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Showing papers by "State University of New York System published in 1996"


Journal ArticleDOI
01 Nov 1996-Icarus
TL;DR: In this article, the authors presented a self-consistent, interactive simulation of the formation of the giant planets, in which for the first time both the gas and planetesimal accretion rates were calculated in a selfconsistent and interactive fashion.

2,931 citations


Journal ArticleDOI
TL;DR: Novel features are a suite of operations relating to the determination, modeling, and correction of the contrast transfer function and the availability of the entire documentation in hypertext format.

2,117 citations


Journal ArticleDOI
TL;DR: It is proposed that after the cationic lipid/DNA complex is internalized into cells by endocytosis it destabilization induces flip-flop of anionic lipids from the cytoplasmic-facing monolayer, which laterally diffuse into the complex and form a charge neutral ion pair with the cationsic lipids.
Abstract: To understand how DNA is released from cationic liposome/DNA complexes in cells, we investigated which biomolecules mediate release of DNA from a complex with cationic liposomes. Release from monovalent[1,2-dioleoyl-3(1)-1(trimethylammonio)propane] or multivalent (dioctadecylamidoglycylspermine) lipids was quantified by an increase of ethidium bromide (EtBr) fluorescence. Plasmid sensitivity to DNAse I degradation was examined using changes in plasmid migration on agarose gel electrophoresis. Physical separation of the DNA from the cationic lipid was confirmed and quantified on sucrose density gradients. Anionic liposomes containing compositions that mimic the cytoplasmic-facing monolayer of the plasma membrane (e.g. phosphatidylserine) rapidly released DNA from the complex. Release occurred near a 1/1 charge ratio (-/+) and was unaffected by ionic strength or ion type. Water soluble molecules with a high negative linear charge density such as dextran sulfate or heparin also released DNA. However, ionic water soluble molecules such as ATP, tRNA, DNA, poly(glutamic acid), spermidine, spermine, or histone did not, even at 100-fold charge excess (-/+). On the basis of these results, we propose that after the cationic lipid/DNA complex is internalized into cells by endocytosis it destabilizes the endosomal membrane. Destabilization induces flip-flop of anionic lipids from the cytoplasmic-facing monolayer, which laterally diffuse into the complex and form a charge neutral ion pair with the cationic lipids. This results in displacement of the DNA from the cationic lipid and release of the DNA into cytoplasm. This mechanism accounts for a variety of observations on cationic lipid/DNA complex-cell interactions.

1,154 citations


Journal ArticleDOI
TL;DR: In this article, a series of gold nanocrystals, passivated by self-assembled monolayers (SAMs) of straight-chain alkylthiolate molecules (RS, R) are described.
Abstract: The creation of perfect nanometer-scale crystallites (nanocrystals), identically replicated in unlimited quantities, in a state that can be manipulated and understood as pure macromolecular substances, is an ultimate challenge of modern materials research with outstanding fundamental and potential technological consequences.[’l We report on the prediction, isolation, and characterization of a series of gold nanocrystals, passivated by self-assembled monolayers (SAMs) of straight-chain alkylthiolate molecules (RS, R

1,097 citations


Journal ArticleDOI
23 Aug 1996-Cell
TL;DR: It is demonstrated that MADR2 is specifically regulated by TGFbeta and not bone morphogenetic proteins, and that mutations acquired in colorectal carcinomas may function to disrupt TGF beta signaling.

866 citations


Journal ArticleDOI
TL;DR: In this article, Fourier analysis of the azimuthal distribution on an event-by-event basis in relatively narrow rapidity windows is proposed to study transverse flow effects in relativistic nuclear collisions.
Abstract: We propose a new method to study transverse flow effects in relativistic nuclear collisions by Fourier analysis of the azimuthal distribution on an event-by-event basis in relatively narrow rapidity windows. The distributions of Fourier coefficients provide direct information on the magnitude and type of flow. Directivity and two dimensional sphericity tensor, widely used to analyze flow, emerge naturally in our approach, since they correspond to the distributions of the first and second harmonic coefficients, respectively. The role of finite particle fluctuations and particle correlations is discussed.

