333 results on '"Tsutomu Aoki"'
Search Results
302. ortho-Specific α-Hydroxyalkylation of Phenols with Aldehydes. An Efficient Synthesis of Saligenol Derivatives
- Author
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Wataru Nagata, Kyo Okada, and Tsutomu Aoki
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chemistry.chemical_compound ,Chemistry ,Organic Chemistry ,Organic chemistry ,Phenols ,Catalysis - Published
- 1979
303. Practical procedure for epimerization of 7α-amino-1-oxacephems to 7β-amino epimers
- Author
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Toshiro Konoike, Mitsuru Yoshioka, Wataru Nagata, Yuji Sendo, Nobuhiro Haga, and Tsutomu Aoki
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Schiff base ,Bicyclic molecule ,Stereochemistry ,Organic Chemistry ,Chloral ,Borohydride ,Biochemistry ,Hydrolysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Lactam ,Organic chemistry ,Epimer - Abstract
7α-Amino-1-oxacephems can be epimerized to their 7β-amino epimers by treatment with chloral to give Schiff bases, followed by dehydrochlorination with Hunig base, borohydride reduction, and hydrolysis.
- Published
- 1985
304. cis-Halovinylthioacetamido side chain, a new effective structural element for 7.BETA.-substitution in cephem and oxacephem antibiotics. II. 7.BETA.-cis-Fluorovinylthioacetamino-7.ALPHA.-methoxy-1-oxacephems
- Author
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YASUHIRO NISHITANI, TSUTOMU AOKI, TOSHIRO KONOIKE, HIROMU TAKAHASHI, SADAO YAMAMOTO, YUTAKA NISHINO, MITSURU YOSHIOKA, TERUJI TSUJI, YOSHIHIDE KOMATSU, SHINZO MATSUURA, TADASHI YOSHIDA, and WATARU NAGATA
- Subjects
Pharmacology ,Structure-Activity Relationship ,Drug Discovery ,Microbial Sensitivity Tests ,Moxalactam - Abstract
The synthesis and in vitro activity of 1-oxacephem derivatives having a substituted or a non-substituted cis-fluorovinylthioacetamido side chain at C-7 are described. Of these new 1-oxacephem antibiotics, 2355-S (42a) shows good antibacterial activity against Gram-positive and Gram-negative bacteria, and very favorable pharmacokinetic properties.
- Published
- 1988
305. New route to 3-(substituted) methyl 1-oxa- and (1-thia)cephems from 3-exomethylene intermediates via sulfenyl chloride adducts
- Author
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Toshiro Konoike, Mitsuru Yoshioka, Tsutomu Aoki, Hikaru Itani, Wataru Nagata, and Teruji Tsuji
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Sulfenyl chloride ,chemistry.chemical_compound ,chemistry ,Organic Chemistry ,Drug Discovery ,Nucleophilic substitution ,Organic chemistry ,Ester hydrolysis ,Ring (chemistry) ,Biochemistry ,Adduct - Abstract
Addition of methane- and benzenesulfenyl chlorides to 3-exomethylene-1-oxacephams 10 and 14 gave 3β-sulfenyl-3α-chloromethyl adducts 11 and 15. Nucleophilic substitution of the adducts proceeded facilely to afford compounds 18–23, which were converted into Δ3-derivatives 26 and 27 by oxidative elimination. This new route, as illustrated by the sequence 6→7→8→3, has an essential advantage in using the saturated intermediates 7 and 8 with a stabler β-lactam ring which is compatible in nucleophilic substitution, alkaline ester hydrolysis and further manipulations. These synthetic features are well demonstrated by successful synthesis of 1-oxacefamandol 35 and 7β-(2-thienylacetyl-amino)-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3- acid (45)
