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1.
Appl Ergon ; 74: 1-9, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30487087

ABSTRACT

Human visual inspection skills remain superior for ensuring product quality and conformance to standards in the manufacturing industry. However, at present these skills cannot be formally shared with other workers or used to develop and implement new solutions or assistive technologies because they involve a high level of tacit knowledge which only exists in skilled operators' internal cognitions. Industry needs reliable methods for the capture and analysis of this tacit knowledge so that it can be shared and not lost but also so that it can be best utilised in the transfer of manual work to automated systems and introduction of new technologies and processes. This paper describes two UK manufacturing case studies that applied systematic task analysis methods to capture and scrutinise the tacit knowledge and skills being applied in the visual inspection of aerospace components. Results reveal that the method was effective in eliciting tacit knowledge, and showed that tacit skills are particularly needed when visual inspection standards lack specification or the task requires greater subjective interpretation. The implications of these findings for future research and for developments in the manufacturing industry are discussed.


Subject(s)
Ergonomics/methods , Task Performance and Analysis , Adult , Female , Humans , Knowledge , Male , Manufacturing and Industrial Facilities
2.
J Med Entomol ; 53(3): 598-606, 2016 05.
Article in English | MEDLINE | ID: mdl-27026161

ABSTRACT

Ixodes scapularis Say, the black-legged tick, is the primary vector in the eastern United States of several pathogens causing human diseases including Lyme disease, anaplasmosis, and babesiosis. Over the past two decades, I. scapularis-borne diseases have increased in incidence as well as geographic distribution. Lyme disease exists in two major foci in the United States, one encompassing northeastern states and the other in the Upper Midwest. Minnesota represents a state with an appreciable increase in counties reporting I. scapularis-borne illnesses, suggesting geographic expansion of vector populations in recent years. Recent tick distribution records support this assumption. Here, we used those records to create a fine resolution, subcounty-level distribution model for I. scapularis using variable response curves in addition to tests of variable importance. The model identified 19% of Minnesota as potentially suitable for establishment of the tick and indicated with high accuracy (AUC = 0.863) that the distribution is driven by land cover type, summer precipitation, maximum summer temperatures, and annual temperature variation. We provide updated records of established populations near the northwestern species range limit and present a model that increases our understanding of the potential distribution of I. scapularis in Minnesota.


Subject(s)
Ixodes/physiology , Animal Distribution , Animals , Ecosystem , Minnesota , Models, Biological
3.
Domest Anim Endocrinol ; 44(1): 26-35, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23017303

ABSTRACT

The bovine mammary alveolar cell-T (MAC-T) cell line is able to uniformly differentiate and secrete casein proteins in response to dexamethasone, insulin, and prolactin and is extensively used to study bovine mammary epithelial cell (MEC) function. Somatotropin, or growth hormone (GH), has been shown to increase milk protein synthesis both in vivo and in mammary cell models and to induce cytoskeletal rearrangement in a 3T3 fibroblast cell line and a Chinese hamster ovary cell line. To identify the nature of the effects of GH in MECs cultured with lactogenic hormones, changes in global protein expression were assessed in the MAC-T cell line with the use of two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization tandem time of flight mass spectrometry. Forty proteins were differentially expressed in response to GH (P < 0.05) and were related to metabolism, the cytoskeleton, protein folding, RNA and DNA processing, and oxidant stress. These widespread changes in protein expression are indicative of a global role of GH in overall cellular differentiation that may underlie the direct modulation of milk component synthesis in MEC models that have been described to date.


