Search PubMed⌕ Search

Biomedical subjects

R C Lin

Publications and source records attributed to R C Lin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist.

Despite significant progress in understanding of the potential of adenosine A1 receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A2A receptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A2 receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5'-N- ethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A2A receptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A2A receptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A2 receptors may be useful in treatment of stroke and other neurodegenerative disorders.

Adenosine↗
PubMed1995

Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors.

It is known that stimulation of adenosine A1 receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N6-cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1995

Biosynthesis and metabolism of 4-hydroxynonenal in canine ceroid-lipofuscinosis.

Canine ceroid-lipofuscinosis (CCL) is a model of the juvenile type of Batten disease in human patients. Abnormalities have been reported previously in 4-hydroxynonenal (HNE) levels in English setters with CCL. The purpose of this study was to examine the sources of HNE in neutrophil membranes and plasma of CCL dogs. The fatty acid composition of neutrophil phospholipids, i.e., phosphatidyl ethanolamine and phosphatidyl serine, was determined by gas-liquid-chromatography (GLC) since some polyunsaturated fatty acids (PUFA) are precursors of HNE. The copper catalyzed peroxidation of low density lipoprotein (LDL) was examined to determine the susceptibility of LDL from CCL dogs to peroxidation. The results indicated that a number of PUFA precursors of HNE decreased in affected an carrier neutrophil phospholipids, indicating that this source of HNE may be disease specific. The Cu++ catalyzed formation of HNE from LDL demonstrated that carrier and normal LDL produced large amounts of HNE, while LDL from affected dogs required much higher concentrations of Cu++ for maximal HNE production. These results provide additional support for the role of HNE in the pathogenetic events in NCL and support the view that lipid peroxidation may be an important contributor to the complex pathogenesis of the NCL.

Aldehydes↗
PubMed1995

Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system.

Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

Animals↗
PubMed1995

Noradrenergic enhancement of GABA-induced input resistance changes in layer V regular spiking pyramidal neurons of rat somatosensory cortex.

Previous in vivo studies have shown that microiontophoretic application of norepinephrine (NE) and isoproterenol (ISO) can enhance gamma-aminobutyric acid (GABA)-induced depressant responses of rat somatosensory cortical neurons. In the present investigation we have examined the transmembrane electrophysiological events which are associated with interactions between NE and GABA in layer V pyramidal neurons of rat barrel field cortex. Intracellular recordings were made from electrophysiologically identified cells in a superfused cortical tissue slice preparation before, during and after bath or microdrop application of GABA, NE and ISO, alone or in combination. GABA application produced a small depolarization from resting membrane potential associated with a reduction (22%) in input resistance. NE and ISO (10-100 microM) also produced in some cases small membrane depolarizations (1-4 mV) but little concomitant changes in input resistance. Simultaneous application of NE with GABA potentiated amino acid-induced changes in input resistance in 4 cases and antagonized (n = 4) or had no effect (n = 4) on GABA-associated membrane events in 8 other cases. When the alpha-blocker, phentolamine (20 microM), was added to the medium, NE-induced enhancement of the GABA response was observed in 3 of 5 cases (60%), suggesting both, a beta-adrenergic mediation and a possible alpha-receptor masking of this noradrenergic-potentiating action. Consistent with this interpretation was the finding that the beta-agonist, ISO (10-100 microM), produced net increases in GABA-induced input resistance changes in 64% of cases tested (9 of 14). The potentiating effect of NE and ISO was mimicked by the adenyl cyclase activator, forskolin (n = 2), and a membrane permeant analog of cyclic-AMP, 8-bromo-cyclic AMP (n = 3); and could also be demonstrated when the GABAA agonist muscimol (0.5-1 microM) was substituted for GABA. The reversal potential for GABA and GABA + NE remained the same. These findings suggest that previous demonstrations of NE-potentiating effects on GABA inhibition may be mediated by beta-receptor/cyclic-AMP-linked actions on mechanisms which regulate GABAA receptor-induced membrane conductance changes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

The effects of adenosine A3 receptor stimulation on seizures in mice.

