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Biomedical subjects

R C Lin

Publications and source records attributed to R C Lin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Oxidative-modified and acetylated low-density lipoproteins differ in their effects on cholesterol synthesis and stimulate synthesis of apolipoprotein E in rat peritoneal macrophages by different mechanisms.

Apolipoprotein (apo) E plays an important role in the recognition of lipoproteins by cellular lipoprotein receptors. Unlike other apolipoproteins, apo E is expressed by many extrahepatic tissues including macrophages (M phi). Resident M phi express low levels of apo E. However, their synthesis of apo E is substantially increased after M phi have been incubated with acetylated low-density lipoprotein (LDL). But acetylation of LDL is not known to occur in vivo. On the other hand, modification of LDL by oxidation and by enzymatic action is believed to happen physiologically. In this report, we compared the effects of various modified LDLs on the synthesis of apo E by M phi. Freshly isolated human LDL was modified by (1) repeated addition of acetic anhydride (Ac-LDL); (2) incubation with 20 mumol/L CuSO4 at 37 degrees C for 24 hours (Ox-LDL); and (3) incubation with phospholipase C at 37 degrees C for 1 hour (PI-LDL). Resident peritoneal M phi were collected by lavage from rats and allowed to attach to plastic culture dishes. Although native LDL had no effect, treatment with Ac-, Ox-, and PI-LDL (50 micrograms/mL each) was found to increase medium apo E by (-fold) 4.19 +/- 0.26, 4.20 +/- 0.34, and 2.02 +/- 0.20 (mean +/- SEM, n = 5), respectively, as compared with untreated cells. Northern blot analysis revealed that cellular apo E mRNA was increased in parallel to apo E protein by Ac-LDL and PI-LDL. However, increases of apo E protein and mRNA by Ox-LDL were not equal.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Immunohistochemical demonstration of neuron-specific enolase and microtubule-associated protein 2 in reactive astrocytes after injury in the adult forebrain.

Transformation of normal resting astrocytes to reactive astrocytes in the adult brain after injury has been well documented. Using double immunofluorescent labeling methods, we report that astrocytes in both the ischemically damaged and the retrogradely/anterogradely degenerating forebrain nuclei express not only the glial cell markers glial fibrillary acidic protein and vimentin, but also the neuronal markers neuron-specific enolase and microtubule-associated protein 2. Since these neuronal markers are expressed in glial precursor cells, these results suggest that one of the characteristic responses of astrocytes in the adult brain after injury may be re-expression of fetal trait(s) of early differentiating glial cells/neurons.

Animals↗
PubMed1994

Microtubule-associated protein 2 as an early indicator of ischemia-induced neurodegeneration in the gerbil forebrain.

Microtubule-associated protein 2 (MAP-2) was studied in the gerbil hippocampus and striatum after transient ischemia. Western immunoblot analysis shows that there is a significant decrease of MAP-2 in the dorsolateral sector of the striatum and a slight decrease of MAP-2 in the CA1 region of the hippocampus 6-12 h after ischemia in the gerbil forebrain. The immunohistochemical staining pattern of MAP-2 in these two regions also shows a loss of immunostaining of MAP-2. In particular, a beaded MAP-2 immunostaining pattern at the apical dendritic region of the CA1 neurons of the hippocampus was found within 12 h after ischemia compared with the smooth dendritic immunostaining of MAP-2 in normal CA1 neurons. In vitro assays of MAP-2 degradation suggest that dendritic loss of immunoreactivity after ischemia seen on western blots may be due to calpain I degradation of MAP-2. Loss of MAP-2 in both the striatum and hippocampus was found to occur earlier than spectrin degradation by western blot analysis. These results suggest that loss of MAP-2 may participate in the initial phase of neuronal dysfunction and that dendritic breakdown may be a first sign of neurodegeneration.

Animals↗
PubMed1994

Daidzin, an antioxidant isoflavonoid, decreases blood alcohol levels and shortens sleep time induced by ethanol intoxication.

