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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 37 records · Page 2Linked to original sources

Phenotype severity and genetic variation at the disease locus: an investigation of nail dysplasia in the nail patella syndrome.

The genetic bases underlying the range and severity of phenotypes in Mendelian disorders is poorly understood; however, improvements in this area have the potential to facilitate analysis of oligogenic disorders. The nail dysplasia observed in Nail Patella Syndrome (NPS) was selected as a quantifiable variable within a Mendelian disorder, for which data could be readily obtained, to allow investigation of the genetic basis of variation. Analysis of SNP haplotypes across the LMX1B gene demonstrated association between the haplotype of the mutant allele and the variability in the nail score (p = 0.024). These results are in contrast to those obtained previously, which supported a modifying role for the wild-type allele. Since there is no evidence that particular mutations, or classes of mutation, are associated with the variation (p > 0.5), further work is required to identify the elements associated with the LMX1B gene that mediate phenotypic severity.

DNA Mutational Analysis↗

Plaque excision for the treatment of infrainguinal arterial occlusive disease.

Lower extremity peripheral vascular disease has a broad spectrum of presentations, ranging from intermittent claudication, rest pain, to limb threatening tissue loss and gangrene. Over the last 10 to 15 years, short focal stenoses or occlusions have been treated using endovascular techniques, but conventional angioplasty and stenting is limited by high restenosis rates especially in longer lesions. Moreover, multilevel, complex disease is still generally considered best managed by surgical intervention. However, with the improvements in atherectomy technology, namely plaque excision and laser plaque ablation, the full spectrum of arterial occlusive lesions may now be addressed by percutaneous means with excellent limb salvage rates. Excisional atherectomy is currently exemplified by the SilverHawk Plaque Excision System, which is available in four sizes for the treatment of all infrainguinal vessels. As the apparatus is advanced, the rotational cutting blade excises a ribbon of plaque that is concurrently collected into a nosecone. Multiple passes are made, during which the blade is directed sequentially toward all quadrants of the vessel lumen. The stenotic lesion is grossly debulked by this technique with the proposed advantage of avoiding the arterial wall barotrauma that hampers the durability of angioplasty and stenting.

Angiography↗

Thumb replantation: a retrospective review of 103 cases.

Replantation has become the state of the art reconstruction for an amputated thumb. The aim of our study was to review our series of thumb replantations over a period of 12 years at the Bellevue Hospital Center in New York City. The mechanism of injury, level of amputation, and use of vein grafts was reviewed and correlated with survival rates of the replanted thumbs. The overall survival rate was 91.3%. Of the 12 thumbs that were re-explored for vascular compromise, 75% were successfully salvaged. Our study also indicates that there is no statistical difference in survival of thumb replants when comparing the mechanism of injury, the level of amputation, and the use of vein grafts. However, the use of vein grafting seemed to be beneficial in the successful outcome of replantation in severe crush and avulsion injuries, even though the values did not reach statistical significance. We conclude that thumb replantation is associated with very high survival rate, regardless of the mechanism of injury or level of amputation, and should be attempted in all cases. An early reexploration for vascular problems yields a high salvage rate and should be performed in all cases. We also recommend the use of vein grafts in severe crush and avulsion injuries.

Adolescent↗

Ultrasound biomicroscopy: role in diagnosis and management in 130 consecutive patients evaluated for anterior segment tumours.

BACKGROUND/AIM: Ultrasound biomicroscopy (UBM) is an important tool for assessing anterior segment pathology. This study sought to evaluate UBM in the management of anterior segment tumours. METHODS: Retrospective analysis of medical records of consecutive patients referred to the ocular oncology unit, University of California San Francisco (UCSF), for suspected anterior segment tumours from 1999 to 2004. RESULTS: 132 eyes from 130 patients were evaluated, including 55 uveal melanomas (UM), 21 iris naevi, 30 iris cysts, and 26 remaining lesions. Of the melanomas, 45 were also evaluated with conventional A/B-scan. There was 29% correspondence between the anatomical structures invaded by melanoma as identified by B-scan v disease extent defined by UBM. Ciliary body and peripheral iris involvement by melanomas was significantly more frequently observed by UBM than B-scan. Seven of 30 benign cysts were diagnosed as cystic before UBM evaluation. In three cases, neuroepithelial cysts were associated with intercurrent pathology including iris naevus (n = 2) and ciliary body melanoma (n = 1). Two ciliary body melanomas showed cavitation, including one patient with a pseudocyst. Histopathological correlation was possible in six cases. CONCLUSION: UBM is an indispensable tool for the management of anterior segment tumours. This study demonstrates the superiority of UBM v conventional B-scan for the precise localisation of uveal melanoma, especially involving the ciliary body and peripheral iris.

