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Biomedical subjects

D D Lin

Publications and source records attributed to D D Lin.

12 recordsLinked to original sources

Hand-assisted laparoscopic autoaugmentation gastrocystoplasty.

BACKGROUND: Autoaugmentation gastrocystoplasty has been previously performed successfully. This set of experiments was conducted to determine the feasibility of performing autoaugmentation gastrocystoplasty laparoscopically. METHODS: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty was performed on 15 mongrel dogs. The surgery was carried out with two 10-mm trocars and a 6-cm Pfannenstiel incision. The gastric wedge, supplied by the right gastroepiploic artery, was resected with two applications of an endoscopic gastrointestinal anastomosis (GIA) stapler. The pedicle was demucosalized, and the anastomosis to the bladder was completed through the Pfannenstiel incision. RESULTS: All of the dogs were successfully treated laparoscopically and were eating at 48 h. There was no evidence of anastomotic leak dehiscence at the gastric resection staple line. CONCLUSION: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty can be performed successfully in dogs. This operation may offer a superior alternative to standard bladder autoaugmentation procedures in children suffering from congenital bladder disorders.

Animals↗

Hand-assisted demucosalized gastrocystoplasty comparing different tissue closure methods.

OBJECTIVES: To perform experiments to determine whether a new tissue sealant (SynthaSeal) could be an alternative for suture closure in minimally invasive bladder autoaugmentation gastrocystoplasty using demucosalized stomach. Alternative methods to suture closure for tissue approximation such as laser tissue welding and fibrin glue have been reported. METHODS: Minimally invasive autoaugmentation gastrocystoplasty with demucosalized stomach was performed on 14 female mongrel dogs. Two dogs were used to refine the technique. The remaining dogs were assigned to a suture group (n = 6) or a SynthaSeal group (n = 6). Anastomoses were performed using either SynthaSeal or suture. The in vivo bladder volumes and pressures of the groups were measured before and after gastrocystoplasty. The animals were studied on day 14. Samples of the anastomotic area were taken to measure the tensile strength and stress. Histologic analysis was conducted to assess tissue healing. The anastomotic time was recorded for each group. RESULTS: The tensile strength of the anastomoses in the SynthaSeal group was significantly increased (9.99 +/- 1.14 Newtons) compared with the suture group (5.66 +/- 0.97 Newtons) (P <0.05). The breaking stress comparisons and anastomosis times were equivalent between the two groups. The histologic evaluation revealed minor tissue devitalization and a normal inflammatory response in both groups. CONCLUSIONS: Minimally invasive gastrocystoplasty using demucosalized stomach can be successfully performed with SynthaSeal tissue sealant. This may provide a reliable alternative to suture closure.

Anastomosis, Surgical↗

Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor responses in hippocampal CA3 neurons.

Zinc is found throughout the CNS at synapses co-localized with glutamate in presynaptic terminals. In particular, dentate granule cells' (DGC) mossy fiber (MF) axons contain especially high concentrations of zinc co-localized with glutamate within vesicles. To study possible physiological roles of zinc, visualized slice-patch techniques were used to voltage-clamp rat CA3 pyramidal neurons, and miniature excitatory postsynaptic currents (mEPSCs) were isolated. Bath-applied zinc (200 microM) enhanced median mEPSC peak amplitudes to 153.0% of controls, without affecting mEPSC kinetics. To characterize this augmentation further, rapid agonist application was performed on perisomatic outside-out patches to coapply zinc with glutamate extremely rapidly for brief (1 ms) durations, thereby emulating release kinetics of these substances at excitatory synapses. When zinc was coapplied with glutamate, zinc augmented peak glutamate currents (mean +/- SE, 116.6 +/- 2.8% and 143.8 +/- 9.8% of controls at 50 and 200 microM zinc, respectively). This zinc-induced potentiation was concentration dependent, and pharmacological isolation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated currents (AMPAR currents) gave results similar to those observed with glutamate application (mean, 115.0 +/- 5.4% and 132.5 +/- 9.1% of controls at 50 and 200 microM zinc, respectively). Inclusion of the AMPAR desensitization blocker cyclothiazide in the control solution, however, abolished zinc-induced augmentation of glutamate-evoked currents, suggesting that zinc may potentiate AMPAR currents by inhibiting AMPAR desensitization. Based on the results of the present study, we hypothesize that zinc is a powerful modulator of both excitatory synaptic transmission and glutamate-evoked currents at physiologically relevant concentrations. This modulatory role played by zinc may be a significant factor in enhancing excitatory neurotransmission and could significantly regulate function at the mossy fiber-CA3 synapse.

