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Biomedical subjects

L A Anderson

Publications and source records attributed to L A Anderson.

At least 91 records · Page 5Linked to original sources
PubMed1989

1-[4-[3-[4-[bis(4-fluorophenyl)hydroxymethyl]-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone(AHR-5333): a selective human blood neutrophil 5-lipoxygenase inhibitor.

In this study we report the in vitro inhibition of leukotriene synthesis in calcium ionophore (A23187)-stimulated, intact human blood neutrophils by AHR-5333. The results showed that AHR-5333 inhibits 5-HETE, LTB4 and LTC4 synthesis with IC50 values of 13.9, 13.7 and 6.9 microM, respectively. Further examination of the effect of AHR-5333 on individual reactions of the 5-lipoxygenase pathway (i.e. conversion of LTA4 to LTB4, LTA4 to LTC4, and arachidonic acid to 5-HETE) showed that this agent was not inhibitory to LTA4 epoxyhydrolase and glutathione-S-transferase activity in neutrophil homogenates. However, conversion of arachidonic acid (30 microM) to 5-HETE was half maximally inhibited by 20 microM AHR-5333 in the cell-free system. The inhibition of LTB4 and LTC4 formation in intact neutrophils by AHR-5333 appears to be entirely due to a selective inhibition of 5-lipoxygenase activity and an impaired formation of LTA4, which serves as substrate for LTA4 epoxyhydrolase and glutathione-S-transferase. AHR-5333 did not affect the transformation of exogenous arachidonic acid to thromboxane B2, HHT and 12-HETE in preparations of washed human platelets, indicating that this agent has no effect on platelet prostaglandin H synthase, thromboxane synthase and 12-lipoxygenase activity. The lack of inhibitory activity of AHR-5333 on prostaglandin H synthase activity was confirmed with microsomal preparations of sheep vesicular glands.

Animals↗
PubMed1989

Ethnopharmacology and Western medicine.

The contribution of plants to western medicine is briefly considered using alkaloids as examples of one class of pharmacologically active natural product. Plants and plant products are present in 14 of the 15 therapeutic categories of pharmaceutical preparations which are currently recommended to medical practitioners in the U.K. and they form an important part of our health-care system in the western world. There is considerable scope for new drug discovery from traditional medicines which are used throughout the world and some recent developments are commented upon and conclusions are made.

Ethnology↗
PubMed1989

Effect of bopindolol on renin secretion and renal excretory function in rats.

We investigated the effects of the new beta-adrenoceptor antagonist, bopindolol, on stimulated renin secretion and on renal function in conscious rats. Intravenous doses of 10, 31.6, and 100 micrograms/kg of bopindolol antagonized the rise in plasma renin activity (PRA) induced by the administration of isoproterenol (10 micrograms/kg, s.c.). Peak PRA, evident at 15 min after isoproterenol, reached 27 +/- 3 ng/ml/h with bopindolol (100 micrograms/kg) pretreatment vs. 105 +/- 7 ng/ml/h in saline controls. Antagonism by bopindolol (100 micrograms/kg, i.v.) of isoproterenol-stimulated rise in PRA persisted through 12 h. Within this dosage range, bopindolol itself had no significant effect on PRA. Significant antagonism of beta-adrenoceptor-induced hypotension resulted with 31.6 and 100 micrograms/kg of i.v. bopindolol. Orally administered bopindolol produced significant antagonism of isoproterenol-induced increase in PRA at a dose of 316 micrograms/kg; however, oral doses of 31.6-316 micrograms/kg of bopindolol failed to significantly alter furosemide-stimulated increase in PRA. Bopindolol alone had little effect on renal excretory function but caused a slight attenuation of furosemide-induced diuresis and electrolyte excretion. Plasma electrolytes and osmolarity were unaffected by bopindolol alone or in conjunction with furosemide. These results indicate that bopindolol (a) is a potent, long-acting, orally active, antagonist of beta-adrenoceptor-stimulated renin secretion in the rat, (b) is ineffective in antagonizing furosemide-induced rise in PRA, (c) does not elevate basal levels of PRA by virtue of its intrinsic sympathomimetic activity, and (d) does not cause dramatic alteration of renal excretory function at effective beta-blocking doses.

