Search PubMed⌕ Search

Biomedical subjects

C R Lee

Publications and source records attributed to C R Lee.

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

Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb.

A possible mechanism of the vasodilator effect of scoparone was investigated. Scoparone (10(-6)-3 x 10(-5) M) dilated rat aortic rings precontracted with phenylephrine in a dose-dependent manner. The presence of endothelium facilitated the vasodilator effect. Scoparone depressed the contractile responses to phenylephrine and serotonin, but not that to potassium chloride. Both the vasoconstriction and O2- production induced by alloxan, a diabetogenic compound, were depressed by scoparone. It appears that scoparone exhibited a free radical scavenger-like effect. The dilatation elicited by acetylcholine was potentiated by scoparone. The dilator activity of scoparone was markedly inhibited by methylene blue and hemoglobin, guanylate cyclase inhibitors. Furthermore, the basal guanosine 3',5'-cyclic monophosphate (cGMP) level was elevated in the presence of scoparone. The dilator activity of scoparone was also inhibited by quinacrine (inhibitor of phospholipase A2) and indomethacin (inhibitor of cyclooxygenase). Our results showed further that the output of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, was enhanced by scoparone. It is suggested that the vasodilator effect of scoparone in rat aorta may be mediated through the enhancement of prostacyclin release, protecting against EDRF inactivation, and activating guanylate cyclase.

Animals↗
PubMed1992

Effects of higher-order harmonics on phase determination in an ultrasonic interferometer.

The effect of higher-order harmonic components on phase determination were analyzed to improve the accuracy of transient time measurement in an ultrasonic interferometer with a quadrature detector system. Under ideal conditions the locus of output signals of the phase sensitive detector forms a circle on the phase plane as the frequency changes and any nonideal factor would distort the circle, leading to erratic phase determination. This analysis has shown that the nth-order contribution to the phase is mostly determined by the product of the amplitudes of corresponding components of the reference and echo signals fed to the phase detector. The distortion parameters were obtained by least-squares fitting of the data to the distorted circle in the phase plane, and compared with those roughly estimated from the frequency components of the reference and echo signals. The exemplary numerical phase corrections for the third-order harmonics were carried out, so as to illustrate the improvement in the accuracy of the ultrasonic interferometer.

Acoustics↗
PubMed1992

Patterns of alpha-1-adrenergic receptor expression in regenerating and neoplastic hepatic tissue.

As norepinephrine is a potent hepatocyte comitogen through binding to the alpha 1-adrenergic receptor, we have examined mRNA levels of the alpha 1a- and alpha 1b-adrenergic receptor subtypes in normal and regenerating rat hepatocytes as well as in several different rat hepatoma cell lines. All rat hepatomas examined lacked both alpha 1a- and alpha 1b-receptor message and receptor binding in radioligand binding experiments, suggesting that the growth of dedifferentiated neoplastic rat hepatocytes is not regulated by the alpha 1-adrenergic receptor. Interestingly, unlike the rat hepatomas analyzed, the human hepatocellular carcinoma cell line, HepG2, was positive for both alpha 1a and alpha 1b message at 4.5 kb, yet this cell line lacked receptor binding in radioligand binding assays. While normal and regenerating liver is negative for alpha 1a-receptor expression, it is positive for alpha 1b expression and is characterized by the presence of two bands at approximately 4.0 and 3.2 kb which peaked between 20 and 48 h after partial hepatectomy. A dramatic decrease in message level of the lower band and the continued presence of the upper band between 6 and 12 h after partial hepatectomy, and before the peak in DNA synthesis in regenerating rat liver, may correspond with observed differences in alpha 1-receptor function during liver regeneration.

Animals↗
PubMed1992

Patient compliance with oral chemotherapy as assessed by a novel electronic technique.