Subject(s)
Cattle/metabolism , Cell Differentiation/physiology , Growth Hormone/metabolism , Mammary Glands, Animal/metabolism , Milk Proteins/biosynthesis , Animals , Cell Line , Dexamethasone/pharmacology , Electrophoresis, Gel, Two-Dimensional/veterinary , Epithelial Cells , Female , Insulin/pharmacology , Mammary Glands, Animal/cytology , Prolactin/pharmacology , Proteomics/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinary
4.
Water Sci Technol ; 53(12): 75-81, 2006.
Article in English | MEDLINE | ID: mdl-16889243

ABSTRACT

While biological phosphorus removal (BPR) has been practised for 30 years, up to recently it has been restricted mainly to activated sludge processes, with the corresponding need for large basin volumes. Yet, research with biofilm reactors showed that the principle of alternate anaerobic and aerated conditions was applicable to fixed bacteria by changing the conditions in time rather than in space. Attached growth enhanced biological phosphorus removal (EBPR) systems are attractive because of their compactness and capability to retain high biomass levels. However, the phosphorus extraction depends on backwashes to enhance the phosphorus-rich attached biomass, and correct control of unsteady effluent quality created by frequently modified process conditions. Accordingly, EBPR remains a challenging task in terms of combining nitrogen and phosphorus removal using attached growth systems. Nevertheless, a combination of activated sludge and biofilm carriers, in the integrated fixed-film activated sludge system, provides treatment opportunities not readily available using suspended growth systems. Current practice is only at the beginning of exploiting the full potential of this combination, but the first full-scale results show that compact tankage and low nutrient results based on biological principles are possible.


Subject(s)
Biofilms/growth & development , Phosphorus/analysis , Sewage/microbiology , Water Pollutants, Chemical/analysis , Water Purification/methods , Aerobiosis , Anaerobiosis , Biomass , Water Purification/instrumentation
5.
Contemp Top Lab Anim Sci ; 40(6): 22-4, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11703052

ABSTRACT

The identification of a tapeworm (Rodentolepis nana, formerly named Hymenolepis nana) infection in a research breeding colony of sand rats (Psammomys obesus obesus) was complicated because of the unexpected long length (< 150 mm) of the worms. Other morphologic features that were consistent with this identification included the number (24), size (16 mm), and shape of the hooks on the rostellum. No evidence of intermediate hosts was found in the colony. Previous surveys of natural populations of sand rats had not identified this tapeworm. However, a detailed search of the literature revealed that variation in the size of R. nana had been reported, thus supporting the final identification of the tapeworm. R. nana is important and interesting because of its zoonotic potential and because it is the only tapeworm that is able to infect its definitive host without use of an intermediate host. This report is presented to help clarify the ambiguity found in the laboratory animal literature about the differences in the size of R. nana among rodent species used in research.


Subject(s)
Gerbillinae/parasitology , Hymenolepiasis/veterinary , Hymenolepis/anatomy & histology , Hymenolepis/isolation & purification , Animals , Animals, Laboratory , Female , Hymenolepiasis/pathology , Hymenolepis/pathogenicity , Male
7.
J Air Waste Manag Assoc ; 51(10): 1452-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11686250

ABSTRACT

The decoupling of fossil-fueled electricity production from atmospheric CO2 emissions via CO2 capture and sequestration (CCS) is increasingly regarded as an important means of mitigating climate change at a reasonable cost. Engineering analyses of CO2 mitigation typically compare the cost of electricity for a base generation technology to that for a similar plant with CO2 capture and then compute the carbon emissions mitigated per unit of cost. It can be hard to interpret mitigation cost estimates from this plant-level approach when a consistent base technology cannot be identified. In addition, neither engineering analyses nor general equilibrium models can capture the economics of plant dispatch. A realistic assessment of the costs of carbon sequestration as an emissions abatement strategy in the electric sector therefore requires a systems-level analysis. We discuss various frameworks for computing mitigation costs and introduce a simplified model of electric sector planning. Results from a "bottom-up" engineering-economic analysis for a representative U.S. North American Electric Reliability Council (NERC) region illustrate how the penetration of CCS technologies and the dispatch of generating units vary with the price of carbon emissions and thereby determine the relationship between mitigation cost and emissions reduction.