Adrenergic beta-Antagonists↗
PubMed1989

Oncogenes and human breast cancer.

The role of oncogenes in breast tumorigenesis is unclear. Alterations and/or amplification of several oncogene sequences have been observed in primary human breast tumors, in breast tumor cell lines, and in mammary tumors in model systems. In principle, such alterations could be sites of primary lesions for human breast cancer, causes of tumor progression or metastasis, or simply secondary lesions of highly aberrant tumor genomes. The present study tested genetic linkage of breast cancer susceptibility to nine oncogenes in 12 extended families including 87 affected individuals. Lod scores for close linkage of each candidate sequence to breast cancer were -19.6 for HRAS, -12.3 for KRAS2, -1.0 for NRAS, -6.0 for MYC, -6.1 for MYB, -8.2 for ERBA2, -7.9 for INT2, and -5.1 for RAF1. Regions of chromosome 11p associated with tumor homozygosity and the region of 3p carrying the gene for Von Hippel-Lindau disease could also be excluded from linkage to human breast cancer. The 5-kb allele of the MOS oncogene, previously proposed to be associated with breast cancer, was absent in these families, suggesting that polymorphism at this locus is not associated with inherited susceptibility. These results strongly suggest that oncogenes are not the sites of primary alterations leading to breast cancer. On the other hand, alterations in one or more of these sequences may be associated with tumor progression.

Breast Neoplasms↗
PubMed1988

Satisfaction with clinical encounters among residents and geriatric patients.

A total of 69 clinical encounters between 15 internal medicine residents and 69 geriatric patients were examined to determine the residents' attitudes toward specific patients and to assess their mutual satisfaction with the clinical encounter. The residents rated their attitudes toward each patient and indicated their beliefs about the patients' health status, adjustment to medical care, and expected benefits of health education activities. In general, both the residents and the patients expressed satisfaction with their clinical encounters. Little similarity in the satisfaction ratings of the residents and patients was found. The patients tended to express higher levels of satisfaction than the residents. The residents' perceptions of the expected benefits of health education and attitudes toward the patient were found to be statistically significant predictors of the residents' satisfaction. These findings suggest that specific attitudes and beliefs of residents toward their geriatric patients are linked to the residents' satisfaction and hold important implications for medical training.

Aged↗
PubMed1987

Effects of modeling on patient communication, satisfaction, and knowledge.

This experimental study investigated the efficacy of two modeling procedures on enhancing patient communication. A pretreatment interview assessed knowledge, assertiveness, and other concomitant variables. A total of 150 subjects were randomly assigned to one of three treatment conditions. The two modeling conditions were videotaped presentations of a health educator interacting with a patient (i.e., model) who either asked questions or revealed problems. The control videotape included only the educator's presentation; no patient was shown. A subsequent standardized face-to-face patient education session was used to assess the impact of the intervention on patient communicative behaviors. A posttreatment interview assessed knowledge and satisfaction. Subjects who viewed a modeling videotape spoke more than subjects who viewed a control videotape. The bulk of our findings indicated that a question-asking model was generally more effective than a disclosive model in eliciting communicative behaviors. Knowledge scores were found to increase after the intervention, regardless of subjects' verbal participation. Subjects in either of the modeling conditions who spoke more indicated higher affective satisfaction.

Adult↗
PubMed1987

The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14.

Human liver glycogen phosphorylase deficiency, also known as glycogen storage disease type VI (GSD VI) or Hers disease, is characterized by hepatomegaly and reduced or absent glycogenolytic response to the injection of glucagon. The recently isolated cDNA encoding the liver isozyme of glycogen phosphorylase was used to map the gene and identify restriction-fragment polymorphisms in normal Caucasians as a prerequisite for detecting linked GSD VI abnormalities. Results of restriction-enzyme analysis using a downstream fragment of the liver glycogen phosphorylase cDNA indicated the existence of a single gene copy per haploid genome. Hybridization of this downstream liver phosphorylase probe to dual laser-excited, sorted human chromosomes localized the gene to human chromosome 14. When the downstream probe was tested on genomic DNA cut with seven different restriction enzymes, a single MspI restriction-fragment-length polymorphism (RFLP) was observed in a single individual. In contrast, similar Southern blots performed with an upstream portion of the cDNA encoding liver phosphorylase revealed common RFLPs for four of eight enzymes tested, with minor polymorphic allele frequencies ranging from 33% to 44%. One of the four enzymes (TaqI) revealed two independent polymorphisms. If random distribution of these haplotypes among normal and disease loci, is assumed, approximately 92% of fetuses at risk for Hers disease will be informative when tested with the upstream liver phosphorylase probe.

