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PubMed2000

Inverse agonism by Dmt-Tic analogues and HS 378, a naltrindole analogue.

The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1, 2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse agonism (EC(50)=6.35 nM, E(max)=-18.87%) for [35S]GTPgammaS binding and H-Dmt-Tic-NH(2) was a neutral antagonist (no effect up to 30 microM). In contrast N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50)=2.66 nM, E(max)=-35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline) but with a 3.5-fold higher EC(50). In comparison, naltrindole was a neutral antagonist while its analogue HS 378 was a partial inverse agonist (E(max)=-12.99%).

Benzamides↗

PubMed2003

Estratest and Estratest HS (esterified estrogens and methyltestosterone) therapy: a summary of safety surveillance data, January 1989 to August 2002.

BACKGROUND: The use of hormone-replacement therapy (HRT) to treat menopausal symptoms has been influenced over the years by various safety concerns. These concerns include endometrial cancer, breast cancer, and cardiovascular disease, and have altered how HRT is prescribed. Evaluating postmarketing surveillance data for a product can help pharmaceutical manufactures and health care providers detect early safety signals that may call for further investigation of the product for safety risks. OBJECTIVE: This review summarizes the safety surveillance data for Estratest and Estratest HS from January 1989 to August 2002. METHODS: All adverse-event (AE) data reported to Solvay Pharmaceuticals, Inc., on this brand from January 1989 to August 2002 were accessed from a database system that uses a comprehensive software package for reporting and tracking clinical and postmarketing AEs. RESULTS: Exposure to the Estratest brand during the 13-year assessment period is estimated at >3.0 million patient-years. A total of 1372 unique case reports containing 2556 AEs were found. Assessment of the 43 (3.1%) serious AE cases reported did not generate any signals that might raise concern on the part of the medical community or consumers. Nonserious events comprising >4% of total AEs were all labeled events and included alopecia (8.8%), acne (5.6%), and hirsutism (4.5%). CONCLUSIONS: The relatively small number of serious AE reports compared with the significant patient exposure did not generate any signals that might raise concern on the part of the medical community or consumers. The safety profile suggests that continued use at the lowest effective dose is acceptable in menopausal women whose symptoms are not improved by estrogen alone.

Acne Vulgaris↗

PubMed2003

Purification and properties of an esterase from Aspergillus nomius HS-1 degrading ethylene glycol dibenzoate.

We isolated a fungal strain HS-1 utilizing either ethylene glycol dibenzoate or ethyl benzoate as sole source of carbon and energy, and identified it as Aspergillus nomius, based on morphological and rDNA analyses. An enzyme hydrolyzing the esters was purified from the culture supernatant of the strain to an electrophoretically homogeneous state. The enzyme was a carboxyl esterase with a monomeric structure, of which the molecular mass was about 60000, and inhibited by phenylmethylsulfonyl fluoride. The enzyme hydrolyzed various benzoate esters and p-nitrophenyl esters, and its hydrolysis rates for the most favorable substrates, n-butyl benzoate and p-nitrophenyl valerate, were comparable.

Aspergillus↗

PubMed1996

An efficient synthesis of methyl tetra-O-hexyl gentiooctaoside, an octaosyl analogue of ANP receptor antagonist HS-142-1.

Methyl 0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)-[0-(beta-D-glucopyranosyl)-(1 ->6)-0-(3-0-hexyl-beta-D-glucopyranosyl)-(1->6)3-beta-D- glucopyranoside, a 3-0 hexyl analogue of the octaosyl component of fungal lipooligosaccharide HS-142-1, was stereo- and regioselectively synthesized as a potent antagonist for the tetrameric atrial natriuretic peptide (ANP) receptors.

Animals↗

PubMed2006

Nucleophilic substitution of phosphorothionate ester pesticides with bisulfide (HS-) and polysulfides (S(n)2-).

