Showing papers by "University of Alabama published in 1996"

A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) with Conventional Therapy for Primary Pulmonary Hypertension

Abstract: Background Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. Methods We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). Results Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P<0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P<0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated pat...

The Length of the Cervix and the Risk of Spontaneous Premature Delivery

Abstract: Background The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. Methods At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. Results We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P Conclusions The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.

The Resource-Advantage Theory of Competition: Dynamics, Path Dependencies, and Evolutionary Dimensions:

Abstract: The authors respond to the thoughtful concerns raised by Dickson (1996) about the issue of path dependencies and the dynamics of resource-advantage (R-A) theory (Hunt and Morgan 1995). Rather than ...

Microbial Reduction of Crystalline Iron(III) Oxides: Influence of Oxide Surface Area and Potential for Cell Growth

Abstract: Quantitative aspects of microbial crystalline iron(III) oxide reduction were examined using a dissimilatory iron(III) oxide-reducing bacterium (Shewanella alga strain BrY). The initial rate and lon...

Decision quality using ranked attribute weights

Abstract: Three published approximation formulae for selecting the best multiattribute alternative based on rank-ordered weights are evaluated. All formulae are surprisingly efficacious in determining the best multiattribute alternative. Rank order centroid ROC weights are more accurate than the other rank-based formulae; furthermore, the ROC formula generalizes to incorporate both other forms of partial information about attribute weights and partial rank order information as well. Because a ROC-based analysis is so straightforward and efficacious, it provides an appropriate implementation tool.

Reward dominance: Associations with anxiety, conduct problems, and psychopathy in children

Abstract: The associations between children's behavior and their performance on a task with a steadily increasing ratio of punished to rewarded responses was investigated in a group of clinic-referred (n= 92) and normal control (n= 40) children between the ages of 6 and 13. Clinic-referred children with an anxiety disorder played significantly fewer trials than clinic-referred children without an anxiety disorder but the response style of the anxious children did not differ from that of a normal control group. Children with severe conduct problems who had no anxiety disorder played more trials than (a) children with severe conduct problems and a comorbid anxiety disorder, (b) nonanxious children with attention-deficit hyperactivity disorder, and (c) children in the normal control group. The strongest evidence for the reward dominant response style was for nonanxious subjects with elevations on a measure of psychopathic features, irrespective of whether they also had conduct problems and irrespective of whether they were clinic-referred.

Organic carbon oxidation and suppression of methane production by microbial Fe(III) oxide reduction in vegetated and unvegetated freshwater wetland sediments

Abstract: High concentrations (20-75 pmol cm-3) of amorphous Fe(III) oxide were observed in unvegetated surface and Juncus eflusus rhizosphere sediments of a freshwater wetland in the southeastern United States. Incubation experiments demonstrated that microbial Fe(III) oxide reduction suppressed sulfate reduction and methanogenesis in surface scdimcnts and mediated 240% of depth-integrated (O-10 cm) unvegetated sediment carbon metabolism, compared to I 10% for sulfate reduction. In situ CO2 and CH, flux measurements verified that nonmethanogenic pathways accounted for - 50% of unvegetated sediment carbon metabolism. Lower (- 1 O-fold) rates of dark/anaerobic CH, flux from experimental vegetated cores relative to unvegetated controls suggested that methanogenesis was inhibited in the Juncus rhizosphere, in which active Fe(III) oxide reduction was indicated by the presence of low but readily detectable levels of dissolved and solid-phase Fe(II). Fe(III) oxide reduction accounted for 65% of total carbon metabolism in rhizosphere sediment incubations, compared to 22% for methanogenesis. In contrast, methanogenesis dominated carbon metabolism (72% of total) in experimental unvegetatcd sediment cores. The high Fe(III) oxide concentrations and reduction rates observed in unvegetated surface and Juncus rhizosphere sediments were perpetuated by rapid Fe(III) regeneration via oxidation of Fe(II) compounds coupled to 0, input from the overlying water and plant roots, respectively. The results indicate that Fe(III) oxide reduction could mediate a considerable amount of organic carbon oxidation and significantly suppress CH, production in freshwater wetlands situated within globally extensive iron-rich tropical and subtropical soil regimes.