We have previously shown that acute preischemic adenosine A3 receptor stimulation results in an increased postischemic damage, while chronic stimulation of this receptor diminishes it. Since several pathophysiological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenosine A3 receptor selective agonist IB-MECA (N6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide) prior to seizures induced by N-methyl-D-aspartate (NMDA), pentamethylenetetrazole, or electric shock. At 100 micrograms/kg, acutely injected IB-MECA was protective in chemically but not electrically induced seizures. In chronic administration of IB-MECA, significant protection against chemically induced seizures was obtained in all studied measures, i.e., seizure latency, neurological impairment, and survival. Although threshold voltage was unchanged in electrically induced seizures, a chronic regimen of IB-MECA significantly reduced postepileptic mortality. Since the combination of an arteriole-constricting compound 48/80 and hypotension-inducing clonidine injected prior to NMDA results in a significant protection against seizures, and since acute stimulation of adenosine A3 receptor causes both arteriolar constriction and severe hypotension, there is a possibility that the protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB-MECA is related to the effect of the drug on blood flow, neuronal mechanisms, or both.

Adenosine↗
PubMed1995

Re-expression of the intermediate filament nestin in reactive astrocytes.

The intermediate filament nestin is highly expressed in multipotential stem cells of the developing central nervous system (CNS). During neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g. neurofilaments and glial fibrillary acidic protein (GFAP). In this study, we demonstrate that nestin expression is re-induced in reactive astrocytes in the lesioned adult brain. Following ischaemic and mechanical lesioning, a strong and sustained expression of nestin was noted in GFAP-positive cells surrounding the lesion site. Lesion experiments in transgenic mice carrying the lacZ gene under control of regulatory sequences from the nestin gene suggested that the upregulation of nestin in reactive astrocytes is mediated via the same sequences that control nestin expression during CNS development. These observations and recent data on the co-expression of glial and neuronal marker antigens in reactive astrocytes point to a close relationship between proliferating astrocytes and neuroepithelial precursor cells.

Animals↗
PubMed1995

Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat.

The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function.

Animals↗
PubMed1995

Distinct domains of syntaxin are required for synaptic vesicle fusion complex formation and dissociation.

Membrane fusion resulting in neurotransmitter secretion forms the basis of neural communication. Three multimeric complexes of the protein syntaxin are important in this process: syntaxin and n-sec1; syntaxin, VAMP, and SNAP-25; and syntaxin, VAMP, SNAP-25, alpha SNAP, and NSF (20S complex). In this report, we demonstrate that unique, yet overlapping, domains of syntaxin are required to form these complexes. The formation of higher order heteromultimers has a set of structural requirements distinct from those required for dimeric interactions. Dissociation of the 20S complex by NSF following ATP hydrolysis requires amino-terminal regions of syntaxin that are outside of the binding domains for the 20S constituent proteins. These data are consistent with the hypothesis that conformational changes in syntaxin, resulting from protein-protein interactions and ATP hydrolysis by NSF, mediate neurotransmitter release.

Adenosine Triphosphate↗
PubMed1995

Neuroprotective actions of 1-aminocyclopropanecarboxylic acid (ACPC): a partial agonist at strychnine-insensitive glycine sites.

1-Aminocyclopropanecarboxylic acid is a high affinity ligand with partial agonist properties at strychnine-insensitive glycine sites associated with the N-methyl-D-aspartate subtype of glutamate receptors. Since occupation of these sites appears required for operation of N-methyl-D-aspartate, receptor coupled cation channels, it was hypothesized that a glycine partial agonist could function as an N-methyl-D-aspartate antagonist. This hypothesis was examined by evaluating the in vivo and in vitro neuroprotective actions of 1-aminocyclopropanecarboxylic acid. 1-Aminocyclopropanecarboxlic acid (150-600 mg kg-1) administered to gerbils five minutes following twenty minutes of forebrain ischemia significantly improved seven day survival; the optimal dose (300 mg kg-1) increased 7 days survival > 4-fold, from 20% to 92%. Survival of hippocampal CA1 neurons (quantitated 7 days post-ischemia) was significantly (approximately 3-fold) increased by the 600 mg kg-1 dose. Seven day survival was not significantly increased when the interval between reperfusion and drug administration (300 mg kg-1) was increased from 5 to 30 min. In cerebellar granule cell cultures, NMDA combined with a saturating concentration of glycine (10 microM) resulted in a 500% increase in cGMP levels. cGMP levels were increased by 100% over basal when NMDA was combined with a saturating (10 microM) concentration of ACPC, indicating that in this measure, the efficacy of ACPC relative to glycine was approximately 0.2. Consistent with previous findings, 1-aminocyclopropanecarboxylic acid significantly reduced glutamate-induced neurotoxicity in cerebellar granule cell cultures. ACPC was most effective in blocking neurotoxicity at glutamate concentrations producing low to moderate levels of cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Structural analysis of peptide-acetaldehyde adducts by mass spectrometry and production of antibodies directed against nonreduced protein-acetaldehyde adducts.

