Biomedical subjects

C H Lin

Publications and source records attributed to C H Lin.

At least 253 records · Page 14Linked to original sources

PubMed1996

Encapsulating an amino acid in a DNA fold.

Here we present the first solution structure of a ligand-DNA aptamer complex. Our NMR-molecular dynamics structural studies of the interaction between argininamide and a DNA stem-loop complex establishes that the hairpin loop DNA binding site undergoes an adaptive conformational transition on complex formation. The tip of the DNA loop folds down towards the stem and sandwiches the bound argininamide between reversed Hoogsteen A.C and Watson-Crick G.C base pairs. The argininamide is encapsulated within the structured DNA loop and is stabilized by an intricate set of intermolecular hydrogen bonds and stacking interactions. The structure of the complex lays out the molecular principles defining both the architecture of the internal cavity and the recognition elements that could contribute to ligand discrimination.

Arginine↗

PubMed1996

The salvage of a degloved hand skin flap by arteriovenous shunting.

Nine cases of hand degloving injuries were treated successfully with arteriovenous shunting technique. Of these nine cases, four were degloved from the wrist level and one from the forearm, three were degloved at the palm and one at the dorsum of the hand. All injuries resulted in distally based skin flaps, which were either superficial to the palmar fascia or within the subcutaneous layer. Lack of active bleeding from the periphery of the avulsed flaps substantiated circulatory compromise before revascularization. Survival of the avulsed flaps was achieved by directing the proximal arterial flow into the venous channel within the avulsed skin flaps. The post-operative care and rehabilitation were straightforward, and functional results were satisfactory.

Adolescent↗

PubMed1996

Aesthetic refinements in toe-to-hand transfer surgery.

Techniques for aesthetic refinement are as important as those for functional improvement in toe-to-hand transfer. The appearance of the thumb reconstructed using various types of great toe transfer can be improved by reduction of the soft tissue, bone, interphalangeal joint, and nail and by secondary pulp reduction and contouring procedures. Finger and thumb reconstructions using lesser toes can be improved aesthetically by minimal inclusion of adipofibrous tissue under the plantar skin flap especially at the metatarsophalangeal joint region, thus decreasing the anterior-posterior bulkiness. Tight extensor repair, temporary K-pin fixation of the proximal and distal interphalangeal joint in extension, followed by prolonged use of a nighttime extension splint and secondary pulp reduction help to avoid the claw and drumstick appearances of the transferred lesser toe. Adequate soft-tissue coverage, cruciate skin incisions, extensive mobilization, and thinning and trimming of the skin flaps of the digital amputation stump lead to a smooth junction between the amputated digit and the transferred toe. In the distal digital reconstruction, skeletonization of medial and lateral neurovascular bundles of the harvested toe helps primary closure of the digital wound, thus avoiding the unsightly skin graft on the sides of the reconstructed digit. Regarding the donor foot, preservation of the proximal 0.5 to 1 cm of the proximal phalangeal stump of the great toe maintains the span of the foot, thus improving donor site appearance. In single lesser toe or combined second and third toe transfer, the proximal phalanx should not be preserved but an optimal web space should be reconstructed. Primary closure without skin graft is essential for aesthetic appearance of the donor foot.

Amputation, Traumatic↗

PubMed1996

Pharmacological characteristics of BDTI, a new isoquinoline-derived beta 2-adrenoceptor agonist, in canine trachea and rat heart.

The tracheal relaxing effects and beta 2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other beta-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 +/- 0.08) > BDTI (6.11 +/- 0.06) approximately salbutamol (6.14 +/- 0.08). ICI-118,551 (a selective beta 2-antagonist) and atenolol (a selective beta 1-antagonist) inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The Kd values of radioligand ([3H]-CGP12177) were 453.3 +/- 30.8 and 563.4 +/- 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the Bmax values were 64.6 +/- 10.7 and 245.7 +/- 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 +/- 0.15, 0.75 +/- 0.21 and 0.24 +/- 0.05 mumol/l, respectively) and rat cardiomyocytes (Ki 2.76 +/- 0.36, 2.31 +/- 0.26 and 0.22 +/- 0.03 mumol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to beta 2-adrenoceptors as judged from the Ki (heart)/Ki (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 +/- 0.2 and 0.4 +/- 0.1 mumol/l, respectively) and rat cardiomyocytes (EC50 6.2 +/- 0.5 and 5.7 +/- 0.6 mumol/l, respectively). The selectivity of BDTI and salbutamol for beta 2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a beta 2-selective adrenoceptor agonist.

