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Biomedical subjects

K Y Lin

Publications and source records attributed to K Y Lin.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for inhibition of low density lipoprotein oxidation and cholesterol accumulation by apolipoprotein H (beta2-glycoprotein I).

Low density lipoprotein (LDL) oxidation and lipid accumulation are thought to enhance the progression of atherosclerosis. Apolipoprotein H (apoH) has been implicated in the development of human atherosclerosis. However, the roles of apoH in the oxidative modification of LDL and cellular accumulation of lipid constituents remained uncharacterized. In this study, the level of plasma apoH was found to be significantly associated with the oxidative susceptibility of LDL in human subjects. Plasma levels of apoH were positively correlated with the lag time but negatively correlated with LDL oxidation rate in conjugated diene formation. By using a J774 A.1 macrophage culture system, we found that apoH could not only inhibit the formation of conjugated diene and thiobarbituric acid-reactive substances, but also reduce the electrophoretic mobility of oxidized LDL. Furthermore, apoH decreased cellular accumulation of cholesterol via a reduction in cholesterol influx and an increase in cholesterol efflux. This is the first demonstration that apoH appears to have "antioxidant"-like effects on LDL oxidation. The results also suggest that apoH can inhibit the translocation of cholesterol from extracellular pools to macrophages, suggesting that apoH may play an important role in the prevention of atherosclerosis.

Arteriosclerosis↗
PubMed2001

Effects of external beam irradiation on the TRAM flap: an experimental model.

The rat model of the transverse rectus abdominis musculocutaneous (TRAM) flap was used in the present study to determine the effects of external beam radiation on myocutaneous flap histology and pathophysiology. A total of 57 adult Sprague-Dawley rats underwent a TRAM procedure. A pilot study with 17 animals was first performed to determine proper radiation dosages, and the remaining 40 rats were then used in the definitive study. In half of the definitive study group, the flaps were subjected to fractionated doses of external beam radiation, whereas the other half served as controls. Six weeks after the last radiation dose, all animals were killed and the flaps were harvested for mechanical assessment and histopathologic evaluation. All TRAM flaps survived in both groups. The irradiated and nonirradiated flaps were minimally distinguishable in viscoelastic properties, as well as by histopathologic examination. Growth of the flap in the irradiated animals was significantly diminished (48 percent average surface area increase in irradiated flaps, versus 92 percent increase in nonirradiated flaps, p < 0.05). These findings suggest that the myocutaneous flap is relatively resistant to some of the known adverse affects of radiation on living tissues.

Animals↗
PubMed2001

Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency.

Chitosan-DNA nanoparticles were prepared using a complex coacervation process. The important parameters for the nanoparticle synthesis were investigated, including the concentrations of DNA, chitosan and sodium sulfate, temperature of the solutions, pH of the buffer, and molecular weights of chitosan and DNA. At an amino group to phosphate group ratio (N/P ratio) between 3 and 8 and a chitosan concentration of 100 microg/ml, the size of particles was optimized to approximately 100--250 nm with a narrow distribution, with a composition of 35.6 and 64.4% by weight for DNA and chitosan, respectively. The surface charge of these particles was slightly positive with a zeta potential of +12 to +18 mV at pH lower than 6.0, and became nearly neutral at pH 7.2. The chitosan-DNA nanoparticles could partially protect the encapsulated plasmid DNA from nuclease degradation as shown by electrophoretic mobility analysis. The transfection efficiency of chitosan-DNA nanoparticles was cell-type dependent. Typically, it was three to four orders of magnitude, in relative light units, higher than background level in HEK293 cells, and two to ten times lower than that achieved by LipofectAMINE-DNA complexes. The presence of 10% fetal bovine serum did not interfere with their transfection ability. Chloroquine could be co-encapsulated in the nanoparticles at 5.2%, but with negligible enhancement effect despite the fact that chitosan only showed limited buffering capacity compared with PEI. The present study also developed three different schemes to conjugate transferrin or KNOB protein to the nanoparticle surface. The transferrin conjugation only yielded a maximum of four-fold increase in their transfection efficiency in HEK293 cells and HeLa cells, whereas KNOB conjugated nanoparticles could improve gene expression level in HeLa cells by 130-fold. Conjugation of PEG on the nanoparticles allowed lyophilization without aggregation, and without loss of bioactivity for at least 1 month in storage. The clearance of the PEGylated nanoparticles in mice following intravenous administration was slower than unmodified nanoparticles at 15 min, and with higher depositions in kidney and liver. However, no difference was observed at the 1-h time point.

Animals↗
PubMed2001

An outcome study of breast reconstruction: presurgical identification of risk factors for complications.