Adolescent↗

Endovascular stent graft selection for the treatment of abdominal aortic aneurysms.

Minimally invasive endovascular techniques for the treatment of abdominal aortic aneurysms (AAA) have significantly reduced the morbidity of these procedures as compared with standard surgical repair. In addition, patients with extensive comorbid medical illnesses in whom standard operative repair is contra-indicated, may be successfully treated using endovascular means. A variety of endovascular stent grafts are currently being used clinically for endovascular AAA repair. The characteristics of these stent grafts vary significantly. In selecting the specific stent graft to be used for endovascular AAA repair, these specific characteristics must be considered particularly with regard to the individual patient's anatomic and physiologic characteristics. The United States Food and Drug Administration (FDA) has approved 4 endovascular stent grafts for the treatment of AAA: the Medtronic AneuRx, the W. L. Gore Excluder, the Cook Zenith and the Guidant Ancure. The Zenith graft received approval for marketing in 2003 and has gained relatively wide usage, in part due to its ability to treat aneurysms with relatively large diameter implantations zones. Also in 2003 the Guidant Corporation withdrew the Ancure graft from marketing and distribution. Enrollment has also been recently completed for the phase II FDA trials of the Medtronic Talent graft and the Cordis Fortron graft. These devices have been approved for use in the European Union and are awaiting FDA panel meeting in the United States. Comparative analysis of several of the available stent grafts has been performed. Results have varied with regard to the need for secondary interventions, aneurysm sac size reduction and the occurrence of continued perfusion of the aneurysm sac. Several significant advances have also occurred recently in stent graft research and development. Of particular significance has been the initiation of the phase I trial of the Trivascular Enovus graft. Deployment of the Trivascular graft may be accomplished through a delivery system that is considerably reduced in profile. The potential for percutaneous application of the graft may be available in the future. The indications for use of endovascular grafts as compared to standard open surgery have not yet been fully defined. Endovascular stent grafts in current use have limitations and their use must be tempered accordingly, until their long-term effectiveness is more completely evaluated. This article describes the general principles of use for endovascular devices for the repair of AAAs. It details the features and results for the devices in current use and highlights the factors that influence the selection of specific stent graft types.

Aortic Aneurysm, Abdominal↗

[Endodontic surgery (apicoectomy)--success rate of more than 90% using dental operating microscope and ultrasonic tips].

The main cause of root canal treatment failure is presence of bacteria in the root canal. Surgical endodontic retreatment is indicated as a valuable treatment choice for failed endodontic treatment. The aim of the article is to describe the advantages of a new technique for apicoectomy using dental operating microscope and ultrasonic tips in comparison to the traditional technique. Precise root end resection with minimal or no bevel and accurate preparation of the root end cavity to the depth of 3-4 mm allows minimal bone removal and reduces procedural accidents such as perforation of the lingual canal wall. Zink oxide eugenol based materials allow sealing of the retrograde preparation adequately to prevent bacteria and toxins to penetrate the periradicular tissues. Literature review demonstrates success rate to above 90% when employing dental operating microscope and ultrasonic tips for retrograde cavity preparation.

Aluminum Compounds↗

[Periodontal-endodontal interactions].

The periodontal ligament and the root canals system have a common developmental, anatomical and functional link. Those include the apical foramina, accessory canals and dental tubules whereas the pathological pathways perforation and vertical fractures. Similar microflora- bacteria, virus and yeast also have documented at the both nisus. This article describes the influence of the periodontium on the pulp and vise versa. The pulp is highly survivable and posses high ability to sustain the disease and treatment and periodontal disease and periodontal treatment exhibit small effect on the pulp. However, pulp necrosis is a risk factor to damage the periodontal ligament of the teeth.

Dental Pulp Cavity↗

Compensatory changes in [125I]-PYY binding in Y receptor knockout mice suggest the potential existence of further Y receptor(s).

