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Biomedical subjects

R Li

Publications and source records attributed to R Li.

At least 577 records · Page 32Linked to original sources
PubMed1982

A comparison of the inhibitory action of 5-(substituted-benzyl)-2,4-diaminopyrimidines on dihydrofolate reductase from chicken liver with that from bovine liver.

Forty-four 5-(substituted-benzyl)-2,4-diaminopyrimidines have been tested as inhibitors of chicken and bovine liver dihydrofolate reductase. The chicken enzyme is, on the average, about 10 times less easily inhibited than bovine enzyme. Substituents which show the greatest selectivity are 4-NHCOCH3, 3-OC4H9, 3-I, 3-CF3-4-OCH3, and 3,4,5-(OCH3)3. The inhibition constants have been used to formulate quantitative structure-activity relationships for comparative purposes.

Animals↗
PubMed1982

Inhibition by 5-(substituted-benzyl)-2,4-diaminopyrimidines of murine tumor (L5178Y) cell cultures sensitive to and resistant to methotrexate. Further evidence for the sensitivity of resistant cells to hydrophobic drugs.

Forty-three 5-(substituted-benzyl)-2,4-diaminopyrimidines have been studied as inhibitors of murine tumor cell cultures (L5178Y). Two types of cells were used--one resistant to methotrexate and one sensitive to methotrexate. The formulation of quantitative structure--activity relationships showed that the methotrexate-resistant cells are more sensitive to the more hydrophobic congeners. pi 0 for the sensitive cells is about 1.4, while pi 0 for the methotrexate-resistant cells is above 3. These results are similar to those found for 2,4-diaminotriazines (Selassie, C.D.; Guo, Z. R.; Hansch, C.; Khwaja, T. A.; Pentecost, S. J. Med. Chem. 1982, 25, 157).

Animals↗
PubMed1982

Comparison of the inhibition of Escherichia coli and Lactobacillus casei dihydrofolate reductase by 2,4-diamino-5-(substituted-benzyl)pyrimidines: quantitative structure-activity relationships, X-ray crystallography, and computer graphics in structure-activity analysis.

The inhibition constants (Kiapp) obtained from the action of 44 2,4-diamino-5-(substituted-benzyl)pyrimidines on dihydrofolate reductase (DHFR) from Escherichia coli and Lactobacillus casei bacteria are used to derive quantitative structure-activity relationships (QSAR). These equations bring out a number of differences in the DHFR which can be understood at the atomic level by studying color stereo computer graphics models constructed from the X-ray coordinates of the enzyme-inhibitor complexes. The combination of QSAR and X-ray crystallography interpreted via high-performance computer graphics offers a new level of sophistication to extend our understanding of enzyme-ligand interactions, which, when the crystallography is known, opens up a more scientific approach to drug development.

Binding Sites↗
PubMed1981

Ureteral injuries during vascular surgery.

The rapid increase in the number of vascular surgical procedures done has led to a new class of iatrogenic ureteral injuries. Vena caval ligation, bilateral lumbar sympathectomy, bypass procedures and abdominal aortic aneurysmectomy produce the majority of these injuries. Established principles useful in the repair of iatrogenic injuries following a gynecologic or colonic operation often are inapplicable.

Aged↗
PubMed1981

Sensitivity and specificity of early diagnostic tests of lung function in smokers.

What are the relative sensitivities and specificities of the "early" tests of lung dysfunction? We describe the findings from a study of virtually the entire population of a rural pollution-free community. Using abnormal spirometry as a marker of obstructive disease, we evaluated the two tests obtained from the single-breath nitrogen curve, closing volume (CV/VC) and the slope of the alveolar plateau (delta N2/L), as well as combinations of the two tests. While CV/VC is highly specific (92.3 percent in male and 94.0 percent in female subjects), it lacks sensitivity (36.8 percent in male and 13.3 percent in female subjects) and is abnormal in only 10.0 and 6.5 percent of male and female smokers, respectively, a percentage not dissimilar from the percentage with abnormal spirometry. However, delta N2/L, abnormal in 24.1 percent of male smokers and 28.8 percent of female smokers, rates reasonably well with regard to both sensitivity (63.2 percent in male and 66.7 percent in female subjects) and specificity (79.3 percent in male and 74.0 percent in female subjects). The group of smokers with abnormal delta N2/L did include fair numbers with abnormal spirometry (20.7 percent in male and 16.1 percent in female subjects). A combination of the two tests (abnormal in either delta N2/L and/or CV/VC) has good sensitivity (68.4 and 80.0 percent for male and female subjects, respectively) and specificity (74.3 and 69.0 percent for male and female subjects, respectively).

