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Biomedical subjects

S Kuo

Publications and source records attributed to S Kuo.

At least 37 records · Page 2Linked to original sources
PubMed1992

Dopaminergic modulation of striatal neuropeptides: differential effects of D1 and D2 receptor stimulation on somatostatin, neuropeptide Y, neurotensin, dynorphin and enkephalin.

Dopaminergic modulation of neuropeptides in rat striatum was investigated by examining the effects of prolonged D1 or D2 receptor stimulation on levels of somatostatin, neuropeptide Y, neurotensin, dynorphin and enkephalin. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 7 days with either the D1 agonist SKF 38393 (12.5 mg/kg/day) or the D2 agonist quinpirole (1 mg/kg/day). Two regimens of agonist treatment were compared: continuous infusion via osmotic pump implanted i.p. and intermittent (once daily) i.p. injection. Rats were sacrificed 3 h after the last injection and peptide levels measured in the striatum bilaterally by radioimmunoassay; alterations in peptide content were observed primarily in the denervated striatum. In comparison to values from lesioned, vehicle-treated controls, intermittent administration of SKF 38393 reduced somatostatin and neuropeptide Y (down 61% and 57%, respectively), increased neurotensin (up 105%) and dynorphin (up 184%) and had no effect on enkephalin; continuous SKF 38393 decreased neuropeptide Y by 39% but did not alter levels of the other peptides. Continuous quinpirole elevated somatostatin and neuropeptide Y levels (up 43% and 33%, respectively), but reduced the lesion-induced increases in both neurotensin (down 51%) and enkephalin (down 24%) content. Conversely, intermittent quinpirole decreased somatostatin (down 35%) and neuropeptide Y (down 27%), increased neurotensin content by 79% and had no effect on enkephalin. Dynorphin levels were not altered by either continuous or intermittent quinpirole. These findings reveal the complexity of dopaminergic influences on striatal neuropeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Antimutagenicity of secondary metabolites from higher plants.

Higher plants contain both mutagens and antimutagens and are susceptible to mutagenesis but screening programs for detection of antimutagenesis rarely employ higher plant systems. Short-term bacterial and mammalian tissue culture systems are the norm. Using modified screening tests for detecting antimutagenic agents, higher plants have been shown to contain a variety of structurally novel antimutagenic agents. Systematic bioassay-directed methodology resulted in the isolation in pure form and biological and chemical characterization of the responsible individual active components from various plants. The methodology in use is illustrated by the isolation of cinnamic acid, cinnamyl cinnamate and cinnamyl ricinoleate as the active constituents of the classic medicinal plant product, Styrax asiatica. The methods which may be used to reveal structure-activity relationships and to explore putative molecular modes of action are illustrated with excerpts from the same study.

Antimutagenic Agents↗
PubMed1992

Glycyrrhiza glabra extract as an effector of interception in Escherichia coli K12+.

Glycyrrhiza glabra polar lipid extract contains a number of flavonoids and related chemical compounds. Studies on the effectiveness of Glycyrrhiza glabra polar lipid extract in intercepting reactive molecules generated from the illumination of the photosensitizers rose bengal and phenosafranin indicate that it is effective in preventing cytotoxicity against E. coli K12+ in a dose-related fashion using illuminated rose bengal. Since only a modest scavenging of singlet oxygen generated from phenosafranin is observed, the effects of the extracts are less related to singlet oxygen-mediated oxidation of substrate (type II reactions) than non-singlet oxygen-mediated oxidation of substrate (type I reactions). Elevated levels of glutathione observed in exponentially growing cells of E. coli K12 were also observed.

Antioxidants↗
PubMed1991

Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats.

The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Prolonged infusion of quinolinic acid into rat striatum as an excitotoxic model of neurodegenerative disease.