- Published
- 1983
306. Total Synthesis of dl-3α-Acetoxy-5β-pregna-9 (11), 16-dien-20-one
- Author
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Tsutomu Aoki, Wataru Nagata, and Tadao Terasawa
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Adrenal Cortex Hormones ,Adrenal cortex hormones ,Chemistry ,Stereochemistry ,Chemistry, Pharmaceutical ,Research ,Drug Discovery ,Total synthesis ,Steroids ,General Chemistry ,General Medicine - Published
- 1963
307. Stereospecific total synthesis of rac. 5α-pregnan-3β-ol-20-one
- Author
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W. Nagata, Tsutomu Aoki, and T. Terasawa
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Stereospecificity ,Chemistry ,Stereochemistry ,Organic Chemistry ,Drug Discovery ,Total synthesis ,Biochemistry - Published
- 1963
308. Uber angular substituierte polycyclische Verbindungen. III. Alkalische Degradation von 3α-Alkoxy-3β-amino-5β-cholestan-5-carbonsaure-γ-laktam
- Author
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Wataru Nagata, Shoichi Hirai, Ken'ichi Takeda, and Tsutomu Aoki
- Subjects
Chemistry ,Drug Discovery ,General Chemistry ,General Medicine ,Medicinal chemistry - Abstract
3α-Alkoxy-3β-amino-5β-cholestan-5-carbonsaure-γ-laktam, (IV oder VI), wurde einer alkalischen Degradation in Athylenglykol unterworfen und durch die nachfolgenden Umsetzungen des rohen Produktes wurde gezeigt, daβ dabei je nach der Konzentration von Alkali, 3α-Hydroxy-carbonsaure (XIV) oder 3-Oxo-carbonsaure (XII) zum groβten Teil entstanden ist, wenn auch in nicht genugender Ausbeute. Es wurde ferner gezeigt, daβ diese Degradation nach der Art der sogenannten "1, 4-Eliminierung unter Fragmentierung" verlief.
- Published
- 1961
309. Totalsynthetische Untersuchungen an Steroiden. VI. Einfuhrung der C-Substituenten in die angulare Stellung der kondensierten Ringsysteme. (1). Einwirkung von Kaliumcyanid auf rac-D-Homo-18-nor-androstan-derivaten
- Author
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Wataru Nagata, Ken'ichi Takeda, Tsutomu Aoki, and Tadao Terasawa
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Stereochemistry ,Chemistry ,Drug Discovery ,General Chemistry ,General Medicine - Abstract
Durch Einwirkung von Kaliumcyanid und anschlieβende Acetylierung lieβ sich rac-3β-Hydroxy-D-homo-18-nor-5α-androst-13 (17a)-en-17-on (I) unter der 1, 4-Additionsreaktion des Cyanidions und nachfolgender Verseifung glatt in die epimere Brucken-Verbindung, namlich (13∼17) β-sowie (13∼17) α-Laktamol (IV), (V) und deren Acetate (VI) und (VII) verwandeln. Ferner wurden durch Abanderung der nachtraglichen Reaktionsfolgen, z. B. Alkylierung und Acetylierung oder Oxydierung, eine Reihe von beim C13 epimeren C17-Alkoxylaktamolen, z. B. (VIII), (IX), (X), (XI), (XX) und (XXI), synthetisiert. Die 13-Cyanverbindungen, wie (XV), (XVI) und (XVII), konnten erst durch kurze Einwirkung von Kaliumcyanid auf (III) oder durch Verwendung einer begrenzten Menge von Kaliumcyanid an (I)-Acetat (II) hergestellt werden. Die raumlichen Strukturen aller hierbei erhaltenen Verbindungen wurden ermittelt. Die hier eingefuhrten Reaktionsfolgen stellen eine neue Method fur die Einfuhrung der angularen C-Substituente dar und lieferten einen Anhaltspunkt zur Totalsynthese der normalen sowie 18-funktionierten Steroide.