Adult↗
PubMedDate not supplied

Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose.

Plasma concentrations and urinary excretion of DTZ and its metabolites were determined in 20 healthy volunteers (10 males and 10 females) after they had each been given a single oral 90 mg dose of DTZ. DTZ and six of its metabolites which included N-monodesmethyl DTZ (MA), deacetyl DTZ (M1), deacetyl N-monodesmethyl DTZ (M2), deacetyl O-desmethyl DTZ (M4) and deacetyl DTZ N-oxide (M1NO) and deacetyl N,O-didesmethyl DTZ (M6), were determined by a sensitive and specific HPLC assay. The major metabolites measurable in the plasma of all the volunteers were MA, M1, and M2. The terminal half-lives (t1/2) of M1 and M2 were considerably longer than those of DTZ and MA. Less than 5% of the dose was excreted as unchanged DTZ in the urine over the 24 h period. The major urinary metabolite was MA, followed by M6, M2, and then M1. Except for the urinary excretion of M4 there were no statistically significant differences in any of the pharmacokinetic parameters between the males and the females. The mean 24 h urinary recovery of M4 was higher in the males than in the females (P < 0.05). However there were large inter-individual variations in the plasma concentrations and urinary excretion of DTZ and its metabolites with some parameters differing by more than 20-fold. In addition, O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) were identified as two other major urinary metabolites.

Administration, Oral↗
PubMedDate not supplied

Assessment of a polyester-covered nitinol stent in the canine aorta and iliac arteries.

PURPOSE: To evaluate the patency and healing characteristics of a woven polyester fabric-covered stent in the canine model. METHODS: Twenty-four self-expanding covered stents were placed in the infrarenal aorta and bilateral common iliac arteries of eight dogs and evaluated at 1 (n = 2), 3 (n = 2), and 6 (n = 4) months. Stent assessment was done using angiography prior to euthanasia, and light and scanning electron microscopy. RESULTS: Angiographically, just prior to euthanasia, 8 of 8 aortic and 14 of 16 iliac endovascular covered stents were patent. Histologically, the stented regions showed complete endothelialization 6 months after graft implantation. A neointima had formed inside the stented vessel regions resulting in complete encasement of the fabric-covered stent by 3 months after graft implantation. Medial compression with smooth muscle cell atrophy was present in all stented regions. Explanted stent wires, examined by scanning electron microscopy, showed pitting but no cracks or breakage. CONCLUSION: The covered stent demonstrated predictable healing and is effective in preventing stenosis in vessels 10.0 mm or greater in diameter but does not completely preclude stenosis in vessels 6.0 mm or less in diameter.

Alloys↗
PubMedDate not supplied

Ouabain induction of cycling of multiple spike responses in hippocampal slices is delayed by lithium.

Alterations in sodium- and potassium-activated adenosine triphosphatase (Na,K-ATPase) activity have been associated with changes of mood states and lithium treatment in bipolar illness. We examined the effects of ouabain and lithium on evoked population responses in rat hippocampal slices. In vitro 3.3 microM ouabain induced cycling between epliptiform activity and unresponsiveness in 18.5% of slices. In vitro ouabain, at 1-10 microM, induced epileptiform multiple spike responses. In vivo lithium pretreatment for 10-21 days produced a significant delay in the onset of this ouabain-induced epileptiform activity compared to control animals. These findings are consistent with other work which suggests that Na, K-ATPase inhibition can both activate and suppress excitable tissues and that lithium pretreatment can mitigate these effects. The implications of these results and others regarding the pathophysiology of bipolar illness are discussed.

Animals↗
PubMedDate not supplied

Percutaneous transthoracic needle biopsy of the lung: review of 612 lesions.

