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Biomedical subjects

M B Anderson

Publications and source records attributed to M B Anderson.

At least 19 recordsLinked to original sources
PubMed2002

Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of mammary carcinogenesis is potentiated by the pineal hormone melatonin.

Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with melatonin (Mlt) followed 24h later with physiological concentrations of all-trans retinoic acid (atRA) results in apoptosis. These studies were extended into trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model. Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the chow) and administering melatonin by subcutaneous injection in the late afternoon demonstrated that the combination of Mlt and 9cRA was able to significantly prevent tumor development, and that the combination was more efficacious that either Mlt or 9cRA alone. In this report, we conducted studies to determine if lower doses of 9cRA could be used in combination with Mlt while still maintaining anti-tumor activity and if the route of administration of 9cRA (bolus (gavage) v.s. chronic (chow) routes) affected its interaction with Mlt. The studies presented here demonstrate that significantly reduced doses of 9cRA can be used in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our studies demonstrate that 9cRA is equally effective when it is administered chronically (chow) or as a bolus (gavage). These data demonstrate that the combined use of Mlt and 9cRA produces additive or synergistic effects, which are more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a potentially useful clinical treatment regimen for breast cancer since it allows the use of lower doses of retinoic acid, thus, avoiding the toxic side effects associated with the use of high dose retinoids.

Administration, Oral↗
PubMed2001

Chemoprevention of NMU-induced rat mammary carcinoma with the combination of melatonin and 9-cis-retinoic acid.

In experimental trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model, a significant decrease in tumor incidence (to 5%) was observed in rats treated with melatonin and 9-cis-retinoic acid (9 cRA) compared to controls (55%). Although 9cRA alone decreased tumor incidence to 26%, this response did not reach statistical significance. Tumor incidence was significantly inhibited to 20% in the animals that received melatonin and 9cRA on alternating days. Latency to tumor onset was prolonged in animals receiving either of the combination treatments compared with controls, and tumor multiplicity was also significantly decreased.

Adenocarcinoma↗
PubMed2001

Thoracic epidural anesthesia for coronary bypass via left anterior thoracotomy in the conscious patient.

Cardiac surgery is perceived to be maximally invasive and fraught with complications. Secondary to this, cardiothoracic surgeons have been refining traditional techniques to minimize their invasive nature. Epidural anesthesia has been utilized safely and effectively for numerous surgical procedures to reduce the associated morbidity. In hopes of achieving a similar result, we utilized thoracic epidural anesthesia for a coronary artery bypass via a left anterior thoracotomy, in an awake, spontaneously breathing patient. To the best of our knowledge, this is the first reported case utilizing this approach. Herein we report the results and technique utilized.

Anesthesia, Epidural↗
PubMed2000

A Christmas story.

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Transformation of medical students' education: work in progress and continuing challenges.

In his book Time to Heal: American Medical Education from the Turn of the Century to the Era of Managed Care, Ludmerer expresses concern about the erosion of the environment in which medical students and residents learn the clinical skills, attitudes, and behaviors that they will need to practice high-quality medicine. Importantly, while he attributes the erosion of the clinical environment largely to the impact of managed care, he also places some responsibility within academic medicine itself, primarily the redirection of the clinical faculty's efforts away from traditional academic pursuits to the generation of clinical revenues. The Association of American Medical Colleges has information about the kinds of changes already occurring. In the preclinical curriculum, schools have introduced a wide range of new courses and topics, and there is more attention on professionalism and values. Schools are making fundamental changes in the design and conduct of the curriculum, primarily by adopting more integrated (non-departmental) approaches to course design and management. The clinical curriculum is changing primarily through the greatly expanded use of ambulatory care sites, and medical schools are developing new approaches to managing dispersed and varied instruction. Also, faculty are paying more attention to the role of residents as teachers and role models. These changes speak well for medical education. Nonetheless, substantial and sustained work remains to be done despite the present uncertainty about the future of academic medical centers. This work is essential--a challenge that the leaders of academic medicine must not fail.

Clinical Clerkship↗
PubMed1999

Blue light-directed destabilization of the pea Lhcb1*4 transcript depends on sequences within the 5' untranslated region.