Subject(s)
Air Pollution/economics , Air Pollution/prevention & control , Carbon Dioxide/analysis , Fossil Fuels , Power Plants/economics , Commerce , Costs and Cost Analysis , Electricity , Engineering , Humans , Private Sector , Public Sector
8.
Genes Dev ; 15(15): 1957-70, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11485990

ABSTRACT

Spliceosome assembly has been characterized as the ordered association of the snRNP particles U1, U2, and U4/U6.U5 onto pre-mRNA. We have used an in vitro trans-splicing/cross-linking system in Saccharomyces cerevisiae nuclear extracts to examine the first step of this process, 5' splice site recognition. This trans-splicing reaction has ATP, Mg(2+), and splice-site sequence requirements similar to those of cis-splicing reactions. Using this system, we identified and characterized a novel U4-5' splice site interaction that is ATP-dependent, but does not require the branch point, the 3' splice site, or the 5' end of the U1 snRNA. Additionally, we identified several ATP-dependent U6 cross-links at the 5' splice site, indicating that different regions of U6 sample it before a U6-5' splice site interaction is stabilized that persists through the first step of splicing. This work provides evidence for ATP-dependent U4/U6 association with the 5' splice site independent of ATP-mediated U2 association with the branch point. Furthermore, it defines specific nucleotides in U4 and U6 that interact with the 5' splice site at this early stage, even in the absence of base-pairing with the U1 snRNA.


Subject(s)
5' Untranslated Regions/genetics , RNA Splicing , RNA, Small Nuclear/genetics , Ribonucleoprotein, U4-U6 Small Nuclear/metabolism , Saccharomyces cerevisiae/genetics , Actins/genetics , Adenosine Triphosphate/metabolism , Base Sequence , Binding Sites , Cross-Linking Reagents , Magnesium/metabolism , Models, Molecular , Molecular Sequence Data , Nucleic Acid Conformation , RNA Precursors/genetics , RNA, Fungal/chemistry , RNA, Fungal/genetics , RNA, Messenger/genetics , RNA, Small Nuclear/chemistry , Saccharomyces cerevisiae/metabolism , Substrate Specificity
9.
Bioorg Med Chem Lett ; 11(9): 1157-60, 2001 May 07.
Article in English | MEDLINE | ID: mdl-11354366

ABSTRACT

Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.


Subject(s)
Cyclin-Dependent Kinases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Quinazolines/chemical synthesis , Binding, Competitive/drug effects , Cell Line , Crystallography, X-Ray , Enzyme Inhibitors/pharmacology , Models, Molecular , Structure-Activity Relationship
10.
Connect Tissue Res ; 42(3): 175-86, 2001.
Article in English | MEDLINE | ID: mdl-11913489

ABSTRACT

Although the biological factors which regulate tendon homeostasis are poorly understood, recent evidence suggests that Growth and Differentiation Factor-5 (GDF-5) may play a role in this important process. The purpose of this study was to investigate the effect of GDF-5 deficiency on mouse tail tendon using the brachypodism mouse model. We hypothesized that GDF-5 deficient tail tendon would exhibit altered composition, ultrastructure, and biomechanical behavior when compared to heterozygous control littermates. Mutant tail tendons did not display any compositional differences in sulfated glycosaminoglycans (GAG/DNA), collagen (hydroxyproline/DNA), or levels of fibromodulin, decorin, or lumican. However, GDF-5 deficiency did result in a 17% increase in the proportion of medium diameter (100-225 nm) collagen fibrils in tail tendon (at the expense of larger fibrils) when compared to controls (p < 0.05). Also, mutants exhibited a trend toward an increase in irregularly-shaped polymorphic fibrils (33% more, p > 0.05). While GDF-5 deficient tendon fascicles did not demonstrate any significant differences in quasistatic biomechanical properties, mutant fascicles relaxed 11% more slowly than control tendons during time-dependent stress-relaxation tests (p < 0.05). We hypothesize that this subtle alteration in time-dependent mechanical behavior is most-likely due to the increased prevalence of irregularly shaped type I collagen fibrils in the mutant tail tendons. These findings provide additional evidence to support the conclusion that GDF-5 may play a role in tendon homeostasis in mice.


