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Biomedical subjects

L H Lin

Publications and source records attributed to L H Lin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Synthesis and transport of GAP-43 in entorhinal cortex neurons and perforant pathway during lesion-induced sprouting and reactive synaptogenesis.

Metabolic labeling and quantitative 2D gel autoradiography were used to assess changes in the synthesis and transport of GAP-43 in entorhinal cortex (EC) neurons and perforant pathway during lesion-induced sprouting and reactive synaptogenesis. In normal adult rats, there is a high constitutive level of GAP-43 synthesis and transport in EC neurons projecting to the hippocampus. Following unilateral EC lesions, there is a 2-fold (100%) increase in the transport of newly synthesized GAP-43 to the contralateral or 'sprouting' hippocampus. The timing of this upregulation (between 6 and 15 days) suggests that changes in GAP-43 expression occur in response to the growth of presynaptic terminals during sprouting.

Animals↗
PubMed1992

General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium.

Potentiation of the gamma-aminobutyric acid (GABAA) receptor-gated Cl- channel response has been suggested to be a primary action of some anesthetic agents. We asked whether the GABAA receptor is a target site common for general anesthetics that are chemically and structurally diverse. This hypothesis was tested in Xenopus oocytes expressing mouse cortical mRNA, and GABA-activated Cl- currents were measured using two-electrode voltage clamping. General anesthetics, including inhalational (halothane, diethylether, enflurane and isoflurane), i.v. (3 alpha-hydroxy-5 alpha-dihydroprogesterone, ketamine and propofol) and alcohol (pentanol) anesthetics, enhanced GABA-induced currents by 56 to 1089% at concentrations that were clinically relevant. The results suggest that potentiation of the GABAA receptor/channel response may be a common action for anesthetic agents. Moreover, anesthetic effects were dependent on GABA concentrations; the enhancement was marked with low GABA concentrations and was exponentially decreased as the GABA concentration increased. Also, anesthetic effects were dependent on anesthetic concentrations. The apparent EC50 of halothane was found to be similar to the anesthetic ED50. We also investigated the role of intracellular Ca++ in mediating anesthetic enhancement of the GABA current. We found that intracellular injection of the Ca++ chelator, EGTA, did not change the enhancement by anesthetics. In addition, these anesthetics alone did not produce significant currents, suggesting that the Ca(++)-dependent Cl- current was not activated by these anesthetics per se. Thus, we found that diverse anesthetics potentiate GABA-induced Cl- currents, but this action is not mediated by a release of intracellular Ca++.

20-alpha-Dihydroprogesterone↗
PubMed1991

The Rett and Rett-like syndromes: a broad concept.

Eight patients who satisfied the following three criteria: 1) autistic behavior, 2) mental retardation and 3) stereotypic hand movements were evaluated. Four patients fulfilled the diagnostic criteria for the Rett syndrome developed by representatives of the International Rett Syndrome Association and the Center for Disease Control, Atlanta, USA. The other four Rett-like patients were atypical in the sense that the manifestations were incomplete or psychomotor development throughout the first 6 months of life was abnormal or the disease was heralded by infantile spasms with transient stereotypic hand movements or the baby was born with congenital microcephaly. All eight patients were girls. No laboratory test result specific for the Rett syndrome or Rett-like syndrome was obtained.

Electroencephalography↗
PubMed1990

Analysis of a splice acceptor site mutation which produces multiple splicing abnormalities in the human argininosuccinate synthetase locus.

The cloned argininosuccinate synthetase gene from a citrullinemia patient's fibroblast cell line revealed a single base substitution (G to C) within the splice acceptor site of the last intron. The mutation abolished normal RNA splicing, and, by cDNA analysis, three abnormal splicing pathways were demonstrated. The major pathway involved the activation of a cryptic acceptor site in the last exon that resulted in a deletion of seven nucleotides in the mature RNA. Another pathway involved a downstream cryptic acceptor site, that is 388 nucleotides downstream from the first cryptic site. Northern blot analysis showed that this second cryptic site is present on the minor 2.7-kilobase mRNA, but not on the major species of argininosuccinate synthetase mRNA, which is 1.7-kilobases in length. Using this aberrant cDNA as a probe, the cDNA of the 2.7-kilobase mRNA was isolated and studied. Sequence analysis suggests that this species of RNA is the one that bypasses the polyadenylation signal employed by the 1.7-kilobase RNA. Since both transcripts encounter the same translation termination codon, both RNAs should encode identical protein. Furthermore, a tract of 22 repeats of d(CA).(GT) is found at the 3' end of the gene and this repeat sequence is present on the 2.7-kilobase RNA. The third pathway of the abnormal splicing revealed a rare class of transcript that has the last intron retained in the mature RNA. This study shows that in human the intron inclusion can occur through a naturally occurring point mutation. All these abnormally spliced RNAs resulted in a protein reading frame shift.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Hypothalamic monoamines and their metabolites in the deermouse, Peromyscus maniculatus, during daily torpor.

