experience with IFN protein therapy of solid tumors has been disappointing. IFN-beta has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. The antiproliferative effect, however, relies on IFN-beta concentrations that cannot be achieved by parenteral protein administration because of rapid protein clearance and systemic toxicities. We demonstrate here that ex vivo IFN-beta gene transduction by a replication-defective adenovirus in as few as 1% of implanted cells blocked tumor formation. Direct in vivo IFN-beta gene delivery into established tumors generated high local concentrations of IFN-beta, inhibited tumor growth, and in many cases caused complete tumor regression. Because the mice were immune-deficient, it is likely that the anti-tumor effect was primarily through direct inhibition of tumor cell proliferation and survival. Based on these studies, we argue that local IFN-beta gene therapy with replication-defective adenoviral vectors might be an effective treatment for some solid tumors.

Adenoviridae↗

Constitutive and antibody-induced internalization of prostate-specific membrane antigen.

Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein expressed predominantly by prostate cancer cells. We have characterized four monoclonal antibodies that bind to the extracellular domain of PSMA (Liu et al., Cancer Res., 57: 3629-3634, 1997). Here we report that viable LNCaP cells internalize these antibodies. Laser scanning confocal microscopy reveals that the internalized antibodies accumulate in endosomes, and immunoelectron microscopy reveals that endocytosis of the PSMA-antibody complex occurs via clathrin-coated pits. In addition, a quantitative cell surface biotinylation assay demonstrates that PSMA is constitutively endocytosed in LNCaP cells and that anti-PSMA antibodies increase the rate of internalization of PSMA. These studies suggest that PSMA might function as a receptor mediating the internalization of a putative ligand. The availability of prostate-specific internalizing antibodies should aid the development of novel therapeutic methods to target the delivery of toxins, drugs, or short-range isotopes specifically to the interior of prostate cancer cells.

Antibodies, Monoclonal↗

MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma.

BACKGROUND: Expression of Major Histocompatibility Complex (MHC) class I and II antigens are critical for the cellular immune response. Loss of MHC expression represents one mechanism by which cancer cells escape immune recognition. PURPOSE: To define MHC class I and II expression by prostate cancer (PCa) in vivo and in vitro and the ability to modulate MHC expression in vitro with IFN-alpha and -gamma. METHODS: Frozen tissue sections of 25 benign prostatic hyperplasia (BPH) and 18 PCa specimens were studied by immunohistochemistry. PCa cell lines LNCaP, PC-3, and DU-145 were studied by FACS, ELISA, and cytospin. Class I was detected by monoclonal antibody (mAb) W6/32, and class II by mAb 13.17. The effects of IFN-alpha and -gamma were assessed by testing the three cell lines in the presence or absence of varying concentrations of the cytokine for varying incubation times. RESULTS: Class I was strongly expressed by 24/25 BPH specimens; 4/18 (22%) PCa were homogeneously class I-positive, while 5/18 (28%) were heterogeneously positive and 9/18 (50%) were class I-negative. PC-3 and DU-145 expressed normal levels of class I, while LNCaP expressed only low levels. All line except LNCaP demonstrated significant up-regulation of class I with either IFN-alpha or -gamma. Class II expression was not seen in BPH epithelium nor in 17/18 PCa. Class II could be only weakly induced in the three PCa lines. CONCLUSIONS: These findings confirm prior studies demonstrating that class I expression is commonly lost or diminished in PCa. In addition, class II up-regulation by IFN-gamma appears very limited in relation to other normal or neoplastic epithelium. IMPLICATIONS: The present findings, taken together with previous studies, are most consistent with the expression of neoantigens by PCa, which are recognized and appropriately eliminated by the cellular immune system. This selective pressure favors outgrowth of cells which down-regulate or lose class I and/or class II expression. Understanding PCa immunobiology will help in the development of effective immunotherapy for this disease.

Enzyme-Linked Immunosorbent Assay↗

Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium.

Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is not available for binding. Herein, we report the initial characterization of the first four reported IgG mAbs that bind the external domain of PSMA. Competitive binding studies indicate these antibodies define two distinct, noncompeting epitopes on the extracellular domain of PSMA. In contrast to 7E11, these mAbs bind to viable LNCaP cells in vitro. In addition, they show strong immunohistochemical reactivity to tissue sections of prostate epithelia, including prostate cancer. These mAbs were also strongly reactive with vascular endothelium within a wide variety of carcinomas (including lung, colon, breast, and others) but not with normal vascular endothelium. These antibodies should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide variety of carcinomas.

Animals↗

Tat-mediated protein delivery can facilitate MHC class I presentation of antigens.

We have previously shown that the tat protein of HIV-1 can be used as a carrier to promote the intracellular delivery of heterologous proteins. Here we have tested if the tat-delivery technology can be used to direct MHC class I presentation of native protein, using ovalbumin (OVA) as a model system. We show that a tat-ovalbumin conjugate (tatOVA) can be delivered into cells and that subsequent processing and presentation occurs, resulting in effective and specific killing of these target cells by an OVA specific cytotoxic T-lymphocyte (CTL) line. Comparison with the E.G7 line that expresses the OVA gene indicates that tat-mediated delivery is as efficient as endogenous expression in this system. Tat-mediated antigenic protein delivery may be useful both as a research technique and, potentially, as a therapeutic or prophylactic vaccine.

Amino Acid Sequence↗

Cloning of an inflammation-specific phosphatidyl inositol-linked form of murine vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo. VCAM1 cDNAs cloned from mouse, rat, rabbit, and human libraries contain six, seven, or eight extracellular Ig-like domains generated by alternate splicing, but to date shorter forms have not been found. We have cloned a novel cDNA encoding only the three N-terminal domains of murine VCAM1 followed by a unique C-terminal tail generated by alternate splicing of a previously undescribed exon. This truncated form of murine VCAM1 (3D-VCAM1) is expressed in COS cells as a functional adhesion molecule which is lost from the cell surface following treatment with phosphatidylinositol-specific phospholipase C. 3D-VCAM1 is found only in endotoxin-treated but not control murine and rat tissues. Thus in rodents alternate splicing of the VCAM1 gene generates a unique truncated inflammation-specific phosphatidylinositol-linked form of VCAM1.

Alternative Splicing↗

Structure/function studies on vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo. The major form of human VCAM1 contains seven extracellular Ig-like domains, with domain 1 designated as the most N-terminal. We have examined the relationship between human VCAM1 structure and function using a combination of domain truncation mutants and proteolytic fragmentation of recombinant soluble VCAM1. We have characterized two regions of VCAM1, localized to domains 4 and 5, which are highly sensitive to proteolytic cleavage, localized the epitope of the blocking monoclonal antibody 4B9 to domain 1, and found that domains 1-3 are sufficient for both its adhesive function and its ability to initiate T cell activation.

Amino Acid Sequence↗

Cloning of murine and rat vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen 4 (VLA4). We have cloned the cDNAs for both murine and rat VCAM1 from endotoxin-treated lung libraries. Both sequences encode proteins with seven extracellular Ig-like domains, which show 75.9% and 76.9% identity, respectively, with human VCAM1. Both murine and human cell lines show VLA4-dependent binding to COS cells transiently expressing murine and rat VCAM1. Two mAbs, M-K/1 and M-K/2, which recognize an antigen on murine bone marrow stromal cell lines, bind to murine VCAM1 expressed in COS cells and block VCAM1-dependent adhesion, confirming that these mAbs recognize murine VCAM1.

Amino Acid Sequence↗

Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1).

Vascular cell adhesion molecule-1 (VCAM1) of the Ig superfamily is induced by the inflammatory cytokines interleukin-1 and tumor necrosis factor on human umbilical vein endothelial cells (HUVECs). It binds to mononuclear leukocytes via the integrin VLA-4. We have cloned and expressed a cDNA encoding a new form of human VCAM1 containing an additional Ig homologous domain inserted between the third and fourth domains of the original six-domain protein. Characterization of mRNA from HUVECs from three individuals at various time points after induction by tumor necrosis factor indicates that both the long and short VCAM1 mRNAs are made by all three individuals, with the long form predominating quantitatively. Immunoprecipitation of VCAM1 protein from cos7 cells transfected with each cDNA and from cultured endothelial cells followed by deglycosylation suggests that the long form is the major form found on endothelium. The two forms may result from alternate splicing of a precursor mRNA. Both forms support adhesion of VLA-4-expressing cell lines.

