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1.
J Am Coll Health ; 64(6): 438-47, 2016.
Article in English | MEDLINE | ID: mdl-27088240

ABSTRACT

OBJECTIVE: To examine the efficacy of different methods (ie, in-class policy reading; in-class policy reading and discussion; no reading or discussion) to deliver campus sexual misconduct policy information to students on 7 campuses. PARTICIPANTS: A total of 1,195 participants at 7 colleges and universities participated in the study from August to October 2014. Participants were randomly assigned at the class level and completed pretest and posttest surveys assessing knowledge of campus policy and resources and confidence to seek help for sexual assault. RESULTS: Students exposed to a larger dosage of material (in-class policy reading plus discussion) showed greater positive changes in attitudes and knowledge than students who did not receive information or were only read the policy. However, on some indices, students who were only read the policy showed positive outcomes compared with students receiving no intervention. CONCLUSION: Colleges and universities must use engaging methods to disseminate campus sexual misconduct policies to students.


Subject(s)
Health Knowledge, Attitudes, Practice , Information Dissemination/methods , Sex Offenses/prevention & control , Sexual Behavior , Adolescent , Female , Humans , Male , Policy , Students , United States , Universities , Young Adult
2.
Plant Dis ; 98(6): 855, 2014 Jun.
Article in English | MEDLINE | ID: mdl-30708675

ABSTRACT

Pipturus albidus (Hook. & Arn.) A. Gray or mamaki is a flowering plant species in the Urticaceae (nettles) endemic to the Hawaiian Islands. Mamaki is a forest and agricultural commodity, as well as a traditional medicinal and fiber crop. In August 2013, leaf rust was observed in Kuristown, Hawaii, on 15 mamaki plants. Infected leaves had vein-delimited chlorotic spots on the adaxial surface and yellow to orange uredinia on the abaxial surface. Uredinia were scattered, minute, pulverulent, subepidermal, and dome-shaped with a central pore, consistent with Pucciniastrum. Urediniospores were 16 to 23 × 10 to 14 µm, echinulate, ellipsoid to pyriform, walls hyaline, 0.5 µm thick, contents pale yellow to bright yellow. No teliospores were observed. A voucher specimen was deposited in the U.S. National Fungus Collections (BPI 892695). The only species of Pucciniastrum previously known on Pipturus, Pucciniastrum pipturi Syd. [syn. Uredo pipturi (Syd.) Hirats. f.], has larger urediniospores, 26.5 to 40.0 × 19.5 to 27.5 µm, and is currently reported from Japan and the Philippines (3). The pathogen was identified as Pucciniastrum boehmeriae (Dietel) Syd. & P. Syd., which infects Boehmeria Jacq., also in the Urticaceae, and has urediniospores that are 18 to 27 × 13 to 18 µm and similar in shape (2). DNA was extracted from uredinial lesions and the nuclear ribosomal internal transcribed spacer (ITS2) region and the 5' end of large subunit (28S) rDNA were amplified and sequenced following the protocol of Aime (1). The resulting fragment (GenBank Accession No. KF711854) was 100% identical to authenticated and vouchered P. boehmeriae ITS2/28S rDNA sequences (AB221449 to AB221451 and AB221391 to AB221393) (4). Sequences from P. pipturi are not available for comparison, but host family, molecular, and morphological data support the identification of the rust as P. boehmeriae, which is found throughout eastern Asia. To our knowledge, this is the first report of P. boehmeriae on mamaki and the first report in Hawaii on any host. Plant health professionals and regulatory officials can utilize this information to establish survey methods and implement appropriate management practices for this rust disease. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) N. Hiratsuka. Revision of Taxonomy of the Pucciniastreae. Kasai Publishing and Printing, Tokyo, 1958. (3) M. Kakishima and T. Kobayashi. Mycoscience 35:125, 1994. (4) Y.-M. Liang et al. Mycoscience 47:137, 2006.