The Liberal Peace: Interdependence, Democracy, and International Conflict, 1950-85:

Abstract: The classical liberals believed that democracy and free trade would reduce the incidence of war. Here we conduct new tests of the `democratic peace', incorporating into the analyses of Maoz & Russe...

Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III registry.

Abstract: Objective. —To investigate the natural history and response to treatment of patients with unstable angina or non—Q-wave myocardial infarction (MI). Design. —Inception cohort. Setting. —Patients in general community, primary care, or referral hospitals. Patients. —All patients with an episode of unstable exertional chest pain or chest pain at rest presumed to be ischemic in origin lasting 5 minutes or more but without persisting ST-segment elevation greater than 30 minutes or the development of Q-waves were identified and enumerated in 18 participating hospitals. A subset of enumerated patients was selected to be followed prospectively using specific sampling strategies that would provide adequate numbers of black, women, and elderly (aged ≥75 years) patients for comparison with their respective counterparts. Main Outcome Measures.—The primary analysis compared the incidence of death or Ml at 42 days after entry into the prospective study according to race, sex, and age. Other outcomes considered were recurrent ischemia and the combined outcomes of death, Ml, or recurrent ischemia by 42 days after entry. Results. —A total of 8676 admissions with unstable angina or non—Q-wave Ml were enumerated and, of these, 3318 patients were selected for the prospective study. The direct adjusted mean age of the 3318 patients was 63.8 years. There were 943 blacks and 2375 nonblacks. Compared with nonblacks, blacks were less likely to be treated with intensive anti-ischemic therapy for their qualifying anginal episode and less likely to undergo invasive procedures (risk ratio [RR], 0.65; 95% confidence interval [CI], 0.58 to 0.72;P Conclusions. —Among patients presenting with acute ischemic chest pain without persistent ST-segment elevation, blacks appeared to have less severe coronary disease, received revascularization less frequently, and had less recurrent ischemia compared with nonblacks. Women also were found to have less severe coronary disease and were treated less intensely than men, but experienced similar outcomes. Elderly patients had more severe coronary disease than younger patients on coronary angiography, but were more likely to be treated medically, and they experienced far more adverse outcomes. These data suggest that more aggressive strategies should be directed to those patients with the greatest likelihood of adverse outcomes. (JAMA. 1996;275:1104-1112)

A Quantitative Review of Research on Charismatic Leadership

Abstract: This study used meta-analysis to explore the relationship between charismatic leadership and satisfaction with the leader, perceived leader's effectiveness, and performance. To maintain construct consistency Bass' 1985 conceptualization of charisma was used. Results indicate potential moderating effects for two moderators of research design (objective/subjective performance and percept-percept/multisource study design) and for two theoretically predicted moderators (organizational level of focal leader and organizational context). The results are discussed in relation to implicit leadership theory and cognitive classification theory.

Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats.

Abstract: Genistein, a component of soy, was administered to prepubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 microgram/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c.) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 microgram dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 +/- 0.6 micromol and 102 +/- 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estrus phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17 beta and progesterone concentrations were not significantly altered by the prepubertal genistein treatment. Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.

Nevirapine, Zidovudine, and Didanosine Compared with Zidovudine and Didanosine in Patients with HIV-1 Infection: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Objective : To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design : A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. Patients : 398 adults who had HIV-1 infection, had 350 or fewer CD4 + T lymphocytes/mm 3 , and had had more than 6 months of previous nucleoside therapy. Intervention : 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing ≥60 kg). Measurements : CD4 + T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA ; HIV-1 infectivity titer in peripheral blood mononuclear cells ; serum p24 antigen levels ; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. Results : After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% CI, 7% to 29% ; P = 0.001), a 0.32 log 10 lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (CI, 0.05 to 0.59 log 10 infectious units per million cells ; P = 0.023), and a 0.25 log 10 lower mean plasma HIV-1 RNA level (CI, 0.03 to 0.48 log 10 RNA copies/mL ; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2% ; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [CI, 0.75 to 2.06] ; P > 0.2), although the study had only moderate power to detect a major difference. Conclusions : Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens.