- Published
- 1961
310. Tela de polipropileno versus correção sítio-especifica no tratamento do prolapso de parede vaginal anterior: resultados preliminares de ensaio clínico randômico
- Author
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Tsutomu Aoki, Eliana Duarte, Jacqueline Leme Lunardelli, Antonio Pedro Flores Auge, André Lima de Oliveira, Silvia da Silva Carramão, and Nucelio Lemos
- Subjects
medicine.medical_specialty ,Telas Cirúrgicas ,lcsh:Surgery ,Procedimentos Cirúrgicos Ginecológicos ,law.invention ,Gynecologic Surgical Procedures ,Randomized controlled trial ,law ,Uterine Prolapse ,Prolapso Uterino ,medicine ,Soalho Pélvico ,Prospective randomized study ,Stage (cooking) ,Anterior vaginal wall prolapse ,Pelvis ,Pelvic floor ,business.industry ,Pelvic Floor ,lcsh:RD1-811 ,Surgical Mesh ,Surgery ,Surgical morbidity ,Polypropylene mesh ,medicine.anatomical_structure ,business - Abstract
OBJETIVO: Comparar o uso de tela de polipropileno e correção sitio-específica no tratamento cirúrgico do prolapso vaginal anterior. MÉTODOS: Estudo prospectivo randômico comparativo em que foram operadas 32 pacientes com idades entre 50 e 75 anos, que apresentavam prolapso vaginal anterior estádio III ou IV, ou recidivado. A estática pélvica foi avaliada segundo as recomendações da International Continence Society (ICS), o sistema POP-Q e pelo Índice de Quantificação de Prolapso (POP-Q-I) Absoluto e Relativo. Para o rastreamento da incontinência urinária de esforço oculta todas as pacientes, sintomáticas ou não, foram submetidas a estudo urodinâmico em posição semi-ginecológica e semi-sentada, com redução do prolapso com pinça de Cheron. Registrou-se o tempo cirúrgico, o volume de sangramento intra-operatório e as complicações intra e pós-operatórias. O tempo de seguimento médio do estudo foi de 8,5 meses. RESULTADOS: Em relação aos resultados anatômicos ocorreu melhores resultados com a utilização de tela de polipropileno sobre o reparo sitio-específico. Em relação à morbidade cirúrgica, observou-se menor tempo cirúrgico no grupo em que utilizou-se tela. CONCLUSÃO: Houve superioridade dos resultados anatômicos obtidos com a utilização de tela de polipropileno sobre o reparo sitio-específico. OBJECTIVE: Pelvic organ prolapse is a disorder caused by the imbalance between the forces responsible for supporting the pelvic organs in their normal position and those that tend to expel them from the pelvis. Anterior vaginal wall prolapse, known as cystocele, is the most common form of prolapse and can result from lesions in different topographies of the endopelvic fascia. Currently, a woman has an 11% risk of being submitted to a surgical procedure to correct pelvic floor disorder, and a 29% chance of being reoperated due to failure in the first surgery. METHODS: A prospective randomized study was conducted to compare the use of polypropylene mesh with site-specific repair in the surgical treatment of anterior vaginal prolapse. Thirty-two patients aged between 50 and 75 years, who had previous vaginal prolapse at stage III or IV, or prolapse recurrence, were operated. Mean follow-up was 8.5 months. RESULTS: The results demonstrate the superiority of the anatomical outcomes with the use of polypropylene mesh over site-specific repair. Regarding surgical morbidity, shorter operative time was observed for the mesh group. CONCLUSION: The results observed in this study indicate the superiority of anatomical results obtained with the use of polypropylene mesh over site-specific repair.
311. Validation of the Pelvic Organ Prolapse Quantification Index (POP-Q-I): a novel interpretation of the POP-Q system for optimization of POP research.
- Author
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Antonio Auge, Jacqueline Lunardelli, Silvia Carramão, Ana Faria, and Tsutomu Aoki
- Subjects
PELVIS ,UROGYNECOLOGY ,UROLOGY ,GYNECOLOGY - Abstract
Abstract Even though very precise at describing pelvic organ position, our criticism to the Pelvic Organ Prolapse Quantification (POP-Q) system is its limited ability to quantify the prolapse itself, since it still classifies prolapse into four stages, almost the same way as Baden and Walker (Clin Obstet Gynecol 15(4):1070–1072, 1972) did in 1972. As a result, the same grade can include a wide prolapse intensity range. The objective of this study was to assess inter-observer reliability in the Pelvic Organ Prolapse Quantification Index (POP-Q-I; Lemos et al., Int Urogynecol J 18(6):609–611, 2007) on a prospective randomized trial. Fifty consecutive women were prospectively examined by two members of the urogynecology staff, blinded to each other’s results. Spearman’s rank correlation was used to assess inter-observer reliability. Excellent correlation coefficients were observed, with an overall coefficient of 96.5% (CI: 0.889–1.042; p [ABSTRACT FROM AUTHOR]