Adrenergic beta-2 Receptor Agonists↗

PubMed1996

An Aplysia cell adhesion molecule associated with site-directed actin filament assembly in neuronal growth cones.

During neuronal growth cone-target interactions, a programmed sequence of cytoskeletal remodeling has been described, involving increased actin assembly at the target site and directed microtubule extension into it. The cell adhesion protein apCAM rapidly accumulates at such interaction sites, suggesting a possible role in regulating cytoskeletal remodeling. To test this hypothesis we crosslinked apCAM to varying degrees with antibodies. Secondary immunocomplexes exhibited a classical patching and capping response; in contrast, high density crosslinking of apCAM by antibody coated beads triggered localized actin assembly accompanied by formation of tail-like actin structures referred to as inductopodia. When beads were derivatized with increasing amounts of anti-apCAM they displayed three sequential dose-dependent kinetic states after binding: (1) lateral diffusion in the plane of the membrane; (2) restricted diffusion due to coupling with underlying F-actin; and (3) translocation in the plane of the membrane driven by de novo actin filament assembly local to bead binding sites, i.e. inductopodia formation. In contrast, lectin coated beads were far less efficient in triggering inductopodia formation despite demonstrated membrane protein binding. This work provides evidence that crosslinking of a diffusable membrane protein, apCAM, to threshold levels, can trigger highly localized actin filament assembly and rapid remodeling of neuronal cytoarchitecture.

Actins↗

PubMed1996

Triflavin, an Arg-Gly-Asp-containing peptide, inhibits the adhesion of tumor cells to matrix proteins via binding to multiple integrin receptors expressed on human hepatoma cells.

Integrins are a superfamily of cell surface glycoproteins that promote cellular adhesion. The interaction of integrins with extracellular matrices such as fibronectin and vitronectin has been shown to be mediated through an arginine-glycine-aspartic acid (RGD) sequence within adhesive proteins. Triflavin, a 7.5-kDa cysteine-rich polypeptide purified from Trimeresurus flavoviridis snake venom, belongs to a family of RGD-containing peptides, termed disintegrins. Disintegrins have been isolated from the venom of various vipers and have been shown to be potent inhibitors of platelet aggregation. In this study, we found that human hepatoma cell adhesion to immobilized matrix proteins (i.e. fibronectin, collagen, laminin, and vitronectin) was differentially affected by various anti-integrin monoclonal antibodies (mAbs) (i.e., alpha3beta1, alpha5beta1, alpha6beta1, and alpha v beta3) as well as by the peptide GRGDS. Indirect flow cytometric analysis of hepatoma cells with anti-integrin mAbs demonstrated that alpha6beta1 was uniformly expressed at a high density, while alpha3beta1, and alpha5beta1 were moderately expressed and alpha v beta3 was expressed in small amounts on hepatoma cells, consistent with the results obtained from immunofluorescence microscopic analysis. When immobilized on plastic wells, triflavin promoted hepatoma cell attachment; this cell attachment was inhibited by either GRGDS or mAbs against integrins alpha3beta1, alpha5beta1 and alpha v beta3). In addition, the binding of FITC-conjugated triflavin to hepatoma cells was inhibited by GRGDS, anti-alpha3beta1, antialpha5beta1, and anti-alpha v beta3 mAbs. Among these mAbs, anti-alpha5beta1 exerted the most pronounced inhibitory effect (>70%) on the binding of triflavin to hepatoma cells. Taken together, these results suggest that triflavin binds via its RGD sequence to multiple integrin receptors (i.e., alpha5beta1, alpha3beta1, and alpha v beta3) expressed on the surface of hepatoma cells, resulting in inhibition of hepatoma cell adhesion to extracellular matrices (i.e., fibronectin and vitronectin).

Antibodies, Monoclonal↗

PubMed1996

Obstructive jaundice caused by calcified portal venous thrombosis: a case report.