Chromosome Mapping↗
PubMed1987

Cardiac glycoside poisoning in sheep caused by Urginea physodes (Jacq.) Bak. and the isolated physodine A.

Urginea physodes (Jacq.) Bak., a species closely related to or possibly synonymous with U. pusilla, is described and its distribution given. Four bufadienolides were isolated from U. physodes and the approximated LD50 and cumulative effect of some of them determined in guinea pigs. The most toxic one proved to be mildly cumulative. Typical signs of acute cardiac glycoside poisoning, involving the locomotory, gastro-intestinal, respiratory and cardiac system, were seen in the field cases and/or were experimentally induced by the plant. Similar signs could also be induced by injecting the isolated bufadienolide, physodine A, to a sheep.

Animals↗
PubMed1987

Experimental evidence that the active principle of the poisonous plant Thesium lineatum L.f. (Santalaceae) is a bufadienolide.

The toxicity of Thesium lineatum is confirmed in sheep. A toxic crystalline bufadienolide, with the suggested trivial name thesiuside, has been isolated from it. This is the first cardiac glycoside to be isolated from a member of the Santalaceae. The toxin appears to have no cumulative effect and the symptoms of intoxication and pathology in sheep are similar to that expected from acute cardiac glycoside intoxication.

Animals↗
PubMed1985

Selection of patients for lumbar sympathectomy.

We successfully predicted that patients presenting with critical ischemia of a limb and Doppler ratios greater than or equal to 0.3 would benefit from lumbar sympathectomy alone. However, we found that the procedure failed in 14 per cent of limbs whose ratios were greater than or equal to 0.3. In retrospect, all these patients were found to have deep infection. Had we known this fact prospectively, our predictions for success would have been close to 100 per cent. We were less than 50 per cent successful in predicting failure of the procedure, but the number of patients in this group is too small to draw reliable conclusions. We believe that patients with arm-ankle Doppler ratios greater than or equal to 0.3 whose manifestations of ischemia are limited to the skin will have a greater than 95 per cent chance of receiving a good result from lumbar sympathectomy alone and that this result will be maintained for many years.

Aged↗
PubMed1985

Enhanced polyglutamylation of aminopterin relative to methotrexate in the Ehrlich ascites tumor cell in vitro.

The polyglutamylation of aminopterin and methotrexate (N10-methylaminopterin) was compared in the Ehrlich ascites tumor in vitro. Three poly-gamma-glutamyl conjugates of methotrexate and aminopterin were detected, although at an equal (1 microM) extracellular drug concentration, the net accumulation of aminopterin polyglutamates exceeded that for the methotrexate polyglutamyl derivatives by a factor of 9. When compensation was made for transport differences between these compounds by adjusting the extracellular drug concentrations to achieve equivalent intracellular monoglutamyl substrate levels, the polyglutamylation of aminopterin was still 2.8-fold greater than that for methotrexate, suggesting that aminopterin is a better substrate for the folylpolyglutamate synthetase as well as the transport carrier. An additional metabolite of aminopterin was detected within seconds following drug exposure. This derivative did not bind tightly to dihydrofolate reductase, yet it was rapidly converted to a polyglutamate. The formation of both aminopterin polyglutamates and these novel derivatives was enhanced by increases in the free intracellular level of aminopterin. Aminopterin polyglutamates were bound tightly to dihydrofolate reductase and were retained intracellularly relative to unaltered aminopterin when Ehrlich cells containing these forms were suspended in drug-free medium. These findings support a role for the polyglutamylation of aminopterin as a critical element in drug action and as a factor in addition to membrane transport in the disparate antifolate potencies of aminopterin and methotrexate.

