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Biomedical subjects

S Abel

Publications and source records attributed to S Abel.

At least 19 recordsLinked to original sources
PubMed2006

Long-term stability of a patient-convenient 1 mg/ml suspension of tacrolimus for accurate maintenance of stable therapeutic levels.

Tacrolimus (Prograf, FK506, Fujisawa Healthcare) is a widely used immunosuppressive agent that is used both for the prevention and treatment of solid organ transplant rejection as well as for the prevention and treatment of graft-versus-host disease after allogeneic blood and marrow transplant. Oral preparations of tacrolimus are commercially available in 0.5, 1 and 5 mg gelatin capsules. Previously, only a 0.5 mg/ml oral suspension has been demonstrated to be stable for use in pediatric patients. On our bone marrow transplant service, we found that using this concentration of tacrolimus led to confusion, with patients and their caregivers confusing milligrams and milliliters, thus increasing errors with this formulation. We postulated that a 1 mg/ml oral formulation of tacrolimus would decrease the potential for medication errors. Our findings support new stability information of approximately 4 months for an extemporaneous oral suspension of tacrolimus at a concentration of 1 mg/ml.

Administration, Oral↗
PubMed2005

Animal models and analytical approaches for understanding the relationships between wine and cancer.

We used two approaches for studying the relationships between wine consumption, wine composition and cancer In the first approach, a transgenic mouse model of human neurofibromatosis, combined with the use of well-defined, chemically purified diets, showed that red wine contains nonalcoholic components that can delay tumor onset. In additional studies, catechin, the main monomeric polyphenol of red wine, delayed tumor onset in this mouse model in a positive, linear relationship when incorporated into the diet at levels of 0.5-4 mmol/kg diet. In the second approach, low doses of the chemical carcinogen 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine (PhlP) were administered to rats, and formation of DNA adducts was evaluated by accelerator mass spectrometry. Consumption of red wine solids (the residue from red wine remaining after removal of alcohol and water) and the wine polyphenol quercetin did not influence PhlP-DNA adduct levels or induce liver enzymes (glutathione-S-transferase and quinone reductase). However, quercetin did alter distribution of PhlP in the rat tissues compared to control animals and animals fed other potential dietary chemopreventive agents, including phenylethyl isothiocyanate and sulforaphane. These studies demonstrate the feasibility of these approaches for studying the chemopreventive potential of dietary components at physiologic levels in

Animals↗
PubMed2004

Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: effect of different n-6/n-3 fatty acid ratios.

Male Fischer rats were fed the AIN 76A diet containing varying n-6/n-3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatectomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20:4n-6. In addition, there is an accumulation of 18:1 n-9 and 18:2n-6 and a decrease in the end products of the n-3 metabolic pathway in PC, suggesting a dysfunctional delta-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increase in the glutathione (GSH) concentration. The low n-6/n-3 FA ratio diets significantly decreased 20:4n-6 in PC and PE phospholipid fractions with a concomitant increase in 20:5n-3, 22:5n-3, and 22:6n-3. The resultant changes in the 20:4/20:5 FA ratio and the 20:3n-6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20:4n-6 in PE by equalizing the nodule/surrounding ratio. The low n-6/n-3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n-3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.

Animals↗
PubMed2003

Availability of unrelated donors for hematopoietic stem cell transplantation for hemoglobinopathies.

Hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with hemoglobinopathies. However, fewer than 30% of individuals will have an HLA-identical sibling. Improvement in outcomes after HSCT using unrelated donors (URD), and the development of novel nontoxic preparative regimens may make URD HSCT an option for hemoglobinopathy patients who do not have an HLA-identical sibling donor. The National Marrow Donor Program (NMDP) maintains a Registry of 4 million volunteer donors, and facilitates URD HSCT for patients with life-threatening blood diseases. In light of the increased representation of minorities in the NMDP registry, donor searches were run in April 2001 for a cohort of 272 thalassemia patients and 77 sickle cell disease (SCD) patients for whom searches had been submitted between 1989 and 2001 in order to determine the current likelihood of finding a potential donor of hematopoietic stem cells for hemoglobinopathy patients. About 59.7% SCD patients 80.2% thalassemia patients will find at least one potential 6/6 HLA matched donor or umbilical cord blood (UCB) unit. All patients will find at least one donor or UCB that is a potential 5/6 HLA match. In conclusion the majority of hemoglobinopathy patients will find at least one potential HLA matched unrelated bone marrow donor or UCB.

