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  • 1
    ISSN: 1573-7217
    Keywords: HER-2/neu ; c-erbB-2 ; chemotherapy ; tamoxifen ; drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amplification of the HER-2/neu (c-erbB-2) gene resulting in overexpression of the p185HER-2 growth factor receptor occurs in ~25% of early stage breast cancers. HER- 2/neu has been established as an important independent prognostic factor in early stage breast cancer in large cohorts of patients and in cohorts with very long (30 year) follow-up duration. New data are emerging to suggest that HER-2/neu may be useful not only as a prognostic factor but also as a predictive marker for projecting response to chemotherapeutics, antiestrogens, and therapeutic anti-HER- 2/neu monoclonal antibodies. In this review we highlight recent data on HER-2/neu as a predictive marker of response to breast cancer therapy and discuss the clinical implications of this information. The difficulty in comparing results from different data sets due to the wide variety of reagents and technologies used to detect HER-2/neu amplification/overexpression in clinical specimens is also discussed. Finally, we report results from experimental models of HER-2/neu overexpression which have been used in an effort to understand the relationship between HER- 2/neu and response to chemotherapeutics and antiestrogens in breast cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of software engineering 6 (1998), S. 131-144 
    ISSN: 1573-7489
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Software engineering is entering the educational mainstream at a time when budgets are tight, growth opportunities are limited, and existing disciplines are fighting to retain their share of a shrinking educational pie. This paper discusses some of the fundamental reasons why this situation is not likely to improve, and addresses ways software engineering can utilize modern computing and communication technology to overcome these limitations and, indeed, to lead the way in innovative education.
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  • 3
    ISSN: 1573-904X
    Keywords: drug delivery ; diabetes mellitus ; excipient ; insulin ; eye ; nose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 180 (1998), S. 33-41 
    ISSN: 1573-4919
    Keywords: mitochondrial metabolism ; long chain fatty acids ; acyl carnitine derivitives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The results of clinical and animal studies suggest that a short term period of moderate secondary carnitine deficiency, in and of itself, does not have a major effect on the cardiac contractile function, although substrate oxidation may be altered. However, with longer durations of carnitine deficiency, alterations occur within the heart that may result in impaired contractile performance, particularly at high workloads. At this point, the mechanisms responsible for the cardiac depression are uncertain. We hypothesize that the alterations in substrate metabolism produced by the carnitine deficient state results in inadequate ATP production under high workload conditions which result in impaired cardiac contractile performance. Carnitine deficiency may also induce a number of changes in gene expression of key enzymes required for normal cardiac contractile function and metabolism.
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  • 5
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Citrullinaemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthase. The deficiency of this enzyme results in an interruption in the urea cycle and the inability to dispose of excess ammonia derived from the metabolism of protein. The only treatment for this disorder has been dietary restriction of protein and supplementation with medications allowing for alternative excretion of excess nitrogen. Gene therapy offers the possibility of a long-term cure for disorders like citrullinaemia by expressing the deficient gene in the target organ. We have explored the use of adenoviral vectors as a treatment modality for citrullinaemia in two animal models, a naturally occurring bovine model and a murine model created by molecular mutagenesis. Mice treated with adenoviral vectors expressing argininosuccinate synthase lived significantly longer than untreated animals (11 days vs 1 day); however, the animals did not exhibit normal weight gain during the experiment, indicating that the therapeutic effectiveness of the transducing virus was suboptimal. It is speculated that part of the failure to observe better clinical outcome might be due to the deficiency of arginine. In the bovine model, the use of adenoviral vectors did not result in any change in the clinical condition of the animals or in the level of plasma ammonia. However, the use of 15N isotopic ammonia allowed us to assess the flux of nitrogen through the urea cycle during the experiment. These studies revealed a significant increase in the flux through the urea cycle following administration of adenoviral vectors expressing argininosuccinate synthase. We conclude that the use of adenoviral vectors in the treatment of citrullinaemia is a viable approach to therapy but that it will be necessary to increase the level of transduction and to increase the level of enzyme produced from the recombinant viral vector. Future experiments will be designed to address these issues.
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  • 6
    ISSN: 1436-5081
    Keywords: 53A35 ; 57M50 ; 11J06 ; geodesic ; punctured torus ; Markoff spectrum, diophantine approximation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We classify the free homotopy classes of closed curves with minimal self intersection number two on a once punctured torus,T, up to homeomorphism. Of these, there are six primitive classes and two imprimitive. The classification leads to the topological result that, up to homeomorphism, there is a unique curve in each class realizing the minimum self intersection number. The classification yields a complete classification of geodesics on hyperbolicT which have self intersection number two. We also derive new results on the Markoff spectrum of diophantine approximation; in particular, exactly three of the imprimitive classes correspond to families of Markoff values below Hall's ray.