Deermice, subjected to food rationing, an ambient temperature below thermal neutrality and short photoperiod, were sacrificed in euthermia or during daily torpor. Hypothalamic monoamine and metabolite levels were quantified by HPLC with electrochemical detection. Significant elevations in the levels (pg/microgram protein) of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were noted in the torpid animals. The concentrations of norepinephrine and serotonin displayed no significant alterations between the euthermic and torpid states. However, the serotonin metabolite, 5-hydroxyindole-3-acetic acid, was elevated by almost 300%. These data suggest that an increase in activity of the hypothalamic serotonergic and dopaminergic systems occurs during daily torpor in the deermouse.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Comparison of spatial and temporal characteristics of neuronal activity in sequential stages of hippocampal processing.

The activity of individual pyramidal cells in the CA1 and CA3 subfields of the rodent hippocampus exhibits a remarkable selectivity for specific locations and orientations of the rat within spatially-extended environments. These cells exhibit high rates of activity when the animal is present within restricted regions of space, referred to as place fields, and are extremely quiet when it is elsewhere. Although this phenomenon has been well studied in the CA fields of the hippocampus, relatively little is known about the spatial and temporal firing characteristics either of the entorhinal cortical inputs to the hippocampus, or of the subicular recipients of the output of hippocampal place cells. We report here on a comparison of spatial and temporal discharge characteristics among entorhinal cortex, CA3 and CA1, and the subiculum. CA3 complex spike cells were significantly more spatially specific than their CA1 counterparts. Neither entorhinal cortex nor subiculum exhibited the highly localized patterns of spatial firing observed in the CA fields. In addition, average discharge rates in these areas were substantially higher. However, particularly in subiculum, there was evidence for spatially consistent, but dispersed, firing in some cells, suggestive of the convergence of a number of CA1 place cells. The patterns observed are not consistent with the hypothesis that spatial selectivity is progressively refined at the various levels of hippocampal processing. Rather, hippocampal output appears to be expressed as a much more highly distributed spatial code than activity within the hippocampus proper. We suggest that the sparse coding used within the hippocampus itself represents a mechanism for increasing the storage capacity of a network whose function is to form associations rapidly.

Action Potentials↗
PubMed1990

Breath hydrogen test for assessment of lactose malabsorption following rotavirus gastroenteritis.

Ninety infants and young children with acute gastroenteritis were investigated for lactose malabsorption. Each of them was given an oral lactose load of 2g per kg of body weight after which breath hydrogen excretion was measured, and each was observed for clinical symptoms of lactose intolerance. Only 2 patients, given 2g per kg of lactose, had clinical lactose intolerance. Forty-nine of the 90 patients studied were found to have the rotavirus antigen in their stools. Forty-five of them were found to have an abnormal lactose breath hydrogen test (LBHT). Twenty-three patients with abnormal LBHT were restarted on a diluted lactose-containing formula for oral feeding. They required longer hospitalization (mean 6.7 days, range 3-14 days) and were free of diarrhea in 14 days (mean 7.5 days). Twenty-two patients found to have an abnormal LBHT were given a nonlactose-containing formula (Isomil, Nursoy, Alsoy, ProSobee, or Bebelac FL) when restarted on oral feeding. All patients require less than 5 days of hospitalization and free of diarrhea in 5 days (mean 3.4 days). The difference was statistically significant (p less than 0.05).

Breath Tests↗
PubMed1990

Persistence of neurochemical changes in dopamine systems after repeated cocaine administration.