PURPOSE: Previous reports have suggested low rates of compliance with the oral component of cancer chemotherapy, which, if confirmed, would have serious implications on treatment. Because of the uncertainties in the methodology used in previous studies, we have assessed compliance with a novel technique. PATIENTS AND METHODS: An "intelligent" tablet bottle was used, which, unknown to the patient, electronically records the times of opening over a period of weeks. The records were scored for overall compliance (total number of bottle openings as a percentage of the prescribed number) and for daily and hourly irregularity indices. Twenty-one patients undergoing treatment for Hodgkin's or non-Hodgkin's lymphoma were monitored for a total of 65 treatment periods, each of up to 2 weeks (852 days in total). Eight measures of side effects and quality of life were self-assessed daily by the patients using a diary card. RESULTS: The overall compliance was 100.6% +/- 20.6% (mean +/- SD). Overall compliance was lower (mean reduction, 10%) in treatment periods with drugs prescribed to be taken three times a day. It was not possible to demonstrate convincingly any relationship between compliance and any of the following: drug type, monitoring period sequence, the diary card scores of side effects and quality of life, number of relapses, and time since initial diagnosis. CONCLUSION: These results are reassuring, but further work is in progress to measure compliance in other treatment regimens in which the side effects are more severe and the prognosis is worse.

Administration, Oral↗
PubMed1991

Vasorelaxant effect of emodin, an anthraquinone from a Chinese herb.

The possible mechanism underlying the vasorelaxant effect of emodin isolated from a Chinese herb, was investigated in this study. Emodin dose dependently relaxed isolated vascular rings of human internal mammary artery and saphenous vein, rabbit thoracic aorta, abdominal aorta and mesenteric artery, and rat thoracic aorta. There were no differences in the sensitivity (IC50) and maximal relaxation between intact and endothelium-denuded preparations of rat aorta. In the presence of emodin (10 microM), the contractile responses of rat aorta to phenylephrine, serotonin and potassium chloride were depressed. The relaxation response to acetylcholine was attenuated by emodin, whereas that to isoproterenol was unaffected. The relaxation response to emodin was inhibited by free radical scavengers, superoxide dismutase, catalase and mannitol, and guanylate cyclase inhibitors, methylene blue and hemoglobin. Catalase was the most effective scavenger. Quinacrine (phospholipase A2 inhibitor), indomethacin (cyclooxygenase inhibitor) and nordihydroguaiaretic acid (NDGA, lipoxygenase inhibitor) potentiated the relaxation induced by emodin. NDGA was the most effective potentiator. Exposure of aortic rings to emodin (10 microM) increased the basal level of guanosine 3',5'-cyclic monophosphate (cGMP). It is suggested that the vasorelaxant effect of emodin may be mainly due to cGMP accumulation as a result of guanylate cyclase activation by free radicals and/or hydrogen peroxide generated from semiquinone.

Animals↗
PubMed1991

Pegademase bovine: replacement therapy for severe combined immunodeficiency disease.

Severe combined immunodeficiency (SCID) represents a syndrome characterized by abnormal function of cellular and humoral immunity. Of the various types of SCID, approximately one-fourth are associated with adenosine deaminase (ADA) deficiency. Treatment consists of bone marrow transplantation, red blood cell transfusions, enzyme replacement, and, more recently, gene therapy. Pegademase bovine is the sole agent available for enzyme replacement therapy of SCID associated with ADA deficiency. The drug is administered intramuscularly to infants from birth and to children of any age at time of diagnosis. At present, few adverse effects or drug interactions have been documented. Although it is expensive (approximately $60,000 annually), pegademase bovine offers an alternative to standard means of therapy.

Adenosine Deaminase↗
PubMed1991

Imidazoles for vaginitis.

Vaginal candidiasis is a common infection in women for which several effective therapeutic agents are currently available. Clotrimazole and miconazole were introduced in 1975, and both recently became available over the counter. These imidazole agents have largely replaced nystatin as primary therapy because of greater antifungal activity and shorter treatment regimens, thereby enhancing patient compliance. The cost for these OTC regimens ranges from $12.00 to $24.00 for the patient.

Female↗
PubMed1990

Total and direct-reacting bilirubin values by automated methods compared with liquid chromatography and with manual methods for determining delta bilirubin.

This study compares total and direct-reacting bilirubin values in 40 serum samples from patients with various diagnoses, as measured by automated methods (Beckman Synchron CX-5, Beckman Astra 8, Kodak Ektachem 700) and HPLC and by a manual method for delta bilirubin. For total bilirubin, within-run CVs were less than 6%. The Ektachem 700 method underestimated bilirubin with serum samples from patients with Crigler-Najjar syndrome and from newborns in whom unconjugated bilirubin concentrations were increased but conjugated bilirubins were not present or were present only in small amounts. The Astra 8 and Synchron CX-5 methods were inaccurate with cholestatic serum samples, in which conjugated bilirubin concentrations were increased and other compounds such as bile acids could be expected to interfere. We conclude that each automated method examined provides reasonable estimates for total and direct-reacting bilirubin values for routine clinical use. The need for each laboratory to select the appropriate bilirubin method for its particular situation is obvious.