Amino Acid Sequence↗

Optimum placement of osseointegrated implants.

A method was described that includes a stent provided by the restorative dentist indicating optimum implant location. The stent, with imbedded metal bearings, is worn by the patient during tomographic radiographic survey. The tomogram provides a more accurate image of the quantity and quality of the osseous structures. The same template may be used as a surgical stent to aid the surgeon in initial bur placement. Through careful planning and systematic control, the predictable placement of osseointegrated implants can be achieved. With cooperative efforts of restorative dentists and surgeons, more than 400 implants have been successfully placed at University of California, Los Angeles, School of Dentistry.

Cephalometry↗

A comparison of the persistence in a clay loam of single and repeated annual applications of seven granular insecticides used for corn rootworm control.

In May 1983, granular formulations of carbofuran, chlorpyrifos, disulfoton, fonofos, isofenphos, phorate, and terbufos were applied in incorporated bands to duplicate 2 m2 field plots of clay loam. Insecticide concentrations were determined in the bands at 0,1,2,3,4,6,8,10,12,16, and 20 wk. Following spring cultivation, the insecticides were applied to the same plots in 1984 and 1985. In addition, carbofuran was applied to previously untreated plots in 1984 and all 7 materials were applied to previously untreated plots in 1985. Sampling and analysis were carried out as in 1983. Persistence was assessed on the basis of the disappearance rates measured for the 1st 8 wk and of a calculated Effectiveness Potential (the ratio of the average residue in the upper 5 cm of the band at 8, 10 and 12 wk and the published LC95 for western corn rootworm in clay loam soil). Soils treated with carbofuran and isofenphos in 1984 and all soils treated in 1985 were tested for anti-insecticide activity. Soil cores from some carbofuran, chlorpyrifos and terbufos treated plots were sectioned vertically to establish the distribution of the insecticides during 1985. In addition, granular and pure chemical forms of isofenphos and carbofuran were applied at 10 ppm to anti-isofenphos and anti-carbofuran active and control soils (from field plots) maintained at 10 and 20% moisture in the laboratory to assess the effect of formulation and moisture on persistence in active soils. Insecticide concentrations were determined at 0,1,3,7, 10,14,21,28, and 35 days. The persistence of chlorpyrifos, terbufos and phorate was relatively constant over the 3 years and between plots receiving single and multiple treatments. Disulfoton and fonofos behavior was more variable and that of carbofuran and isofenphos was extremely variable. Anti-insecticide activity against carbofuran and isofenphos was detectable 2 wk after an initial application and was still present the following spring. Anti-insecticide activity against fonofos, terbufos sulfoxide, phorate sulfone and disulfoton sulfone was also generated in this soil. Anti-insecticide activity against chlorpyrifos, disulfoton, terbufos and phorate was not present. Carbofuran, chlorpyrifos and terbufos (+ metabolites) present in the upper 5 cm of soil averaged 93, 94 and 94%, respectively, of the total core contents over 12 wk. Significant moisture dependent differences were observed between the behavior of granular carbofuran and granular isofenphos in anti-insecticide active soils.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, Gas↗

Degradation of the insecticide fensulfothion by a mixed culture of soil microorganisms.

Fensulfothion was incubated in nutrient media with a mixed culture of soil microorganisms obtained from sandy loam. The half life of fensulfothion in both inoculated samples and sterile controls was about 16 wk. There was some conversion to fensulfothion sulfone (16% at 6 wk) in inoculated samples, but not in the controls. Traces of fensulfothion sulfide were found in both inoculated samples (less than 3%) and controls (less than 2%). When 1% ethanol was added to the inoculated nutrient mixture the fensulfothion disappeared rapidly (t1/2 congruent to 1 1/2 wk) with 32% conversion at 20 wk to fensulfothion sulfide.

Biodegradation, Environmental↗