The purpose of this study was to test whether persistent changes consistent with behavioral sensitization occur in dopamine (DA) uptake, release or receptors following repeated cocaine administration. Our neurochemical experiments focused primarily on the striatum; however, quantitative autoradiography was used to measure D-1 and D-2 DA receptors in both cell body and terminal regions of the nigrostriatal and mesolimbic dopaminergic pathways. After receiving eight once-daily injections of cocaine (10 mg/kg, i.p.), rats remained behaviorally sensitized for 1 week. This repeated treatment with cocaine induced two changes consistent with increased dopaminergic transmission. Postsynaptic D-2 DA receptors were selectively increased in nucleus accumbens one day after termination of the repeated cocaine administration; however, these receptors returned to control levels one week after cocaine administration had been terminated. In contrast, amphetamine-stimulated [3H] DA release from striatal slices was increased in rats receiving repeated cocaine injections, but this increase was not apparent until 1 week after the drug administration had been terminated. While neither of these two changes is sufficient to explain cocaine-induced behavioral sensitization, both are consistent with increased dopaminergic responsiveness and may contribute to sensitization.

Amphetamine↗
PubMed1989

Analysis of hepatitis B virus transcripts in infected human livers.

The hepatitis B virus transcripts in human hepatoma and its adjacent nontumorous liver were examined with probes specific to hepatitis B virus surface antigen, core antigen, X region and pre-S region. The study shows that the patterns of hepatitis B virus transcripts for tumorous tissue and the counterpart in nontumorous liver differ. In most of the tissues examined, the surface antigen gene is transcribed. Most of these transcripts, besides having surface antigen sequences, also have an X region; some also include a pre-S region. The transcripts that hybridized to a core-specific probe were a pair of poly(A+) RNA, 3.5 and 2.2 kilobases in size, present in two of the nontumorous hepatocytes where the virus was actively replicating. The 3.5-kilobase transcript not only hybridized to the core probe, but was able to be hybridized to other hepatitis B virus subgenomic probes and might represent the RNA pregenome involving hepatitis B virus DNA replication. Whereas most of the transcripts hybridizable to hepatitis B virus probe are in the size range of 2.1 to 2.7 kilobases, some transcripts other than the pregenomic RNA appear to be greater than 3.2 kilobases in size and may represent the hybrid RNAs of viral and host sequences.

Blotting, Northern↗
PubMed1989

Study of restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus and evaluation of its potential application in prenatal diagnosis of phenylketonuria in Chinese.

Using a human phenylalanine hydroxylase cDNA probe, the restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus have been determined with the restriction enzymes BglII, PvuII, EcoRI + BamHI, MspI, XmnI, HindIII and EcoRV. The frequency of the observed heterozygosity of the restriction site polymorphisms at this locus in a Chinese population is approximately 54%, which is significantly lower than that in Caucasians. No DNA rearrangement or deletion of the phenylalanine hydroxylase locus was detected among mutant phenylalanine hydroxylase genes in seven Chinese classical phenylketonuria (PKU) families. Haplotype analysis of these seven families revealed that the mutant alleles belonged to five different haplotypes, i.e. haplotype 4, 11 and three unreported haplotypes. The majority of normal and mutant phenylalanine hydroxylase genes are confined to hyplotype 4. These results indicate that approximately 42% of Chinese PKU families are informative for prenatal diagnosis of PKU when eight restriction sites linked to the phenylalanine hydroxylase locus are examined.

Alleles↗
PubMed1989

Analysis of serotonin, dopamine and their metabolites in the caudate putamen, the suprachiasmatic nucleus and the median raphe nucleus of euthermic and torpid deermice, Peromyscus maniculatus.

Deermice, subjected to food rationing and low ambient temperature, were sacrificed in normothermia or during daily torpor. Levels of monoamines and their metabolites in the caudate putamen (CPN), the suprachiasmatic nuclear area (SCN), and the median raphe nucleus (MRN) were quantified through the use of HPLC with electrochemical detection. Significant elevations in levels (pg/mg protein) of the serotonin (5-HT) metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were noted in torpid individuals in all nuclei examined. The dopamine (DA) metabolite, homovanillic acid (HVA) was significantly elevated in the CPN and MRN of torpid individuals. Moreover, a significant increase in the HVA to DA ratio was also noted in the CPN and the MRN. In the SCN, the concentrations of 5-hydroxytryptophan (5-HTP), 5-HT, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were also increased significantly during torpor. These significant elevations suggest that an increase in the activity of the serotonergic and dopaminergic systems occurs in these nuclei during daily torpor in the deermouse.

Animals↗
PubMed1989

An unexpected pH effect on the stability of moexipril lyophilized powder.