Autoanalysis↗
PubMed1989

Effect of dietary fat and cholesterol supplements on glucagon receptor binding and adenylate cyclase activity of rat liver plasma membrane.

We have examined the effect on rat liver glucagon receptors and adenylate cyclase activity of a high saturated fat diet (butter fat), a high n-6 polyunsaturated fat diet (corn oil), and a high n-3 polyunsaturated fat diet (menhaden fish oil) with or without additional cholesterol. The number and affinity of the glucagon receptors were unaffected by diet. The glucagon-stimulated adenylate cyclase activity from fish oil-fed animals exhibited the greatest stimulation, followed by corn oil-fed animals. Butter fat-fed and all cholesterol-supplemented groups showed a depression in stimulation. The pattern of adenylate cyclase activity with fluoride stimulation was similar to that observed with glucagon. The effect of dietary fat on forskolin stimulation was similar to glucagon and fluoride for the groups without added cholesterol. However, the cholesterol-supplemented groups did not exhibit a decreased activity. It is suggested that the effect of dietary lipid on glucagon-stimulated adenylate cyclase is not due to changes in the glucagon receptor, but rather due to changes in signal transduction, the Gs-protein or the catalytic unit.

Adenylyl Cyclases↗
PubMed1989

Analysis of monoamines in the cerebrospinal fluid of Chinese patients with neurological diseases.

Levels of dopamine (DA), 3-methoxy-4-hydroxy-phenylacetic acid (HVA), 5-hydroxy-indoleacetic acid (HIAA), 5-hydroxytryptamine (HT), 5-hydroxytryptophan (HTP), and 3, 4-dihydroxyphenylalanine (DOPA) in cerebrospinal fluids (CSF) of twenty-four Chinese with or without neurological diseases were determined simultaneously. The level of HIAA in the CSF of myelopathy-spondylosis patients and the level of DA in CSF of the myelopathy-tumor patients were higher than that of the control. No difference in levels of monoamines and their metabolites was observed between the control and patients with dementia.

Adolescent↗
PubMed1988

Determination of melatonin in blood plasma, using capillary gas chromatography and electron impact medium-resolution mass spectrometry.

Determination of the low concentrations (less than 10-100 pg ml-1) of melatonin in blood plasma by gas chromatography/mass spectrometry has previously required the use of negative ionization (electron capture) mass spectrometry, a technique particularly delicate to set up. We show that a general-purpose medium-resolution instrument gives adequate sensitivity in electron impact mode, when used with a capillary gas chromatographic column-switching device. A straightforward extraction procedure gives good specificity, and the limit of useful measurement is better than 10 pg per 1 ml sample.

Animals↗
PubMed1988

Determination of the beta-blocker betaxolol and labelled analogues by gas chromatography/mass spectrometry with selected ion monitoring of the alpha-cleavage fragment (m/z 72).

Low concentrations of betaxolol in blood plasma and physiological buffers were determined by selected ion monitoring of the intense m/z 72 fragment [CH2 = NH-CH(CH3)2]+ formed by electron impact ionization of the O-trimethylsilyl derivative. At a mass spectrometric resolution of 3000, fewer potentially interfering peaks were seen than at low resolution. There remained a chemical interference, corresponding to 100 pg/sample, which arose during treatment of the samples. This method is more sensitive than previous ones, but it is restricted to situations where the specificity can be controlled. When the m/z 72 fragment was mass-shifted by using betaxolol appropriately labelled with deuterium or 13C, both the interference and the baseline noise were greatly reduced; concentrations of labelled betaxolol as low as 10-20 pg/sample can be determined with little difficulty.

Adrenergic beta-Antagonists↗
PubMed1988

The beta 1-adrenoceptor antagonist, betaxolol, is not released from the heart of the anaesthetized dog during sympathetic nerve stimulation.

1. We investigated the hypothesis that the beta 1-adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation. 2. Dogs were chronically treated with betaxolol (1 mg kg-1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the beta 1-adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly. 3. Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline. 4. These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve.