Subject(s)
Bone Morphogenetic Proteins , Collagen Type I/biosynthesis , Growth Substances/deficiency , Tail/abnormalities , Tail/growth & development , Tendons/abnormalities , Tendons/growth & development , Animals , Collagen Type I/ultrastructure , DNA/metabolism , Elasticity , Growth Differentiation Factor 5 , Growth Substances/genetics , Male , Mice , Mice, Mutant Strains , Microscopy, Electron , Molecular Weight , Proteoglycans/metabolism , Stress, Mechanical , Tail/ultrastructure , Tendons/ultrastructure
11.
J Child Neurol ; 15(11): 759-61, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11108511

ABSTRACT

We identified a G-->A transition at nt-8363 in the mitochondrial DNA transfer ribonucleic acidLys gene in blood and muscle from a 13-month-old girl who had clinical and neuroradiologic evidence of Leigh syndrome and died at age 27 months. The mutation was less abundant in the same tissues from the patient's mother, who developed myoclonus epilepsy with ragged red fibers (MERRF) in her late 20s. In both mother and daughter, muscle histochemistry showed ragged red and cytochrome c oxidase-negative fibers and biochemical analysis showed partial defects of multiple respiratory-chain enzymes. A maternal half-sister of the proband had died at 2.5 years of age from neuropathologically proven Leigh syndrome. The G8363A mutation, which previously had been associated with cardiomyopathy and hearing loss, MERRF, and multiple lipomas, also should be included in the differential diagnosis of maternally inherited Leigh syndrome.


Subject(s)
DNA, Mitochondrial/genetics , Leigh Disease/genetics , MERRF Syndrome/genetics , Muscle Fibers, Skeletal/pathology , Mutation, Missense , RNA, Transfer, Lys/genetics , Adult , Child, Preschool , Diagnosis, Differential , Electron Transport Complex IV/analysis , Fatal Outcome , Female , Genotype , Humans , Immunohistochemistry , Infant , Leigh Disease/complications , Leigh Disease/diagnosis , Leigh Disease/pathology , MERRF Syndrome/complications , MERRF Syndrome/diagnosis , MERRF Syndrome/pathology , Muscle Fibers, Skeletal/chemistry , Muscle, Skeletal/pathology , Pedigree
12.
Ultrasound Obstet Gynecol ; 15(5): 354-64, 2000 May.
Article in English | MEDLINE | ID: mdl-10976474

ABSTRACT

The effect of ovarian cancer screening on survival is enabled by women who continue to actively participate in screening. In this report, factors that affect participation are examined. Participants included 13,963 Kentucky women who received 56,392 screens accounting for a 46,113 screening year experience. Background, health history and reasons for participating in transvaginal sonographic screening were collected via a self-reported questionnaire. Screening participants were characterized as > 50 years old, mostly married, well educated, medically insured, health conscious women, living in the vicinity of the screening centre or 51-150 miles away. Approximately 70% of the participants can be considered active in the study based upon a screening visit during the 1997-1998 2-year period. The probabilities of a return screen at 1, 2, 5 and 7.5 years were 77.8%, 72.0%, 58.7% and 50.6%, respectively. A total of 96% of return visits occurred within 2 years, with 33.7% having intervals of < 1 year. Perceived family history was not observed to affect continuation. However, abnormal findings were associated with a shortened participation. These high levels of continuation in ultrasound screening indicate that women take this disease seriously and demonstrate that this disease is of consequence to them.