3.
Environ Toxicol Chem ; 26(6): 1100-8, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17571673

ABSTRACT

Many have demonstrated that anadromous Pacific salmon are significant vectors of nutrients from the ocean to freshwaters. Recently. however, it has been recognized that salmon spawners also input significant quantities of contaminants. The objectives of this paper are to delineate the extent to which salmon-derived nutrients are integrated into the freshwater food web using delta(15)N and delta(13)C and to assess the influence of the salmon pathway in the accumulation of contaminants in rainbow trout (Oncorhynchus mykiss). We found that the delta(15)N and delta(13)C of food web components were related positively and significantly to sockeye salmon (Oncorhynchus nerka) spawner density. Contaminant concentrations in rainbow trout also positively and significantly were related to sockeye salmon spawner density. These data suggest that the anadromous salmon nutrient and contaminant pathways are related and significantly impact the contaminant burden of resident fish.


Subject(s)
Food Chain , Water Pollutants, Chemical/analysis , Animals , Reproduction , Salmon/physiology
4.
Ann Chir ; 131(4): 250-5, 2006 Apr.
Article in French | MEDLINE | ID: mdl-16442071

ABSTRACT

INTRODUCTION: The purpose of this study was to identify, through recursive partitioning, clinically relevant criteria which predict the need for acute neurosurgical intervention in a group of patients with mild head injury. MATERIALS AND METHODS: A retrospective cohort of all adult patients, from April 2000 to March 2001, who sustained a blunt trauma and underwent head CT scan, was reviewed. The following inclusion criteria for mild head injury were used: initial Glasgow Coma Scale (GCS) ranging from 13 to 15; no loss of consciousness lasting more than one hour; no obvious skull fracture; a cranial CT scan performed. We collected demographic and trauma related data, interventions and outcome. Univariate and multivariate analyses were undertaken. In parallel, recursive partitioning was carried out using all variables to elaborate a decision algorithm. RESULTS: There were 405 patients in the sample. CT identified lesions in 12% of patients. Twelve patients (3%) required acute neurosurgical intervention. The recursive partitioning analysis identified three significant sequential nodes: deterioration of the GCS; an initial GCS of 13 vs 14 or 15; and the presence of associated injuries or comorbid conditions. CONCLUSIONS: A simple three step rule predicts the need for acute neurosurgical intervention based on clinical findings: a deteriorating GCS; an initial GCS of 13; and the presence of associated injuries or comorbid conditions.


Subject(s)
Algorithms , Craniocerebral Trauma/diagnostic imaging , Tomography, X-Ray Computed , Wounds, Nonpenetrating/diagnostic imaging , Adolescent , Adult , Aged , Craniocerebral Trauma/therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Wounds, Nonpenetrating/therapy
5.
J Anim Sci ; 82(2): 452-8, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14974543

ABSTRACT

Several laboratory assays have been designed to assess the fertility potential of a semen sample before insemination, but none have been consistent and accurate predictors of fertility. To determine whether zona-binding ability may be a useful fertility predictor, we validated and used an in vitro competitive assay to measure the ability of porcine sperm to bind to the zona pellucida. The zona-binding ability of sperm from 11 boars that exhibited a broad range in average litter size and farrowing rate was determined. Sperm from each boar were compared directly with sperm from eight other boars in a systematic, pairwise fashion. Sperm from two semen samples were labeled with fluorophores at concentrations that did not affect motility or zona-binding ability. An equal number of labeled sperm from each boar was coincubated with homologous oocytes. Least squares means from analysis of variance were used to rank boars based on zona-binding ability. The competitive assay was effective in establishing a ranking of the boars (R2 = 0.62). Furthermore, there was a correlation between zona-binding ability and fertility when estimated by average litter size (r = 0.64, P < 0.05) but not when estimated by farrowing rate (r = -0.28). The explanation for this difference was that litter size and farrowing rate were poorly correlated (r = 0.14). In conclusion, a competitive zona-binding assay distinguished boars that sired either small or large litters. Competitive zona-binding ability may be useful for identifying boars with reduced fertility that produce smaller litters following insemination.


