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Biomedical subjects

R Li

Publications and source records attributed to R Li.

At least 487 records · Page 27Linked to original sources
PubMed1993

Biosynthesis and shedding of murine lymphoma gangliosides.

Ganglioside biosynthesis and subsequent shedding are a potential mechanism contributing to tumor cell escape from the host immune response. As a first step in identifying active molecular species, structural characterization and quantification of the purified individual cellular and shed gangliosides of YAC-1 murine lymphoma cells were undertaken. These studies uncovered three striking changes in ganglioside metabolism in cells passaged in vivo, compared with cells cultured in vitro. (i) Marked inhibition of GalNAcGM1b synthesis: GM1b was present in an equal proportion to its biosynthetic product GalNAcGM1b in vitro, but was present in a 6-fold higher concentration in vivo. (ii) Marked inhibition of NeuGc synthesis: NeuGc, present in vitro in an up to 7-fold higher concentration than its biosynthetic precursor NeuAc, was decreased in relative concentration in vivo (1:1). (iii) Selectivity of shedding: ganglioside shedding in vitro was generalized with respect to both carbohydrate structure and ceramide structure (mainly d18:1-C24:1 and d18:1-C16:0), while in vivo, there was selective shedding of gangliosides containing NeuGc and the shorter chain fatty acid. The reduced synthesis of NeuGc and of GalNAcGM1b in vivo, and the selective shedding of more polar ganglioside species, also in vivo, show that the extracellular environment can markedly affect cellular ganglioside metabolism.

Animals↗
PubMed1993

A leukocyte integrin binding peptide from intercellular adhesion molecule-2 stimulates T cell adhesion and natural killer cell activity.

Adhesion is of pivotal importance for a number of leukocyte functions. Little is known about the binding between leukocyte integrins and the intercellular adhesion molecules (ICAMs). Normally integrins are nonadhesive, and require a stimulus to become active. We have now identified a peptide from ICAM-2, which binds to leukocyte integrins and activates adhesion. Furthermore, the peptide strongly increased the binding and cytotoxicity of natural killer cells. These findings show that adhesion-dependent leukocyte functions can be activated by ligand-derived peptides, and therefore provide evidence that the avidity of leukocyte integrins is up-regulated by integrin-ligand interactions.

Alkaloids↗
PubMed1993

A peptide from ICAM-2 binds to the leukocyte integrin CD11a/CD18 and inhibits endothelial cell adhesion.

Numerous leukocyte functions depend on adhesive intercellular interactions. The leukocyte-specific integrins CD11a/CD18 (lymphocyte function-associated antigen-1 (LFA-1)) and CD11b/CD18 (complement type 3 receptor (Mac-1)), which bind to the intercellular adhesion molecules ICAM-1 and ICAM-2, play a key role in adhesion. Little is known about the binding in molecular detail. We have now defined a peptide region from the first immunoglobulin domain of ICAM-2 that is specifically involved in binding to CD11a/CD18. A synthetic peptide from this part of ICAM-2, covering residues 21-42, bound to purified CD11a/CD18 and inhibited the adhesion of endothelial cells to this integrin. It also inhibited the binding of B lymphoblastoid cells to endothelial cells. Leukocytes bound to the peptide coated on plastic. Several shorter peptides from the same region showed less or no activity.

Amino Acid Sequence↗
PubMed1993

The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication.

For papillomavirus DNA replication, the E2 enhancer protein cooperatively assists in binding of the E1 helicase to the origin. We report that, at limiting E1 and E2 levels, the enhancer proteins GAL4-VP16 and GAL4-p53(1-73) stimulate BPV in vitro DNA replication. This cell-free system was used to ascertain whether the acidic activation domains have a cellular target important for replication. Cellular extracts were depleted of replication activity by passage through a VP16 affinity column. The protein depleted was the cellular factor replication protein A. The direct interaction between replication protein A and VP16, as well as the activation of replication by VP16, is dependent upon the C-terminus of the VP16 activation domain. E2 and the activation domain of p53 also interact with replication protein A. We suggest that a link between transcription and replication involves factors that help convert a closed DNA complex to an open complex.