One case of bile duct obstruction because of calcified thrombosis of the portal vein is described. The patient had received splenectomy 20 years previously. He was admitted for fever, right upper abdominal pain and jaundice. The initial sonography and computed tomography showed dilatation of bilateral intrahepatic ducts and common bile duct with adjacent calcified portal vein mimicking common bile duct stones. Endoscopic retrograde cholangio-pancreatography showed external compression of the common bile duct by the calcified portal vein. Because of the patient's poor liver condition, biliary endoprosthesis was performed to relieve obstruction. This was an indication that the possibility of portal venous thrombosis should be included in the differential diagnosis of patients with obstructive jaundice who had previously received splenectomy.

Aged↗

PubMed1996

Infantile hypertrophic pyloric stenosis after surgery for esophageal atresia with tracheoesophageal fistula.

Infants with esophageal atresia and tracheoesophageal fistula may have other associated anomalies. The development of infantile hypertrophic pyloric stenosis in the postoperative course of esophageal atresia with tracheoesophageal fistula is rarely reported. Because its symptoms may mimick postoperative complications such as gastroesophageal reflux or anastomotic stricture, the diagnosis may be delayed. We report an infant who had surgery for esophageal atresia with tracheoesophageal fistula at birth. The infant presented with nonbilious projectile vomiting at 4 weeks of age. Plain abdominal x-ray, barium upper gastrointestinal series and abdominal ultrasonography all supported the diagnosis of hypertrophic pyloric stenosis. The diagnosis was confirmed during surgery. After pyloromyotomy, the patient's condition improved.

Abnormalities, Multiple↗

PubMed1996

Comparison of technetium-99m-HMPAO and technetium-99m-ECD cerebral SPECT images in Alzheimer's disease.

UNLABELLED: SPECT has shown increasing promise as a diagnostic tool in Alzheimer's disease (AD). Recently, a new SPECT brain perfusion agent, 99mTc-ethyl cysteinate dimer (99mTc-ECD) has emerged with purported advantages in image quality over the established tracer, 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO). This research aimed to compare cerebral images for 99mTc-HMPAO and 99mTc-ECD in discriminating patients with AD from control subjects. METHODS: Twenty-four AD patients (mean age +/- s.d. = 68.9 +/- 8.2 yr) and 13 healthy subjects (68.4 +/- 8.0 yr) were scanned sequentially with 20 mCi of each tracer using the CERASPECT system within 1 mo. Scanning began on average 11.5 +/- 2.8 min after 99mTc-HMPAO injection and 41.8 +/- 10.1 min after 99mTc-ECD. A ratio, R, was derived of count densities in "typically affected" brain structures (parietal and temporal association cortices) to "unaffected" structures (cerebellum, basal ganglia, thalamus, occipital cortex, and sensorimotor cortex). RESULTS: Analysis of variance revealed significant interaction between diagnostic group and radiopharmaceutical (F = 4.71; df = 1.35; p = 0.04), with 99mTc-ECD demonstrating better separation of R values between AD patients and control subjects than 99mTc-HMPAO. Receiver operating characteristic (ROC) analysis, revealed no significant difference in the ability of the two tracers to correctly classify AD patients and control subjects. Both tracers showed high diagnostic accuracy (99mTc-ECD: sensitivity = 100%, specificity = 92%; 99mTc-HMPAO: sensitivity = 100%, specificity = 85%). CONCLUSION: Technetium-99m-ECD shows greater contrast than 99mTc-HMPAO between affected and unaffected brain structures in AD when patients are compared to age-matched control subjects. Both tracers perform equally well in correctly classifying patients and control subjects.

Aged↗

PubMed1996

Outcome after surgical intervention in children with chronic inflammatory bowel disease.

A retrospective review of 32 children and adolescents (18 males and 14 females) with chronic inflammatory bowel disease (CIBD) requiring surgery was undertaken. These patients were followed between 1979 and 1992. Their age range was from 4 to 17 years at the time of diagnosis (mean age, 11 years). The interval between the time of diagnosis and surgery ranged from 2 months to 11 years (mean, 3.7 years). Ten patients had ulcerative colitis and 22 had Crohn's disease. These patients represented 12 per cent of patients with CIBD seen at the Gastroenterology Clinic of Children's Hospital of Michigan during these 13 years. Indications for surgery included failure of medical treatment (seven patients), localized disease with significant side effects of therapy (nine), partial or complete obstruction (five), growth retardation (six), perforation (two), abscess and fistula (three). The extent of disease was as follows: panenteric, 2 patients; enteric, 2 patients; ileocecal, 15 patients; and colonic, 13 patients. In 15 patients (47%) surgery led to complete relief of symptoms for a minimum of 1 year after surgery. Seven patients (22%) had recurrence of symptoms that were controlled by medical treatment. Two patients required a second surgery and additional medical and nutritional treatment. All six patients having surgery for growth retardation showed catch-up growth in weight and height. We conclude that surgery can decrease morbidity and improve quality of life in CIBD patients. Best results are obtained in patients with localized disease.