Subject(s)
Fertility , Sperm-Ovum Interactions , Spermatozoa/physiology , Swine/physiology , Zona Pellucida/physiology , Animals , Cells, Cultured , Female , Fertility/physiology , Fertilization in Vitro/veterinary , Male , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Sensitivity and Specificity
6.
Bone Marrow Transplant ; 33(6): 605-11, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14743192

ABSTRACT

Cord blood (CB) is an alternative to other sources of stem cells for transplantation. However, the impact of including CB in the initial strategy of unrelated graft search in a cohort of patients has been the object of limited analysis. Here, we report the results of such a strategy in 91 consecutive children. Absence of mismatch was required for adult donors, and up to two mismatches were allowed for CB grafts, with a nucleated cell dose over 2.5 x 10(7) cells/kg. A graft was found for 84 of the 85 children who remained available for a 3-month search. In all, 64 patients were transplanted, 36 with CB and 28 with bone marrow (BM). Primary graft failure, acute grade II-IV and extensive chronic graft-versus-host disease occurred in five, five and zero CB, and in three, one and two BM patients, respectively. The 3-year survival was 59% in CB and 57% in BM patients. Accepting CB as a source of stem cells offers a graft to almost every child in need of an unrelated transplantation, with a probability of survival similar to that of unrelated BM transplantation.


Subject(s)
Bone Marrow Cells/immunology , Fetal Blood/cytology , Leukemia/therapy , Stem Cell Transplantation/methods , Stem Cells/cytology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dose Fractionation, Radiation , Fetal Blood/immunology , HLA Antigens/immunology , Histocompatibility Testing , Humans , Immunosuppression Therapy/methods , Leukemia/drug therapy , Leukemia/mortality , Male , Stem Cell Transplantation/mortality , Survival Analysis , Time Factors , Treatment Outcome , Whole-Body Irradiation
7.
Ann Pharmacother ; 35(10): 1217-20, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11675850

ABSTRACT

OBJECTIVE: To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse drug reaction (ADR). CASE SUMMARY: A 26-year-old white woman with a 12-year history of anorexia nervosa was being treated with fluvoxamine. After mirtazapine was added to her therapy, she developed tremors,restlessness, twitching, flushing, diaphoresis, and nausea,symptoms that are consistent with serotonin syndrome. DISCUSSION: The possible causes of this ADR are discussed, including the effects of fluvoxamine and mirtazapine alone, the possible pharmacodynamic and pharmacokinetic interactions of these two drugs, and the patients underlying anorexia nervosa. CONCLUSIONS: An increasing number of drugs that affect serotonin are available and are indicated for various disorders. Since there is a significant likelihood of these agents being prescribed concomitantly, clinicians must be aware of possible interactions that could lead to serotonin syndrome.


Subject(s)
Adrenergic alpha-Antagonists/adverse effects , Anorexia Nervosa/drug therapy , Fluvoxamine/adverse effects , Mianserin/analogs & derivatives , Mianserin/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Serotonin Syndrome/chemically induced , Adrenergic alpha-Antagonists/pharmacokinetics , Adult , Adverse Drug Reaction Reporting Systems , Drug Interactions , Female , Fluvoxamine/pharmacokinetics , Humans , Mianserin/pharmacokinetics , Mirtazapine , Serotonin Syndrome/physiopathology , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Tissue Distribution
8.
Opt Lett ; 24(4): 250-2, 1999 Feb 15.
Article in English | MEDLINE | ID: mdl-18071470

ABSTRACT

An 800-MHz self-mode-locked femtosecond Ti:sapphire laser has been developed whose mode-lock frequency can be robustly scanned and modulated. The laser is based on the three-element design of Ramaswamy-Paye and Fujimoto [Opt. Lett. 19, 1756 (1994)]. By translation and modulation of the position of the prismatic output coupler, the mode-lock frequency can be reliably scanned more than 1% and modulated at 80 Hz with a deviation of 2.5 kHz without interrupting the mode lock, changing the pulse length, or inducing significant amplitude modulation. An application in tunable high-resolution terahertz spectroscopy is also demonstrated.