The extract from an edible vine, Pueraria lebata, has been reported to be efficacious in lessening alcohol intoxication. In this study, we have tested the efficacy of one of the major components, daidzin, from this plant extract. When ethanol (40% solution, 3 g/kg body weight) was given to fasted rats intragastrically, blood alcohol concentration (BAC) peaked at 30 min after alcohol ingestion and reached 1.77 +/- 0.14 mg/ml (mean values +/- SD, n = 6). If daidzin (30 mg/kg) was mixed with the ethanol solution and given to animals intragastrically, BAC was found to peak at 90 min after alcohol ingestion and reached only 1.20 +/- 0.30 mg/ml (n = 6) (p < 0.05 vs. controls). The ability of daidzin to delay and decrease peak BAC level after ethanol ingestion was also observed in fed animals. In both fasted and fed rats given alcohol without daidzin, BAC quickly declined after reaching its peak at 30 min. By contrast, BAC levels receded more slowly if daidzin was also fed to the animals. Daidzin showed a chronic effect. Rats fed daidzin for 7 days before ethanol challenge, but not on the day of challenge, also produced lower and later peak BAC levels. Interestingly, daidzin, whether fed to rats only once or chronically for 7 days, did not significantly alter activities of either alcohol dehydrogenase or mitochondrial aldehyde dehydrogenase in the liver. Further experiments demonstrated that daidzin shortened sleep time for rats receiving ethanol intragastrically (7 g/kg) but not intraperitoneally (2 g/kg). To test whether daidzin delayed stomach-emptying, [14C]polyethylene glycol was mixed with ethanol and fed to rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗
PubMed1993

Neuroprotective activity of dimer of 16,16'-dimethyl-15-dehydroprostaglandin B1 (di-Calciphor) in cerebral ischemia.

Post-ischemic treatment of di-Calciphor (16,16'-dimethyl-15- dehydroprostaglandin B1) significantly improves animal survival and prevents ischemia-induced neurodegeneration of vulnerable forebrain regions assessed with histochemical and biochemical techniques in gerbils. Neuronal degeneration seen by Cresyl violet staining and silver impregnation in the CA1 sector of the hippocampus and the dorso-lateral sector of the striatum was significantly reduced in animals treated with di-Calciphor. In addition, the early onset of selective degradation of calpain I substrates spectrin and microtubule-associated protein (MAP2) in these same vulnerable regions was prevented. The lack of adverse side effects may facilitate the potential therapeutic use of this drug in preventing neuronal damage caused by stroke.

Animals↗
PubMed1993

MK-801 is neuroprotective but does not improve survival in severe forebrain ischemia.

The effects of MK-801 on postischemic recovery, survival and neuronal preservation in the cortex, hippocampus and striatum were studied in Mongolian gerbils. The drug was administered 30 min prior to 20 of min forebrain ischemia induced by bilateral ligation of the carotids. Neurological recovery and survival were monitored for 7 days. At the end of the monitoring period neuronal damage was analyzed in the brains of the survivors in both groups. Treatment with MK-801 did not improve either neurological recovery or end-point survival. However, significant (P < 0.01) neuronal protection was observed in the hippocampi and striata of the drug treated animals while cortical neurons were not significantly protected. These findings demonstrate that protection against ischemic neuronal damage can be observed without concomitant improvement in either postischemic neurological recovery or survival. Protection of selectively vulnerable brain regions, often used as the predictor of the therapeutic potential of an agent, does not appear to correlate well with postischemic survival in this animal model of ischemia.

Animals↗
PubMed1993

Dynamic and distributed properties of many-neuron ensembles in the ventral posterior medial thalamus of awake rats.