Anemia, Sickle Cell↗
PubMed2002

Additional stringy sources for electric dipole moments.

We show that string models with low energy supersymmetry which accommodate the fermion mass hierarchy generally give nonuniversal soft trilinear couplings (A terms). In conjunction with the apparently large Cabibbo-Kobayashi-Maskawa (CKM) phase, this results in large fermion electric dipole moments (EDMs) even in the absence of CP violating phases in the supersymmetry breaking auxiliary fields and the micro term. Nonobservation of the EDMs therefore implies that strings select special flavor and/or supersymmetry breaking patterns.

Journal Article↗
PubMed2002

Lipids and delta6-desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1.

Alterations in the membrane structure and function of hepatocyte membranes by fumonisin B1 (FB1) have been proposed to play an important role in the disruption of growth regulatory effects and hence in the cancer-promoting ability of the mycotoxin. Detailed analyses of lipids in liver microsomal fractions of rats exposed to different dietary levels of FB1 over a period of 21 d indicated an increase in PC, PE, PI, and cholesterol (Chol). These changes decreased the PC/PE and increased the total phospholipid/Chol ratios. When considering FA content, the quantities of total FA increased (P < 0.05) in the major phospholipid fractions as a result of the increased phospholipid levels. However, when considering the relative levels (mg/100 mg of the total FA) of specific FA, the monounsaturated FA (16:1 n-7 and 18:1n-9) and 18:2n-6 increased (P < 0.05), whereas the long-chain PUFA decreased (P < 0.05) in the main phospholipid fractions. Enzyme analyses indicated that the activity of the delta6-desaturase was significantly reduced in liver microsomal preparations in a dose-dependent manner. An increase in the 20:3n-6/20:4n-6 ratio also suggested a decrease in the activity of the delta5-desaturase. Disruption of microsomal lipid metabolism at different levels by FB1 could play an important role in the alteration of growth regulatory effects in the liver.

Administration, Oral↗
PubMed2001

Cancer initiation by fumonisin B(1) in rat liver--role of cell proliferation.

Fumonisin B(1) (FB(1)), a carcinogenic mycotoxin produced by the fungus Fusarium verticillioides in corn, causes cancer initiation in rat liver in a similar manner to genotoxic carcinogens although apparently with different kinetics. The present experiment was designed to evaluate the role of regenerative cell proliferation, effected by partial hepatectomy (PH) and carbontetrachloride (CCl(4)) and direct mitogen-induced hyperplasia, induced by lead nitrate (PbNO(3)), on FB(1)-induced cancer initiation. Initiation was effected over a period of 14 days by gavage administration of FB(1) at different daily doses ranging from 0.14 to 3.5 mg FB(1)/100 g body weight while the stimuli for cell proliferation were introduced 7 days after the start of the FB(1) treatment. Based on the proliferative stimulus used, cancer promotion was effected 3 weeks after completion of the initiating treatment by 2-acetylaminofluorene (2-AAF) treatment followed by PH or carbon tetrachloride CCl(4) on day 4. Cancer initiation by FB(1) was associated with a hepatotoxic effect and an increase in lipid peroxidation. In contrast to compensatory liver cell proliferation induced by PH and CCl(4), mitogen-induced hyperplasia (PbNO(3)) failed to enhance the cancer initiating potential of FB(1) suggesting that cancer induction by a non-genotoxic carcinogen is supported by regenerative cell proliferation. Cognizance of the enhancing role of cell proliferation during cancer initiation by FB(1) is required in assessing the risks posed by this mycotoxin to humans.