The neurotoxic effects of prolonged exposure of rat striatum to quinolinic acid in vivo was evaluated through assays of neurochemical markers for major neuronal populations. Continuous intrastriatal quinolinic acid infusion for 14 days produced a dose-dependent depletion of striatal choline acetyltransferase (ChAT) activity, glutamic acid decarboxylase (GAD) activity, and somatostatin content. ChAT activity was significantly reduced by quinolinic acid at doses of 90, 270, and 540 nmol/day, while GAD activity and somatostatin content were decreased only at doses of 270 and 540 nmol/day. NADPH-diaphorase histochemistry revealed a loss of striatal NADPH-diaphorase neurons as a result of quinolinic acid infusion at a dose of 270 nmol/day. The neurotoxic lesion induced by prolonged quinolinic acid exposure in vivo can be used as a potential model for studying excitotoxic mechanisms in neurodegenerative disease.

Animals↗
PubMed1990

Conversion of Pseudomonas aeruginosa to the phenotype characteristic of strains from patients with cystic fibrosis.

Isolates of Pseudomonas aeruginosa from cystic fibrosis patients are unusual; they are often susceptible to the bactericidal effect of human serum, have a rough lipopolysaccharide, and produce an exopolysaccharide that is responsible for the characteristic mucoid phenotype. In contrast, strains from the environment and from patients with other diseases usually have smooth lipopolysaccharide, do not produce very much mucoid exopolysaccharide, and are phenotypically nonmucoid. The predominance of mucoid strains of P. aeruginosa in infections of patients with cystic fibrosis has not been explained. In the lower airways, where P. aeruginosa persists in cystic fibrosis, nutrients for bacterial growth may be limited. We investigated whether growth of P. aeruginosa under conditions of suboptimal nutrition causes conversion to the characteristic cystic fibrosis phenotype. Ninety-two strains of P. aeruginosa were maintained for up to 90 days in a minimal medium with acetamide as the sole carbon source. In 56 (52%) of 107 cultures, isolates with rough lipopolysaccharide emerged, and in 20 (19%) of 104 nonmucoid cultures, mucoid isolates were recovered. Strains with rough lipopolysaccharide also were sensitive to the bactericidal effect of normal human serum. Under conditions of suboptimal nutrition in vitro, isolates of P. aeruginosa emerged that produced rough lipopolysaccharide and were mucoid, typical of many isolates from cystic fibrosis patients. This peculiar phenotype may arise as a consequence of nutritional limitation within the cystic fibrosis respiratory tract rather than from features unique to these strains of bacteria.

Blood Bactericidal Activity↗
PubMed1990

Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization.

The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Central cholecystokinin octapeptide reduces glucose utilization in subcortical but not cortical rat brain.

Cholecystokinin octapeptide was administered intraventricularly to laboratory rats in a behaviorally active dose. Quantitative regional glucose utilization was assessed as a measure of neuronal activity using [14C]2-deoxyglucose. CCK-8 reduced glucose utilization in selected subcortical nuclei, but left most areas of cortex unaffected. The subcortical nuclei were chiefly extrapyramidal systems. The diminutive pharmacologic action on cortical neuronal activity implies CCK-8 may act here as a neuronal modulator, in concert with other central transmitters, rather than having prominent singular actions.

Animals↗
PubMed1987

PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent.

The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [14C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

Acylation↗
PubMed1987

Colonial dissociation and susceptibility to phagocytosis of Pseudomonas aeruginosa grown in a chamber implant model in mice.

Pseudomonas aeruginosa strains were grown in 1-cm plastic chambers sealed at both ends with porous Millipore filters and implanted in the peritonea of mice. Mucoid and nonmucoid strains of P. aeruginosa isolated from a patient with cystic fibrosis largely retained their phenotypes when grown for up to 1 year in this in vivo system, although colonial dissociation occurred, as observed in chronic lung infections of patients with cystic fibrosis. In the absence of added opsonins, P. aeruginosa M2 cells taken directly from the in vivo system were significantly more susceptible to phagocytosis than were the same P. aeruginosa cells after being washed in buffer. Phagocytosis of in vivo-grown P. aeruginosa cells could be further enhanced by using a porin protein F-specific monoclonal antibody.

Antibodies, Bacterial↗
PubMed1983

Evidence that inhibitors of anion exchange induce a transmembrane conformational change in band 3.