The traditional view that the map of the face in the ventral posterior medial thalamus (VPM) is static and highly discrete was derived largely from qualitative studies that reported only small, robust, and nonoverlapping receptive fields (RFs). Here, by using more quantitative techniques, we have provided evidence for an alternative hypothesis: the RFs in the VPM are large and overlapping and tend to shift as a function of post-stimulus time. These results were obtained through simultaneous recordings of up to 23 single neurons across the whisker representation in the VPM of rats. Under both awake and anesthetized conditions, these neurons responded robustly at short (4-6 ms) and/or long (15-25 ms) latencies to discrete vibromechanical stimulation of single facial whiskers. Computer graphics were used to construct three-dimensional plots depicting the magnitudes of neuronal responses to stimulation of each of several whiskers as a function of post-stimulus time. These "spatiotemporal RFs" demonstrated that (i) the RFs of VPM neurons are quite large, covering up to 20 whiskers and (ii) the spatial locations of these RFs may shift dramatically over the first 35 ms of post-stimulus time, especially from the caudal-most to the rostral-most whiskers on the face. These results suggest that the VPM contains a dynamic and distributed representation of the face, in which stimulus information is coded in both spatial and temporal domains.

Animals↗
PubMed1993

Induction of immediate spatiotemporal changes in thalamic networks by peripheral block of ascending cutaneous information.

Peripheral sensory deprivation induces reorganization within the somatosensory cortex of adult animals. Although most studies have focused on the somatosensory cortex, changes at subcortical levels (for example the thalamus) could also play a fundamental role in sensory plasticity. To investigate this, we made chronic simultaneous recordings of large numbers of single neurons across the ventral posterior medial thalamus (VPM) in adult rats. This allowed a continuous and quantitative evaluation of the receptive fields of the same sample of single VPM neurons per animal, before and after sensory deprivation. Local anaesthesia in the face induced an immediate and reversible reorganization of a large portion of the VPM map. This differentially affected the short latency (4-6 ms) responses (SLRs) and long latency (15-25 ms) responses (LLRs) of single VPM neurons. The SLRs and LLRs normally define spatiotemporally complex receptive fields in the VPM. Here we report that 73% of single neurons whose original receptive fields included the anaesthetized zone showed immediate unmasking of SLRs in response to stimulation of adjacent cutaneous regions, and/or loss of SLRs with preservation or enhancement of LLRs in response to stimulation of regions just surrounding the anaesthetized zone. This thalamic reorganization demonstrates that peripheral sensory deprivation may induce immediate plastic changes at multiple levels of the somatosensory system. Further, its spatiotemporally complex character suggests a disruption of the normal dynamic equilibrium between multiple ascending and descending influences on the VPM.

Animals↗
PubMed1993

Expression of gamma-aminobutyric acid immunoreactivity in reactive astrocytes after ischemia-induced injury in the adult forebrain.

Transient ischemia induces an increase in glial fibrillary acidic protein (GFAP) immunoreactivity which can be detected in specific forebrain regions of the adult gerbil as early as day 2, becomes prominent by day 4-7 and persists for at least 3 months. These forebrain areas include layers 2/3 of the somatosensory and auditory cortices, the CA1 and CA4 sectors of the hippocampus, the dorsolateral region of the striatum, and the dorsolateral subregion of the medial septal nucleus. In addition, astrocytes in the ischemically lesioned areas stain with gamma aminobutyric acid (GABA) antiserum. These GABA-immunoreactive astrocytes are not found in non-damaged areas. The time-course of expression of GABA immunoreactivity is similar to that of GFAP immunoreactivity. Using a double immunofluorescent staining method, reactive astrocytes which express GABA immunoreactivity were also found to immunostain with either GFAP or vimentin. On the other hand, astrocytes were not found to be immunoreactive with antibodies to glutamic acid decarboxylase or glutamate. Our present finding demonstrates, in an in vivo model, an aberrant expression of GABA immunoreactivity by astrocytes which is not observed in non-ischemic adult animals.

Animals↗
PubMed1993

Zonal distribution of protein-acetaldehyde adducts in the liver of rats fed alcohol for long periods.