BACKGROUND: Breast reconstruction following mastectomy has been shown to have a salutary effect on the overall psychological well-being of women being treated for breast cancer. Unfortunately, however, not every patient is an ideal candidate for reconstruction. Complications stemming from reconstructive surgery can cause significant morbidity, the most important of which may be the delay of subsequent adjuvant antineoplastic therapies, and therefore may not be in the best interests of the patient. METHODS: A retrospective study was performed on a consecutive series of 123 breast reconstructions in 98 patients, performed by one of two plastic surgeons, in a university setting over a 5-year period, for all surgical outcomes. Specifically, wound-healing complications, infections, and reoperations leading to the potential delay of subsequent chemotherapy or radiotherapy were recorded, and possible risk factors leading to these were sought. RESULTS: Three presurgical risk factors were found to have a statistically significant influence on the development of complications following breast reconstruction. These were: (1) increasing obesity, defined by the body mass index, (2) an active or recent (<5 year) history of cigarette smoking, and (3) a history of previous radiation exposure. Odds ratios were used to describe the magnitude of the effect of each factor for the development of complications. An ordinal regression analysis was used to create a nomogram based on this information that can be used to calculate any individual patient's presurgical risk for developing major complications following breast reconstruction, based on the presence of these factors. CONCLUSIONS: It is possible, based on the presence of specific presurgical risk factors, to predict the probability of developing major complications following breast reconstruction. This information can be useful to the referring physician and plastic surgeon alike in determining which patients are the best candidates for breast reconstruction and which type of reconstruction would be best suited for each individual patient.

Adult↗
PubMed2001

Hazards of powder on surgical and examination gloves: a collective review.

This article reviews information on the hazards associated with dusting powders on latex surgical and examination gloves. Dusting powders were first applied to latex gloves to facilitate donning. After 1980, manufacturers devised innovative techniques to manufacture gloves without dusting powders. It has been well documented that the powders on gloves present a health hazard to patients, as well as to operating-room personnel. First, these powders elicit tissue toxicity in every tissue in the body. Second, these powders serve as carriers of latex allergen and may precipitate a life-threatening allergic reaction in sensitized patients. These well-documented hazards of glove powders have caused a growing number of hospitals in the world to abandon the use of examination and surgical gloves coated with powder, and instead to use only powder-free gloves.

Foreign-Body Reaction↗
PubMed2001

The scientific basis for selecting surgical sutures.

The purpose of this study was to examine the handling properties of synthetic absorbable and monofilament polypropylene sutures made by two different manufacturers and to compare a subjective evaluation by surgeons to the results of standardized biomechanical performance tests. The surgeons' clinical subjective evaluation of the monofilament polypropylene sutures correlated with the results of the biomechanical performance studies, whereas the biomechanical evaluation of the two synthetic absorbable sutures detected notable differences in their performance. These distinct differences in biomechanical performance of the absorbable sutures did not alter their performance in the subjective clinical evaluation.

Abdominal Muscles↗
PubMed2000

Conformational analysis of long spacers in PROSITE patterns.

To determine if variable sequences (spacers) between conserved positions in a sequence motif or pattern share a consensus structure, three-dimensional structures containing PROSITE patterns with spacers of fixed length greater than three residues were analyzed. Structural similarities of a given pattern were evaluated by computing the backbone phi, psi and side-chain chi1 dihedral order parameters. The exact bias information in analyzing the conformational variability of the patterns was taken into account by introducing a new parameter, the bias coefficient, which describes the number and distribution of residue types found at each position of a pattern in the structures. The results of the analyses show that backbone conformational heterogeneity at a given position in a sequence motif does not necessarily correlate with the residue-type variability at that position, and the long spacer region can adopt a well-defined backbone conformation, in addition to the conserved residues. Furthermore, a PROSITE pattern may be redefined to yield two or more "refined" regular expressions, each corresponding to a distinct backbone conformation. A way in which the observed structural consensus in a pattern may be employed to improve the accuracy of function prediction from sequence is suggested.

Amino Acid Motifs↗
PubMed2000

Complete breast absence revisited.

Congenital absence of the breast is a rare condition. The literature shows that there is much heterogeneity in its presentation as well as its inheritance. We described a mother and daughter with the condition and how the mother underwent breast reconstruction with use of bilateral transverse rectus abdominis myocutaneous flaps.

Abnormalities, Multiple↗
PubMed1999

Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors.