749 citations


Journal ArticleDOI
TL;DR: Although the specific function of the circuits and cellular properties of the thalamic relay for waking behavior is far from clear, two related hypotheses are offered based on recent experimental evidence: one is that theThalamus is not used just to relay peripheral information from, for example, visual, auditory, or cerebellar inputs, but that someThalamic nuclei are arranged instead to relay information from one cortical area to another.
Abstract: The thalamus has long been seen as responsible for relaying information on the way to the cerebral cortex, but it has not been until the last decade or so that the functional nature of this relay has attracted significant attention. Whereas earlier views tended to relegate thalamic function to a simple, machine-like relay process, recent research, reviewed in this article, demonstrates complicated circuitry and a rich array of membrane properties underlying the thalamic relay. It is now clear that the thalamic relay does not have merely a trivial function. Suggestions that the thalamic circuits and cell properties only come into play during certain phases of sleep to effectively disconnect the relay are correct as far as they go, but they are incomplete, because they fail to take into account interesting and variable properties of the relay that, we argue, occur during normal waking behavior. Although the specific function of the circuits and cellular properties of the thalamic relay for waking behavior is far from clear, we offer two related hypotheses based on recent experimental evidence. One is that the thalamus is not used just to relay peripheral information from, for example, visual, auditory, or cerebellar inputs, but that some thalamic nuclei are arranged instead to relay information from one cortical area to another. The second is that the thalamus is not a simple, passive relay of information to cortex but instead is involved in many dynamic processes that significantly alter the nature of the information relayed to cortex.

736 citations


Journal ArticleDOI
27 Dec 1996-Cell
TL;DR: A novel 15-subunit complex with the capacity to remodel the structure of chromatin, termed RSC, has been isolated from S. cerevisiae on the basis of homology to the SWI/SNF complex and is essential for mitotic growth.

710 citations


Journal ArticleDOI
TL;DR: Periodontal diseases are infections, and many forms of the disease are associated with specific pathogenic bacteria which colonize the subgingival area and also invade the periodontal tissue and are virulent organisms.
Abstract: Periodontal diseases are infections, and many forms of the disease are associated with specific pathogenic bacteria which colonize the subgingival area. At least two of these microorganisms, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, also invade the periodontal tissue and are virulent organisms. Initiation and progression of periodontal infections are clearly modified by local and systemic conditions called risk factors. The local factors include pre-existing disease as evidenced by deep probing depths and plaque retention areas associated with defective restorations. Systemic risk factors recently have been identified by large epidemiologic studies using multifactorial statistical analyses to correct for confounding or associated co-risk factors. Risk factors which we know today as important include diabetes mellitus, especially in individuals in whom metabolic control is poor, and cigarette smoking. These two risk factors markedly affect the initiation and progression of periodontitis, and attempts to manage these factors are now an important component of prevention and treatment of adult periodontitis. Systemic conditions associated with reduced neutrophil numbers or function are also important risk factors in children, juveniles, and young adults. Diseases in which neutrophil dysfunction occurs include the lazy leukocyte syndrome associated with localized juvenile periodontitis, cyclic neutropenia, and congenital neutropenia. Recent studies also point to several potentially important periodontal risk indicators. These include stress and coping behaviors, and osteopenia associated with estrogen deficiency. There are also background determinants associated with periodontal disease including gender (with males having more disease), age (with more disease seen in the elderly), and hereditary factors. The study of risk in periodontal disease is a rapidly emerging field and much is yet to be learned. However, there are at least two significant risk factors-smoking and diabetes-which demand attention in current management of periodontal disease. J Periodontol 1996;67:1041-1049.

706 citations


Journal ArticleDOI
01 Feb 1996-Nature
TL;DR: Investigation of 11 kindreds with renal tubular disorders for CLCN5 abnormalities identified three nonsense, four missense and two donor splice site mutations, together with one intragenic deletion and one micro-deletion encompassing the entire gene.
Abstract: Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients and are most commonly associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7). A microdeletion in one Dent's disease kindred allowed the identification of a candidate gene, CLCN5 (refs 8,9) which encodes a putative renal chloride channel. Here we report the investigation of 11 kindreds with these renal tubular disorders for CLCN5 abnormalities; this identified three nonsense, four missense and two donor splice site mutations, together with one intragenic deletion and one microdeletion encompassing the entire gene. Heterologous expression of wild-type CLCN5 in Xenopus oocytes yielded outwardly rectifying chloride currents, which were either abolished or markedly reduced by the mutations. The common aetiology for Dent's disease, XRN and XLRH indicates that CLCN5 may be involved in other renal tubular disorders associated with kidney stones.