Animals↗

Vertebroplasty: a simple solution to a difficult problem.

Vertebroplasty is the percutaneous injection of bone cement into a symptomatic fractured vertebral body under fluoroscopic guidance. It is a safe and simple outpatient procedure. We discuss patient selection, the techniques, and the results based on our experience and that of our radiology colleagues.

Aged↗

A baseline study on the importance of bovines for human Schistosoma japonicum infection around Poyang Lake, China.

We hypothesize that bovine infections are responsible for the persistence of human schistosomiasis transmission in the Yangtze marshlands of China. To test this hypothesis, we are carrying out a comparative intervention among four administrative villages in the Poyang Lake region, Jiangxi Province, two of which are experimental and two are control. The primary design involves treating, at the onset of the study, all the inhabitants in all four villages with praziquantel and all the bovines in two villages (the experimental or intervention villages). Following treatment, rates of reinfection in people of all villages, and in bovines in the experimental villages, will be assessed as will the ongoing prevalence of infection in bovines in the control villages. Before treatment, the prevalence and intensity of infection among humans and bovines was ascertained in the four villages. Our study design and baseline information are presented here, along with a description of the ecology of the study villages.

Adolescent↗

Detection of intracranial hemorrhage: comparison between gradient-echo images and b(0) images obtained from diffusion-weighted echo-planar sequences.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging (DWI) is commonly used as the initial and sole imaging examination for the detection of acute cerebral infarction, yet it remains controversial whether MR can detect hyperacute (<24 h) hemorrhage. Hemorrhage is best detected with gradient-echo (GRE) T2*-weighted sequences, because of their magnetic susceptibility effects. DWI uses a spin-echo echo-planar technique (EPI) that is more sensitive than spin-echo T2-weighted imaging to susceptibility effects. Our aim was to determine whether the b(0) image from the DWI-EPI sequence is as sensitive as GRE in detecting hemorrhagic lesions on imaging studies performed to identify acute infarction or hemorrhage. METHODS: All MR studies performed for clinically suspected or radiographically confirmed acute infarction or hemorrhage from 2/1/98 to 8/15/99 were retrospectively interpreted by one neuroradiologist in a blinded fashion. The sensitivity of hemorrhage detection, conspicuity of lesions, and diagnostic certainty were compared between the b(0) EPI and GRE sequences. RESULTS: We found 101 acute infarcts, of which 13 were hemorrhagic, as evidenced by the presence of hypointensity within the infarction on the GRE sequence. This finding served as the reference standard for detection of hemorrhage. Hemorrhage was diagnosed with confidence in only seven cases (54%) on b(0) images; 22 acute hematomas were hypointense on GRE images whereas 19 were hypointense on b(0) images (86%); 17 chronic hematomas were depicted on GRE images and 12 on b(0) scans (63%). Punctate hemorrhages and linear cortical staining were detected on 37 GRE studies but on only four b(0) studies. Hemorrhage was always more conspicuous on the GRE sequences. CONCLUSION: b(0) images from a DWI sequence failed to detect minimally hemorrhagic infarctions and small chronic hemorrhages associated with microangiopathy. GRE scans were more sensitive than b(0) images in the detection of these hemorrhages and should be included in emergency brain MR studies for acute infarction, especially when thrombolytic therapy is contemplated.

Acute Disease↗

Protracted postnatal development of inhibitory synaptic transmission in rat hippocampal area CA1 neurons.

