Rapid characterization of mutagenic aromatic amines in energy-related materials by short column liquid chromatography with electrochemical detection

A liquid Chromatograph equipped with a short (3 cm) reverse phase column and electrochemical detector was used to characterize aromatic amines in shale oil, synthetic oil, and coal gasification streams. Five major peaks were produced from each sample mixture. The composition of the peaks was determined by high performance liquid chromatography with a long (25 cm) reverse phase column and by gas chromatography/mass spectrometry. Amines in the various peaks included aminonaphthalenes, aminobiphenyls, aminofluorenes, and aminophenanthrenes plus aminoanthracenes. The concentration of aminofluorenes, and aminophenanthrenes plus aminoanthracenes correlated with relative mutagenicity of the base fraction from the oils or tars. The levels of 2- and 3-ringed aromatic amines from shale oil and oil from the Great Plains commercial coal gasification plan were 24 and 184 g/g tar, respectively, while the respective mutagenicities were 8 and 214 revertants/g base fraction. This technique has the advantages of high sensitivity and rapid analysis, and could be used to screen for the presence of mutagens in synthetic fuel samples.     

Immunohistochemical Localization of Neuropeptide Y in Nerves of the Male Genital Tract of the Photoperiodically Responsive Djungarian Hamster, Phodopus Sungoras/Immunhistochemische Lokalisation von Neuropeptid Y in Nerven der männlichen Genitalorgane des photoperiodisch sensiblen Djungarischen Zwerghamsters, Phodopus sungorus

Neuropeptide Y (NPY) was demonstrated by immunohistochemistry in nerves of the male genital tract of Phodopus sungorus at long (LD 16:8) und short (LD 8:16) photoperiods. No immunoreactive nerve fibres could be demonstrated in the testis, caput and corpus epididymidis and the ventral prostate gland. Dense networks of NPY-containing nerve fibers were demonstrated in the smooth muscle layer of the sperm-transporting duct, beginning in the cauda epididymidis with increasing density towards the distal part of the ductus deferens, and in the smooth muscle layer of the seminal vesicles. At short photoperiods, the density of the NPY-containing nerve plexus decreased only in the smooth muscle layer of the ductus deferens. A "trophic" influence of the large smooth muscle cells of the ductus deferens on their nerves not only in regard to their noradrenaline, but also on their NPY content is discussed.     

Ureteral stents — materials and new forms

Summary Three different types of polymers are currently used for self-retained ureteral stents: thermoplastic materials such as polyurethanes, and thermoset elastomers such as silicone and hydrogels. Polyurethane stents are easy to form and have high drainage capacity, whereas silicone shows the best biocompatibility but a lower drainage efficacy than the former. A mock urinary system consisting of a collecting system and a 9-F tube was used to evaluate the flow characteristics of various double-pigtail stents in cases of urinary obstruction. For simulation of an unobstructed urinary system a human urogenital system was used. Inner flow polyurethane stents showed the best drainage as compared with inner flow silicone and outer flow ESWL stents in an obstructed ureter, whereas ESWL stents maintained the best flow in an unobstructed ureter or in respect to conventional stents with obstructed sideports.     

Effect of dipyridamole on fluorodeoxyuridine cytotoxicity in vitro and in cancer patients

Summary Dipyridamole (DP) has previously been studied both in vitro and in vivo in combination with various antimetabolites, including methotrexate and 5-fluorouracil (5FU). We evaluated in vitro and clinically the effects of adding DP to fluorodeoxyuridine (FUDR) in colorectal cancer. Using a human colony-forming assay, we observed that 0.05 M DP increased the cytotoxicity of FUDR by a median of 33.5-fold vs 1.5-fold for 5FU against human colon-cancer cell lines. The mechanism of the DP-enhanced antitumor activity of FUDR is not completely understood but appears to be related to a profound inhibition by DP of thymidine accumulation in and FUDR efflux from colon-cancer cell lines. On the basis of these in vitro results, 28 patients with metastatic colon cancer were entered in a clinical trial of monthly courses of 0.1 mg/kg FUDR daily for 14 days and 75 mg oral DP 5 times daily for 14 days starting on the 3rd day of continuous i.v. FUDR infusion. The pharmacokinetics of DP was studied in three patients; the results showed that 98% of total serum DP was protein-bound and that free DP levels were significantly lower than the concentrations necessary for the expected in vitro DP/FUDR modulation. Treatment was well tolerated, with only 12 patients developing mild to moderate toxicity. Of 27 evaluable patients, 4 achieved a partial response that lasted 2, 3, 5, and 6+ months. This relatively low response rate (15%), which is similar to that achieved with FUDR alone, may be explained by the low steady-state plasma concentrations of free DP achieved in our patients. Other means of DP administration, such as i.v., i.a., and i.p. injection, may be required to achieve free DP concentrations necessary for successful biochemical modulation of FUDR in patients.Supported in part by grants CA17094, CA23074, and CA39629 from the National Institutes of Health, Bethesda, Md 20205, and a grant from the Arizona Chronic Disease Commission. HSG is a recipient of an American Cancer Society Career Development Award     