Gene knockout approaches have helped to better understand the functions of the different Y receptors. However, some results obtained from these knockout mice are unexpected and differ from the results of pharmacological intervention experiments. One possible explanation for this is that germ-line gene deletion of a particular Y receptor can influence expression and function of the remaining Y receptors. Here we show that such compensation in mRNA and protein expression does occur in Y receptor single, double and triple knockout models. Radio-ligand binding experiments using [(125)I]-PYY revealed significant up- and down-regulation of remaining Y receptor binding sites in various Y receptor knockout models compared to results from control mice employing Y receptor preferring agonist or antagonists for displacement of the radio-ligand. The most obvious change can be seen in the hippocampus of Y(1) knockout mice, where the level of the remaining Y receptors is strongly down-regulated. In Y(2) knockout mice no such trend can be seen, however, the expression pattern is significantly changed with a strong up-regulation of [(125)I]-PYY specific binding in the dentate gyrus. Interestingly, this pattern was also seen in Y(1)Y(2)Y(4) triple knockout mice. Y(5) receptor mRNA was approximately 20% higher in the hippocampus and dentate gyrus in the triple knockout mice compared to wild-type controls, while Y(6) mRNA expression could not be detected. However, competition binding experiments in Y(1)Y(2)Y(4) triple knockout mice with the Y(5) receptor preferring ligands [Leu(31), Pro(34)] NPY and [A(31), Aib(32)] NPY were able to replace only approximately 50% of [(125)I]-PYY binding in the dentate gyrus suggesting the existence of further yet unidentified Y receptor(s).

Animals↗

Predicted ATP-binding cassette systems in the phytopathogenic mollicute Spiroplasma kunkelii.

Spiroplasma kunkelii is a cell wall-free, helical, and motile mycoplasma-like organism that causes corn stunt disease in maize. The bacterium has a compact genome with a gene set approaching the minimal complement necessary for cellular life and pathogenesis. A set of 21 ATP-binding cassette (ABC) domains was identified during the annotation of a draft S. kunkelii genome sequence. These 21 ABC domains are present in 18 predicted proteins, and are components of 16 functional systems, which account for 5% of the protein coding capacity of the S. kunkelii genome. Of the 16 systems, 11 are membrane-bound transporters, and two are cytosolic systems involved in DNA repair and the oxidative stress response; the genes for the remaining three hypothetical systems harbor nonsense and/or frameshift mutations, so their functional status is doubtful. Assembly of the 11 multicomponent transporters, and comparisons with other known systems permitted functional predictions for the S. kunkelii ABC transporter systems. These transporters convey a wide variety of substrates, and are critical for nutrient uptake, multidrug resistance, and perhaps virulence. Our findings provide a framework for functional characterization of the ABC systems in S. kunkelii.

ATP-Binding Cassette Transporters↗

Behavioral effects of inhibition of cannabinoid metabolism: The amidase inhibitor AM374 enhances the suppression of lever pressing produced by exogenously administered anandamide.

Biochemical investigations have identified putative enzymatic pathways for the synthesis and metabolism of endogenous cannabinoids. Anandamide amidase is an enzyme that metabolizes anandamide into arachadonic acid and ethanolamine. Using in vitro methods, various inhibitors of amidase have been identified. The present studies were undertaken to determine if the amidase inhibitor AM 374 could enhance the effects of intraperitoneal (IP) injections of anandamide. Three studies were conducted to investigate the effects of various drug treatments on fixed ratio 5 operant lever pressing for food reinforcement. In the first study, the effects of different doses of anandamide were assessed, and it was demonstrated that 5.0 and 10.0 mg/kg anandamide IP significantly suppressed lever pressing, while 2.5 mg/kg produced very little effect. The second study tested the effects of intraventricular (ICV) injections of AM 374, and it was observed that doses up to 10.0, 20.0 and 40 microg AM 374 had no significant effect upon lever pressing. The third study investigated the combined effect of AM374 with a low dose of anandamide. Rats received two drug injections: one ICV and one IP. Four different drug treatments were assessed: 1) ICV vehicle + IP vehicle, 2) ICV vehicle + 2.5 mg/kg anandamide IP, 3) ICV 20.0 microg AM 374 + IP vehicle, and 4) ICV 20 microg AM 374 + 2.5 mg/kg anandamide IP. Combined administration of AM 374 plus anandamide led to a significant decrease in lever pressing compared to either AM374 or anandamide administered alone. Observations of the animals treated with the combination of AM374 plus anandamide indicated that the drug combination resulted in motor slowing, which is consistent with the notion that stimulation of cannabinoid receptors produced a motor deficit that interfered with lever pressing. Although AM374 produced no effect on its own, this amidase inhibitor did enhance the behavioral effect of a low dose of anandamide. These results are consistent with the notion that AM 374 inhibited the enzymatic breakdown of exogenously injected anandamide. This type of procedure can be used to assess a variety of different compounds for their ability to inhibit cannabinoid metabolism.