Adenovirus E2 Proteins↗
PubMed1993

Effects of haloperidol, lithium, and valproate on phosphoinositide turnover in rat brain.

The effects of acute, subacute, and chronic treatment with haloperidol, lithium, and valproate on inositol phosphate (IP) formation were examined. Acute treatment with haloperidol or the combination of haloperidol and lithium significantly reduced IP basal cortical levels. Subacute (three days) treatment with lithium decreased the IP basal level in the frontal cortex. Chronic treatment with haloperidol (14 and 28 days) caused a significant attenuation of carbachol-sensitive IP accumulation in the frontal cortex and striatum and a significant decrease in norepinephrine (NE)-induced IP formation in the frontal cortex (14 and 28 days) and striatum (28 days). Lithium treatment for 14 days produced a significant reduction in the IP basal cortical value, and a significant reduction in cortical carbachol- and NE-induced IP formation was found after 28 days of lithium treatment. The combination of haloperidol and lithium for 28 days decreased the striatal carbachol- and cortical NE-induced IP accumulation and caused a significant increase in NE-sensitive IP formation in the striatum at 14 days. Valproate treatment for 28 days was associated with a significant attenuation in striatal agonist-stimulated IP formation. Therefore, three drugs with different specificities for primary neurotransmitters may have common effects on second-messenger systems.

Animals↗
PubMed1993

Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs.

An erythrocyte (RBC) model based on whole blood was used to investigate the effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole blood obtained from healthy volunteers was allowed to equilibrate with various concentrations (5-1000 microM) of a tested agent. (2-3H)-Adenosine was used as a substrate, and the reaction was terminated after 2 sec of incubation at room temperature by rapid addition of a "Stopping Solution" which was a mixture of erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was centrifuged (1760 g, 4 degrees C, 10 min), and the radioactivity of an aliquot of the supernatant was determined by a scintillation counter. The results showed that dipyridamole was the most potent agent tested (IC50 = 0.2 microM). Amongst the calcium antagonists studied, isradipine was most potent, followed by verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two metabolites of diltiazem, MX and MB, were more potent than the parent drug. The antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as active as verapamil. The beta-receptor antagonist propranolol and the angiotensin converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In addition, the model was stereoselective such that the S(-)-enantiomer of verapamil was considerably more potent than the R(+)-antipote, whereas d(+)-sotalol was practically inactive compared to racemic sotalol.

Adenosine↗
PubMed1993

Expression of bone protein mRNA at physiological fluoride concentrations in rat osteoblast culture.

Fluoride causes an increase in the amount of unmineralized osteoid. To determine whether the increase in osteoid is due to greater protein expression in the presence of fluoride, we measured the relative amount of mRNA expressed by fetal rat calvaria cells maintained in culture for either 18 or 26 days in the presence of 0, 5, 20 or 300 microM fluoride. There were no differences in the level of expression of mRNA for collagenous or non-collagenous proteins in fluoride-treated cells as compared with control cells at 18 days in culture. Expression of mRNA for osteocalcin and alpha 1-type 1 collagen was decreased at 300 microM fluoride after 26 days culture. The amount of [3H]thymidine incorporation in cells exposed to the different amounts of fluoride was measured at various time points. Fluoride did not alter the time at which rapid cell proliferation ended. These studies indicate that at physiological serum levels, fluoride does not increase expression of mRNA by osteoblasts. The relative increase in osteoid in bone may be related to other mechanisms such as altered matrix mineralization.

Animals↗
PubMed1993

Comparison of body composition assessments by bioelectrical impedance and by anthropometry in premenopausal Chinese women.