Pea seedlings grown in continuous red light accumulate significant levels of Lhcb1 RNA. When treated with a single pulse of blue light with a total fluence >10(4) micromol m(-2), the rate of Lhcb1 transcription is increased, whereas the level of Lhcb1 RNA is unchanged from that in control seedlings. This RNA destabilization response occurs in developing leaves but not in the apical bud. The data presented here indicate that the same response occurs in the cotyledons of etiolated Arabidopsis seedlings. The blue light-induced destabilization response persists in long hypocotyl hy4 and phytochrome phyA, phyB, and hy1 mutants as well as in far-red light-grown seedlings, indicating that neither CRY1 (encoded by the hy4 locus) nor phytochrome is the sole photoreceptor. Studies with transgenic plants indicate that the destabilization element in the pea Lhcb1*4 transcript resides completely in the 5' untranslated region.

5' Untranslated Regions↗
PubMed1999

Thoracic complications in solid organ transplantation.

Thoracic complications of solid organ transplantation are common and can arise from the implantation surgical procedure or can be secondary to the need for lifelong immunosuppression. Problems that arise can be general to cardiothoracic surgery or unique to transplant patients. This article provides an overview of these complications and some approaches to their avoidance and management.

Esophagitis↗
PubMed1998

Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure.

The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 micromol/kg CdCl2). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 micromol/kg ZnAc), given 24 h prior to 20 micromol/kg CdCl2 administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible reproductive organs.

Animals↗
PubMed1998

Antagonism of selectin-dependent adhesion of human eosinophils and neutrophils by glycomimetics and oligosaccharide compounds.

Early in inflammation, adhesion occurs between leukocytes and endothelium when selectins bind to sialyl Lewis X (sLex) and related oligosaccharides. We tested novel compounds that mimic sLex for their ability to inhibit selectin-mediated adhesion of human eosinophils and neutrophils in vitro. Neutrophils and eosinophils were isolated by density gradient centrifugation, and eosinophils were further purified by immunomagnetic negative selection. Adhesion to unstimulated or interleukin-1beta-stimulated (5 ng/ml, 4-6 h) umbilical vein endothelial monolayers was tested under static or rotating conditions, where adhesion is primarily E- or L-selectin dependent, respectively. P-selectin-dependent adhesion was tested on immobilized platelets treated with or without phorbol myristate acetate (10(-7) M, 10 min). Stimulus-induced adhesion was always at least 4-fold higher than without stimulus, and selectin dependence was confirmed with specific blocking monoclonal antibodies. E-selectin-dependent adhesion of eosinophils and neutrophils was inhibited by compound GM2296 (the concentration producing 50% inhibition of adhesion [IC50] approximately 0.5-1 mM). E-selectin-dependent adhesion of neutrophils, but not eosinophils, was also inhibited by another compound, sLex with a lipid tail (30 +/- 6% inhibition at 3 mM), whereas compound GM1292 slightly inhibited adhesion of both (23 +/- 5 and 20 +/- 6% inhibition, respectively, at 1 mM). L-selectin-dependent adhesion was more effectively inhibited by GM2296 (IC50 approximately 0.2-0.5 mM), although P-selectin-dependent adhesion was also inhibited (IC50 approximately 1 mM). Inhibition was reversible without affecting viability, and no effect was seen with these compounds in assays testing neutrophil adhesion to immobilized intercellular adhesion molecule-1. Thus, compound GM2296, a carbon-fucosylated derivative of glycyrrhetinic acid, inhibits E-, L-, and P-selectin-dependent eosinophil and neutrophil adhesion. The ability of these and perhaps other related glycomimetic compounds to interfere with the function of more than one type of selectin makes them desirable candidates as anti-inflammatory agents.

Antibodies, Monoclonal↗
PubMed1998

Reduction of myocardial infarct size in vivo by carbohydrate-based glycomimetics.