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  • 7
    ISSN: 1573-5176
    Keywords: alginate ; pilot plant process ; pre-extraction ; Macrocystis pyrifera ; acid treatment ; formalin treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In the extraction of alginate from brown seaweeds, the acid pre-extraction treatment has been considered by many authors as an essential step because it makes the alginate more readily soluble in an alkaline solution. At pilot plant level, extractions were made (i) using formalin treatment prior to the acid pre-extraction treatment (ii) using different acid treatments so the calcium ions exchanged varied from 83% to 4%. The use of formalin treatment gave a product with less color. During the acid pre-extraction treatment, it was possible to reduce the calcium exchanged from 33.4% to almost zero with a maximum reduction in alginate yield of 7%. The degree of acid treatment was positively correlated to calcium exchanged and yield but negatively correlated with alginate viscosity. Using strong acid conditions the viscosity was 168 mPa s, while mild acid conditions produced an alginate with 623 mPa s. The direct extraction from calcium alginate to sodium alginate is possible because strong alkaline conditions were used, pH 10 at 80 °C for two hours and with a low water volume. The best pre-extraction treatment to obtain an alginate with high viscoity is to hydrate the alga with 0.1% formalin overnight, then wash the alga once with hydrochloric acid at pH 4 using a batch system with continuous agitation during 15 min.
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  • 8
    ISSN: 0173-0835
    Keywords: Capillary electrophoresis ; DNA ; Mitochondrial DNA ; Forensic DNA typing ; Polymerase chain reaction analysis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: The polymorphic control region of mitochondrial DNA (mtDNA) is becoming more commonly used in forensic applications to differentiate among individuals in a population. Two hypervariable regions (HV1 and HV2) are often sequenced following amplification of the mtDNA via the polymerase chain reaction (PCR). More rapid screening assays would reduce both the effort and the expenses of comparing two samples. A methodology has been developed that first uses restriction endonuclease digestion of the PCR-amplified mtDNA using RsaI and Mn/I and then capillary electrophoresis (CE) to separate and size the PCR-RFLP fragments. This rapid procedure offers an alternative method for screening of polymorphisms in amplified mtDNA samples. In addition, the presence of a T→C transition at position 16189, which gives rise to the so-called “C-stretch” in HV1, may be predicted from the presence of nonspecific PCR products in the CE results.
    Additional Material: 4 Ill.
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  • 9
    ISSN: 0173-0835
    Keywords: Trypanosoma brucei ; Free-flow electrophoresis ; Endosomes ; Lysosomes ; Transferrin ; Percoll ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: In this paper we demonstrate the power of preparative free-flow electrophoresis (FFE) for the study of endocytosis by African trypanosomes. Endocytosis of extracellular macromolecules by these parasites occurs through a specialized region of the parasite called the flagella pocket. The uptake of fluid phase markers such as horseradish peroxidase (HRP) into the various compartments of the endocytic pathway of bloodstream forms of Trypanosoma brucei brucei was manipulated by regulating the external environment (e.g., by altering the temperature of incubation). The various subcellular compartments were then separated by free-flow electrophoresis (FFE) or isopycnic density gradient centrifugation and analyzed for marker uptake. At low temperatures, HRP was found predominantly in the flagellar pocket. Increasing the temperature resulted in a time-dependent uptake of HRP into more positively charged endosomal fractions. However, little HRP activity was detected in lysosomal compartments, suggesting that either HRP had not yet entered the lysosome or was degraded immediately upon entry. Through the use of FFE we were able to identify and analyze compartments of the endosomal pathway that were not possible to identify by density gradient centrifugation alone. Although the differences in FFE separation of the endocytic compartments as seen in HRP uptake were striking, the minor changes seen within the lysosomal system were more subtle, as depicted in the protease profiles. In conlusion, we show that preparative FFE is a powerful technique for the analysis and separation of flagellar pocket-derived membranes from other endosomal and lysosomal compartments of African trypanosomes.
    Additional Material: 7 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 109 (1998), S. 9300-9305 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Monoiodogermylene has been detected for the first time using pulsed discharge and laserinduced fluorescence techniques. HGeI and DGeI were produced by an electric discharge through argon seeded with H3GeI or D3GeI. Although the vibronic structure in the spectra was very limited, all three excited state vibrational frequencies have been obtained for both isotopomers. Analysis of the partially resolved rotational structure of the 000 bands gave the following approximate r0 structures, with the bond angles constrained to previous ab initio values: r0″(Ge–I)=2.525(10) Å, r0″(H–Ge)=1.593(15) Å, θ0″(HGeI)=93.5°, r0′(Ge–I)=2.515(10) Å, r0′(H–Ge)=1.618(15) Å, and θ0′(HGeI)=116.2°. The fluorescence lifetime of monoiodogermylene in the lowest rovibronic levels is 1.515±0.004 μs and shows significant variations on deuteration and with rotational and vibrational level. © 1998 American Institute of Physics.
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