Acetaldehyde can form protein-acetaldehyde adducts (AAs) in vivo and may play a role in the genesis of alcoholic liver disease. The nature of the chemical modification of proteins by acetaldehyde in vivo has not been elucidated. In vitro, acetaldehyde can form reversible adducts including a Schiff's base with lysine (K) and imidazolidinone with terminal amino groups of proteins such as human hemoglobin (Hb). In this study, we used FAB/MS to analyze the products of peptide-AAs (pep-AAs) formed by incubating acetaldehyde with Hb peptides. We then used an octabranched multiple antigen peptide (MAP) system containing Hb peptide-AAs to raise antibodies. Three Hb peptides [i.e., 8-pep consisting of 8 residues (V1HLTPVEK8) at the N-terminus of beta-chain of human sickle-cell Hb, 11-pep-gly consisting of 11 residues (G56NPKVKAHGKK66) in a segment of beta-chain rich in lysine, and 11-pep-pro that consists of the same sequence as 11-pep-gly, except G56 was replaced by proline (P)] were incubated with 1 mM acetaldehyde at 4 degrees C for 7d without NaCNBH3 (nonreduced conditions). Analysis by FAB/MS showed that 8-pep formed an imidazolidinone at the N-terminal valine, 11-pep-gly formed a Schiff's base and imidazolidinone at the N-terminus, whereas 11-pep-pro that lacks a free alpha-amino group formed only a Schiff's base at K59. By contrast, incubation of these Hb peptides with 250 mM acetaldehyde and NaCNBH3 at 37 degrees C for 1 hr (reduced conditions) produced mono- and diethylated modifications of all available K residues, as well as the N-terminal amino group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1995

Serum low density lipoprotein of alcoholic patients is chemically modified in vivo and induces apolipoprotein E synthesis by macrophages.

This work was carried out to investigate the effect of alcohol drinking on serum LDL. Agarose gel electrophoresis showed that LDL samples from alcoholic patients without serious liver disease were more negatively charged and moved faster toward the cathode than LDL from nondrinking control subjects. Rabbit antibodies raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal or by acetaldehyde as immunogens reacted more strongly with patients' LDL than with control LDL, indicating the presence of oxidatively modified epitopes and acetaldehyde adducts in alcoholic patients' LDL. LDL of alcoholic patients has decreased vitamin E contents. The electromobility of LDL decreased after abstinence from alcohol and returned to normal in 2 wk, but this was not accompanied by a significant increase in its vitamin E contents. When incubated with mouse peritoneal macrophages, patients' LDL induced apolipoprotein E secretion by threefold over control LDL with a concomitant increase in cellular cholesterol. Our results thus demonstrate that LDL of alcoholic patients has lower vitamin E content, is chemically modified in vivo, and exhibits altered biological function. These changes in heavy alcoholic drinkers may render LDL more atherogenic and thereby may counter the antiatherosclerosis effects of moderate alcohol consumption.

Adult↗
PubMed1995

Preoperative assessment of choledocholithiasis in laparoscopic cholecystectomy.