The transport inhibitor, eosin 5-maleimide, reacts specifically at an external site on the membrane-bound domain of the anion exchange protein, Band 3, in the human erythrocyte membrane. The fluorescence of eosin-labeled resealed ghosts or intact cells was found to be resistant to quenching by CsCl, whereas the fluorescence of labeled inside-out vesicles was quenched by about 27% at saturating CsCl concentrations. Since both Cs+ and eosin maleimide were found to be impermeable to the red cell membrane and the vesicles were sealed, these results indicate that after binding of the eosin maleimide at the external transport site of Band 3, the inhibitor becomes exposed to ions on the cytoplasmic surface. The lifetime of the bound eosin maleimide was determined to be 3 ns both in the absence and presence of CsCl, suggesting that quenching is by a static rather than a dynamic (collisional) mechanism. Intrinsic tryptophan fluorescence of erythrocyte membranes was also investigated using anion transport inhibitors which do not appreciably absorb light at 335 nm. Eosin maleimide caused a 25% quenching and 4,4'-dibenzamidodihydrostilbene-2,2'-disulfonate) caused a 7% quenching of tryptophan fluorescence. Covalent labeling of red cells by either eosin maleimide or BIDS (4-benzamido-4'-isothiocyanostilbene-2,2'-disulfonate) caused an increase in the susceptibility of membrane tryptophan fluorescence to quenching by CsCl. The quenching constant was similar to that for the quenching of eosin fluorescence and was unperturbed by the presence of 0.5 M KCl. Neither NaCl nor Na citrate produced a large change in the relative magnitude of the tryptophan emission. The tryptophan residues that can be quenched by CsCl appear to be different from those quenched by eosin or BIDS and are possibly located on the cytoplasmic domain of Band 3. The results suggest that a conformational change in the Band 3 protein accompanies the binding of certain anion transport inhibitors to the external transport site of Band 3 and that the inhibitors become exposed on the cytoplasmic side of the red cell membrane.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

Twenty-four hour plasma levels of growth hormone and prolactin in Huntington's disease.

Since hypothalamic neural degeneration is thought to occur in individuals with Huntington's disease, anterior pituitary hormone secretion which is in part regulated by the hypothalamus, was postulated to be altered in patients with this disease. To test this proposal, nine females with Huntington's disease were matched with controls to participate in a 24-hour basal level study of growth hormone and prolactin concentration in plasma. Patients who were free from all centrally active medication for at least six months and normal volunteers had blood sampled at 30-minute intervals over 24 hours in a minimal stress environment. The results demonstrated that plasma levels of growth hormone were elevated throughout the 24-hour time period in Huntington's disease individuals. Despite the elevation, the mean growth hormone curve of the Huntington's disease group retained characteristics similar to the control curve throughout the 24-hour time. Basal 24-hour plasma prolactin concentrations in Huntington's disease patients showed no difference from those in control individuals.

Adult↗
PubMed1981

Increased ascorbic acid content in chronic lymphocytic leukemia B lymphocytes.

Human lymphocyte extracts analyzed by high-performance liquid chromatography reveal a major UV-absorbing peak that was shown to be ascorbic acid by spectral, chemical, and enzymatic criteria. Because this peak appeared very prominent in the elution profile of chronic lymphocytic leukemia (CLL) lymphocyte extracts, we measured the ascorbic acid content in lymphocytes from the blood of normal subjects and untreated patients with chronic lymphocytic leukemia. A significantly higher concentration of 111 +/- 15.3 nmol per 10(8) cells (mean +/- SEM) was found in CLL lymphocytes than in normal blood lymphocytes, which contained 42.2 +/- 3.3 nmol per 10(8) cells. Selective enrichment with B and T cells showed that this difference was limited to the chronic lymphocytic leukemia B cell, which had a 5- to 15-fold higher content of ascorbic acid than normal B cells had. In contrast, the ascorbic acid level was similar in normal and CLL T cells. The very high ascorbic acid content provides the chronic lymphocytic leukemia B cell with a reducing substance that could react with oxidants or free radicals.

Ascorbic Acid↗