Amidohydrolases↗

A study of radiotherapy modalities combined with continuous 5-FU infusion for locally advanced gastrointestinal malignancies.

AIM: We describe the feasibility of combining infusional 5-fluorouracil (5-FU) with intraoperative radiation therapy (IORT). METHODS: Patients with surgically resectable locally advanced gastrointestinal cancers were treated concurrently during surgery with IORT and a 72 h infusion of 5-FU. Patients without previous external beam radiation therapy (EBRT) were subsequently treated with EBRT (40-50Gy) concurrent with a 21-day continuous infusion of 5-FU. Pancreatic, gastric, duodenal, ampullary, recurrent colorectal, and recurrent anal cancer were included. RESULTS: During IORT/5-FU, no chemotherapy-related grade III or IV hematologic or gastrointestinal toxicity was noted. Post-surgical recovery or wound healing was not affected. One of nine patients who received post-operative radiation required a treatment break. During follow-up, there were more complications in patients with pelvic tumours, especially those with previous radiation. Nine patients have had local and/or local regional recurrences, two of these in the IORT field. CONCLUSIONS: Treatment with a combination of IORT and 5-FU followed by EBRT and 5-FU is feasible. However, long-term complications may be increased in previously irradiated recurrent pelvic tumours.

Adenocarcinoma↗

Epidermal growth factor (EGF) in the human placental infection with Trypanosoma cruzi.

Maternal infection of Trypanosoma cruzi is associated with premature births, abortions and placentitis. A decrease in EGF levels has been suggested to occur in animals infected by T. cruzi, but there is no research about the levels of EGF in human patients with Chagas' disease. We evaluated serum EGF levels in pregnant women with and without the disease, and with immunological methods detected EGF receptors and EGF in both groups of placentae and in cultures of normal placental villi with and without parasites. PLAP in placentae from those women was also immunologically detected, since EGF can induce the release of PLAP from the trophoblast surface and PLAP is suggested to be a receptor allowing parasite invasion of the placenta. Plasma from women with Chagas' disease contained lower level of EGF when compared to plasma of healthy women. Placentae from women with Chagas' disease showed lower PLAP expression but same level of detectable EGF receptors and EGF when compared with placentae from women without the disease. Culture with parasites did not reduce EGFr level. Results suggest a lower availability of EGF in women with Chagas' disease, which could explain several malfunctions of the placenta associated with maternal Chagas' disease.

Adult↗

Disturbed trafficking of dystrophin and associated proteins in targetoid phenomena after chronic muscle denervation.

Dystrophin and associated proteins form a complex with an important role at the sarcolemma. Expression of this protein complex is highly regulated during development and regeneration. In order to better understand assembling patterns of these proteins, we have studied their expression in targetoid-like phenomena found in human muscle after chronic denervation, a situation known to give rise to abnormal protein trafficking. In eight biopsies of patients with chronic denervation, mainly resulting from amyotrophic lateral sclerosis, we found a number of targetoid phenomena. Selective accumulation of a number of sarcolemmal and sarcoplasmatic proteins occurred in targetoid phenomena. The larger majority of them contained gamma-sarcoglycan (gammaSG), but none contained the developmental heavy chain myosin isoform. In a series of 166 targetoid phenomena which could be studied with 17 different antibodies recognizing sarcolemmal and cytoplasmatic proteins, a high level of colocalization of gammaSG with desmin and alpha-actinin was found. Colocalization rate was much lower with other proteins, including other members of the dystrophin-associated protein complex. These data show that selective changes in expression of otherwise closely related proteins occur during disturbed trafficking leading to target formation. Because members of the dystrophin-associated protein complex do not accumulate in a similar fashion within targets, we suggest that a complex molecular control of gene expression and trafficking of this complex is involved after chronic muscle denervation.

Amyotrophic Lateral Sclerosis↗

De novo interstitial duplication 4(q28.1q35) associated with choanal atresia.

We report a case of direct interstitial duplication of chromosome 4 from 4q28.1 to 4q35 associated with bilateral choanal atresia. The child also had dysmorphic features including a broad nasal bridge, telecanthus, downward slanting palpebral fissures, prominent ears, mild bilateral clinodactyly of the 5th fingers and bilateral hypoplasia of the 2nd-5th toenails. There was also a slightly dilated renal collecting system. At the age of 2.5 years, he had moderate global developmental delay, short, wide and tapering fingers, and short toes with hypoplastic toenails. To our knowledge, this is the second report of choanal atresia in a patient with trisomy 4q involving this region.