687 citations


Journal ArticleDOI
TL;DR: The results support considering severe periodontitis as a risk factor for poor glycemic control and suggest that physicians treating patients with NIDDM should be alert to the signs of severeperiodontitis in managing NID DM.
Abstract: This study tested the hypothesis that severe periodontitis in persons with non-insulin-dependent diabetes mellitus (NIDDM) increases the risk of poor glycemic control. Data from the longitudinal study of residents of the Gila River Indian Community were analyzed for dentate subjects aged 18 to 67, comprising all those: 1) diagnosed at baseline with NIDDM (at least 200 mg/dL plasma glucose after a 2-hour oral glucose tolerance test); 2) with baseline glycosylated hemoglobin (HbA1 ) less than 9%; and 3) who remained dentate during the 2-year follow-up period. Medical and dental examinations were conducted at 2-year intervals. Severe periodontitis was specified two ways for separate analyses: 1) as baseline periodontal attachment loss of 6 mm or more on at least one index tooth; and 2) baseline radiographic bone loss of 50% or more on at least one tooth. Clinical data for loss of periodontal attachment were available for 80 subjects who had at least one follow-up examination, 9 of whom had two follow-up examinations at 2-year intervals after baseline. Radiographic bone loss data were available for 88 subjects who had at least one follow-up examination, 17 of whom had two follow-up examinations. Poor glycemic control was specified as the presence of HbA1 of 9% or more at follow-up. To increase the sample size, observations from baseline to second examination and from second to third examinations were combined. To control for non-independence of observations, generalized estimating equations (GEE) were used for regression modeling. Severe periodontitis at baseline was associated with increased risk of poor glycemic control at follow-up. Other statistically significant covariates in the GEE models were: 1) baseline age; 2) level of glycemic control at baseline; 3) having more severe NIDDM at baseline; 4) duration of NIDDM; and 5) smoking at baseline. These results support considering severe periodontitis as a risk factor for poor glycemic control and suggest that physicians treating patients with NIDDM should be alert to the signs of severe periodontitis in managing NIDDM. J Periodontol 1996;67:1085-1093.

Journal ArticleDOI
TL;DR: It is argued that the two kinds of uncertainty should be propagated through mathematical expressions with different calculation methods, basically, interval analysis should be used to propagate ignorance, and probability theory should beused to propagate variability.

Journal ArticleDOI
TL;DR: In this article, a model of factors thought to affect the treatment of disabled individuals in organizations is presented, which suggests that person characteristics (e.g., attributes of the disabled person, attributes of an observer), environmental factors (i.e., legislation), and organizational characteristics combine to affect how disabled individuals are treated in organizations.
Abstract: A model of factors thought to affect the treatment of disabled individuals in organizations is presented. Specifically, the model suggests that person characteristics (e.g., attributes of the disabled person, attributes of the observer), environmental factors (i.e., legislation), and organizational characteristics (e.g., norms, values, policies, the nature of jobs, reward systems) combine to affect the way disabled individuals are treated in organizations. Furthermore, the model indicates that the relationships just noted are mediated by observers' cognitions (i.e., categorization, stereotyping, expectancies) and affective states. Finally, the model predicts that the disabled person's responses feed back to modify observers' expectancies and organizational characteristics. Implications for conducting research on disability issues and facilitating the inclusion of disabled individuals in organizational settings are discussed.

Proceedings ArticleDOI
01 Aug 1996
TL;DR: The idea of simplification envelopes for generating a hierarchy of level-of-detail approximations for a given polygonal model is proposed and guarantees that all points of an approximation are within a user-specifiable distance from the original model.
Abstract: We propose the idea of simplification envelopes for generating a hierarchy of level-of-detail approximations for a given polygonal model. Our approach guarantees that all points of an approximation are within a user-specifiable distance from the original model and that all points of the original model are within a distance from the approximation. Simplificationenvelopes provide a general framework within which a large collection of existing simplification algorithms can run. We demonstrate this technique in conjunction with two algorithms, one local, the other global. The local algorithm provides a fast method for generating approximations to large input meshes (at least hundreds of thousands of triangles). The global algorithm provides the opportunity to avoid local “minima” and possibly achieve better simplifications as a result. Each approximation attempts to minimize the total number of polygons required to satisfy the above constraint. The key advantages of our approach are: General technique providing guaranteed error bounds for genus-preserving simplification Automation of both the simplification process and the selection of appropriate viewing distances Prevention of self-intersection Preservation of sharp features Allows variation of approximation distance across different portions of a model CR