One of the foremost mechanisms involved in the pathogenesis of myocardial reperfusion injury is the adhesion of neutrophils within the myocardium. The initial neutrophil-endothelial cell interactions are mediated by the selectin family of adhesion molecules. Blockade of this group of adhesion molecules, through the use of synthetic carbohydrate analogs to the selectin ligand sialyl Lewisx and glycomimetics, has been beneficial in reducing neutrophil influx and infarct size. In the present study, glycyrrhizin (GM1292), a natural structural glycomimetic, was analyzed for the ability to decrease myocardial infarct size after regional myocardial ischemia/reperfusion. To determine the structural requirements for optimal cardioprotective activity, two additional compounds related to glycyrrhizin, GM3290 and GM1658 (glycyrrhetinic acid), were studied. The molecular structures of the latter two compounds differ in the number of glucuronic acid residues in their respective molecules. Open-chest, anesthetized rabbits were subjected to 30 min occlusion of the left coronary artery followed by 5 hr of reperfusion. Vehicle or glycomimetic (10 mg/kg/hr) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Myocardial infarct size in rabbits treated with GM1292 (two glucuronic acid residues) and GM3290 (one glucuronic acid residue) was reduced significantly when compared with vehicle-treated animals (P < .05). GM1658, which lacks glucuronic acid residues, did not provide a protective effect in vivo. The data suggest that GM1292 and GM3290, which contain carbohydrate moieties, are effective in reducing the degree of myocardial injury after an acute period of ischemia/reperfusion.

Animals↗
PubMed1998

The carbohydrate sialyl Lewis(x) (sLe(x)) sulfated glycomimetic GM2941 attenuates glucan-induced pulmonary granulomatous vasculitis in the rat.

We examined the protective effects of GM2941, a sulfated glycomimetic of the complex carbohydrate sialyl Lewis(x), in a model of pulmonary granuloma development. This study was based on the rationale that formation of glucan-induced lung granulomas is dependent on neutrophils and that sialyl Lewis(x) glycomimetic (GM2941) interferes, in vitro, with P-selectin-dependent neutrophil-endothelial adhesive interactions. Infusion of particulate yeast cell wall glucan into rats results in the rapid (48 hr) formation of monocyte/macrophage-rich angiocentric pulmonary granulomas. Development of granulomas exhibits a temporal pattern characterized by the early, transient influx of neutrophils into blood vessel walls at sites of glucan embolization, followed by accumulation of monocytes and macrophages that constitute the definitive angiocentric lesions. Within 1 hr after the infusion of glucan, immunohistochemical analysis revealed up-regulation of blood vessel wall-associated P-selectin. Previous studies utilizing neutrophil-depleted animals have revealed that neutrophils, although not present in definitive lesions, are required for full granuloma development. The potential of GM2941 to inhibit neutrophil-endothelial cell adhesive interactions was demonstrated by the ability of the compound to inhibit P-selectin-mediated adhesion to histamine-stimulated HUVECs. Infusion of GM2941 retarded pulmonary granuloma development in a dose-dependent manner. Whole-lung myeloperoxidase activity, measured at the time of peak neutrophil accumulation, was significantly reduced in animals pretreated with GM2941 (30 mg/kg, 24 microM/kg), which suggests that this compound affords protection, at least in part, through impedance of neutrophil recruitment. These data indicate that GM2941 affords a significant degree of protection against granuloma formation associated with glucan infusion, probably through the interruption of neutrophil recruitment.

Animals↗
PubMed1997

Sulfo-Lewis(x) diminishes neutrophil infiltration and free radicals with minimal effect on serum cytokines after liver ischemia and reperfusion.

BACKGROUND: Cell adhesion plays a central role in the pathogenesis of neutrophil-induced hepatic injury after ischemia and reperfusion. Sialyl Lewis(x) binds to selectins mediating neutrophil adherence to endothelium, thereby facilitating subsequent migration and tissue damage. AIM: We studied the effect of a novel sulfo-derivative of sialyl Lewis(x), GM-1998, on the liver inflammatory response after ischemia and reperfusion. Specifically, we evaluated its impact on three key inflammatory mediators: neutrophil migration, free radicals, and serum cytokines. MATERIAL AND METHODS: Rats were subjected to total hepatic ischemia for 90 min using an extracorporeal portosystemic shunt to avoid splanchnic congestion. GM-1998 was given at a total dose of 20 mg/kg both prior to and after reperfusion. Liver function tests, liver tissue free radicals, and myeloperoxidase (MPO), serum cytokines (IL-1, TNF-alpha), and liver histology were analyzed 4 hr after reperfusion. Additionally, survival was followed for up to 7 days. RESULTS: Seven-day survival significantly increased from 20% in the control group to 65% in the sulfo-Lewis(x) treated group. Liver function tests and histological damage scores were improved in comparison to controls. We observed significant downregulation of free radicals and neutrophil migration. This compound did not significantly affect serum cytokine levels. CONCLUSIONS: GM-1998 showed a protective effect in an in vivo model of severe liver ischemia and reperfusion by decreasing tissue free radical levels and selectin-mediated neutrophil migration. This protective effect was also reflected in improved liver function tests and histological response leading to better survival. We confirmed the beneficial effect of neutrophil blockade as a key target to prevent damage after the reperfusion phenomenon by using a glycomimetic sulfo-Lewis(x).