Aminopterin↗
PubMed1985

Isolation and characterization of and some observations on poisoning by bufadienolides from Cotyledon orbiculata L. var. orbiculata.

The approximate LD50 and cumulative effect of 4 bufadienolides, isolated from Cotyledon orbiculata, were determined in guinea-pigs. Two of the bufadienolides proved to be mildly cumulative. One of the mildly cumulative bufadienolides induced subacute intoxication with some signs of krimpsiekte when injected intravenously into a sheep over 13 days. In the sheep, the paralysis was accompanied by signs of malaise, such as electrocardiographic changes and ruminal stasis.

Animals↗
PubMed1984

Role of the cellular oxidation-reduction state in methotrexate binding to dihydrofolate reductase and dissociation induced by reduced folates.

5-Formyltetrahydrofolate promotes the net dissociation of methotrexate bound to dihydrofolate reductase in the Ehrlich ascites tumor (L. H. Matherly et al., Cancer Res., 43: 2694-2699, 1983). Treatment of Ehrlich tumor cells with glucose or inhibitors of electron transfer stabilized the association of the antifolate with dihydrofolate reductase as reflected by a 2-fold increased fraction of dihydrofolate reductase-bound methotrexate and an abolition of the 5-formyltetrahydrofolate-induced dissociation of the inhibitor-enzyme complex. Glucose and azide were also found to increase the intracellular ratio of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to oxidized nicotinamide adenine dinucleotide phosphate (NADP+) in the tumor approximately 8- and 11-fold, respectively. However, other agents which enhanced the association between methotrexate and its target enzyme were less effective in increasing the intracellular level of NADPH relative to NADP+. Micromolar concentrations of NADPH promoted methotrexate binding to the purified Ehrlich tumor dihydrofolate reductase. Bound methotrexate could be dissociated from the purified enzyme by 5-methyltetrahydrofolate but less readily by 5-formyltetrahydrofolate and only in the presence of reduced levels of NADPH relative to NADP+. The tetraglutamate derivative of 5-methyltetrahydrofolate was even more effective than the underivatized compound in dissociating methotrexate from dihydrofolate reductase. These findings suggest a critical role for the cellular oxidation-reduction state in determining the affinity of dihydrofolate reductase for methotrexate and thus the cellular sensitivity to the antifolate. In addition, the data are consistent with the possibility that dihydrofolate reductase is a key locus for intracellular competitive interactions between reduced folates and methotrexate during leucovorin rescue from the pharmacological effects of the antifolate.

Animals↗
PubMed1983

Krimpsiekte and acute cardiac glycoside poisoning in sheep caused by bufadienolides from the plant Kalanchoe lanceolata Forsk.

Three toxic bufadienolides , one characterized as hellibrigenin 3-acetate, have been isolated from Kalanchoe lanceolata Forsk. Typical signs of cardiac glycoside poisoning, involving the gastro-intestinal, neuromuscular and cardiovascular systems, could be induced by drenching the milled plant to sheep. Such signs could also be induced by dosing the bufadienolides to sheep or by injecting them into both guinea-pigs (subcutaneously) and sheep (intravenously). The specific paretic syndrome, krimpsiekte , on the other hand, was reproduced only by the repeated intravenous administration of smaller doses of the 2 unknown bufadienolides to sheep. Histopathological examination revealed a mild to severe multifocal cardiomyopathy in sheep receiving plant material or bufadienolides .

Acute Disease↗
PubMed1983

The experimental production of krimpsiekte in sheep with Tylecodon grandiflorus (Burm.f.) Toelken and some of its bufadienolides.

Six bufadienolides were isolated from Tylecodon grandiflorus ( Burm .f.) Toelken . The paretic syndrome, krimpsiekte , could be induced in sheep either by repeated oral administration of small quantities of plant material or the intravenous injection of small quantities of certain bufadienolides . A mild to moderate, acute to subacute, multifocal cardiomyopathy was evident in sheep poisoned by both the plant and the bufadienolides .

Animals↗