Journal ArticleDOI
02 Feb 1996-Science
TL;DR: In this article, the protein bovine serum albumin (BSA) with a molecular weight of 67,000 is soluble in a carbon dioxide-continuous phase with a nontoxic ammonium carboxylate perfluoropolyether surfactant.
Abstract: Carbon dioxide in the liquid and supercritical fluid states is useful as a replacement for toxic organic solvents. However, nonvolatile hydrophilic substances such as proteins, ions, and most catalysts are insoluble. This limitation was overcome by the formation of aqueous microemulsion droplets in a carbon dioxide-continuous phase with a nontoxic ammonium carboxylate perfluoropolyether surfactant. Several spectroscopic techniques consistently indicated that the properties of the droplets approach those of bulk water. The protein bovine serum albumin (BSA) with a molecular weight of 67,000 is soluble in this microemulsion and experiences an environment similar to that of native BSA in buffer.

Journal ArticleDOI
TL;DR: A yeast genetic method to detect and analyze RNA-protein interactions in which the binding of a bifunctional RNA to each of two hybrid proteins activates transcription of a reporter gene in vivo, which enables the rapid, phenotypic detection of specific RNA- protein interactions.
Abstract: RNA-protein interactions are pivotal in fundamental cellular processes such as translation, mRNA processing, early development, and infection by RNA viruses. However, in spite of the central importance of these interactions, few approaches are available to analyze them rapidly in vivo. We describe a yeast genetic method to detect and analyze RNA-protein interactions in which the binding of a bifunctional RNA to each of two hybrid proteins activates transcription of a reporter gene in vivo. We demonstrate that this three-hybrid system enables the rapid, phenotypic detection of specific RNA-protein interactions. As examples, we use the binding of the iron regulatory protein 1 (IRP1) to the iron response element (IRE), and of HIV trans-activator protein (Tat) to the HIV trans-activation response element (TAR) RNA sequence. The three-hybrid assay we describe relies only on the physical properties of the RNA and protein, and not on their natural biological activities; as a result, it may have broad application in the identification of RNA-binding proteins and RNAs, as well as in the detailed analysis of their interactions.

Journal ArticleDOI
TL;DR: It is suggested that cap- and IRES-dependent initiation mechanisms utilize different modes of interaction with this factor to promote ribosomal attachment to mRNA.
Abstract: Translation of picornavirus RNA is initiated after ribosomal binding to an internal ribosomal entry site (IRES) within the 5' untranslated region. We have reconstituted IRES-mediated initiation on encephalomyocarditis virus RNA from purified components and used primer extension analysis to confirm the fidelity of 48S preinitiation complex formation. Eukaryotic initiation factor 2 (eIF2), eIF3, and eIF4F were required for initiation; eIF4B and to a lesser extent the pyrimidine tract-binding protein stimulated this process. We show that eIF4F binds to the IRES in a novel cap-independent manner and suggest that cap- and IRES-dependent initiation mechanisms utilize different modes of interaction with this factor to promote ribosomal attachment to mRNA.

Journal ArticleDOI
TL;DR: The authors take a semiglobal approach to solve some of the central control problems for linear systems with saturating actuators, including stabilization, input-additive disturbance rejection, and robust stabilization in the presence of matched nonlinear uncertainties.
Abstract: This paper deals with the design of linear systems with saturating actuators where the actuator limitations have to be incorporated a priori into control design. The authors take a semiglobal approach to solve some of the central control problems for such systems. These problems include stabilization, input-additive disturbance rejection, and robust stabilization in the presence of matched nonlinear uncertainties. The authors develop further the semiglobal design technology which was initiated in their earlier work (Lin and Saberi, 1995) and utilize it to deal with these control problems.

Journal ArticleDOI
TL;DR: This new method has shown that Streptococcus thermophilus B and Leuconostoc mesenteroides NCDO 523 (LM 523) display maximal affinity for an acidic solvent and a low affinity for basic solvents, which demonstrate that both bacteria are strong electron donors and very weak electron acceptors.