9.
J Med Chem ; 41(16): 2939-45, 1998 Jul 30.
Article in English | MEDLINE | ID: mdl-9685233

ABSTRACT

A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron-attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity. In addition, derivatives 8 and 16, containing the 2, 3-dihydroxybenzanilide structural motif, were potent inhibitors of the autophosphorylation of the KinA kinase, with IC50s of 2.8 and 6. 3 µM, respectively. Compound 8 also inhibited the TCS mediating vancomycin resistance (VanS/VanR) in a genetically engineered Enterococcus faecalis cell line at concentrations subinhibitory for growth. Closantel (1), tetrachlorosalicylanilide (9), and several related derivatives (2, 7, 10, 11, 20) had antibacterial activity against the drug-resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF).


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Bacterial Proteins/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Gram-Positive Bacteria/drug effects , Protein Kinase Inhibitors , Salicylanilides/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/enzymology , Bacillus subtilis/metabolism , Bacillus subtilis/physiology , Drug Evaluation, Preclinical , Drug Resistance, Microbial , Enterococcus faecium/drug effects , Enterococcus faecium/enzymology , Enterococcus faecium/genetics , Enterococcus faecium/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Gram-Positive Bacteria/enzymology , Gram-Positive Bacteria/physiology , Luciferases/genetics , Luciferases/metabolism , Methicillin Resistance , Microbial Sensitivity Tests , Phosphorylation , Protein Kinases/genetics , Salicylanilides/chemistry , Salicylanilides/pharmacology , Spores, Bacterial/drug effects , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Vancomycin/pharmacology
10.
Proc Natl Acad Sci U S A ; 95(9): 5317-22, 1998 Apr 28.
Article in English | MEDLINE | ID: mdl-9560273

ABSTRACT

A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F two-component signal transduction system in vitro. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase::response regulator two-component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Enzyme Inhibitors/pharmacology , Gram-Positive Bacteria/drug effects , Guanidines/pharmacology , Protein Kinases/metabolism , Signal Transduction/drug effects , Trityl Compounds/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Microbial , Phosphorylation
11.
Bioorg Med Chem Lett ; 8(14): 1923-8, 1998 Jul 21.
Article in English | MEDLINE | ID: mdl-9873460

ABSTRACT

This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. Closantel (1) was found to inhibit a two-component system and to have antibacterial activity against drug resistant S. aureus and E. faecium.


Subject(s)
Anti-Bacterial Agents/pharmacology , Gram-Positive Bacteria/drug effects , Salicylanilides/pharmacology , Anti-Bacterial Agents/chemistry , Drug Resistance, Microbial , Enterococcus faecium/drug effects , Microbial Sensitivity Tests , Phosphorylation , Salicylanilides/chemistry , Staphylococcus aureus/drug effects , Structure-Activity Relationship
12.
J Androl ; 19(6): 650-6, 1998.
Article in English | MEDLINE | ID: mdl-9876016