The reactions of five organophosphorus insecticides (OPs) (chlorpyrifos-methyl, parathion-methyl, fenchlorphos, chlorpyrifos, and parathion) with hydrogensulfide/ bisulfide (H2S/HS-) and polysulfides (S(n)2-) were examined in well-defined aqueous solutions over a pH range from 5 to 9. The rates are first-order in the concentration of the different reduced sulfur species. Experiments at 25 degrees C demonstrated that the reaction of the five OPs with the reduced sulfur species follows a SN2 mechanism. The activation parameters of the reaction of OPs with bisulfide were determined from the measured second-order rate constants over a temperature range of 5-60 degrees C. The determined second-order rate constants show that the reaction of an OP with polysulfides is from 15 to 50 times faster than the reaction of the same OP with bisulfide. The dominant transformation products are desalkyl OPs, which indicate that the nucleophilic substitution of reduced sulfur species occurs at the carbon atom of the alkoxy groups. And also the results show that these reduced sulfur species are much better nucleophiles, and thus degrade these pesticides faster than the well-studied base hydrolysis by OH-. When the determined second-order rate constants are multiplied with the concentration of HS- and S(n)2- reported in salt marshes and porewater of sediments, predicted half-lives show that abiotic degradation by sulfide species may be of comparable importance to microbially mediated degradation in anoxic environments.

Chromatography, Gas↗

PubMed2006

Application of HS-SPME in the determination of potentially toxic organic compounds emitted from resin-based dental materials.

Leaching of volatile substances from resin-based dental materials may have a potential impact on the biocompatibility as well as safety of these materials. Information from manufacturers on ingredients in the materials is very often incomplete. Patients and dentists may be in contact with components emitted from cured dental fillings or from substrates applied in their preparation. Therefore, determination of the components of these materials is necessary for better prevention from possible harmful effects caused by dental fillings. The aim of this work was the isolation and identification of organic compounds evolved from four commercial resin-modified glass-ionomer cements (resin-based dental materials applied in dentistry) by using an alternative method of volatile compounds analysis-HS-SPME (headspace-solid phase microextraction). Dental materials were heated in closed vial at various temperatures and volatile substances released into the headspace phase above the sample were isolated on a thin polymeric fibre placed in SPME syringe. Identification was performed by using the GC-MS (gas chromatography-mass spectrometry) technique. Almost 50 RMGIC (resin-modified glass-ionomer cement) components (monomers and additives) were identified. The main identified leachables were: iodobenzene (DPICls-diphenyliodonium chloride degradation product), camphorquinone (photo-initiator), tert-butyl-p-hydroxyanisole (inhibitor), 4-(dimethylamino)ethyl benzoate (co-initiator), ethylene glycol dimethacrylate (monomer).

Compomers↗

PubMed2002

Genetic polymorphism of the major regulatory element HS-40 upstream of the human alpha-globin gene cluster.

The highly conserved 350-bp major regulatory element HS-40 (or alphaMRE) upstream of the human alpha-globin gene cluster is involved in the regulation of alpha-globin gene expression. The study of alphaMRE differences between human populations and the evolution of alphaMRE sequences in mammals may lead to a better understanding of the function and importance of this element in the regulation of expression of the downstream alpha-cluster. Denaturing gradient gel electrophoresis was used to determine the sequence heterogeneity of the alphaMRE region in 276 unrelated individuals, representing seven different populations. Furthermore, we analysed the alpha major regulatory elements of chimpanzee, orang-utan and rhesus monkeys and compared them with the equivalent human and murine sequences. Six different alphaMRE haplotypes (labelled A to F) were found in humans. Haplotype frequencies between the seven populations showed a gradual shift to a higher haplotype A distribution from west to east, being the highest in Indonesians. The African sample shows the largest divergence in haplotypes. Five out of six different haplotypes were present, three of which were exclusively found in Africans. The high prevalence of the haplotype A in humans, together with the conservation of this haplotype in apes, suggests that it is the ancestral one. The alphaMRE fragment appears to be a highly polymorphic marker, which could be used in combination with the regular markers in the alpha-cluster to extend the haplotype and to follow segregation of alpha-thalassaemia genes in population studies more accurately.