Animals↗
PubMed1997

Metal accumulation in crayfish, Procambarus clarkii, exposed to a petroleum-contaminated Bayou in Louisiana.

Red swamp crayfish (Procambarus clarkii) were placed for a period of 7 days in Bayou Trepagnier, a Louisiana waterway which received petroleum-laden effluents from a manufacturing complex several decades ago. However, coolant water from the plant continued to be released into the bayou until 1995. Analyses of sediments at the exposure site revealed heavy contamination by lead, chromium, and copper, while concentrations of arsenic and cadmium were very low. Significant bioaccumulation of lead was observed in the hepatopancreas and gills of 7-day-exposed crayfish, whereas chromium accumulated the most in the gills and blood. Concentrations of copper in the crayfish did not change during the course of the study, suggesting that this essential metal constituent of the respiratory pigment is successfully regulated even when crayfish are exposed to relatively high levels of copper in the sediments. There was no metal accumulation in the abdominal muscle of the crayfish. That damage to the hepatopancreas occurred during the exposure is suggested by histopathological studies which revealed swollen and vacuolated R cells and an increase in the pH of the digestive juices. Blood glucose levels, as well as ovarian and hepatopancreatic indices, were unchanged. This study demonstrates that accumulation of nonessential metals in crayfish tissues in a wetland environment contaminated by mixed pollution (metals and hydrocarbons) reflects the concentrations of metals in the sediment.

Animals↗
PubMed1997

Correct blue-light regulation of pea Lhcb genes in an Arabidopsis background.

Irradiation of etiolated Arabidopsis or pea, or dim-red-light-grown pea seedling with a single, short (under 10 s) pulse of blue light (threshold at 0.1 mumol/m2) is sufficient to induce the expression of specific members of the Lhcb gene family including the pea Lhcb1*4 gene and the Arabidopsis Lhcb1*3 gene. Other Lhcb genes, such as the pea Lhcb1*3 gene and the Arabidopsis Lhcb1*1 and 1*2 genes are unaffected by this blue-light treatment. Transgenic Arabidopsis bearing pea Lhcb1*3::Gus (beta-glucuronidase), pea Lhcb1*4::Gus or Arabidopsis Lhcb1*3::Gus constructs were used to determine if pea and Arabidopsis employ a similar mechanism to achieve blue-light induced Lhcb expression. Examination of the respective Gus expression patterns in white-light-grown seedlings indicates that the pea promoters are active and properly expressed in the Arabidopsis background. Irradiation of dark-grown Arabidopsis with a 20 s pulse of blue light with a total fluence of 100 mumol/m-2 results in expression of the pea Lhcb1*4::Gus (beta-glucuronidase) construct, but not of the pea Lhcb1*3::Gus construct indicating that the pea promoters respond correctly to blue light in the Arabidopsis background. Fluence-response, time-course and reciprocity characteristics for the blue-light-induced expression of the pea Lhcb1*4::Gus construct closely resemble those of the endogenous Arabidopsis Lhcb genes, confirming the proper interpretation of the Arabidopsis blue-light-signaling mechanism by the pea Lhcb1*4 promoter and suggesting that the signaling mechanisms in the two plants are very similar, if not identical. Fluence response data for the steady-state level of transcript derived from an Arabidopsis Lhcb1*3::Gus construct extending 200 bp upstream of the site of transcription indicate that the blue light responsive elements(s) are contained within this 200 bp region.

Arabidopsis↗
PubMed1997

Introducing information technologies into medical education: activities of the AAMC.

Previous articles in this column have discussed how new information technologies are revolutionizing medical education. In this article, two staff members from the Association of American Medical College's Division of Medical Education discuss how the Association (the AAMC) is working both to support the introduction of new technologies into medical education and to facilitate dialogue on information technology and curriculum issues among AAMC constituents and staff. The authors describe six AAMC initiatives related to computing in medical education: the Medical School Objectives Project, the National Curriculum Database Project, the Information Technology and Medical Education Project, a professional development program for chief information officers, the AAMC ACCESS Data Collection and Dissemination System, and the internal Staff Interest Group on Medical Informatics and Medical Education.

Curriculum↗