PURPOSE: The results and complications of 651 pulmonary fine-needle aspiration biopsies (FNABs) were reviewed. The number of needle passes and needle size were correlated to pneumothorax and chest tube placement rates. MATERIALS AND METHODS: FNAB of the lung was performed on 651 occasions in 612 patients with 18- to 22-gauge Franseen needles. Diagnostic rates were calculated. The number of needle passes performed and needle size used were evaluated for their association with pneumothorax and subsequent chest tube placement. RESULTS: Diagnostic accuracy was 94% with sensitivity for malignancy of 95%. Positive and negative predictive values were 99.5% and 90%, respectively. Pneumothorax occurred in 26.9% of patients with 9.2% requiring chest tube placement. Increasing numbers of needle passes and larger needle sizes did not increase the rates of pneumothorax or chest tube placement. CONCLUSIONS: FNAB of the lung has excellent diagnostic rates and remains the procedure of choice for diagnosing pulmonary lesions. This large study contradicts perceptions that pneumothorax and chest tube placement rates decrease with thinner needles and fewer passes.

Adult↗
PubMedDate not supplied

New thrombolytic brush catheter in thrombosed polytetrafluoroethylene dialysis grafts: preclinical animal study.

PURPOSE: To assess the safety, efficacy, endothelial changes, and risks of pulmonary embolic events after the use of a new thrombolytic brush catheter in mature thrombosed polytetrafluoroethylene (PTFE) dialysis grafts in an animal model. MATERIALS AND METHODS: Loop configuration PTFE grafts were implanted in the femoral vessels of 12 canines 4 weeks before mechanical thrombosis was performed. The thrombus was allowed to consolidate for 24 hours in 10 animals, 72 hours in one animal, and 7 days in one animal. Standard percutaneous criss-cross catheter access was performed, and a soft, low-speed, brush (6 mm in diameter), aided by 250,000 U of periprocedural urokinase, was utilized for thrombolysis. The native vessels, just distal to the anastomosis, and lungs were evaluated macro- and microscopically. RESULTS: Thrombolysis was complete in all grafts with the exception of a small segment between the crossing of the access vascular sheaths. The total thrombolysis time ranged from 8 to 12 minutes; this included 5 minutes of pulse-spray lacing. No difference in thrombolysis time was found with regard to the age or amount of thrombus. Minimal endothelial changes were noted and no evidence of acute pulmonary embolus was found on necropsy or histologic studies. CONCLUSION: This method offers a simple, safe, and efficient means of recanalization of thrombosed PTFE dialysis grafts in this canine model.

Animals↗
PubMedDate not supplied

Genetic studies in narcolepsy, a disorder affecting REM sleep.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. It is known to be a complex disorder, with both genetic predisposition and environmental factors playing a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In humans and canines, most cases are sporadic. In Doberman pinschers and Labrador retrievers, however, the disease is transmitted as an autosomal recessive gene canarc-1 with full penetrance. This gene is not linked with the dog leukocyte antigen complex, but is tightly linked with a marker with high homology to the human mu-switch immunoglobulin gene. We have isolated several genomic clones encompassing the canarc-1 marker and the variable heavy chain immunoglobulin region in canines. These have been partially sequenced and have been mapped onto specific dog chromosomes by fluorescence in situ hybridization (FISH). Our results indicate that the mu-switch-like marker is not part of the canine immunoglobulin machinery. We are continuing to extend the genomic contig using a newly developed canine BAC library and attempting to identify the corresponding human region of conserved synteny.

Animals↗
PubMedDate not supplied

Triplet repeat gene sequences in neuropsychiatric diseases.

The human genome has many nucleotide repeat sequences. These range from a single repeating base to entire duplicated genes. Expansion of repeating triplets of nucleotides in the genome has recently been associated with nine degenerative and developmental neuropsychiatric diseases: fragile X syndrome, fragile X-linked mental retardation, myotonic dystrophy, Friedreich's ataxia, spinal and bulbar muscular atrophy, Huntington's disease, spinocerebellar ataxia type 1, dentatorubral-pallidoluysian atrophy, and Machado-Joseph disease. These diseases are all conditions of the central nervous system; in all of them, the inheritance pattern usually exhibits the phenomenon of anticipation (defined as progressively earlier age of onset or a worsening disease severity over successive generations), and the severity of the phenotypic expression and penetrance appears to be related to the extent of the triplet expansion. Identification of this pathological genetic phenomenon solves several of the mysteries that surrounded these conditions but raises many important questions regarding pathogenic mechanisms that may be shared. There is some indication that triplet expansions may also underlie other neuropsychiatric conditions such as schizophrenia or bipolar disorder.

Brain Diseases↗