Subject(s)
Mass Screening , Ovarian Neoplasms/diagnostic imaging , Patient Compliance , Adult , Aged , Aged, 80 and over , Costs and Cost Analysis , Female , Follow-Up Studies , Health Status , Humans , Kentucky , Middle Aged , Ovarian Neoplasms/economics , Patient Acceptance of Health Care , Risk Factors , Socioeconomic Factors , Ultrasonography
13.
J Rehabil Res Dev ; 37(2): 127-33, 2000.
Article in English | MEDLINE | ID: mdl-10850818

ABSTRACT

The importance of mechanical influences during skeletal development has been well established in both experimental studies and computer models. Under conditions of embryonic immobilization, it has been observed that the early stages of joint formation proceed normally (up to and including interzone formation), but the later stages of joint cavitation and maintenance are impaired, resulting in fusion of the cartilaginous elements across the presumptive joint line. Two structures in particular are noticeably absent from late-stage synovial joints in immobilized chick embryos: the menisci of the tibiofemoral joint and the plantar tarsal sesamoid of the tibiotarsal joint. Both of these fibrocartilaginous structures are known to serve mechanical functions in postnatal animals, helping to distribute loads within the joint and, in the case of sesamoid structures, to provide a mechanical advantage to muscles acting across the joint. We demonstrate in this study that embryonic immobilization differentially affects the developmental fate of these two distinct fibrocartilages. The absence of the plantar tarsal sesamoid in late-stage immobilized embryos is due to a failure in the initial formation of this structure. In contrast, the early stages of meniscus formation proceed normally. Without the normal mechanical stimuli of skeletal muscle contractions, however, the meniscus fails to mature and ultimately degenerates.


Subject(s)
Bone and Bones/embryology , Cartilage/embryology , Embryonic and Fetal Development/physiology , Muscle, Skeletal/embryology , Stress, Mechanical , Animals , Bone and Bones/ultrastructure , Cartilage/ultrastructure , Chick Embryo , Knee Joint/embryology , Knee Joint/ultrastructure , Menisci, Tibial/embryology , Menisci, Tibial/ultrastructure , Muscle, Skeletal/ultrastructure , Reference Values
14.
J Dent Educ ; 64(12): 839-46, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11197945

ABSTRACT

A questionnaire assessing comfort levels and behaviors of dental hygienists concerning treatment of patients with special needs or disabilities was mailed to a random sample of 175 practicing dental hygienists in Idaho. All respondents had seen patients with disabilities, although 53 percent had never completed a formal course or received training directed specifically toward this population. Survey respondents were moderately to always comfortable treating special needs and disabled patients. Use of a wheelchair was the only disability in which clinicians were significantly more comfortable with treatment following completion of a course or receipt of training. Severity of a patient's disability and limited time were considered moderate to very high barriers to the provision of dental hygiene care. Recommended treatment planning techniques are being used to a limited extent, and respondents were slightly to moderately confident using alternative communication and treatment techniques. The findings suggest that although education or training was not strongly associated with comfort and confidence levels of these dental hygienists, they were interested in opportunities for further training in caring for patients with special needs.


Subject(s)
Attitude of Health Personnel , Dental Care for Disabled/psychology , Dental Hygienists/education , Dental Hygienists/psychology , Humans , Idaho , Patient Care Planning , Pilot Projects , Surveys and Questionnaires
15.
J Zoo Wildl Med ; 30(1): 151-7, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10367658

ABSTRACT

Over a 9-mo period, three adult ball pythons (Python regius) (one male, two females) were evaluated for severe dyspnea. Partial obstructions of the tracheal lumen were identified radiographically and/or visualized with a 3.0-mm rigid laparoscope inserted into the tracheal lumen in all three snakes. Administration of systemic antibiotics and nebulization resulted in partial improvement of the dyspnea. In two snakes, the tracheal lesions were removed with a rigid laparoscope and a flexible biopsy instrument inserted into the tracheal lumen. The other snake died and was necropsied. Histologically, the lesions from two snakes were determined to be benign chondromas. The chondromas were composed of a variably disorganized chondroid matrix populated by quiescent, normal-appearing chondrocytes within lacunae, although the chondrocytes were increased in density compared with normal hyaline cartilage and contained rare mitotic figures. The tracheal masses in one snake grew by expansion, not invasion, and were focally continuous with a mineralized cartilage tracheal ring, suggesting a benign nature. This is the second report of tracheal chondroma in ball pythons. Tracheal chondromas are exceedingly rare in humans and domesticated animals, suggesting a possible predisposition of ball pythons for this neoplasm.