Detailed gene copy number and RNA expression analysis of the 17q12-23 region in primary breast cancers

Chromosome region 17q12-23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high-resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12-23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12-23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high-resolution analysis of the 17q12-23 region indicates that several established and novel candidate oncogenes, including a Wnt-signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease.     

Activation of influenza A viruses by trypsin treatment.

A comparative analysis has been carried out on the infectivity of virus of several influenza A strains grown in different host systems. Strains A/swine/Shope/31 (Hsw1N1), A/PR/8/34 (HON1), A/FM/1 (H1N1), A/Singapore/1/57 (H2N2), A/equine/Miami/1/63 (Heq2Neq2), and A/chick/Germany/49 (Hav2Neq1) exhibit host-dependent differences in infectivity. Virions grown in embryonated eggs and cultures of chorioallantoic membrane cells are highly infectious, whereas virions grown in cultures of chick embryo cells have a low infectivity that significantly increases after treatment in vitro with trypsin. In contrast, fowl plague viruses do not show host-dependent variations in infectivity. Virions grown in all host systems tested are highly infectious, and the infectivity of virions grown in chick embryo cells cannot be enhanced by trypsin treatment.The activation of virus particles appears to be based on the cleavage of hemagglutinin glycoprotein HA. This concept is supported by the following observations: (i) In virions of low infectivity only uncleaved glycoprotein HA can be detected. Virions of high infectivity exhibit complete or at least partial cleavage of the hemagglutinin. (ii) The activation of virions by trypsin treatment is always paralleled by cleavage of HA. (iii) Cleavage of HA is the only effect which can be detected after trypsin treatment. The neuraminidase is neither inactivated nor removed from the virion. (iv) Studies on recombinants of virus N and fowl plague virus (Rostock) show that host-dependent variation of infectivity and activation by trypsin, features specific for parent virus N, are found only with recombinant N(H)-FPV/Ro(N) but not with recombinant FPV/Ro(H)-N(N).Efficient plaque formation and serial passages are possible only if highly infectious particles are formed in a given host system. Thus, all strains analyzed undergo, in the absence of trypsin, successive growth cycles in eggs and chorioallantoic membrane cells and form plaques in chorioallantoic membrane cells. In contrast, in chick embryo cells only viruses containing the fowl plague virus hemagglutinin produce plaques and replicate under multiple cycle conditions without the addition of trypsin.The data show that cleavage of HA is not a precondition for virus assembly and hemagglutinating activity, but that it is necessary for infectivity. These findings are compatible with the hypothesis that, in addition to its role in adsorption, the hemagglutinin has another function in the infection process and cleavage is required for this function.     

Role of RNA and protein in memory storage: A review

The literature on the possible role of RNA and protein in long-term memory is reviewed in terms of the following five criteria: (1) The molecule should have a defined role in normal brain function. (2) There should be a quantitative and/or qualitative change in the molecule as a function of learning. (3) The molecule should lead to some type of relatively permanent change in the functioning of the brain. (4) Altered synthesis or utilization of the molecule should lead to predictable consequences for memory. (5) The localization of the response should be consistent in terms of the utilization of that portion of the brain in the particular task.     

Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases

Metrazol enhanced the penetration of two proteins (¹²⁵I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.[/p]