Because of the limited stability of moexipril (RS-10085; 1) in aqueous solution, lyophilized parenteral formulations were evaluated as a function of pH in this study. In general, the lyophilized powder of 1 showed about two orders of magnitude less reactivity at 50 degree C than in aqueous solution at pH values below 3 or above 6. At pH 5.1, however, the lyophilized powder had maximum reactivity, with the rate actually comparable to that observed in aqueous solution. When the distribution of the two major products, diketopiperazine (DKP) 2 and ester hydrolysis analogue 3, was compared to the observed kinetics as a function of pH, it was clear that removal of water via lyophilization suppressed the spontaneous k1 cyclization process, the spontaneous k3 hydrolysis process, and the specific base-catalyzed k4 hydrolysis process. The overall spontaneous k2 cyclization process, however, was not affected by lyophilization. The latter result is accounted for by the increased equilibrium constant for the formation of the tetrahedral intermediate, To, as a result of lyophilization. This study demonstrates that stability data in solution can not be used for predicting the stability of moexipril in lyophilized powder form.

Chromatography, High Pressure Liquid↗
PubMed1989

Hepatitis B virus transcript produced by RNA splicing.

A new hepatitis B virus (HBV) transcript of about 2.2 kilobases was identified in HBV DNA-transfected human hepatoma cells. The 5' terminus of this viral RNA appears to map at one or more of the precore initiation sites, contains a deletion of 1,223 bases corresponding to the last codon of the core gene to the middle of the surface antigen gene, and terminates at the 3' polyadenylation site used by the other known HBV RNAs. The junction region of the deleted sequences showed the conserved splice donor and acceptor GT-AG sequences. Moreover, when a mutant HBV DNA in which the splice acceptor site was changed from AG to CG was transfected into human hepatoma cells, no 2.2-kilobase RNA was detected, further suggesting that this RNA represents a spliced transcript. The core gene, although an amino acid shorter, still encoded a functional viral core protein in complementation experiments. Sequence analysis of the cDNA of the 2.2-kilobase RNA suggests that this transcript can potentially encode a new protein that comprises the reverse transcriptase domain of HBV. However, genetic analysis using a transient DNA transfection system suggests that the gene product(s) of this transcript is not essential for viral replication. The function of this transcript remains to be studied.

Base Sequence↗
PubMed1988

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. II. Morphologic, ultrastructural and histochemical changes of the cancer cells after intrarectal and intravenous 5-Fu administration].

From March 1981 to October 1985, 5-Fu was preoperatively given to 65 Dukes B and C rectal cancer patients (intrarectal suppository 40 and emulsion 20, intravenous 5). The results indicated that after intrarectal administration, marked changes and destruction of the cancer cells in morphology were observed in 40% of the resected rectal specimens for suppository and in 45% for emulsion; marked retrograde degeneration in ultrastructure was found in 47.5% for suppository and in 50% for emulsion; DNA synthesis was obviously reduced in 63% for suppository and in 75% for emulsion. It is suggested that the emulsion be a better preparation. No obvious changes or destruction in morphology and ultrastructure were observed in cancer cells treated by intravenous drip of high dose 5-Fu though leukopenia below 4000 was found in 2/5. However, it was 0/60 by rectal administration. This implies that the intrarectal route is more rational than the conventional intravenous route. This study presents an alternate supplementary treatment in addition to radiotherapy for the reduction of postoperative local recurrence of Dukes B and C rectal cancers.

Administration, Rectal↗
PubMed1987

Electrochemical evaluation of the interaction between ascorbic acid and the cardiotonic drug RS-82856.

The solution phase interaction between ascorbic acid and the cardiotonic drug N-cyclohexyl-N-methyl-4(7-oxy 1,2,3,5-tetrahydroimidazol[2,1-b] quinazolin-2-one butyramide (RS-82856) was evaluated using a differential pulse voltammetric technique. Shifts in the peak potential of ascorbic acid to higher energy as well as decreases in peak current values were monitored as a function of RS-82856 concentration. The electrochemical data were obtained under conditions where both the drug and the ascorbic acid concentrations exhibited linear relationships with peak current values. The methodology was extended to the study of two other structurally related phosphodiesterase inhibitors cilostamide and anagrelide. The complexation of these drugs with ascorbic acid were also characterized by decreases in the diffusion currents of ascorbic acid as well as by anodic shifts in the peak potential. The significance of these observations may be related to the inhibition of cyclic nucleotide phosphodiesterase activity by both the drugs tested and the ascorbic acid.

3',5'-Cyclic-AMP Phosphodiesterases↗