Fat-free mass (FFM) was estimated in forty-seven premenopausal Chinese women, aged 18-43 years, from anthropometric data (skinfolds, body mass index (weight/height2; BMI)) or bioelectrical impedance, using several prediction formulas for body composition from the literature, and values compared with the mean of these three individual methods used as a frame of reference. In thirty-six women these values could be compared with FFM calculated from total body water (TBW) determined by D2O dilution. The prediction formulas used were developed from studies on Caucasian adults and their validity will have to be shown in populations with different ethnic backgrounds. The mean difference between FFM predicted from BMI and the frame of reference was 0.1 kg (95% confidence interval (CI) -0.1, 0.4), from bioelectrical impedance it was 0.5 kg (95% CI 0.3, 0.7), and from skinfolds it was -0.6 kg (95% CI -0.9, -0.4). The mean difference between FFM calculated from TBW and the frame of reference was higher (2.2 kg, 95% CI 1.2, 3.3). The results of the present study indicate that the three methods may be valid for predicting body composition in adult Chinese females, but further research is needed on development and cross-validation of prediction equations for body composition for Chinese.

Adolescent↗
PubMed1993

Prevalence and type of anaemia in female cotton mill workers in Beijing, China.

The present study investigates the prevalence and type of anaemia in Chinese female cotton mill workers. The prevalence of anaemia is reported in 447 non-pregnant female workers aged between 19 and 45 years. The mean value for haemoglobin (Hb) was 123 (SD 15) g/l and 150 of the total 447 subjects had Hb values below 120 g/l; thus 34% of the population was anaemic according to World Health Organization (WHO, 1975) criteria. The mean value for free erythrocyte protoporphyrin (FEP) was 419 (SD 215) micrograms/l; 55% of the total population had FEP values higher than 350 micrograms/l and 72% among the anaemic subjects. Serum ferritin (SF) was tested in all the women with a Hb value less than 120 g/l and 71% of them had SF values below 12.0 micrograms/l. Eighty women diagnosed as either Fe deficient or with Fe-deficient anaemia were selected for a diagnostic supplementation trial. They were randomly assigned to FeSO4 (60 or 120 mg Fe/d) or placebo treatment for 12 weeks. Fe supplementation increased mean Hb values from 114 to 127 g/l (P < 0.001) and SF levels from 9.7 to 30.0 micrograms/l (P < 0.001), and decreased mean FEP values from 570 to 277 micrograms/l (P < 0.001). The response rate of Hb in the whole Fe-treated group or Fe-treated subjects with an Hb level less than 120 g/l was 90% or 92% respectively. These findings indicate that the type of anaemia in this population was mainly Fe deficiency. It was also found that in this population the severity of anaemia, not the prevalence, was significantly related to the use of intra-uterine devices (IUD).

Adult↗
PubMed1993

A critical evaluation of heart rate monitoring to assess energy expenditure in individuals.

The prediction of energy expenditure (EE) from minute-by-minute heart rate (HR) recording was evaluated in 40 female workers, with emphasis on the inter- and intraindividual variation of this method. The results show that the relationship between EE and HR varied greatly between and within subjects. The inter- and intraindividual CVs were 14-18% and 11-20%, respectively. The poor limits of agreement in EE (mean difference +/- 2 SD) between group and individual calibration curves indicate that estimated EE from group curves is inferior to estimated EE from individual curves. Therefore, it is concluded that to have the best estimates of individual EE, only individual calibration curves should be used. At different occasions these curves should be generated again. Because the limits of agreement in EE between individual curves based on 18 and 9 different activities were wide (-2399 to 1817 kJ/16 h), it is preferable to have a wide range of different activities in the individual calibration procedure.

Adult↗
PubMed1993

Inadequate treatment of pain in ambulatory HIV patients.