2-Acetylaminofluorene↗
PubMed2001

Electric dipole moment cancellations in D-brane models.

We analyze the possibility of simultaneous electron, neutron, and mercury electric dipole moment (EDM) cancellations in the mSUGRA and D-brane models. We find that the mercury EDM constraint practically rules out the cancellation scenario in D-brane models, whereas in the context of mSUGRA it is still allowed with some fine tuning.

Journal Article↗
PubMed2001

Quantification of HTLV type I and HIV type I DNA load in coinfected patients: HIV type 1 infection does not alter HTLV type I proviral amount in the peripheral blood compartment.

Several reports suggest that HTLV-I/HIV coinfection may be associated with an increased risk of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In HTLV-I-monoinfected patients, the occurrence of HAM/TSP is associated with high peripheral blood HTLV-I proviral load. Using a real-time quantitative PCR assay, we assessed the proviral DNA load in peripheral blood mononuclear cells (PBMCs) from 15 asymptomatic HTLV-I-monoinfected patients, 15 HTLV-I-monoinfected patients with HAM/TSP, and 25 HTLV-I/HIV-1 coinfected patients, including 4 with HAM/TSP. We also measured HIV-1 proviral DNA load in PBMCs from the coinfected patients. The median HTLV-I proviral loads were 6,800 and 4,100 copies per 10(6) PBMCs in the asymptomatic monoinfected and coinfected groups, and 58,800 and 43,300 copies per 10(6) PBMCs in the monoinfected and coinfected patients with HAM/TSP, respectively. The difference between HTLV-I proviral loads in HAM/TSP and asymptomatic monoinfected patients was statistically significant (p < 0.0001), but there was no difference between the HTLV-I-monoinfected and HTLV-I/HIV-1-coinfected groups. There was no correlation between HTLV-I and HIV-1 proviral load. HTLV-I proviral load did not correlate with the CD4+ T lymphocyte count. Among patients with no HTLV-I disease, the median copy number of HTLV-I per 10(6) circulating CD4+ T cells was 114,000 in the coinfected group and 16,700 in the monoinfected group, but the difference was not significant (p = 0.089). These data do not confirm the hypothesis in which HIV-1 coinfection would increase HTLV-I proviral burden in the PBMCs. However, depletion of the CD4+ T cell subset, the main target of HTLV-I, could be counterbalanced by an up-regulation of HTLV-I replication or by greater resistance of HTLV-I-infected cells to HIV-1-induced destruction.

AIDS-Related Opportunistic Infections↗
PubMed2001

Toxicological effects in rats chronically fed low dietary levels of fumonisin B(1).

The toxicity of low dietary levels of fumonisin B(1) (FB(1)), i.e. 1, 10 and 25 mg FB(1)/kg diet, were monitored in rats over a period of 24 months. No effects on the body weight gain and feed intake profiles were noticed, while the relative liver weight was significantly (P<0.05) reduced in the FB(1)-treated rats. Mild toxic effects, including single cell necrosis (apoptosis), proliferation of bile duct epithelial cells (DEC), and early signs of fibrosis, bile duct hyperplasia and in one case, adenofibrosis, were noticed in the liver of the rats fed the highest (25 mg/FB(1)/kg diet) dietary level. A significant (P<0.05) increase in the level of oxidative damage was also noticed in the liver of the rats of high dosage dietary group. The toxic effects were less severe in the 10 mg FB(1)/kg dietary group, whilst only a few ground glass foci were observed in the 1 mg FB(1)/kg dietary group. Hepatocyte nodules, staining positively for glutathione-S-transferase (placental form, PGST), were observed macroscopically in the 25 mg FB(1)/kg treated group and to a lesser extent in the 10 mg FB(1)/kg treated rats. The most prominent toxic lesions by FB(1) (10 and 25 mg FB(1)/kg dietary groups) in the kidneys were restricted to the tubular epithelium manifesting as granular cast, necrosis, apoptosis, calcification and the presence of regenerative foci in the proximal convoluted tubules. The existence of a cytotoxic/proliferative threshold with respect to cancer induction by FB(1) in rat liver became apparent, with a dietary level of <10-mg FB(1)/kg diet as a no effect threshold for the induction of hepatocyte nodules.