Acetaldehyde, a highly reactive intermediate of alcohol metabolism, has been shown to form adducts with liver proteins in rats fed alcohol for long periods. In this report, the zonal distribution of liver protein-acetaldehyde adducts that formed in vivo was studied by means of histoimmunostaining. Rats were pair-fed alcohol-containing and alcohol-free AIN'76 liquid diets for 2 or 11 wk before they were killed and subjected to whole body perfusion with paraformaldehyde. Each liver was cut into 60-microns-thick slices. Slices were first treated with 10% hydrogen peroxide to eliminate endogenous peroxidase activity. They were then incubated sequentially with rabbit antihemocyanin-acetaldehyde adduct, goat antirabbit serum IgG and rabbit peroxidase-antiperoxidase complex. The liver slices were stained with diaminobenzidine and counterstained with methylgreen. In the livers of rats fed alcohol for 2 wk, peroxidase activity was evident in the perivenous zone but not the periportal zone. No staining was obtained when the primary antibody had been preabsorbed with immobilized hemocyanin-acetaldehyde adduct or if the liver slices were incubated with the unimmunized rabbit IgG. Slight staining of the perivenous zone was seen in the livers of control rats, presumably because of minimal protein-acetaldehyde adduct formation emanating from endogenous acetaldehyde. When rats were fed alcohol for longer periods (e.g., 11 wk), protein-acetaldehyde adducts were still seen predominantly in the perivenous zone, but the distribution pattern was more diffuse than that observed in the livers of rats fed alcohol for only 2 wk. More liver cells produced protein-acetaldehyde adducts when rats were fed the alcohol-containing diet supplemented with cyanamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1993

Immunoreactivity for GAD and three peptides in somatosensory cortex and thalamus of the raccoon.

Immunocytochemical methods were used to determine the distributions of glutamic acid decarboxylase (GAD), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), and somatostatin (SOM) in the primary somatosensory cortex and somatosensory thalamus of adult raccoons. The cortex showed extensive immunoreactivity for GAD, revealing a large population of GABAergic neurons. GAD-labeled cells were numerous in all cortical layers, but were most concentrated in laminae II-IV. The cells were nonpyramidal and of varying morphology, typically with somata of small or medium size. GAD-immunoreactive puncta, presumably synaptic terminals, were widespread and often appeared to end on both GAD-negative and GAD-positive neurons. Immunoreactivity for the peptides was much less extensive than that for GAD, with the number of labeled neurons for VIP > CCK > SOM. Peptidergic cells were preferentially located in the upper and middle cortical layers, especially laminae II and III. The cells were nonpyramidal, often bitufted or bipolar in morphology, and small to medium in size. Their processes formed diffuse plexuses of fibers with terminal-like varicosities that occasionally surrounded nonpeptidergic neurons. The thalamus showed a clearly differentiated pattern of immunoreactivity for GAD, but little or no labeling for the three peptides. Nuclei adjoining the ventral posterior lateral (VPL)/ventral posterior medial (VPM) complex--including the reticular nucleus--contained many GAD-positive neurons and fibers. In contrast, the VPL and VPM nuclei displayed considerably less GAD immunoreactivity, somewhat surprising given the raccoon's highly developed somatosensory system. However, the ventral posterior inferior (VPI) nucleus revealed rather dense GAD labeling, perhaps related to a specialized role in sensory information processing. Thus, the primary somatosensory cortex of the raccoon showed patterns of immunoreactivity for GAD and peptides that were similar to those of other species; the somatosensory thalamus revealed a distinctive profile of GAD immunoreactivity, with labeling that was light to moderate in the VPL/VPM complex and relatively extensive in VPL.

Animals↗
PubMed1993

The role of ERCP and therapeutic biliary endoscopy in laparoscopic cholecystectomy.