- Published
- 2008
312. Optimizing pelvic organ prolapse research.
- Author
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Antonio Flores Auge, Jacqueline Lunardelli, Armando Brites Frade, Camila Frade, André de Oliveira, Paulo Ayroza Galvão Ribeiro, and Tsutomu Aoki
- Subjects
PELVIC abnormalities ,MEDICAL innovations ,MEDICAL technology ,PUBLIC health - Abstract
Abstract  For many years, researchers on this field have suffered from the lack of an efficient method for describing pelvic organ prolapse. Struggling to solve this problem, the International Continence Society has proposed a pelvic organ prolapse quantification (POP-Q) system [Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, Klarskov P, Shull B, Smith ARB, Am J Obstet Gynecol, 175(1):1956â1962, 1996], which was validated as a precise and reproducible technique for describing pelvic organ position. However, even though very precise at describing pelvic organ position, our critic to this system is its limited ability to quantify the prolapse itself, since it still classifies prolapse into four grades, almost the same way as Baden and Walker did in 1972. As a result, the same grade can include a wide prolapse intensity range. The objective of this paper is to propose a method that makes POP research more efficient by directly measuring prolapse as a continuous variable that requires lesser number of subjects in order to achieve statistical significance. [ABSTRACT FROM AUTHOR]
- Published
- 2007
313. New Constraint on the Atmosphere of (50000) Quaoar from a Stellar Occultation.
- Author
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Ko Arimatsu, Ryou Ohsawa, George L. Hashimoto, Seitaro Urakawa, Jun Takahashi, Miyako Tozuka, Yoichi Itoh, Misato Yamashita, Fumihiko Usui, Tsutomu Aoki, Noriaki Arima, Mamoru Doi, Makoto Ichiki, Shiro Ikeda, Yoshifusa Ita, Toshihiro Kasuga, Naoto Kobayashi, Mitsuru Kokubo, Masahiro Konishi, and Hiroyuki Maehara
- Published
- 2019
- Full Text
- View/download PDF
314. Reverberation Measurements of the Inner Radii of the Dust Tori in Quasars.
- Author
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Takeo Minezaki, Yuzuru Yoshii, Yukiyasu Kobayashi, Shota Sugawara, Yu Sakata, Keigo Enya, Shintaro Koshida, Hiroyuki Tomita, Masahiro Suganuma, Tsutomu Aoki, and Bruce A. Peterson
- Subjects
SEYFERT galaxies ,QUASARS ,ACTIVE galactic nuclei ,HARD X-rays ,DUST ,DECOMPOSITION method ,TORUS ,GAMMA ray bursts - Abstract
We present the results of a dust-reverberation survey of quasars at redshifts z < 0.6. We found a delayed response of the K-band flux variation after the optical flux variation in 25 out of 31 targets, and obtained the lag time between them for 22 targets. Combined with the results for nearby Seyfert galaxies, we provide the largest homogeneous collection of K-band dust-reverberation data for 36 type 1 active galactic nuclei (AGNs). This doubles the sample and includes the most distant AGN and the largest lag so far measured. We estimated the optical luminosity of the AGN component of each target using three different methods: spectral decomposition, the flux-variation-gradient method, and image decomposition. We found a strong correlation between the reverberation radius for the innermost dust torus and the optical luminosity over a range of approximately four orders of magnitude in luminosity, as is already known for Seyfert galaxies. We estimated the luminosity distances of the AGNs based on their dust-reverberation lags, and found that the data in the redshift–distance diagram are consistent with the current standard estimates of the cosmological parameters. We also present the radius–luminosity relations for isotropic luminosity indicators such as the hard X-ray (14–195 keV), [O IV] 25.89 μm, and mid-infrared (12 μm) continuum luminosities, which are applicable to obscured AGNs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
315. cis-Halovinylthioacetamido side chain, a new effective structural element for 7 beta-substitution in cephem and oxacephem antibiotics. I. 7 beta-cis-Chlorovinylthioacetamino-7 alpha-methoxy-1-oxacephems
- Author
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Wataru Nagata, Tadashi Yoshida, Yasuhiro Nishitani, and Tsutomu Aoki
- Subjects
Pharmacology ,Cephem ,Bicyclic molecule ,Stereochemistry ,medicine.drug_class ,Carboxamide ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Drug Discovery ,Side chain ,Lactam ,medicine ,Antibacterial activity ,Oxacephem ,Antibacterial agent ,Moxalactam - Abstract
The synthesis and in vitro activity of 7 beta-(substituted vinylthioacetamido)-1-oxacephem antibiotics are described. The compounds having a cis-chlorovinylthioacetamido group at C-7 showed high activity against Gram-positive as well as Gram-negative bacteria. The most interesting compound of the series was 51 I because of its high activity and high plasma level in mice.