In order to determine the predictive value of noninvasive investigations for choledocholithiasis, we conducted a prospective preoperative study on 82 patients with symptomatic gallstones who received laparoscopic cholecystectomy. Ultrasonography (US), liver function tests and endoscopic retrograde cholangiography (ERC) were routinely performed in all cases prior to operation. The results showed a strong correlation between noninvasive procedures (liver function tests and US) and the presence of choledocholithiasis as shown by ERC. Using ERC as a reference, the sensitivity and selectivity of ductal dilatation at US and the elevation of alkaline phosphatase (ALP), gamma-glutamyltransferase and total bilirubin in the serum were studied for the detection of common bile duct (CBD) stones. The values of the combination of these tests were also calculated. From receiver operator characteristics curves, the best cut-off point for US in conjunction with ALP was chosen. ERC should be restricted to patients with possible CBD stones, suspected after a combination of the noninvasive US and ALP tests. This study emphasized the necessity and timing of performing ERC as a preoperative modality in the detection of choledocholithiasis in patients who are to undergo laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed1995

Concentrations of apolipoprotein AI, AII, and E in plasma and lipoprotein fractions of alcoholic patients: gender differences in the effects of alcohol.

Previous studies have shown that plasma levels of high-density lipoprotein (HDL) cholesterol and the two major protein components of HDLs, i.e., apolipoproteins AI and AII, were elevated in male alcoholic patients without serious liver injury. By contrast, alcohol effect on apolipoprotein E remains unclear. Apolipoprotein E is a major component of very low-density lipoprotein (VLDL) and a minor component of human high-density lipoprotein. It plays a critical role in lipoprotein metabolism through cellular lipoprotein receptors. Furthermore, previous works were carried out mostly with male subjects, whereas alcohol effects on serum apolipoproteins in female subjects have not yet been adequately addressed. In this study, we have raised antibodies specifically to recognize human apolipoprotein AI, AII, and E, respectively, to quantify apolipoprotein concentrations in plasma and lipoprotein fractions of male and female alcoholic patients. We have also measured plasma apolipoprotein concentrations in patients who had abstained from alcohol while in the hospital. Our results showed the following: (1) plasma concentrations of apolipoprotein AI and AII were significantly elevated yet plasma apolipoprotein E decreased (33%) significantly (P < .01) in male alcoholic patients; (2) apolipoprotein AI concentrations in female nondrinking control subjects were higher than in male controls, and the concentrations of apolipoprotein AI in female alcoholic patients were not significantly elevated over those of female controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ultrasound-guided percutaneous transhepatic gallbladder drainage followed by laparoscopic cholecystectomy: a new trial in the treatment of severe acute suppurative cholecystitis.

Seven cases of acute suppurative cholecystitis underwent percutaneous transhepatic gallbladder drainage followed by laparoscopic cholecystectomy at the Tainan Municipal Hospital. All the patients had frank septic phenomena clinically, including fever, jaundice, leukocytosis and unstable blood pressure. Organisms were cultured from both blood and bile specimens. Ultrasound-guided transhepatic puncture of the gallbladder was performed for bile drainage, and laparoscopic cholecystectomy was subsequently performed two to five days later after the patients had stabilized. No procedure-related complications from either percutaneous transhepatic gallbladder drainage or laparoscopic cholecystectomy were observed. All patients had early recovery, shortened hospital stay and good cosmetic results. These preliminary results show that laparoscopic cholecystectomy is a safe method and can be employed in those patients with symptomatic gallstone associated with suppurative cholecystitis after preoperative biliary drainage.

Acute Disease↗
PubMed1995

Spontaneous perforation of the left hepatic duct--a case report.

We report on a patient with spontaneous perforation of the left hepatic duct who presented with abdominal pain, jaundice and fever. The correct diagnosis was not established until extravasation of contrast medium from the left hepatic duct, as demonstrated by the cholangiogram, was observed. The patient developed two bile-stained intraperitoneal encapsulated fluid collections, which were diagnosed by ultrasonography, and high bilirubin levels in the fluid aspirated from the encapsulations, which were also found at operation. Closure of the perforation with sutures, decortication of the encapsulations and choledocholithotomy for stone extraction with T-tube insertion were performed. Recovery was complete at follow-up examinations.

Abdominal Pain↗