Multiple Roles of Carbonic Anhydrase in Cellular Transport and Metabolism

Abstract: Carbonic anhydrase (CA) is a central enzyme to both transport and metabolic processes at the cellular level. In metabolically active tissue such as muscle, CA in the cytoplasm and on the sarcolemma appears to be important in facilitating CO2 transport out of the cell. Membrane-associated CA, with an extracellular orientation, also appears to be important in acidifying the outer boundary layer through the catalyzed hydration of excreted CO2. This facilitates cellular ammonia transport by providing H+ ions for the protonation of NH3, thus maintaining the trans-membrane NH3 gradient. Mitochondrial CA is known to supply HCO3- for the initial reactions of gluconeogenesis and ureagenesis in mammalian tissues, but systematic comparative studies of CA as a metabolic enzyme are lacking. CA probably evolved as an enzyme of trans-membrane facilitated CO2 transport and took on a secondary metabolic role later in metazoan evolution.

The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1

Abstract: A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodysplastic syndrome and acute myeloid leukemia (AML) was found to rearrange part of the nucleophosmin (NPM) gene on chromosome 5 with sequences from a novel gene on chromosome 3. Chimeric transcripts expressed by these cells contain 5' NPM coding sequences fused in-frame to those of the new gene, which we named myelodysplasia/myeloid leukemia factor 1 (MLF1). RNA-based polymerase chain reaction analysis revealed identical NPM-MLF1 mRNA fusions in each of the three t(3;5)-positive cases of AML examined. The predicted MLF1 amino acid sequence lacked homology to previously characterized proteins and did not contain known functional motifs. Normal MLF1 transcripts were expressed in a variety of tissues, most abundantly in testis, ovary, skeletal muscle, heart, kidney and colon. Anti-MLF1 antibodies detected the wild-type 31 kDa protein in K562 and HEL erythroleukemia cell lines, but not in HL-60, U937 or KG-1 myeloid leukemia lines. By contrast, t(3;5)-positive leukemia cells expressed a 54 kDa NPM-MLF1 protein, but not normal MLF1. Immunostaining experiments indicated that MLF1 is normally located in the cytoplasm, whereas NPM-MLF1 is targeted to the nucleus, with highest levels in the nucleolus. The nuclear/nucleolar localization of NPM-MLF1 mirrors that of NPM, indicating that NPM trafficking signals direct MLF1 to an inappropriate cellular compartment in myeloid leukemia cells.

Carotid Stent-Supported Angioplasty: A Neurovascular Intervention to Prevent Stroke

Abstract: Obstructive carotid artery disease is responsible for 60% of strokes in the United States and is the third major cause of death. Stent-supported carotid artery angioplasty has the potential to prevent stroke in thousands of patients and offers a number of potential advantages over surgical revascularization (carotid endarterectomy). Results of the prospective observational study at the University of Alabama at Birmingham indicate that carotid stent-supported angioplasty is safe and probably effective in reducing stroke in patients with high-risk cerebrovascular disease. Technical success was achieved in 99% of 146 procedures; 210 stents were placed in 152 vessels, with only 1 instance of stent thrombosis. The rate of major in-hospital complications was unexpectedly low-only 1 death and 2 major strokes. Seven patients suffered minor strokes, but only 2 were left with minor weakness. When compared with a projected complication rate of 6% had these patients undergone carotid endarterectomy, stenting resulted in fewer major events. At 6-month follow-up, 69 of 74 patients were evaluated by angiography or ultrasound, which detected 8 cases of stent deformation and a restenosis rate of < 5%. Because of these instances of stent deformation, use of the Palmaz (biliary) stent was discontinued. Although 1 patient had a transient ischemic attack, no strokes occurred during follow-up. To date, carotid stenting is an investigational procedure. Cardiovascular interventionalists, industry, and the FDA are encouraged to validate this approach through clinical testing. However, improvements in technique, devices, and adjunctive therapies are needed before the method can be tested in randomized trials.

Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.

Abstract: We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2-type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2 as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+ CD4- cells revealed that only the latter cell population had consistently elevated IL-6 gene expression, whereas both sorted populations exhibited increased IFN-gamma and IL-10 gene expression. Thus, orally administered recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in both mucosal and systemic tissues. Macrophages producing IL-6 were also evident. Our results are consistent with the suggestion that Ag-specific Th1 cells and their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with IL-6 produced by macrophages provide important signals for the development of mucosal IgA and serum IgG subclass responses in the absence of preferential expression of Th2 cytokines IL-4 and IL-5.

Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats.

Abstract: Curcumin and quercetin were evaluated in rats for their ability to modulate the carcinogenic activity of azoxymethane (AOM) in the colon and 7,12-dimethylbenz[a]anthracene (DMBA) in the mammary gland. In the AOM-induced colon cancer model, male Fischer 344 rats at 8 weeks of age started to receive either curcumin (8 and 16 g/kg) or quercetin (16.8 and 33.6 g/kg) in the diet and 1 week later, were administered AOM (30 mg/kg body wt.) by subcutaneous injection. The animals continued to receive the two agents in the diet until sacrificed 45 weeks later. Curcumin mediated a dose-dependent inhibition of the incidence and multiplicity of adenomas from 47% and 0.58 +/- 0.12 adenomas/rat in the AOM-treated control group to 19% and 0.22 +/- 0.08 and 0.06% and 0.08 +/- 0.06 adenomas/rat for the low and high dose groups, respectively. A low yield of adenocarcinomas (0.06 +/- 0.04 adenocarcinomas/rat) was induced by AOM which was not significantly altered by curcumin. Treatment with quercetin caused a dose-dependent increase in the yield of AOM-induced tumors in the colon from 0.06 +/- 0.04 adenocarcinoma/rat to 0.64 +/- 0.12 and 1.14 +/- 0.17 for the low and high dose groups, respectively. In the DMBA-induced mammary cancer model, curcumin or quercetin was administered at either 10 or 20 g/kg diet, beginning 7 days prior to DMBA and continually throughout the remainder of the experiment. Neither curcumin nor quercetin significantly altered the incidence of animals with tumors or the tumor multiplicity, while the high concentration of both agents significantly increased tumor latency. These results demonstrate different responses to these agents in the two models. While curcumin was highly effective as a chemopreventive agent in the colon model, it was only weakly effective in the mammary model. In contrast, quercetin which was also only weakly effective in the mammary model, caused a dose-dependent enhancement of tumors induced by AOM in the colon model.

A Comparison of Multivariate Control Charts for Individual Observations

Abstract: For multivariate statistical process control with individual observations the usually recommended procedure in the retrospective phase is the Hotelling's T2 control chart. All the observations are pooled to estimate the mean vector and covariance matrix..

Adolescents at Risk

Abstract: Adolescence is a developmental period of rapid physical, psychological, sociocultural, and cognitive changes characterized by efforts to confront and surmount challenges and to establish a sense of identity and autonomy. While many adolescents navigate the sometimes turbulent course from childhood to adulthood to become productive and healthy adults, there is growing concern that far too many others may not achieve their full potential as workers, parents, and individuals. Unfortunately, adolescence is also a period fraught with many threats to the health and well-being of adolescents, many of whom suffer substantial impairment and disability. Much of the adverse health consequences experienced by adolescents are, to a large extent, the result of risk behaviors (Ginzberg, 1991). As such, they are preventable.

Coping strategies predict disability in patients with primary fibromyalgia.