DNA vaccination is an attractive approach for tumor immunotherapy because of its stability and simplicity of delivery. Advances demonstrate that helper T cell responses play a critical role in initiating immune responses. The aim of the current study is to test whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DNA vaccines. We linked the lysosome-associated membrane protein 1 (LAMP-1) to HPV-E7 to construct a chimeric DNA, Sig/E7/LAMP-1 DNA. For in vivo tumor prevention experiments, mice were vaccinated with E7 DNA or Sig/E7/LAMP-1 DNA via gene gun, followed by tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with E7-DNA or Sig/E7/LAMP-1 DNA. Intracellular cytokine staining with flow cytometry analysis, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunoabsorbent assay (ELISA), and enzyme-linked immunospot (ELISPOT) assays were used for in vitro E7-specific immunological studies. In both tumor prevention and tumor regression assays, Sig/E7/LAMP-1 DNA generated greater antitumor immunity than did wild-type E7 DNA. In addition, mice vaccinated with Sig/E7/LAMP-1 DNA had greater numbers of E7-specific CD4+ helper T cells, higher E7-specific CTL activity, and greater numbers of CD8+ T cell precursors than did mice vaccinated with Sig/E7 or wild-type E7 DNA. Sig/E7 generated a stronger E7-specific antibody response than did Sig/E7/LAMP-1 or wild-type E7 DNA. Our results indicate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DNA vaccines.

Animals↗
PubMed1999

A cytosine analog that confers enhanced potency to antisense oligonucleotides.

Antisense technology is based on the ability to design potent, sequence-specific inhibitors. The G-clamp heterocycle modification, a cytosine analog that clamps on to guanine by forming an additional hydrogen bond, was rationally designed to enhance oligonucleotide/RNA hybrid affinity. A single, context-dependent substitution of a G-clamp heterocycle into a 15-mer phosphorothioate oligodeoxynucleotide (S-ON) targeting the cyclin-dependent kinase inhibitor, p27(kip1), enhanced antisense activity as compared with a previously optimized C5-propynyl-modified p27(kip1) S-ON and functionally replaced 11 C5-propynyl modifications. Dose-dependent, sequence-specific antisense inhibition was observed at nanomolar concentrations of the G-clamp S-ONs. A single nucleotide mismatch between the G-clamp S-ON and the p27(kip1) mRNA reduced the potency of the antisense ON by five-fold. A 2-base-mismatch S-ON eliminated antisense activity, confirming the sequence specificity of G-clamp-modified S-ONs. The G-clamp-substituted p27(kip1) S-ON activated RNase H-mediated cleavage and demonstrated increased in vitro binding affinity for its RNA target compared with conventional 15-mer S-ONs. Furthermore, incorporation of a single G-clamp modification into a previously optimized 20-mer phosphorothioate antisense S-ON targeting c-raf increased the potency of the S-ON 25-fold. The G-clamp heterocycle is a potent, mismatch-sensitive, automated synthesizer-compatible antisense S-ON modification that will have important applications in the elucidation of gene function, the validation of gene targets, and the development of more potent antisense-based pharmaceuticals.

Animals↗
PubMed1999

Biomechanical performance of latex and non-latex double-glove systems.

The purpose of this study was to evaluate ten commercially available latex, powder-free surgical gloves and four commercially available non-latex, powder-free surgical gloves using standardized, reproducible biomechanical parameters that included glove thickness, puncture resistance, and glove donning force. For all gloves tested, with one exception (Neolontrade mark PF), puncture resistance increased for double-gloves as compared to single-gloves. In addition, single-glove thickness was not a reliable determinant of puncture resistance for either latex or non-latex gloves. For the latex gloves, the Ultrafree double and single-gloves exhibited the highest puncture resistance. The glove donning forces for the Biogeltrade mark M and Biogel Sensortrade mark single-gloves were the lowest. In contrast, the Biogel Revealtrade mark and Encoretrade mark Ultra-Thick exhibited the lowest double-glove donning forces. On the basis of these performance tests of latex gloves, the surgeon should consider the Biogel Reveal as well as the Ultrafree gloves for their latex double-glove system. For the non-latex gloves, the Pure Advantage Nitriletrade mark glove had the highest puncture resistance for one layer and two layers of glove material. The thin Pure Advantage Nitrile glove was the most resistant to glove puncture. The Pure Advantage Nitrile glove had low glove donning forces for both single-glove donning configurations and double-glove donning configurations. Consequently, we recommend the Pure Advantage Nitrile glove as the powder-free, non-latex, double-glove system.

Biomechanical Phenomena↗
PubMed1999

Mechanisms of premature closure of cranial sutures.

Craniosynostosis is defined as premature closure of the sutures of the skull, resulting in cranial deformity. Since Virchow's original paper describing the relationship between premature suture closure and skull morphology, we have learned much about the underlying mechanisms and consequences of premature suture closure. In this paper we will describe the biology of suture closure, the rules governing the resulting phenotypes seen clinically, and a prospective study of skull growth during the 1st year of life.

Case-Control Studies↗
PubMed1999

Cellular penetration and antisense activity by a phenoxazine-substituted heptanucleotide.