Animals↗

PubMed2005

Relativistic effects on the electronic structure and volatility of group-8 tetroxides MO4, where M=Ru, Os, and element 108, Hs.

The influence of relativistic effects on properties and volatility of the group-8 tetroxides MO4, where M=Ru, Os, and element 108, Hs, was studied on the basis of results of the fully relativistic (four component) and nonrelativistic density functional theory calculations. Relativistic effects were shown to increase bond strengths and decrease bond lengths in these molecules. They are responsible for a decrease in molecular polarizabilities and an increase in ionization potentials. The effects are much stronger in HsO4 than in the lighter congeners. Relativistic effects were also shown to slightly decrease dispersion interaction energies of RuO4, OsO4, and HsO4 with an inert (quartz or silicon nitride) surface, i.e., they increase volatility of these compounds as studied in the "one-atom-at-a-time" gas-phase chromatography experiments. They do, however, not influence the trend in group 8: both relativistically and nonrelativistically, volatility should change as RuO4<OsO4<HsO4. The reason for that is identical trends in the relativistic and nonrelativistic space distributions of the valence d electrons.

Journal Article↗

PubMed1973

Nucleotide sequence of HS-beta satellite DNA from kangaroo rat Dipodomys ordii.

The sequence of the highly repetitive satellite HS-beta DNA fraction from kangaroo rat Dipodomys ordii was determined independently by RNA and DNA sequencing techniques. A basic iterated sequence of 10 nucleotides with several mutational variations was found. Base-composition data are consistent with the proposed sequence and revealed a high content of 5-methylcytosine. DNA and RNA sequencing techniques used gave identical results, showing that the fidelity of synthesis of riboguanidine-substituted DNA under our conditions is adequate for nucleotide sequence studies.

Adenosine Triphosphate↗

PubMed1998

Mortality and biomarkers of aging in heterogeneous stock (HS) mice.

A longitudinal study was undertaken to evaluate the relationships among a battery of aging biomarkers and subsequent survival time in 319 genetically heterogenous stock (HS) mice. The biomarker variables chosen were selected from the broad domains of behavior, homeostatic physiology, oxidative defense, and immune function; biomarkers were measured at 45, 90, 360, 630, and 900 days of age. Sex differences were found in the survivor and mortality functions, with a mortality rate crossover occurring at about 525 days and a survival curve crossover at about 750 days of age. Females experienced lower initial mortality but had more sharply increasing mortality with age than did males. Survival analysis using Gompertz parametric models with biomarkers as time-varying covariates yielded significant biomarkers from each domain. Following backward elimination procedures, the final set of independent mortality predictors included headpokes in the File activity apparatus, maximum cord drop time, weight, hematocrit, urine concentration, natural killer cell activity, and concanavalin A response.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Changes in HS mouse erythrocyte mass and area with respect to donor age.

Interferometric photographs of blood smears from heterogeneous stock (HS) mice were analyzed for age-related changes in erythrocyte mass using quantitative cytophotometry. Blood smears were obtained from 96 mice (half male/half female) sacrificed at 172, 272, 374, 482, 581, and 664 days of age as part of a larger biomarkers of aging study. Blood smears from each animal were photographed with a Leitz Mach-Zehnder interferometer, and the erythrocyte images on these negatives were measured for dry mass using a Vickers M85a microdensitometer. Cell area measurements were made from a video-microscope image traced with a computer digitizer. Results indicated that animals from middle-age groups (272, 374, and 482 days) have higher red blood cell mass than animals at either young (172 days) or older (581 and 664 days) age groups. Mass changes with respect to age followed similar trends when data were further examined with regard to sex of the animals. Erythrocyte area measurements showed a general age-related decrease in cell size.

Aging↗

PubMed1998

The effects of E mu, 3'alpha (hs 1,2) and 3'kappa enhancers on mutation of an Ig-VDJ-Cgamma2a Ig heavy gene in cultured B cells.