Book ChapterDOI
01 Jan 1996-Memory
TL;DR: This chapter illustrates how forgetting might be linked to inhibitory processes underlying selective attention, according to a new perspective that builds upon insights from modern work, while validating intuitions underlying several of the classical interference mechanisms.
Abstract: Publisher Summary This chapter discusses the causes of memory interference and the extent of situations in which these mechanisms operate. First, the chapter discusses some widely held assumptions about the situation of interference, focusing on the idea that such effects arise from competition for access via a shared retrieval cue. This notion is sufficiently general that it may be applied in a variety of interference settings, which is illustrated briefly. Then the classical interference paradigms from which these ideas emerged are reviewed. The chapter also reviews more recent phenomena that both support and challenge classical conceptions of interference. These phenomena provide compelling illustrations of the generality of interference and, consequently, of the importance of understanding its mechanisms. A recent perspective on interference is highlighted that builds upon insights from modern work, while validating intuitions underlying several of the classical interference mechanisms. According to this new perspective, forgetting derives not from acquiring new memories per se, but from the impact of later retrievals of the newly learned material. After discussing findings from several paradigms that support this retrieval-based view, the chapter illustrates how forgetting might be linked to inhibitory processes underlying selective attention.

Journal ArticleDOI
TL;DR: Electron beam computed tomographic calcium scores correlate moderately well with angiographic findings and predict coronary heart disease-related events in patients undergoing angiography as well as do the number of angiographically affected arteries.

Journal ArticleDOI
TL;DR: High-resolution tridimensional isochronal mapping of both activation and repolarization patterns in puppies exposed to AP-A that developed LQTS and polymorphic ventricular tachyarrhythmias (VTs) shows that the initial beat of polymorphic VT consistently arose as focal activity from a subend cardiac site, whereas subsequent beats were due to successive subendocardial focal activity, reentrant excitation, or a combination of both.
Abstract: We have previously developed a canine in vivo model of the long QT syndrome (LQTS) using the neurotoxin anthopleurin A (AP-A), which acts by slowing sodium channel inactivation. The recent discovery of a genetic mutation in the cardiac sodium channel in some patients with the congenital LQTS, resulting in abnormal gating behavior similar to sodium channels exposed to AP-A, provides a strong endorsement of this animal model as a valid surrogate to the clinical syndrome of LQTS. In the present study, we conducted high-resolution tridimensional isochronal mapping of both activation and repolarization patterns in puppies exposed to AP-A that developed LQTS and polymorphic ventricular tachyarrhythmias (VTs). To map repolarization, we measured activation-recovery intervals (ARIs) using multiple unipolar extracellular electrograms. We demonstrated, for the first time in vivo, the existence of spatial dispersion of repolarization in the ventricular wall and differences in regional recovery in response to cycle-length changes that were markedly exaggerated after AP-A administration. Analysis of tridimensional activation patterns showed that the initial beat of polymorphic VT consistently arose as focal activity from a subendocardial site, whereas subsequent beats were due to successive subendocardial focal activity, reentrant excitation, or a combination of both mechanisms. Reentrant excitation was due to infringement of a focal activity on the spatial dispersion of repolarization, resulting in functional conduction block and circulating wave fronts. The polymorphic QRS configuration of VT in the LQTS was due to either changing the site of origin of focal activity, resulting in varying activation patterns, or varying orientations of circulating wave fronts.

Journal ArticleDOI
TL;DR: New mixed 0 1 linear formulations with tight linear programming relaxations are developed with a potential impact in a number of other problem settings, where efficient heuristic solutions exist and are probably, but not provably optimal.

Journal ArticleDOI
TL;DR: In this article, the Lebesgue spaces L p. Modes of Convergence and Integrable Functions are discussed. But they do not consider the nonmeasurable and non-borel sets.
Abstract: THE ELEMENTS OF INTEGRATION. Measurable Functions. Measures. The Integral. Integrable Functions. The Lebesgue Spaces L p . Modes of Convergence. Decomposition of Measures. Generation of Measures. Product Measures. THE ELEMENTS OF LEBESGUE MEASURE. Volumes of Cells and Intervals. The Outer Measure. Measurable Sets. Examples of Measurable Sets. Approximation of Measurable Sets. Additivity and Nonadditivity. Nonmeasurable and Non--Borel Sets. References. Index.

Journal ArticleDOI
01 Apr 1996-Neuron
TL;DR: Results indicate that while some cytoplasmic K+ channel beta subunits affect the inactivation kinetics of alpha subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+Channel complexes.