Abstract: We administered the Coping Strategies Questionnaire (CSQ) to 80 patients with fibromyalgia (FM) to determine the relationship between coping strategies and functional disability A principal components factor analysis revealed two dimensions of patients' CSQ responses: Coping Attempts and Catastrophizing Coping Attempts consists of five scales: Reinterpreting Pain, Ignoring Pain Sensations, Diverting Attention, Coping Self-Statements and Increasing Activity Level Catastrophizing is comprised solely of the CSQ Catastrophizing scale Both coping strategy dimensions were significantly related to patients' disability scores on the Sickness Impact Profile even after controlling for demographic and clinical variables as well as neuroticism Coping Attempts was associated with higher levels of Physical (P < 005) and Total Disability (P < 001), and lower levels of Psychosocial Disability (P < 005) Catastrophizing was associated with higher levels of Total Disability (P < 001) These relationships suggest that investigators should attempt to identify Coping Attempts strategies that best reduce patients' psychological distress in the laboratory It then may be possible to teach patients to use these strategies to reduce distress in their home and work environments

Extremal functions for Moser’s inequality

Abstract: Let Q be a bounded smooth domain in RI, and u(x) a C1 function with compact support in Q. Moser's inequality states that there is a constant co, depending only on the dimension n, such that 1 wn1 . n_ j ee n-U dx < co, where IQI is the Lebesgue measure of Q, and Wn-1 the surface area of the unit ball in Rn. We prove in this paper that there are extremal functions for this inequality. In other words, we show that the sup{ j nw U dx: u E WJ' , 11VuH1n < 1} is attained. Earlier results include Carleson-Chang (1986, Q is a ball in any dimension) and Flucher (1992, Q is any domain in 2-dimensions).

Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts

Abstract: Renal glomerular capillary tufts have been believed to arise from angiogenic ingrowth of extrinsic vessels. We found, however, that when embryonic day 12 (E12) mouse kidneys were maintained in culture for 6 days and then grafted into anterior eye chambers of adult transgenic ROSA26 host mice (which carry the beta-galactosidase transgene), glomerular endothelial cells within the grafts were predominantly of intrinsic, kidney origin. To identify potential endothelial precursors, we immunolabled kidneys with antibodies against the vascular endothelial growth factor receptor, flk-1. Numerous discrete cells expressing flk-1 were scattered throughout the nephrogenic mesenchyme of both E12 and newborn kidneys, and with development these cells became concentrated in microvessels, glomerular vascular clefts, and glomerular tufts. In adults, flk-1 was weakly expressed in glomeruli but absent elsewhere. To examine abilities of flk-1-positive cells to establish glomeruli, E12 kidneys were grafted into kidney cortices of adult and newborn ROSA26 hosts. Grafts into adults resulted in few glomeruli containing host-derived endothelium, whereas a majority of glomeruli grafted into newborns contained host cells. Cells of graft origin were found in vessels forming in renal cortices of newborn hosts, but not in adults. Our findings indicate that embryonic kidney cells expressing flk-1 are angioblasts that create microvessels and glomeruli by vasculogenesis.

Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein

Abstract: We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV irradiation or the Fenton reaction system. Under the conditions used we observed that UV light and the Fenton reaction significantly increase 8-OHdG formation in DNA. Co-incubation with genistein inhibits the formation of 8-OHdG induced by either UV light irradiation or the Fenton reaction in a dose-dependent manner. The quenching effect of genistein on 8-OHdG formation induced by UV light is much more potent than that by the Fenton reaction, suggesting that the mechanisms of 8-OHdG formation may differ between the two systems. We further compared the antioxidant activities and quenching effect on 8-OHdG formation of genistein with biochanin A. Genistein potently scavenges both hydrogen peroxide in the medium and superoxide anion generated by xanthine/xanthine oxidase, whereas biochanin A has either a weak or no scavenging effect on these reactive oxygen species. However, both genistein and biochanin A display a similar quenching effect on UV light-induced 8-OHdG formation. These results suggest that the quenching effect of genistein and biochanin A on UV light-induced 8-OHdG formation is different from their ability to scavenge hydrogen peroxide and superoxide anion. The potent inhibition of UV light-induced oxidative DNA damage by genistein suggests its potential anticarcinogenic role in photocarcinogenesis.