One of the major barriers to the development of antisense therapeutics has been their poor bioavailability. Numerous oligonucleotide modifications have been synthesized and evaluated for enhanced cellular permeation with limited success. Phenoxazine, a tricyclic 2' deoxycytidine analog, was designed to improve stacking interactions between heterocycles of oligonucleotide/RNA hybrids and to enhance cellular uptake. However, the bioactivity and cellular permeation properties of phenoxazine-modified oligonucleotides were unknown. Incorporation of four phenoxazine bases into a previously optimized C-5 propyne pyrimidine modified 7-mer phosphorothioate oligonucleotide targeting SV40 large T antigen enhanced in vitro binding affinity for its RNA target and redirected RNAse H-mediated cleavage as compared with the 7-mer C-5 propynyl phosphorothioate oligonucleotide (S-ON). The phenoxazine/C-5 propynyl U 7-mer S-ON showed dose-dependent, sequence-specific, and target-selective antisense activity following microinjection into cells. Incubation of the phenoxazine/C-5 propynyl U S-ON with a variety of tissue culture cells, in the absence of any cationic lipid, revealed unaided cellular penetration, nuclear accumulation, and subsequent antisense activity. The unique permeation properties and gene-specific antisense activity of the 7-mer phenoxazine/C-5 propynyl U S-ON paves the way for developing potent, cost-effective, self-permeable antisense therapeutics.

Animals↗
PubMed1999

Wound complications of abdominoplasty in obese patients.

The records of 90 patients who underwent an abdominoplasty at the University of Virginia Health Sciences Center were analyzed to determine the effect of obesity on the incidence of complications after this surgery. The study patients were divided into three groups-obese, borderline, and nonobese-based on the degree to which their preoperative weights varied from their ideal body weight. A history of previous bariatric surgery was also analyzed to determine what impact that might have on subsequent abdominoplasty. Results showed that 80% of obese patients had complications compared with the borderline and nonobese patients, who had complication rates of 33% and 32.5% respectively (p = 0.001). Previous gastric bypass surgery had no significant effect on the incidence of postabdominoplasty complications. Based on these findings the authors conclude that obesity at the time of abdominoplasty has a profound influence on the wound complication rate following surgery, regardless of any previous weight reduction surgery.

Adult↗
PubMed1999

Long-term outcome analysis of two treatment methods for cleft palate: combined levator retropositioning and pharyngeal flap versus double-opposing Z-plasty.

OBJECTIVE: Two surgical techniques for repair of a cleft palate include levator retropositioning in combination with a pharyngeal flap and the Furlow double-opposing Z-plasty. This study compared morbidity and speech results from the use of these two methods in an effort to determine which was the superior technique. DESIGN: Patient records from 1986 to 1996 were retrospectively reviewed, and 10 patients with a cleft palate who underwent repair with a levator retropositioning and pharyngeal flap were compared to 14 patients who underwent a double-opposing Z-plasty repair. Postoperative complications including fistula formation, obstructive sleep apnea, and residual velopharyngeal insufficiency were recorded. Speech was assessed perceptually and through the use of nasometry. RESULTS: Both surgical techniques resulted in good speech in the majority of patients. Only two patients in the study, both in the Z-plasty group, had severe postoperative hypernasality. Two patients in the levator retropositioning and pharyngeal flap group developed severe postoperative obstructive sleep apnea, requiring additional surgery. CONCLUSION: The levator retropositioning and pharyngeal flap technique was successful in achieving good speech results, but it also caused more serious postoperative complications when compared to the double-opposing Z-plasty technique.

Cleft Palate↗
PubMed1999

Distraction osteogenesis of the midface: a new implantable distraction device.

This report describes the use of a new implantable device for distraction osteogenesis of the maxilla in treatment of midface hypoplasia seen in craniofacial syndromes. The technique of distraction osteogenesis is a recent advance in plastic surgery for treatment of bone growth disorders. The device is totally implantable except for the activating pin and can provide up to 30 mm of total advancement. We will describe our surgical technique and distraction protocol, illustrated by a case report of the device successfully used in a child with Crouzon syndrome.

Child↗
PubMed1998

Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein.

An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia-based vaccine (Sig/E7/LAMP-1) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/ LAMP-1 vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV-16) E6/E7 expressing tumor cells, designated TC-1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 x 10(6) TC-1 cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/ LAMP-1 followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor-free 2 months post-tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC-1 cells and then vaccinated with Sig/E7/ LAMP-1. Treatment with Sig/E7/LAMP-1 was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-1 resulted in regression of fully established lung tumors in 10% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-1 vaccine is effective in controlling the hematogenous spread of TC-1 tumor cells. In addition, the TC-1 lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.

Animals↗