The widespread use of laparoscopic cholecystectomy for the treatment of symptomatic gallstones has been associated with an increased use of diagnostic and therapeutic biliary endoscopy to treat common bile duct stones and postoperative complications. In 250 patients with successful laparoscopic cholecystectomy, 35 were selected for preoperative ERCP evaluation after fitting the criterion of clinical evidence with common bile duct stones (ultrasound and biochemical data). Stones were found in 16 of 35 patients (45.7%). Endoscopic sphincterotomy with stone removal was successfully carried out during the procedure. Laparoscopic cholecystectomy was performed 1 or 2 days after endoscopic sphincterotomy with good result. Only one patient without clinical evidence of common bile duct stones developed postoperative retained stone; he was successfully treated by endoscopic sphincterotomy. Three patients with postoperative bile leakage were successfully treated with endoscopic nasobiliary drainage. Diagnostic and therapeutic ERCP procedures should incorporate the newly developed method of laparoscopic cholecystectomy in order to provide a more safe and minimal invasive therapy.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1993

Measurement of hemoglobin-acetaldehyde adduct in alcoholic patients.

A sensitive and specific test for chronic alcohol abuse is useful in the diagnosis and management of alcoholic patients. Herein, we report the measurement of hemoglobin-acetaldehyde adducts (Hb-AA) in alcoholic patients by a sandwich ELISA using different antibodies. Keyhole limpet hemocyanin (KLH), a peptide consists of eight amino acid residues (8-pep, V1 to K8) at the N-terminus of beta-chain of human sickle-cell Hb and a segment of HbA beta-chain consists of 11 amino acids rich in lysine or K (11-pep, G56-K66) were incubated with acetaldehyde and NaCNBH3 to form protein-AAs. 8-Pep-AA and 11-pep-AA were individually conjugated to unmodified KLH as the carrier. Anti-protein-AA IgGs were raised in rabbits using these three protein-AA immunogens. When anti-KLH-AA IgG was used in ELISA, optical densities for alcoholic patients and controls were 0.311 +/- 0.124 and 0.147 +/- 0.042 (means +/- SD, n = 40/group, p < 0.001), respectively. Using mean value +/- 2 SD of controls as the cut-off, sensitivities to detect alcoholic patients were 78, 75, and 43%, respectively, when anti-KLH-AA, anti-11-pep-AA, and anti-8-pep-AA were used. Correlation among optical densities obtained from the first two IgGs was excellent (R2 = 0.905). We conclude that: (1) Hb-AA has the potential of being a good marker for alcohol abuse, and (2) the site of Hb that is modified by acetaldehyde in vivo is primarily located in a surface-accessible domain near the center of the beta-chain of HbA where several lysine residues are clustered.

Acetaldehyde↗
PubMed1993

Production of antibodies that recognize the heterogeneity of immunoreactive sites in human hemoglobin chemically modified by acetaldehyde.

Human hemoglobin (Hgb) was incubated with acetaldehyde under two different conditions: (a) in the presence of 250 mM acetaldehyde for 1 hr then reduced with 100 mM NaCNBH3 for an additional 4 hr at room temperature; and (b) in the presence of 500 mM acetaldehyde for 10 days at room temperature and then reduced with 1 mM NaBH4 for 1 hr. It was found that 44% and 27% of free amino groups in Hgb-acetaldehyde adduct (AA) remained unmodified when Hgb was treated under conditions (a) and (b), respectively. SDS-PAGE analysis revealed that the molecular weight of Hgb-AA(a) [Hgb modified under condition (a)] was slightly greater than that of unmodified Hgb and extensive protein cross-linking had occurred in Hgb-AA(b) [Hgb modified under condition (b)]. Electrophoresis on agarose gel showed the order of negative charge was Hgb-AA(b) > Hgb-AA(a) > unmodified Hgb. Polyclonal antibody raised in rabbits using keyhole limpet hemocyanin as the carrier protein modified by acetaldehyde under condition (a) [i.e., KLH-AA(a)] preferentially recognized Hgb-AA(a), whereas antibody raised using KLH-AA(b) as the immunogen recognized only Hgb-AA(b). In conclusion, antibodies raised with protein-AA antigens produced under different conditions recognize different epitopes.