The Ig kappa intronic and 3'kappa light chain enhancers have been shown to be necessary for V region hypermutation in kappa light chain transgenes. To investigate the role of the E mu intronic enhancer in V region hypermutation of heavy chain genes, E mu and its associated matrix attachment regions (MAR) were replaced with the SV40 or the cytomegalovirus (CMV) enhancer in a gamma2a construct that hypermutates its rearranged VDJ region in the NSO plasmacytoma and 18.81 pre-B cell lines. In this model in vitro system, mutation rates of stable transfectants were determined by reversion analysis using a V region stop codon that, when mutated, allowed the detection of cellular revertants by ELISA spot assay. The gamma2a constructs with the E mu, SV40 and CMV enhancers mutated at comparably high rates in the B cell lines, but not in L cells, indicating that the E mu enhancer and its associated MAR were not specifically required for IgH hypermutation in this system. In parallel experiments, the addition of the 3'alpha heavy chain enhancer (hs 1,2) or the 3'kappa light chain enhancer did not increase the mutation rate of a related mu reporter construct in which the associated VDJ mutates at a moderately low rate in NSO cells or in cell hybrids made between 18.81 and NSO. These results imply that cis-acting IgH elements that promote hypermutation may not be restricted to Ig-specific transcriptional enhancers.

Animals↗

PubMed1989

Can interstellar H2S be formed via gas-phase reactions? Calculations concerning the rates of the ternary and radiative association reactions between HS+ and H2.

Based on laboratory work involving the ternary association reaction of HS+ and H2 at 80 K, we have estimated the rate of the analogous radiative association reaction under interstellar conditions. Both the ternary and radiative association reactions appear to occur via a mechanism in which the electronic spin of the H3S+ complex changes before the complex is stabilized. Although this spin change is of low probability, it leads to a radiative association rate coefficient at 80 K of 7 x 10(-16) cm3 s-1 if radiative stabilization occurs at a rate of 10(3) s-1. This value of the radiative association rate coefficient at 80 K is large enough to lead to the observed abundance of H2S in the ambient ridge source in Orion.

Extraterrestrial Environment↗

PubMed1994

Analysis of a 70 kb segment of DNA containing the human zeta and alpha-globin genes linked to their regulatory element (HS-40) in transgenic mice.

We have ligated two cosmids through an oligonucleotide linker to produce a single fragment spanning 70 kb of the human alpha-globin cluster, in which the alpha-like globin genes (zeta 2, alpha 2 and alpha 1), their regulatory element (HS-40) and erythroid-specific DNase I hypersensitive sites accurately retain their normal genomic organization. The zeta (embryonic) and alpha (embryonic, fetal and adult) globin genes were expressed in all 17 transgenic embryos. Similarly, all fetal and adult mice from seven transgenic lines that contained one or more copies of the fragment, produced up to 66% of the level of endogenous mouse alpha-globin mRNA. However, as for smaller constructs containing these elements, human alpha-globin expression was not copy number dependent and decreased by 1.5-9.0 fold during development. These findings suggest that either it is not possible to obtain full regulation of human alpha-globin expression in transgenic mice or, more likely, that additional alpha-globin regulatory elements lie beyond the 70 kb segment of DNA analysed.

Animals↗

PubMed2001

Comprehensive drug screening by integrated use of gas chromatography/mass spectrometry and Remedi HS.