- Published
- 1988
316. Synthesis of bridged steroids. V. Cholestane derivatives having a bridged 3-azabicyclo[3.3.1]nonane ring system
- Author
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Wataru Nagata, Tsutomu Aoki, and Tsutomu Sugasawa
- Subjects
Bridged-Ring Compounds ,Chemical Phenomena ,Cholestanes ,Chemistry ,Stereochemistry ,chemistry.chemical_element ,Alcohol ,General Chemistry ,General Medicine ,Ring (chemistry) ,Medicinal chemistry ,Amino Alcohols ,chemistry.chemical_compound ,Stereospecificity ,Yield (chemistry) ,Drug Discovery ,Cholestane ,Lithium ,Nonane - Abstract
Cholestane derivative (IIb) having a bridged 3-azabicyclo [3. 3. 1] nonane ring system was synthesized from 3-oxo-5α-cholestane-5-carbonitrile (III) by a six-step reaction sequence. The over-all yield was very high indicating high stereospecificity or uniformity of the reaction used. Reduction of 3α-formyl-3β-methyl-5α-cholestane-5-carbonitrile (VIII) to the amino alcohol (Xa) was effected by means of lithium aluminum hydride reduction in the presence of aluminum chloride.
- Published
- 1968
317. One-step synthesis of bridged aziridines
- Author
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Kyozo. Kawata, Tsutomu Aoki, Shoichi Hirai, and Wataru Nagata
- Subjects
Colloid and Surface Chemistry ,Chemistry ,One-Step ,General Chemistry ,Biochemistry ,Combinatorial chemistry ,Catalysis - Published
- 1967
318. Improved Synthesis of 3'-Nor-1-oxacephems
- Author
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Wataru Nagata, Kyoji Minami, Tsutomu Aoki, Tadatoshi Kubota, and Yoshio Hamashima
- Subjects
Pharmacology ,Chemistry ,Organic Chemistry ,Combinatorial chemistry ,Analytical Chemistry - Published
- 1982
319. Stereochemistry in Borohydride Reduction of 7-iminocephems: An Improved Method for Conversation of the 7a-Amino-1-oxa(thia)cephems into the 7b-Amino Isomers
- Author
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WaTaru Nagata, Tsutomu Aoki, and Wataru Nagata
- Subjects
Pharmacology ,Bicyclic molecule ,Stereochemistry ,Organic Chemistry ,Improved method ,Borohydride ,Analytical Chemistry ,Reduction (complexity) ,chemistry.chemical_compound ,chemistry ,Chemical reduction ,Hemiaminal ,Lactam ,Organic chemistry ,heterocyclic compounds - Abstract
Methanolyse des derives amino-7α en derives amino-7β methoxy-7α ou derives imino-7 suivie de reduction en derives amino-7β
- Published
- 1989
320. Convenient Synthesis of 3'-Substituted Methyl 7a -Methoxy-1-oxacephems
- Author
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Wataru Nagata, Tsutomu Aoki, Mitsuru Yoshioka, Susumu Kamata, Toshiro Konoike, and Nobuhiro Haga
- Subjects
Pharmacology ,Organic Chemistry ,Analytical Chemistry - Published
- 1981
321. Stereochemical Studies of 1-Oxacephams by Means of NMR Spectroscopy. A Useful Shift Rule for Determination of the 3-Substituent Configration
- Author
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WaTaru Nagata, Tsutomu Aoki, Wataru Nagata, Yohko Yoshimura, Junko Nishikawa, and Kazuo Tori
- Subjects
Pharmacology ,chemistry.chemical_compound ,Shift rule ,Bicyclic molecule ,chemistry ,Computational chemistry ,Stereochemistry ,Organic Chemistry ,Substituent ,Chemical solution ,Nuclear magnetic resonance spectroscopy ,Nuclear Overhauser effect ,Analytical Chemistry - Published
- 1987