Journal ArticleDOI
TL;DR: A functional analysis of eIF4F is presented which defines the subunits and subunit domains necessary for its function in initiation mediated by the prototypical IRES element of encephalomyocarditis virus.
Abstract: Eukaryotic translation is initiated following binding of ribosomes either to the capped 5' end of an mRNA or to an internal ribosomal entry site (IRES) within its 5' nontranslated region. These processes are both mediated by eukaryotic initiation factor 4F (eIF4F), which consists of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G subunits. Here we present a functional analysis of eIF4F which defines the subunits and subunit domains necessary for its function in initiation mediated by the prototypical IRES element of encephalomyocarditis virus. In an initiation reaction reconstituted in vitro from purified translation components and lacking eIF4A and -4F, IRES-mediated initiation did not require the cap-binding protein eIF4E but was absolutely dependent on eIF4A and the central third of eIF4G. This central domain of eIF4G bound strongly and specifically to a structural element within the encephalomyocarditis virus IRES upstream of the initiation codon in an ATP-independent manner and with the same specificity as eIF4F. The carboxy-terminal third of eIF4G did not bind to the IRES. The central domain of eIF4G was itself UV cross-linked to the IRES and strongly stimulated UV cross-linking of eIF4A to the IRES in conjunction with either eIF4B or with the carboxy-terminal third of eIF4G.

Proceedings ArticleDOI
27 Oct 1996
TL;DR: An algorithm for performing view-dependent simplifications of a triangulated polygonal model in real-time, which is more effective than the current level-of-detail-based rendering approaches for most scientific visualization applications where there are a limited number of highly complex objects that stay relatively close to the viewer.
Abstract: Presents an algorithm for performing view-dependent simplifications of a triangulated polygonal model in real-time. The simplifications are dependent on viewing direction, lighting and visibility, and are performed by taking advantage of image-space, object-space and frame-to-frame coherences. A continuous level-of-detail representation for an object is first constructed off-line. This representation is then used at run-time to guide the selection of appropriate triangles for display. The list of displayed triangles is updated incrementally from one frame to the next. Our approach is more effective than the current level-of-detail-based rendering approaches for most scientific visualization applications where there are a limited number of highly complex objects that stay relatively close to the viewer.

Journal ArticleDOI
TL;DR: The data provide direct evidence for the cytotoxic effects of NO produced via iNOS in the course of ischemic acute renal failure, and offer a novel method to selectively prevent the induction of this enzyme.
Abstract: Gene products of all three distinct nitric oxide synthases are present in the mammalian kidney. This mosaic topography of nitric oxide synthase (NOS) isoforms probably reflects distinct functional role played by each enzyme. While nitric oxide (NO) is cytotoxic to isolated renal tubules, inhibition of NO production in vivo invariably results in the aggravation of renal dysfunction in various models of acute renal failure. We reasoned that the existing ambiguity on the role of nitric oxide in acute renal failure is in part due to the lack of selective NOS inhibitors. Phosphorothioated derivatives of antisense oligodeoxynucleotides targeting a conserved sequence within the open reading frame of the cDNA encoding the inducible NOS (iNOS) were designed to produce a selective knock-down of this enzyme. In vivo use of these antisense constructs attenuated acute renal failure in rats subjected to renal ischemia. This effect was due, at least in part, to the rescue of tubular epithelium from lethal injury. Application of antisense constructs did not affect endothelial NOS, as evidenced by a spared NO release after the infusion of bradykinin during in vivo monitoring with an NO-selective microelectrode. In conclusion, the data provide direct evidence for the cytotoxic effects of NO produced via iNOS in the course of ischemic acute renal failure, and offer a novel method to selectively prevent the induction of this enzyme.