Adolescent↗

PubMed1995

Transcription termination at the Escherichia coli thra terminator by spinach chloroplast RNA polymerase in vitro is influenced by downstream DNA sequences.

We have investigated the mechanism of transcription termination in vitro by spinach chloroplast RNA polymerase using templates encoding variants of the transcription-termination structure (attenuator) of the regulatory region of the threonine (thr) operon of Escherichia coli. Fourteen sequence variants located within its d(G+C) stem-loop and d(A+T)-rich regions were studied. We found that the helix integrity in the stem-loop structure is necessary for termination but that its stability is not directly correlated with termination efficiency. The sequence of the G+C stem-loop itself also influences termination. Moreover, the dA template stretch at the 3' end of the terminator plays a major role in termination efficiency, but base pairing between the A and U tract of the transcript does not. From the studies using deletion variants and a series of mutants that alter the sequences immediately downstream from the transcription termination site, we found that termination of transcription by spinach chloroplast RNA polymerase was also modulated by downstream DNA sequences in a sequence-specific manner. The second base immediately following the poly(T) tract is crucial for determining the termination efficiency by chloroplast RNA polymerase, but not of the T7 or E.coli enzymes.

Base Composition↗

PubMed1995

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 2. Effects of 8-amino nitrogen substitution on serotonin receptor binding and pharmacology.

A series of analogs of the potent and selective 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (2b) (OSU191) was prepared in which the dipropylamino group was modified to bear a variety of substituents. These compounds were evaluated for both in vitro and in vivo effects, including the establishment of a receptor binding profile for these analogs at the 5-HT1A, dopamine D-2, dopamine D-3, 5-HT1D alpha, and 5-HT1D beta sites. Several of the analogs were evaluated for their biochemical effects in reserpinized rats, specifically with regard to in vivo changes in brain levels of 5-HTP and DOPA. Nearly all of the compounds prepared for this study were exceedingly potent at the 5-HT1A receptor, although most also displayed significant affinity for the dopamine D-2 receptor. A strong preference for the 5-HT1D alpha over the 5-HT1D beta receptor was also apparent. An analog bearing a butylglutarimide side chain, S-7k, was extremely selective for the 5-HT1A receptor. Although this compound possessed a Ki of 0.6 nM, it elicited only modest changes in 5-HTP brain levels. However, this compound did not appear as an antagonist when tested in a cyclic-AMP-based intrinsic activity assay.

Animals↗

PubMed1995

Characterization of an open reading frame involved in site-specific integration of filamentous phage Cf1t from Xanthomonas campestris pv. citri.

Cf1t is a single-stranded DNA filamentous phage; a 1.9-kb segment of DNA from Cf1t was found to be responsible for site-specific integration into Xanthomonas campestris pv. citri (XW47), in the absence of any Xanthomonas origin of replication. Deletion analysis and introduction of amber stop codons into this fragment from Cf1t revealed an open reading frame (ORF344) which was involved in the integration function. The predicted amino-acid sequence of ORF344 bears no homology with conserved sequences of the integrase family.

Amino Acid Sequence↗

PubMed1995

Solution structure of the covalent duocarmycin A-DNA duplex complex.

Duocarmycin A is an antitumour antibiotic that binds covalently to the minor groove N-3 position of adenine with sequence specificity for the 3'-adenine in a d(A-A-A-A) tract in duplex DNA. The adenine ring becomes protonated on duocarmycin adduct formation resulting in charge delocalization over the purine ring system. We report on the solution structure of duocarmycin A bound site specifically to A12 (designated *A12+) in the sequence context d(T3-T4-T5-T6).d(A9-A10-A11-*A12+) within a hairpin duplex. The solution structure was solved based on a combined NMR-molecular dynamics study including NOE based intensity refinement. The A and B-rings of duocarmycin are positioned deep within the walls of the minor groove with the B-ring (which is furthest from the covalent linkage site) directed towards the 5'-end of the modified strand. Duocarmycin adopts an extended conformation and is aligned at approximately 45 degrees to the helix axis with its non-polar concave edges interacting with the floor of the minor groove while its polar edges are sandwiched within the walls of the minor groove. The T3.*A12+ modification site pair forms a weak central Watson-Crick hydrogen bond in contrast to all A.T and G.C pairs, which align through standard Watson-Crick pairing in the complex. The helical parameters are consistent with a minimally perturbed right-handed duplex in the complex with minor groove width and x-displacement parameters indicative of a B-form helix. A striking feature of the complex is the positioning of duocarmycin A within the walls of the minor groove resulting in upfield shifts of the minor groove sugar protons, as well as backbone proton and phosphorus resonances in the DNA segment spanning the binding site.