In the CNS, inhibitory synaptic function undergoes profound transformation during early postnatal development. This is due to variations in the subunit composition of subsynaptic GABA(A) receptors (GABA(A)Rs) at differing developmental stages as well as other factors. These include changes in the driving force for chloride-mediated conductances as well as the quantity and/or cleft lifetime of released neurotransmitter. The present study was undertaken to investigate the nature and time course of developmental maturation of GABAergic synaptic function in hippocampal CA1 pyramidal neurons. In neonatal [postnatal day (P) 1-7] and immature (P8-14) CA1 neurons, miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger, were less frequent, and had slower kinetics compared with mIPSCs recorded in more mature neurons. Adult mIPSC kinetics were achieved by the third postnatal week in CA1 neurons. However, despite this apparent maturation of mIPSC kinetics, significant differences in modulation of mIPSCs by allosteric agonists in adolescent (P15-21) neurons were still evident. Diazepam (1-300 nM) and zolpidem (200 nM) increased the amplitude of mIPSCs in adolescent but not adult neurons. Both drugs increased mIPSC decay times equally at both ages. These differential agonist effects on mIPSC amplitude suggest that in adolescent CA1 neurons, inhibitory synapses operate differently than adult synapses and function as if subsynaptic receptors are not fully occupied by quantal release of GABA. Rapid agonist application experiments on perisomatic patches pulled from adolescent neurons provided additional support for this hypothesis. In GABA(A)R currents recorded in these patches, benzodiazepine amplitude augmentation effects were evident only when nonsaturating GABA concentrations were applied. Furthermore nonstationary noise analysis of mIPSCs in P15-21 neurons revealed that zolpidem-induced mIPSC augmentation was not due to an increase in single-channel conductance of subsynaptic GABA(A)Rs but rather to an increase in the number of open channels responding to a single GABA quantum, further supporting the hypothesis that synaptic receptors may not be saturated during synaptic function in adolescent neurons. These data demonstrate that inhibitory synaptic transmission undergoes a markedly protracted postnatal maturation in rat CA1 pyramidal neurons. In the first two postnatal weeks, mIPSCs are large in amplitude, are slow, and occur infrequently. By the third postnatal week, mIPSCs have matured kinetically but retain distinct responses to modulatory drugs, possibly reflecting continued immaturity in synaptic structure and function persisting through adolescence.

Age Factors↗

[Studies on risk factors for liver fibrosis of schistosomiasis japonica].

OBJECTIVE: To explore the risk factors for schistosomal liver fibrosis. METHODS: 192 hepatitis-negative patients with schistosomiasis were selected and divided into 3 groups according to the result of B ultrasound examination, that is, grade 2 and 3 fibrosis group(81 patients), grade 1 fibrosis group (61 patients) and control group (non-fibrosis, 50 patiets). The univariate and multivariate ordinal regression model was made to analyse the possibly harmful factors influencing the liver damages of these patients. RESULTS: Four factors were found to be positively associated with schistosomal liver fibrosis. They were: number of treatments of schistosomiasis (OR = 1.75), interval of schistosomal infection(OR = 1.40), history of drinking wine (OR = 1.95) and familial history of advanced schistosomiasis (OR = 2.11). CONCLUSION: Patients with repeated schistosome infection, long duration of schistosomal infection, long history of drinking and familial history of advanced schistosomiasis had higher risk for liver fibrosis than schistosomiasis patients without these factors.

Adult↗

Human neuronal gamma-aminobutyric acid(A) receptors: coordinated subunit mRNA expression and functional correlates in individual dentate granule cells.

gamma-Aminobutyric acid(A) receptors (GABARs) are heteromeric proteins composed of multiple subunits. Numerous subunit subtypes are expressed in individual neurons, which assemble in specific preferred GABAR configurations. Little is known, however, about the coordination of subunit expression within individual neurons or the impact this may have on GABAR function. To investigate this, it is necessary to profile quantitatively the expression of multiple subunit mRNAs within individual cells. In this study, single-cell antisense RNA amplification was used to examine the expression of 14 different GABAR subunit mRNAs simultaneously in individual human dentate granule cells (DGCs) harvested during hippocampectomy for intractable epilepsy. alpha4, beta2, and delta-mRNA levels were tightly correlated within individual DGCs, indicating that these subunits are expressed coordinately. Levels of alpha3- and beta2-mRNAs, as well as epsilon- and beta1-mRNAs, also were strongly correlated. No other subunit correlations were identified. Coordinated expression could not be explained by the chromosomal clustering of GABAR genes and was observed in control and epileptic rats as well as in humans, suggesting that it was not species-specific or secondary to epileptogenesis. Benzodiazepine augmentation of GABA-evoked currents also was examined to determine whether levels of subunit mRNA expression correlated with receptor pharmacology. This analysis delineated two distinct cell populations that differed in clonazepam modulation and patterns of alpha-subunit expression. Clonazepam augmentation correlated positively with the relative expression of alpha1- and gamma2-mRNAs and negatively with alpha4- and delta-mRNAs. These data demonstrate that specific GABAR subunit mRNAs exhibit coordinated control of expression in individual DGCs, which has significant impact on inhibitory function.