Animals↗
PubMed2001

Infant care practices in New Zealand: a cross-cultural qualitative study.

This paper describes and compares the infant care practices and beliefs of Maori, Tongan, Samoan, Cook Islands, Niuean and Pakeha (European) caregivers residing in Auckland, New Zealand. Focusing on four areas--sources of support and advice; infant feeding; infant sleeping arrangements; and traditional practices and beliefs--it explores inter-ethnic similarities and differences and intra-ethnic tensions. The international literature indicates that there can be significant cultural variation in infant care practices and in the meanings attributed to them. There is, however, little New Zealand literature on this topic, despite its importance for effective health service and health message delivery. Participants were primary caregivers of infants under 12 months. An average of six focus groups were conducted within each ethnic group, resulting in a total of 37 groups comprising 150 participants. We found similarities across all ethnic groups in the perceived importance of breastfeeding and the difficulties experienced in establishing and maintaining this practice. The spectrum of behaviours ranged widely with differences most pronounced between Pacific caregivers, especially those Island-raised, and Pakeha caregivers, especially those in nuclear families. Amongst the former, norms included: the family as central in providing support and advice; infant bedsharing; abdominal rubbing during pregnancy; baby massage; and the importance of adhering to traditional protocols to ensure infant well-being. Amongst the latter, norms included: strong reliance on professional advice; looser family support networks; the infant sleeping in a cot; and adherence to Western biomedical understandings of health and illness. Maori caregivers bridged the spectrum created by these groups and exhibited a diverse range of practices. Intra-cultural differences were present in all groups indicating the dynamic nature of cultural practices. They were most evident between Pacific-raised and New Zealand-raised Pacific caregivers, with the latter attempting to marry traditional with Western beliefs and practices.

Humans↗
PubMed2001

Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) is the only treatment for selected inherited metabolic storage diseases (IMSD); a significant shortcoming is failure to achieve donor-derived engraftment. This study was undertaken to determine whether busulfan pharmacokinetics (BU PK) are altered in children with IMSD and whether BU concentrations are important in achieving engraftment. BU samples were obtained from 39 IMSD children, including 20 children with Hurler syndrome, undergoing HCT. Patients received oral BU (40 mg/m(2)/dose x 8 doses), cyclophosphamide (60 mg/kg/day x 2 doses) and TBI (750 cGy in one fraction) as a preparative regimen. Median (range) oral clearance corrected for bioavailability (Cl/F in ml/min/kg), area under the curve (AUC in ng min/ml) and BU plasma concentration (Cp in ng/ml) with the fourth dose were 5.2 (2.1-11.4), 318 294 (112 893-640 995) and 950 (314-1780), respectively. Children < 3 years of age had lower AUC and Cp but higher Cl/F (P < or = 0.03). BU Cp (P = 0.06) or marrow cell dose (P = 0.32) was not different in Hurler syndrome compared to other IMSD. A median BU Cp of 959 and 831 ng/ml was achieved in children with full and failed early engraftment, respectively. There was no difference in early and late engraftment between children with Hurler and other IMSD. In conclusion, we found no significant association between engraftment, marrow cell dose and BU exposure when combined with CY and TBI in children with IMSD.

Administration, Oral↗
PubMed2001

Changes in essential fatty acid patterns associated with normal liver regeneration and the progression of hepatocyte nodules in rat hepatocarcinogenesis.