Journal ArticleDOI
TL;DR: Interestingly, the severity of the mutant phenotype correlates with biochemical measures of loss of function of the receptor tyrosine kinase, suggesting a conserved function for this growth factor family in the regulation of growth and body size.
Abstract: Drosophila contain an insulin receptor homologue, encoded by the inr gene located at position 93E4-5 on the third chromosome. The receptor protein is strikingly homologous to the human receptor, exhibiting the same alpha2beta2 subunit structure and containing a ligand- activated tyrosine kinase in its cytoplasmic domain. Chemical mutagenesis was used to induce mutations in the inr gene and six independent mutations that lead to a loss of expression or function of the receptor protein were identified. These mutations are recessive, embryonic, or early larval lethals, but some alleles exhibit heteroallelic complementation to yield adults with a severe developmental delay (10 days), growth-deficiency, female-sterile phenotype. Interestingly, the severity of the mutant phenotype correlates with biochemical measures of loss of function of the receptor tyrosine kinase. The growth deficiency appears to be due to a reduction in cell number, suggesting a role for inr in regulation of cell proliferation during development. The phenotype is reminiscent of those seen in syndromes of insulin-resistance or IGF-I and IGF-I receptor deficiencies in higher organisms, suggesting a conserved function for this growth factor family in the regulation of growth and body size.

Journal ArticleDOI
TL;DR: In this population, intake of vegetables appears to decrease premenopausal breast cancer risk, and this effect may be related to beta-carotene and lutein + zeaxanthin in vegetables.
Abstract: Background: Given the international variations in breast cancer incidence rates and the changes in breast cancer incidence among migrant populations, it has been hypothesized that diet is a factor influencing risk of this disease. Many studies indicate that a diet high in vegetables and fruits may protect against breast cancer. Purpose: We conducted a case-control study of diet, including the intake of non-food supplements, and premenopausal breast cancer risk. We evaluated in detail usual intake of vegetables and fruits (each measured as the total reported grams consumed for all queried vegetables and fruit), vitamins C and E, folic acid, individual carotenoids, and dietary fiber with its components. Methods: Case patients (n = 297) were identified through pathology records from hospitals in Erie and Niagara counties in western New York. They consisted of premenopausal women 40 years of age or older who were diagnosed with breast cancer from November 1986 through April 1991. Control subjects (n = 311), frequency-matched to case patients on the basis of age and county of residence, were randomly selected from New York State Department of Motor Vehicles records. In-person interviews included detailed reports of usual diet in the period 2 years before the interview. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: There was a reduction in risk associated with high intake of several nutrients. With the lowest quartile of intake as the referent, adjusted ORs for the highest quartile of intake for specific nutrients were as follows: vitamin C (OR = 0.53; 95% CI = 0.33-0.86), a-tocopherol (OR = 0.55; 95% CI = 0.34-0.88), folic acid (OR = 0.50; 95% CI = 0.310.82), a-carotene (OR = 0.67; 95% CI = 0.42-1.08) and Pcarotene (OR = 0.46; 95% CI = 0.28-0.74), lutein + zeaxanthin (OR = 0.47; 95% CI = 0.28-0.77), and dietary fiber from vegetables and fruits (OR = 0.48; 95% CI = 0.300.78). No association with risk was found for p-cryptoxanthin, lycopene, or grain fiber. Fruits were weakly associated with a reduction in risk (fourth quartile OR = 0.67; 95% CI = 0.42-1.09). No association was found between breast cancer risk and intake of vitamins C and E and folic acid taken as supplements. A strong inverse association between total vegetable intake and risk was observed (fourth quartile OR = 0.46; 95% CI = 0.28-0.74). This inverse association was found to be independent of vitamin C, a-tocopherol, folic acid, dietary fiber, and a-carotene. Adjusting for P-carotene or lutein + zeaxanthin somewhat attenuated the inverse association with vegetable intake. Conclusions: In this population, intake of vegetables appears to decrease premenopausal breast cancer risk. This effect may be related, in part, to P-carotene and lutein + zeaxanthin in vegetables. It appears, however, that, of the nutrients and food components examined, no single dietary factor explains the effect. Evaluated components found together in vegetables may have a synergistic effect on breast cancer risk; alternatively, other unmeasured factors in these foods may also influence risk. [J Natl Cancer Inst 1996;88:340-8] Given the international variation in breast cancer incidence rates and the changes in incidence among migrant populations (/), it has been hypothesized that diet is a factor influencing risk of this disease. There has been considerable attention paid to the hypothesis that fat intake is related to increased risk of breast cancer (2). While less research has focused on other dietary constituents, a number of studies (3-9) would appear to indicate that a diet high in vegetables and fruits may protect against breast cancer. While a few studies (10-12) have failed to find a relation, the finding of a protective effect of fruits and vegetables is relatively consistent and, therefore, provocative in terms of breast cancer prevention. The role of vegetables, fruits, and the nutrients and other dietary components found in these foods re