Subject(s)
Boidae , Chondroma/veterinary , Tracheal Neoplasms/veterinary , Tracheal Stenosis/veterinary , Animals , Chondroma/complications , Chondroma/surgery , Female , Tracheal Neoplasms/complications , Tracheal Neoplasms/surgery , Tracheal Stenosis/etiology
16.
Muscle Nerve ; 22(3): 360-71, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10086897

ABSTRACT

Skin is a reservoir of sensory and autonomic nerve fibers that are potential indicators of peripheral nerve disease. Biopsies of skin have shown that sensory nerves in the most superficial layer of skin, the epidermal nerve fibers (ENFs), are reduced in patients with polyneuropathy. This report describes a minimally invasive skin blister method to isolate, image, and obtain quantitative analysis of ENFs. Blisters are made by applying a suction capsule to skin. The epidermal roof of the blister is excised, immunostained, whole mounted, and analyzed for ENF number and distribution. A reduction in number and abnormal distribution of ENFs are early indicators of peripheral nerve disease. Illustrations of skin blister and skin biopsy specimens from patients with different types of peripheral nerve disorders are included. These patients were chosen because their findings demonstrate the complementary information obtained by the blister and biopsy methods and the potential of the blister procedure to evaluate single nerve lesions and polyneuropathy and to follow the progress of ENF degeneration and regeneration.


Subject(s)
Blister/pathology , Epidermis/innervation , Peripheral Nervous System Diseases/pathology , Adult , Blister/etiology , Female , Histological Techniques , Humans , Male , Nerve Fibers/ultrastructure , Neural Conduction/physiology , Peripheral Nervous System Diseases/physiopathology , Reference Values , Sensation/physiology , Skin/pathology , Suction
17.
Health Soc Work ; 23(2): 86-95, 1998 May.
Article in English | MEDLINE | ID: mdl-9598391

ABSTRACT

The Bureau of Primary Health Care (BPHC) was developed to increase access to comprehensive primary and preventive health care and to improve the health status of medically underserved populations. Approximately 43 million Americans fall into this category, and the majority are poor, female, young, and uninsured. Under the Public Health Services Act, BPHC does not provide direct services, but rather assist local communities in identifying populations at risk of poor health outcomes and helps these communities through various programs. One of the newest initiatives of BPHC is the Office of Minority and Women's Health, developed with a mission to help reduce the disparities in the health status of women of racial and ethnic minority populations. This article outlines these disparities and discusses proposals for reducing them.


Subject(s)
Ethnicity , Health Services Accessibility , Medically Underserved Area , Public Health Administration , Social Work , Women's Health , Female , Humans , Medically Uninsured , United States
18.
J Womens Health ; 6(2): 199-207, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9140854