Acetaldehyde↗
PubMed1993

Thalamic afferents of the rat barrel cortex: a light- and electron-microscopic study using Phaseolus vulgaris leucoagglutinin as an anterograde tracer.

Anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase (HRP), were used to study the thalamocortical afferents of the posteromedial barrel subfield (PMBSF) in rat primary somatosensory cortex (SI) at both light- and electron-microscopic levels. The PMBSF, also known as the barrel cortex, can be subdivided into barrel and interbarrel areas on the basis of cytoarchitectonic characteristics. Restricted injections confined to either the ventroposterior medial (VPM) or the rostral part of the posterior (Pom) nucleus allowed us to study and compare their projection patterns to the barrel cortex. We found that the interbarrel area receives inputs exclusively from the Pom, whereas the barrel area receives inputs from both the Pom and VPM. The laminar distributions of these two projections are largely segregated. After an injection of PHA-L or HRP into the VPM, labeled bouton-like swellings are found in layer VI and in layers IV through I of the barrel area, with the highest concentration in layer IV. On the other hand, after an injection of PHA-L or HRP into the Pom, labeled bouton-like swellings are distributed from upper layer V to layer I of the interbarrel area, as well as in layers V and I of the barrel area. Ultrastructural analysis showed that labeled bouton-like swellings of the VPM and the Pom pathways make synaptic contacts onto cortical neurons, and that these contacts are asymmetrical. Therefore, the VPM and the Pom projections are complementary to each other in the barrel cortex, and together they provide thalamic inputs to most layers of both the barrel and interbarrel areas. The differential patterns of terminations of the VPM and the Pom projections in the barrel cortex suggest that they may be involved in different types of cortical processing. Furthermore, our present findings may provide the anatomical basis for two parallel thalamocortical pathways, which previous physiological studies have indicated are each concerned with particular submodalities of somatic information.

Afferent Pathways↗
PubMed1993

Diagnostic and therapeutic interventions in post-laparoscopic cholecystectomy biliary complications.

Radiological imaging and therapeutic interventions were performed in eight patients with biliary complications following laparoscopic cholecystectomy. The diagnostic approach and the outcome of the therapeutic procedures were evaluated. Complications observed were bile leakage from the cystic duct stump (n = 2); erroneous identification of the cystic duct leading to common hepatic duct transection (n = 1) and hepatic duct ligation (n = 2); liver abscess (n = 1); and retained common duct stones (n = 2). Diagnostic ultrasonography is capable of detecting the presence of abnormal fluid collection and the diameter of the common duct with or without the presence of a stone, although bile leaks and retained common duct stones can only be demonstrated by either endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. Once a bile leak had been confirmed, therapeutic endoscopic biliary stenting was successfully applied in one patient while the other received percutaneous transhepatic biliary drainage. Definitive diagnosis of retained common duct stone was established by endoscopic retrograde cholangiopancreatography, and immediate endoscopic sphincterotomy with stone extraction was performed. Follow-up radiological imaging was done to determine the effectiveness of the therapeutic procedures applied in each patient. All our patients improved clinically, and further surgical intervention was not needed.

Biliary Tract Diseases↗
PubMed1992

A novel treatment of global cerebral ischaemia with a glycine partial agonist.

Chronic treatment of gerbils with 1-aminocyclopropanecarboxylic acid (a high affinity, partial agonist at strychnine-insensitive glycine receptors) resulted in a 3-fold increase in survival, a significant improvement in neurological status, and an extensive protection of vulnerable brain regions following severe forebrain ischaemia. A bolus of 1-aminocyclopropanecarboxylic acid 30 min prior to ischaemia did not further improve outcome compared to gerbils receiving their last injection 24 h prior to ischaemia. These findings are consistent with the hypothesis that chronic treatment with a glycine partial agonist desensitizes the N-methyl-D-aspartate receptor complex. Pharmacological intervention at the strychnine-insensitive glycine receptor may be an effective means of ameliorating the consequences of neuronal degeneration caused by excitotoxic phenomena.

Amino Acids↗