Adrenergic beta-Antagonists↗
PubMed1988

Day-night rhythm of 5-methoxytryptamine biosynthesis in the pineal gland of the golden hamster (Mesocricetus auratus).

5-Methoxytryptamine is a potent agonist of presynaptic 5-hydroxytryptamine autoreceptors modulating serotonin release in the central nervous system. This methoxyindole can be synthesized in the pineal gland, but its presence in vivo is still controversial, probably because of rapid catabolism by monoamine oxidase. An improved high-pressure liquid chromatography method, with coulometric detection, has been developed for the simultaneous measurement of melatonin, 5-methoxytryptamine, 5-methoxytryptophol and 5-methoxyindolacetic acid. We have demonstrated a day-night rhythmicity in the amount of 5-methoxytryptamine in the pineal gland of golden hamsters (Mesocricetus auratus) maintained under a long photoperiod (14 h light: 10 h darkness) and pretreated with the monoamine oxidase inhibitor pargyline. Levels of 5-methoxytryptamine were highest at 16.30 h and lowest at 00.30 h. The rhythm for 5-methoxytryptamine appears to be the same as for serotonin (opposite in phase to that of melatonin). The identification of 5-methoxytryptamine has been confirmed by analysis with gas chromatography-mass spectrometry.

5-Methoxytryptamine↗
PubMed1987

Pitfalls in demonstrating an endogenous ligand of imipramine recognition sites.

The recognition sites for the 5-hydroxytryptamine (5-HT) uptake inhibitors imipramine and paroxetine may represent receptors for a presently unknown endogenous ligand, whose function would be to modulate 5-HT uptake. Attempts to isolate such a factor from rat brain tissue are described, following a published procedure. It is shown that chromatographic fractions found to inhibit the binding of [3H]imipramine and [3H]paroxetine to rat brain membranes consisted of material essentially unretained by the reverse-phase HPLC column, and they were of high osmolarity. Thus, the activity was probably unspecific in nature, and the presence in rat brain of the factor has not been unequivocally demonstrated.

Animals↗
PubMed1987

[3H]-5-methoxytryptoline is not actively accumulated by rabbit platelets.

5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro-beta-carboline) inhibits with high affinity [3H]-imipramine binding to the serotonin transporter in platelets. To evaluate whether 5-MeO-TLN is a substrate for the serotonin transporter, the accumulation of [3H]-5-MeO-TLN into rabbit platelets was studied in vitro. At short incubation times (5 min), [3H]-5-MeO-TLN accumulation was temperature-sensitive, but not saturable over a concentration range from 0.06 mumol/l to 10 mumol/l. Moreover, [3H]-5-MeO-TLN uptake was not affected by 100 mumol/l ouabain, its structural analogs tryptoline and 5-hydroxytryptoline, nor by the serotonin uptake inhibitors imipramine and citalopram. After longer incubation times (60 min), [3H]-5-MeO-TLN accumulation at 0 degree C approached that seen at 37 degrees C and temperature-sensitive [3H]-5-MeO-TLN uptake could no longer be observed. It is concluded that temperature-sensitive accumulation of [3H]-5-MeO-TLN is not mediated by the serotonin transporter and most likely represents a passive, diffusional process, the rate of which is temperature-dependent. The present studies thus confirm the hypothesis that 5-MeO-TLN affects [3H]-imipramine binding in platelets through a competitive mechanism and not via an allosteric interaction mediated through the substrate recognition site of the macromolecular complex of serotonin transporter.

Animals↗
PubMed1986

Antidepressant-binding sites in brain and platelets.

[3H]Imipramine and [3H]paroxetine label with high affinity a site associated with the serotonin transporter in brain and platelets. The maximum binding capacity (Bmax) of [3H]imipramine in platelets is reduced in untreated depressed patients, and it may represent a useful biological marker in depression. The existence of an endogenous ligand acting on the [3H]imipramine-recognition site to modulate the serotonin transporter has been proposed by several laboratories. 5-Methoxytryptoline inhibits [3H]imipramine binding and [3H]serotonin uptake in the nanomolar range. This compound has been reported to occur in the pineal gland, but probably only in trace amounts. While the physiological relevance of 5-methoxytryptoline or a close analogue remains an open question, the possibility exists that the 'endocoid' for the [3H]imipramine-recognition site plays a role in the pathogenesis of depression.

Animals↗