Changes in lipid metabolism were monitored in rat hepatocyte nodules at certain time points over 9 months. Tissue obtained from partially hepatectomized rats, collected over a period of 7 days, were included as a control for normal hepatocyte cell proliferation. Two important features regarding the lipid profiles of hepatocyte nodules and normal regenerating liver were the increased concentrations of phosphatidylethanolamine (PE), resulting in a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, and cholesterol. These changes coincided with increased membrane fluidity in the nodules and regenerating liver. With respect to the fatty acid (FA) profiles of the nodules, C18:1omega9 and C18:2omega6 increased in PE and PC whereas C20:4omega6 decreased in PC and increased in PE. C22:5omega6 and C22:6omega3, the end products of the omega6 and omega3 metabolic pathways, respectively, decreased in PC and remained unchanged in PE. The FA levels in PC reflected an impaired delta-6 desaturase enzyme, whereas this effect was masked in PE due to the increased concentration of this phospholipid fraction. In regenerating liver, the FA profiles of PC and PE showed the same pattern as described for the hepatocyte nodules, except for C18:1omega9 which decreased in PC and increased non-significantly in PE. The increased C18:1omega9 level, a FA with anti-oxidative properties, as well as the decreased levels of the long-chain polyunsaturated fatty acids (C20 and C22 carbon chains), have been associated with the decreased lipid peroxidation level in hepatocyte nodules. The resultant decrease in peroxidative metabolites, known to affect apoptosis, could be important in the progression of the nodules into neoplasia. The present results indicate that the altered lipid parameters associated with hepatocyte nodules closely mimics cellular proliferation in regenerating liver and could be responsible for the enhanced proliferation and/or altered growth pattern in these lesions. The altered FA profiles suggest various pathways in which FA could play a role in transmembrane signalling related to the altered cell proliferative and apoptotic pathways. The persistent changes in the hepatocyte nodules suggest that the lipid metabolism escapes the regulatory mechanisms required for normal cellular homeostasis at different levels.

Animals↗
PubMed2001

Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion.

We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides(= Fusarium moniliforme) strain MRC 826 in male BD IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB1 provide information about dose-response effects, relevance of hepatotoxicity during FB1-induced carcinogenesis, and the existence of a no-effect threshold. Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body weight (bw)/day over approximately 2 years produce liver cancer in male BD IX rats. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a cancer initiation/promotion model in rat liver provided important information about the possible mechanisms involved during the initial stages of cancer development by this apparently nongenotoxic mycotoxin. These studies supported the findings of long-term investigations indicating that a cytotoxic/proliferative response is required for cancer induction and that a no-effect threshold exists for cancer induction. The mechanisms proposed for cancer induction are highlighted and include the possible role of oxidative damage during initiation and the disruption of lipid metabolism, integrity of cellular membranes, and altered growth-regulatory responses as important events during promotion.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Attenuation of phosphate starvation responses by phosphite in Arabidopsis.

When inorganic phosphate is limiting, Arabidopsis has the facultative ability to metabolize exogenous nucleic acid substrates, which we utilized previously to identify insensitive phosphate starvation response mutants in a conditional genetic screen. In this study, we examined the effect of the phosphate analog, phosphite (Phi), on molecular and morphological responses to phosphate starvation. Phi significantly inhibited plant growth on phosphate-sufficient (2 mM) and nucleic acid-containing (2 mM phosphorus) media at concentrations higher than 2.5 mM. However, with respect to suppressing typical responses to phosphate limitation, Phi effects were very similar to those of phosphate. Phosphate starvation responses, which we examined and found to be almost identically affected by both anions, included changes in: (a) the root-to-shoot ratio; (b) root hair formation; (c) anthocyanin accumulation; (d) the activities of phosphate starvation-inducible nucleolytic enzymes, including ribonuclease, phosphodiesterase, and acid phosphatase; and (e) steady-state mRNA levels of phosphate starvation-inducible genes. It is important that induction of primary auxin response genes by indole-3-acetic acid in the presence of growth-inhibitory Phi concentrations suggests that Phi selectively inhibits phosphate starvation responses. Thus, the use of Phi may allow further dissection of phosphate signaling by genetic selection for constitutive phosphate starvation response mutants on media containing organophosphates as the only source of phosphorus.

Acid Phosphatase↗