322. Synthetic Studies on b-Lactam Antibiotics 9. Trans-formations of Penicillin to 3'-Substituted Cephalosporins
- Author
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Teruji Tsuji, Shoichiro Uyeo, Tsutomu Aoki, Hikaru Itani, and Wataru Nagata
- Subjects
Pharmacology ,Penicillin ,chemistry.chemical_compound ,Stereochemistry ,medicine.drug_class ,Chemistry ,Organic Chemistry ,Antibiotics ,Cephalosporin ,medicine ,Lactam ,Analytical Chemistry ,medicine.drug - Published
- 1978
323. Synthetic Studies on b-Lactam Antibiotics 8. A Useful Method for Preparation of Penicillin a-Sulfoxides
- Author
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Wataru Nagata, Shoichiro Uyeo, and Tsutomu Aoki
- Subjects
Pharmacology ,Penicillin ,chemistry.chemical_compound ,Chemistry ,medicine.drug_class ,Organic Chemistry ,Antibiotics ,medicine ,Lactam ,Combinatorial chemistry ,Analytical Chemistry ,medicine.drug - Published
- 1978
324. Additions and Corrections - One-Step Synthesis of Bridged Aziridines
- Author
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Kyozu. Kawata, Shoichi Hirai, Tsutomu Aoki, and Wataru Nagata
- Subjects
Colloid and Surface Chemistry ,Computational chemistry ,Chemistry ,One-Step ,General Chemistry ,Biochemistry ,Catalysis - Published
- 1967
325. Calibration of AGN Reverberation Distance Measurements.
- Author
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Shintaro Koshida, Yuzuru Yoshii, Yukiyasu Kobayashi, Takeo Minezaki, Keigo Enya, Masahiro Suganuma, Hiroyuki Tomita, Tsutomu Aoki, and Bruce A. Peterson
- Published
- 2017
- Full Text
- View/download PDF
326. Distinct Elements Confer the Blocking and Bypass Functions of the Bithorax Fab-8 Boundary.
- Author
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Kyrchanova, Olga, Wolle, Daniel, Sabirov, Marat, Kurbidaeva, Amina, Tsutomu Aoki, Oksana Maksimenko, Kyrchanova, Maria, Georgiev, Pavel, and Schedl, Paul
- Subjects
- *
CHROMOSOME analysis , *GENE expression , *INSECTS , *TRANSCRIPTION factors - Abstract
Boundaries in the Drosophila bithorax complex (BX-C) enable the regulatory domains that drive parasegment-specific expression of the three Hox genes to function autonomously. The four regulatory domains (iab-5, iab-6, iab-7, and iab-8) that control the expression of the Abdominal-B (Abd-B) gene are located downstream of the transcription unit, and are delimited by the Mcp, Fab-6, Fab-7, and Fab-8 boundaries. These boundaries function to block cross talk between neighboring regulatory domains. In addition, three of the boundaries (Fab-6, Fab-7, and Fab-8) must also have bypass activity so that regulatory domains distal to the boundaries can contact the Abd-B promoter. In the studies reported here, we have undertaken a functional dissection of the Fab-8 boundary using a boundary-replacement strategy. Our studies indicate that the Fab-8 boundary has two separable subelements. The distal subelement blocks cross talk, but cannot support bypass. The proximal subelement has only minimal blocking activity but is able to mediate bypass. A large multiprotein complex, the LBC (large boundary complex), binds to sequences in the proximal subelement and contributes to its bypass activity. The same LBC complex has been implicated in the bypass activity of the Fab-7 boundary. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
327. Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex.