Adolescent↗

GABA(A) receptor function in epileptic human dentate granule cells: comparison to epileptic and control rat.

Using patch clamp recording techniques in dentate granule cells (DGCs) isolated from patients undergoing temporal lobectomy for intractable epilepsy, we investigated basic properties of GABA(A) receptors (GABA(A)Rs) and pharmacological sensitivity of GABA-evoked currents to modulation by zinc and benzodiazepines (BZ). Properties of human DGC GABA(A)Rs were compared to DGC GABA(A)R properties in control and epileptic rats. Blockade of GABA evoked currents by zinc was significantly enhanced in epileptic human relative to control rat DGCs. Augmentation of the GABA(A)R current by the non-subunit selective BZ agonist, clonazepam (CNZ) and by the BZ1 specific agonist, zolpidem (ZOL), were not significantly different in human DGCs relative to control or epileptic rat. GABA potency was significantly higher in epileptic human DGCs than in control or epileptic rat DGCs. The significantly enhanced efficacy of zinc in blocking GABA currents in epileptic human DGCs mirrors that seen in epileptic rat DGCs, and was coupled with mossy fiber sprouting evident in both epileptic human and rat dentate gyrus. The aberrant mossy fibers provide a novel zinc delivery system within the epileptic dentate gyrus. The mossy fiber release of zinc onto DGCs coupled with the enhanced zinc sensitivity of GABA(A)Rs in epileptic DGCs, may lead to 'dynamic disinhibition' which could compromise inhibitory efficacy in the epileptic rat and human hippocampus.

Animals↗

The type 1 inositol 1,4,5-trisphosphate receptor gene is altered in the opisthotonos mouse.

The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and is the only known, naturally occurring allele of opt. This mutant mouse was first identified based on its ataxic and convulsive phenotype. Genetic and molecular data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium from intracellular stores, is altered in the opt mutant. A genomic deletion in the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the translational reading frame. The altered protein is predicted to have lost several modulatory sites and is present at markedly reduced levels in opt homozygotes. Nonetheless, a strong calcium release from intracellular stores can be elicited in cerebellar Purkinje neurons treated with the metabotropic glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs linked to GTP-binding proteins that stimulate phospholipase C and subsequent production of the intracellular messenger IP3, leading to calcium mobilization via the IP3R1 protein. The calcium response in opt homozygotes shows less attenuation to repeated QA application than in control littermates. These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein.

Amino Acid Sequence↗

Inhibition of nuclear vesicle fusion by antibodies that block activation of inositol 1,4,5-trisphosphate receptors.

Inositol 1,4,5-trisphosphate (IP3) receptors are ligand-gated channels that release intracellular Ca2+ stores in response to the second messenger, IP3. We investigated the potential role of IP3 receptors during nuclear envelope assembly in vitro, using Xenopus egg extracts. Previous work suggested that Ca2+ mobilization is required for nuclear vesicle fusion and implicated IP3 receptor activity. To test the involvement of IP3 receptors using selective reagents, we obtained three distinct polyclonal antibodies to the type 1 IP3 receptor. Pretreatment of membranes with two of the antibodies inhibited IP3-stimulated CA2+ release in vitro and also inhibited nuclear vesicle fusion. One inhibitory serum was directed against 420 residues within the "coupling" domain, which includes several potential regulatory sites. The other inhibitory serum was directed against 95 residues near the C terminus and identifies an inhibitory epitope(s) in this region. The antibodies had no effect on receptor affinity for IP3. Because nuclear vesicle fusion was inhibited by antibodies that block Ca2+ flux, but not by control and preimmune antibodies, we concluded that the activation of IP3 receptors is required for fusion. The signal that activates the channel during fusion is unknown.

Animals↗