Antibiotics, Antineoplastic↗

PubMed1995

C-9 and N-substituted analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3- propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A receptor agonists with various degrees of metabolic stability.

Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R1 in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.

Animals↗

PubMed1995

Two immediate synchronous free flap transfers in a severe traumatic mid-hand defect: a case report.

A 66-year-old patient sustained a severe right hand injury resulting in a thumb pulp defect and unreplantable amputation of the index, long, and ring fingers at the metacarpophalangeal joint with joint exposure. There was also an 8 cm defect of the radial digital nerve of the little finger. Immediate one-stage total reconstruction of all of the defects was accomplished by a free groin flap and a free glabrous skin flap from the foot. Opposable function of the hand was thus preserved.

Aged↗

PubMed1995

The versatility of free rectus femoris muscle flap: an alternative flap.

In the 10-year period from June 1985 to December 1994, 54 free rectus femoris muscle or musculocutaneous flaps were performed at our hospital. It has been one of the most frequently used free muscle flaps in our institution and forms 2% of all free tissue transfers (total, 2,769 cases). In 26 patients, it was used for large wound coverage following debridement or tumor ablation, and in 27 patients, as a functioning free muscle transplantation for brachial plexus palsy or traumatic muscle loss. In one patient the components of the deep aponeurosis, muscle, and overlying skin were used for reconstruction of an abdominal wall defect after neurilemmoma excision. There were two complete failures, one due to diabetic foot infection and one due to venous occlusion. Four had superficial marginal skin necrosis. No significant disability of the donor limb was encountered. Easy approach, rapid harvest, large and reliable overlying skin flap, a single dominant neurovascular pedicle (with large vessel diameter and long motor nerve), easy primary closure of the donor site, and minimal donor site morbidity all make the rectus femoris flap a good alternative flap for free tissue transfer, in addition to the gracilis, rectus abdominis, and latissimus dorsi muscle flap.

Adult↗

PubMed1995

Effects of CIS-19, a novel PAF receptor antagonist, on PAF-induced eosinophil recruitment and enhancement of superoxide anion generation in guinea-pigs.

We examined the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)- 1,2,3,4-tetrahydronaphthalene], on PAF-induced inflammatory cells recruitment into airways and enhancement of superoxide anion (O2-) generation from cells retrieved by bronchoalveolar lavage (BAL) in urethane-anesthetized guinea-pigs. Administration of PAF (30 ng/kg, i.v.) produced a selective increase of eosinophils into airways, but no significant increase of the number of macrophages, neutrophils or lymphocytes. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited the eosinophil recruitment induced by PAF. In vitro, PAF, phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) directly stimulated generation of O2- from BAL cells in a concentration-dependent manner. CIS-19 (10(-7)-10(-4) M) inhibited production of O2- induced by PAF (10(-7) M) in a concentration-dependent manner with an EC50 value of 0.84 microM, but not induced by PMA (0.5 microgram/ml) or FMLP (10(-7) M). Administration of PAF (5 ng/kg, i.v.) enhanced markedly PMA (0.5 microgram/ml) and FMLP (10(-7) M)-induced generation of O2- by 80.2% and 51.3%, respectively. The enhancing effect of PAF was maximal in cells harvested 5 min after the addition of PAF and then declined to baseline level at 60 min. These responses were inhibited by administration of CIS-19 (0.5-2.5 mg/kg, i.v.) or BN 52021 (5 mg/kg, i.v.). The results indicate that CIS-19 is potent in inhibition of PAF-induced airway inflammatory response and may have therapeutic potential as an anti-inflammatory drugs.

Animals↗