ABSTRACT

OBJECTIVE: To determine whether the gender of women's regular physicians, controlling for physician specialty, is associated with women's receiving key preventive services within recommended intervals. DESIGN: Cross-sectional, nationally representative women's health telephone survey conducted by Louis Harris and Associates in February and March 1993 for The Commonwealth Fund. PARTICIPANTS: A total of 2,525 women in the continental United States, > or = 18 years old, including oversamples of African-American and Hispanic women. MAIN OUTCOME MEASURES: Receipt of each of five preventive services (blood pressure reading, Pap smear, cholesterol test, clinical breast examination, and mammogram) within specific periods. RESULTS: Physician gender makes a significant difference for two specialty areas and for three preventive services. Patients of women family or general practitioners are more likely than the patients of men to have received a Pap smear or a blood cholesterol test within the last 3 years, and the patients of women internists are more likely to have received a Pap test. Physician gender is associated with a higher likelihood of mammography, but this finding was limited to patients ages 40-49 of women family or general practitioners. Physician gender does not affect receipt of blood pressure screening or breast examination. CONCLUSIONS: Analyses reveal limited evidence that physician gender affects women's receipt of preventive services. Physician specialty appears to be a more powerful predictor of preventive services received. The limited evidence for a physician gender effect, however, is relevant for those women who rely on a family or general practitioner or an internist for regular care.


Subject(s)
Physicians, Women , Primary Prevention/statistics & numerical data , Women's Health Services/statistics & numerical data , Adolescent , Adult , Aged , Cross-Sectional Studies , Data Collection , Female , Humans , Male , Middle Aged , Patient Compliance , Physician-Patient Relations , Sex Factors , United States
19.
J Med Chem ; 39(21): 4149-55, 1996 Oct 11.
Article in English | MEDLINE | ID: mdl-8863791

ABSTRACT

Novel 3- and 9-substituted analogs (4-19) of 10-deoxoartemisinin, 3, were prepared from the corresponding known lactones by one-pot reduction with sodium borohydride and boron trifluoride etherate. Reproducibility problems associated with this heterogeneous reaction were encountered on small reaction scales, and thus alternative methodology was sought for this reduction. Conversion of the lactones to tetrahydropyrans via the corresponding intermediate lactols was made more reproducible using a two-step sequence involving low-temperature reduction with diisobutylaluminum hydride followed by deoxygenation with boron trifluoride etherate in the presence of triethylsilane. In this manner, 10-deoxoartemisinin (3) could be obtained from artemisinin (1) in greater than 95% overall yield. All analogs were tested in vitro against W-2 and D-6 strains of Plasmodium falciparum. Several of the analogs were much more active than the natural product (+)-artemisinin (1) or 10-deoxoartemisinin (3). Conventional structure-activity relationships are discussed in relation to the bioassay data.


Subject(s)
Antimalarials/pharmacology , Artemisinins , Sesquiterpenes/pharmacology , Animals , Antimalarials/chemistry , Boranes , Borohydrides , Humans , In Vitro Techniques , Molecular Weight , Plasmodium falciparum/drug effects , Sesquiterpenes/chemistry , Structure-Activity Relationship
20.
Diagn Cytopathol ; 14(3): 226-32, 1996 May.
Article in English | MEDLINE | ID: mdl-8732652

ABSTRACT

Metaplastic breast carcinomas (MBC) account for < 5% of breast malignancies and have an uncertain prognostic significance. The tumors tend to grow rapidly, and most are negative for hormone receptors. Adenosquamous carcinomas and various types of carcinosarcomas may be classified as MBC. We evaluated the cytologic, histologic, and clinical parameters of 10 MBC to determine important diagnostic features of these tumors. A cytologic diagnosis of MBC, based on the identification of two distinct malignant components, was made preoperatively in five of 10 (50%) cases, and retrospectively in two additional cases; two specimens were inadequately cellular. Poorly-differentiated adenocarcinoma was the most frequently encountered component of MBC. It is recommended that malignant breast aspirates be carefully scrutinized for multiple neoplastic components. Our series of MBC differs from previous reports in that two cases presented as inflammatory breast cancer, one case was pregnancy-associated, and there was a higher incidence of estrogen and progesterone receptor positivity. No cancer-related deaths occurred during a mean follow-up period of over 6 yr.


Subject(s)
Breast Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Carcinoma/pathology , Carcinoma, Adenosquamous/pathology , Chondrosarcoma/pathology , Female , Humans , Immunohistochemistry , Metaplasia/pathology , Middle Aged , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis
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