OBJECTIVE: To evaluate the prevalence of pain, how pain affects patients' lives, what treatments are being used, and the effectiveness of these pain treatments in ambulatory patients with human immunodeficiency virus (HIV) disease. DESIGN: A self-administered pain survey (modified version of the Wisconsin Brief Pain Questionnaire). SETTING: An ambulatory infectious disease clinic that deals mainly with ambulatory HIV patients. PATIENTS: Ambulatory HIV patients. OUTCOME MEASURES: Results of the response to the questionnaire. RESULTS: Eighty-two of 148 patients surveyed had pain due to their disease in the month prior to completing the survey. Of those reporting pain, 60-70% reported that their pain interfered with aspects of their daily lives from a moderate to severe degree. In patients with pain, 40% reported that they were not receiving any pain treatment. Those patients who were receiving treatment only obtained a mean pain relief of 65%. CONCLUSIONS: Pain is an important problem in terms of its prevalence and impact on patients with HIV disease. Pain control in this patient population is inadequate. Clinicians should realize that pain can be present regardless of the duration of the disease and its severity. Patients need to be educated about the proper use of pain medications and helped to understand that pain medications will not "worsen their disease."

Activities of Daily Living↗
PubMed1993

Is the Na(+)-K(+)-ATPase the link between phosphoinositide metabolism and bipolar disorder?

Recent experimental work suggests involvement of the phosphatidyl inositol second messenger system in the biochemical mechanism of lithium action, but this work has not shed light on the pathophysiology of bipolar illness. Earlier work had established reduction in sodium-potassium-activated adenosine triphosphatase (Na(+)-K(+)-ATPase) activity as a consistent marker of mood in bipolar illness but had only partially illuminated mechanisms of the action of lithium. Now, advances from research in diabetic neuropathy suggest that inositol phosphate and diacylglycerol metabolism are indeed linked to Na(+)-K(+)-ATPase activity. The data are compatible with a model in which a primary decrease in Na(+)-K(+)-ATPase activity in bipolar patients can stimulate an increase in phosphoinositide hydrolysis, thereby generating the equivalent of a second messenger signal in the absence of a first message. Lithium appears to act by blocking this false second message.

Bipolar Disorder↗
PubMed1993

Effects of genotype on age-related alterations in the concentrations of stress hormones in plasma and hypothalamic monoamines in rats.

The adaptive response of the neuroendocrine system to stress is known to be impaired during ageing, and this impairment may be genetically determined. To elucidate further the effect of genotype, inbred male rats of the Wistar-Kyoto (WKY) strain, characterized by their hyper-reactivity to stressors and shorter life span, were compared with Brown-Norway (BN) rats. In young BN rats, resting prolactin concentrations were lower than in WKY animals and were reduced with age, while in WKY rats they remained unchanged with age. In young rats of both strains prolactin concentrations were highest after subjecting them to stressful stimuli for 15 min. After 2 h of restraint stress (during which the animals were confined to a narrow space that restricted movement) prolactin concentrations in young rats returned to pre-stress values, while remaining high in aged rats of both strains. Concentrations of corticotrophin (or adrenocorticotrophic hormone, ACTH) were lower in BN than in WKY rats and did not change with age in either strain. After 2 h of stress, ACTH concentrations were still slightly higher than normal in both young and aged BN rats, but not in WKY rats. Corticosterone concentrations were similar in young WKY and BN rats and were reduced in aged rats of both strains. After 2 h of stress, corticosterone concentrations were still high in aged, but not in young rats of both strains. However, this stress-induced increase was larger (3.7 times as much) in the BN strain than in the WKY strain (in which the increase was 1.7 times as much). The concentrations of hypothalamic monoamines were similar in young rats of both strains, although stress resulted in reduced noradrenaline concentrations, as previously documented, and in minor increases in 3,4-dihydroxyphenylacetic acid in both strains. During ageing, basal noradrenaline concentrations were reduced only in WKY rats, while the amount of 5-HT increased selectively in BN rats. Concentrations of 5-hydroxyindoleacetic acid were increased after stress in aged WKY rats only. The results demonstrate that resting plasma concentrations of the stress hormones ACTH and corticosterone and of prolactin are lower in BN than in WKY rats. In ageing, however, the stress-induced increases in the concentrations of these hormones are relatively higher in the BN strain, which is characterized by a longer life span.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