ABSTRACT

The relationship of most sperm laboratory assays to male fertility is inconsistent. Assays that measure traits required to fertilize oocytes are expected to have the most predictive value. A new assay that measures the competitive ability of two sperm samples to bind to oocytes was developed. Two populations of sperm were labeled using a pair of lipophilic dyes. A concentration of 75 microM of the two dyes, DiQ (4-[4-(dihexadecylamino)styryl]-N-methylquinolinium iodide; an orange-red dye) and DiOC16 (3,3'-dihexadecyloxacarbocyanine perchlorate; a yellow-green dye), intensely stained 66 and 73% of sperm, respectively, without affecting sperm motility or oocyte-binding ability. Because sperm could be stained with fluorescent dyes, sperm from two semen samples were mixed together in a droplet, and oocytes were added to allow sperm to bind oocytes competitively. Oocyte-bound sperm from each sample were counted. Binding was specific; nonspecific sperm binding was estimated by sperm bound to two-cell mouse embryos and averaged one to three sperm per embryo. Staining with DiQ or DiOC16 did not affect oocyte-binding ability since more than 80% of the sperm bound were stained with either dye. Furthermore, if different ratios of DiQ- or DiOC16-stained sperm from the same ejaculate were prepared in droplets and oocytes were added, the percentage of sperm bound to the oocytes reflected the percentage of sperm in the droplet; there was no differential effect of either dye. This assay used fixed oocytes because sperm bound equally to fixed and fresh bovine oocytes. This competitive oocyte-binding assay allows one to make a series of pairwise comparisons between a group of males or to include an internal control sample in sperm-oocyte binding assays. This assay may allow more accurate prediction of the oocyte-binding ability of sperm.


Subject(s)
Carbocyanines/chemistry , Fluorescent Dyes/chemistry , Quinolinium Compounds/chemistry , Sperm-Ovum Interactions , Spermatozoa/cytology , Animals , Binding, Competitive , Cattle , Female , Male , Spermatozoa/physiology
13.
Mod Pathol ; 8(7): 775-81, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8539237

ABSTRACT

This study was performed to investigate the role of DNA cytometry in the evaluation of molar and nonmolar pregnancies. DNA ploidy analysis was performed on paraffin-embedded tissue from 53 molar (35 complete, 18 partial) and 24 nonmolar (13 hydropic, 11 nonhydropic) conceptuses. Nuclear suspensions were analyzed by both flow and image cytometry and there was excellent correlation (96%) in the classification of DNA diploid, triploid, and tetraploid cases using these two methods. DNA ploidy analysis revealed a high proportion of tetraploid nonmolar conceptuses (42%) and complete moles (47%). The majority of partial moles were triploid (89%). Tissue sections from all cases were also studied by image cytometry to identify the cellular subpopulations (decidua, villous stromal cells, inner trophoblast, and extravillous trophoblast) with abnormal DNA content. In the triploid cases, all of the villous cell subtypes had an abnormal DNA content consistent with the development of partial moles from a triploid conceptus. In contrast, the majority of tetraploid cases showed high proliferative activity of the extravillous trophoblast whereas the other villous cell subtypes were diploid. These results suggest that tetraploid complete moles may arise from a diploid conceptus with the development of tetraploidy related to polyploidization of the hyperplastic extravillous trophoblast. Tissue section image cytometric DNA analysis can aid in our interpretation of ploidy results and our understanding of the biology of molar pregnancies.


Subject(s)
Embryo, Mammalian/chemistry , Flow Cytometry , Hydatidiform Mole/pathology , Image Cytometry , Ploidies , Uterine Neoplasms/pathology , Cell Nucleus/genetics , DNA, Neoplasm/analysis , Female , Humans , Hydatidiform Mole/genetics , Paraffin Embedding , Pregnancy , Retrospective Studies , Uterine Neoplasms/genetics
14.
J Cataract Refract Surg ; 21(5): 539-42, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7473116

ABSTRACT

This study determined the rate of anterior chamber aerobic bacterial contamination in 103 eyes that had uncomplicated posterior chamber phacoemulsification. Anterior chamber fluid was aspirated on completion of surgery. Cultures of sterile balanced salt solution served as a control. Of 103 anterior chamber cultures, 4 (3.9%) showed contamination; however, 3 of 103 control cultures (2.9%) also grew micro-organisms. These findings suggest a very low rate of aerobic bacterial contamination after uncomplicated phacoemulsification and underscore the importance of control cultures when determining contamination rates.