The authors evaluated an integrated approach for the screening of drugs in biosamples consisting of gas chromatography/mass spectrometry analysis of serum or whole blood (SB/GC-MS) and of high-performance liquid chromatographic and ultraviolet (HPLC-UV) analysis of urine with the REMEDi HS Biorad system (U/REM) (Bio-rad; Segrate, MI, Italy). Urine and blood samples from 26 suspected intoxicated patients and from 22 suspected lethal poisoning cases were examined. Eighty-one of the 99 parent drugs/main metabolites detected were identified by SB/GC-MS and 54 with U/REM. Thirty-six drugs/metabolites were identified with both methods, 45 by SB/GC-MS alone, and 18 by U/REM alone. Absence of the mass spectrometry (MS) spectra in the reference library and high polarity of the analytes were the main reasons for failed identification by SB/GC-MS. Unsuccessful identifications with U/REM were basically caused by the absence of the UV spectra in the reference library or by low chromatographic and spectroscopic selectivity as in the case of barbiturates and benzodiazepines (BZD), which represented 11% and 51%, respectively, of the 45 SB/GC-MS unique identifications. Urine samples of 14 BZD-positive cases were also submitted to enzymatic hydrolysis and analyzed with the REMEDi UBz assay, and results were compared with those obtained by SB/GC-MS: 14 of the 22 identified BZD were detected with both methods, three by U/REM only, and five by SB/GC-MS only. In conclusion, the integrated use of SB/GC-MS and U/REM approaches greatly enhances the amount and quality of analytical information obtainable by applying either method alone.

Chromatography, High Pressure Liquid↗

PubMed2002

Evaluation of REMEDi HS in the diagnosis of dimethoate poisoning.

The authors describe the evaluation of an automated rapid emergency drug profiling system (REMEDi HS), which is designed for clinical toxicology and therapeutic drug monitoring, in a severe case of dimethoate poisoning. Successful qualitative and quantitative determination of dimethoate in diluted serum samples was achieved. The authors found that dimethoate serum concentrations were properly measured with the REMEDi method and well correlated with gas chromatography-mass spectrometry. The results provide evidence that besides screening and rapid estimation of drug concentrations in human fluids, this system is a suitable tool in cases of symptomatic dimethoate poisoning.

Adult↗

PubMed1998

Subtyping of Campylobacter jejuni Penner heat-stable (HS) serotype 11 isolates from human infections.

High resolution molecular subtyping was applied to Campylobacter jejuni Penner heat-stable (HS) 11 isolates from human infections and other sources. Strains were genotyped by restriction fragment length polymorphism analysis involving PCR-based flagellin gene (flaA) profiling with HinfI and DdeI, and pulsed-field gel electrophoretic (PFGE) profiling with SmaI and KpnI. Fla-genes of the strains were highly conserved as most (95%) had the same fla-profile. PFGE analysis of SmaI digests was more discriminatory with 15 profile subtypes identified, although 36% of isolates had a common profile. The study showed that strains of C. jejuni HS11, unlike those of HS1 and the HS4 complex, were relatively homogeneous at the genomic level and that high resolution molecular techniques were essential for detailed epidemiological subtyping.

Animals↗

PubMed2000

Nucleotide sequencing and transcriptional analysis of two tandem genes encoding glucosyltransferase (water-soluble-glucan synthetase) in Streptococcus cricetus HS-6.

Two tandem genes encoding glucosyltransferase synthesizing water-soluble glucan (GTF-S) were cloned from the lambda gene library of Streptococcus cricetus HS-6 (serotype a) using anti-GTF-S antibody, and the nucleotide sequences were analyzed. The two genes (ORF1 and ORF2) were identified as streptococcal glucosyltransferases based on the following evidence: [1] the deduced amino acid sequences of their products have an active site for catalytic action and C-terminal repeated units for dextran binding, and [2] a homology search revealed that the ORF1 and ORF2 products are homologous to the GtfS protein (77.4%) of S. downei Mfe28 and GtfT protein (83.8%) of S. sobrinus OMZ176, respectively, which are both known to have GTF-S activity. Therefore, ORF1 and ORF2 might be designated gtfS and gtfT of S. cricetus, respectively. A Northern blotting and RNase protection assay suggested that the gtfS and gtfT of S. cricetus are transcribed as a single bicistronic mRNA as well as separate monocistronic mRNAs. Primer extension analysis indicated multiple transcriptional start points for each gene.

Amino Acid Sequence↗