Adolescent↗

Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative.

Hyperexpression of the Saccharomyces cerevisiae multidrug ATP-binding cassette (ABC) transporter Pdr5p was driven by the pdr1-3 mutation in the Pdr1p transcriptional regulator in a strain (AD/PDR5(+)) with deletions of five other ABC-type multidrug efflux pumps. The strain had high-level fluconazole (FLC) resistance (MIC, 600 microg ml(-1)), and plasma membrane fractions showed oligomycin-sensitive ATPase activity up to fivefold higher than that shown by fractions from an isogenic PDR5-null mutant (FLC MIC, 0.94 microg ml(-1)). In vitro inhibition of the Pdr5p ATPase activity and chemosensitization of cells to FLC allowed the systematic screening of a 1.8-million-member designer D-octapeptide combinatorial library for surface-active Pdr5p antagonists with modest toxicity against yeast cells. Library deconvolution identified the 4-methoxy-2,3,6-trimethylbenzensulfonyl-substituted D-octapeptide KN20 as a potent Pdr5p ATPase inhibitor (concentration of drug causing 50% inhibition of enzyme activity [IC(50)], 4 microM) which chemosensitized AD/PDR5(+) to FLC, itraconazole, and ketoconazole. It also inhibited the ATPase activity of other ABC transporters, such as Candida albicans Cdr1p (IC(50), 30 microM) and Cdr2p (IC(50), 2 microM), and chemosensitized clinical isolates of pathogenic Candida species and S. cerevisiae strains that heterologously hyperexpressed either ABC-type multidrug efflux pumps, the C. albicans major facilitator superfamily-type drug transporter Ben(R)p, or the FLC drug target lanosterol 14 alpha-demethylase (Erg11p). Although KN20 also inhibited the S. cerevisiae plasma membrane proton pump Pma1p (IC(50), 1 microM), the peptide concentrations required for chemosensitization made yeast cells permeable to rhodamine 6G. KN20 therefore appears to indirectly chemosensitize cells to FLC by a nonlethal permeabilization of the fungal plasma membrane.

ATP-Binding Cassette Transporters↗

Reuse of fresh water sludge in cement making.

With the increasing demand for high quality water, a large quantity of chemical agent must be added in the water purification process, which in turn generates enormous amount of fresh water sludge. Of all the options for sludge disposal, sludge reuse has been considered most economical and environmentally sound. This study evaluated the possibility of incorporating fresh water sludge in the making of Portland cement through the sintering process. The goal was to search for the optimal condition to maximize the replacement of clay with the fresh water sludge. Characteristics of fresh water sludge were collected and analyzed. The analysis showed that water source and water treatment process dominate th characteristics, particularly the chemical composition of the fresh water sludge. The fresh water sludge was mixed with the cement clay in various percentages, from 0% to 100%, as raw material for cement-making. The effects of its addition on the sintering condition and the quality of cement were evaluated. The analysis of the clinkers showed that the addition of the fresh water sludge did not change the phase form and the f-CaO content of the cement. The compressive strength of the masonry increased with the increasing addition of fresh water sludge. All cement products made from various replacement ratios met the Chinese National Standard of first degree Portland cement.

Aluminum Silicates↗

Gene content and organization of an 85-kb DNA segment from the genome of the phytopathogenic mollicute Spiroplasma kunkelii.

Spiroplasma kunkelii, the causative agent of corn stunt disease in maize (Zea maysL.), is a helical, cell wall-less prokaryote assigned to the class Mollicutes. As part of a project to sequence the entire S. kunkelii genome, we analyzed an 85-kb DNA segment from the pathogenic strain CR2-3x. This genome segment contains 101 ORFs and two tRNA genes. The majority of the ORFs code for predicted proteins that can be assigned to respective clusters of orthologous groups (COGs). These COGs cover diverse functional categories including genetic information storage and processing, cellular processes, and metabolism. The most notable gene cluster in this genome segment is a super-operon capable of encoding 24 ribosomal proteins. The organization of genes in this operon reflects the unique evolutionary position of the spiroplasma. Gene duplications, domain rearrangements, and frameshift mutations in the segment are interpreted as indicators of phase variation in the spiroplasma. To our knowledge, this is the first analysis of a large genome segment from a plant pathogenic spiroplasma.

Base Sequence↗