Subject(s)
Anterior Chamber/microbiology , Phacoemulsification , Aged , Body Fluids/microbiology , Female , Humans , Male , Micrococcus/isolation & purification , Phacoemulsification/adverse effects , Staphylococcus/isolation & purification
15.
Mod Pathol ; 7(2): 195-9, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8008743

ABSTRACT

DNA ploidy has recently been identified as an objective prognostic factor in prostatic carcinoma. Although the diagnosis of prostatic carcinoma is increasingly being made with the use of needle core biopsies, the optimal method for the cytometric analysis of these specimens has yet to be determined. In addition, the degree to which the biopsy is representative of the subsequent prostatectomy specimen with respect to DNA heterogeneity has not been adequately addressed. In this study, image cytometric (ICM) DNA analysis was performed on tissue sections from 12 prostatic needle core biopsies and the results were compared with similar ICM analysis of the subsequent prostatectomy specimens. Multiple blocks (n = 48) of the prostatectomy specimens were utilized to prepare tissue sections and nuclear suspensions and each set of preparations were analyzed by ICM in a parallel comparison study. There was concordance of 0.80 in the classification of DNA diploid and aneuploid tumors by ICM analysis of tissue sections and nuclear suspensions from paraffin blocks. In all of the discordant cases, DNA aneuploid populations were identified by ICM analysis of tissue sections only. This is attributed to difficulties in obtaining a representative nuclear suspension from disaggregated paraffin-embedded prostatic tissue which often has a very desmoplastic stroma. ICM analysis of tissue sections seems to be an optimal method for DNA ploidy analysis of prostatic carcinoma and is well suited to small volume biopsy material. Determination of DNA ploidy status in prostatic biopsies was predictive of the subsequent prostatectomy specimens with a concordance of 0.92.


Subject(s)
Carcinoma/pathology , DNA, Neoplasm/analysis , Prostatic Neoplasms/pathology , Aged , Biopsy, Needle , Carcinoma/genetics , Carcinoma/surgery , Flow Cytometry , Humans , Male , Middle Aged , Ploidies , Prostatectomy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/surgery
16.
J Med Chem ; 35(1): 172-6, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1732525

ABSTRACT

A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.


Subject(s)
Cardiotonic Agents/chemical synthesis , Oxazines/chemistry , Oxazines/chemical synthesis , Pyridazines/chemistry , Pyridazines/chemical synthesis , Animals , Benzoxazines , Cardiotonic Agents/chemistry , Cardiotonic Agents/pharmacology , Dogs , Heart/drug effects , Myocardium/enzymology , Oxazines/pharmacology , Pyridazines/pharmacology , Structure-Activity Relationship
18.
Blood ; 67(4): 993-6, 1986 Apr.
Article in English | MEDLINE | ID: mdl-3513871

ABSTRACT

During a phase I evaluation of diglycoaldehyde (INOX), an intravenous chemotherapeutic agent used to treat children with malignancies, all of eight patients tested developed a positive direct antiglobulin test (DAT) in vivo. The DAT became positive within one to seven days after the first administration of the drug and remained positive for up to 12 days following the last dose. The indirect antiglobulin tests were negative. None of the patients showed clinical or laboratory evidence of hemolysis at the time the DAT became positive or during follow-up. Eluates made from the red cells of two of the eight patients were both negative by indirect antihuman globulin testing. In vitro studies with INOX and glutaraldehyde, both dialdehyde compounds, showed nonimmunologic adsorption of protein onto red cells, probably by the condensation of aldehyde groups of these compounds to form Schiff's bases with amino acids of serum proteins and red cell membrane proteins. This reaction provides an explanation for the globulin detected on the red cells of patients treated with INOX.


Subject(s)
Blood Proteins/metabolism , Coombs Test , Erythrocytes/metabolism , Schiff Bases , Adolescent , Antineoplastic Agents/administration & dosage , Child , Child, Preschool , Female , Humans , Immunosorbent Techniques , Infusions, Parenteral , Inosine/administration & dosage , Inosine/analogs & derivatives , Male , Serum Albumin/immunology
19.
Appl Opt ; 24(16): 2581, 1985 Aug 15.
Article in English | MEDLINE | ID: mdl-18223923
20.
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