- Author
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Kaye, Emily G., Kurbidaeva, Amina, Wolle, Daniel, Tsutomu Aoki, Schedl, Paul, and Larschan, Erica
- Subjects
- *
INSECT chromatin , *DROSOPHILA as laboratory animals , *LOCUS (Genetics) , *X chromosome , *GENETIC regulation , *INSECTS - Abstract
Chromatin entry sites (CES) are 100- to 1,500-bp elements that recruit male-specific lethal (MSL) complexes to the X chromosome to upregulate expression of X-linked genes in male flies. CES contain one or more ~20-bp GA-rich sequences called MSL recognition elements (MREs) that are critical for dosage compensation. Recent studies indicate that CES also correspond to boundaries of X-chromosomal topologically associated domains (TADs). Here, we show that an ~1,000-kDa complex called the late boundary complex (LBC), which is required for the functioning of the Bithorax complex boundary Fab-7, interacts specifically with a special class of CES that contain multiple MREs. Mutations in the MRE sequences of three of these CES that disrupt function in vivo abrogate interactions with the LBC. Moreover, reducing the levels of two LBC components compromises MSL recruitment. Finally, we show that several of the CES that are physically linked to each other in vivo are LBC interactors. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
328. MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women.
- Author
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Queiroz D'Elia, Priscila, dos Santos, Aline Amaro, Bianco, Blanca, Barbosa, Caio Parente, Christofolini, Denise Maria, and Tsutomu Aoki
- Subjects
- *
METHYLENETETRAHYDROFOLATE reductase , *ISOHORMONES , *FERTILIZATION in vitro , *WOMEN , *EMBRYOS , *GENETIC research , *OVUM - Abstract
The aim of this study was to investigate the association between MTHFR gene polymorphisms and IVF outcomes in Brazilian women undergoing assisted reproduction treatment. A prospective study was conducted in the Human Reproduction Department at the ABC University School of Medicine and the Ideia Fertility Institute between December 2010 and April 2012. The patient population was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms C677T and A1298C were evaluated and compared with laboratory results and pregnancy rates. The C677T variant was associated with proportions of mature (P = 0.006) and immature (P = 0.003) oocytes whereas the A1298C variant was associated with number of oocytes retrieved (P = 0.044). The polymorphisms, whether alone or in combination, were not associated with normal fertilization, good-quality embryo or clinical pregnancy rates. This study suggests that the number and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T and A1298C. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
329. Gene expression of prolactin and its receptors in the pituitary and uterus of the metoclopramide-treated female mouse
- Author
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Vinicius Cestari do Amaral, Gustavo Arantes Rosa Maciel, José Maria Soares Júnior, Tsutomu Aoki, Aarão Mendes Pinto Neto, and Manuel de Jesus Simoes
- Abstract
INTRODUÇÃO: A prolactina é um hormônio polipeptídico, que possui reconhecida ação sistêmica, principalmente na fisiologia da reprodução, porém, seu desequilíbrio, em especial a hiperprolactinemia, é cada vez mais frequente na prática clínica. Apesar de ser um distúrbio relativamente comum, ainda existem dúvidas quanto aos efeitos moleculares da hiperprolactinemia no trato genital, particularmente no útero, e também na hipófise. O presente estudo teve por objetivo verificar os efeitos da hiperprolactinemia induzida pela metoclopramida na expressão gênica da prolactina e de seus receptores no útero e na hipófise de camundongo fêmea. MÉTODOS: Utilizaram-se 49 camundongos fêmeas (Wistar), randomicamente divididas em 7 grupos contendo 7 animais cada: 1) SS não ovariectomizadas que receberam solução salina (veículo); 2) M não ovariectomizadas tratadas com metoclopramida; 3) OSS ovariectomizadas tratadas com solução salina (veículo); 4) OM ovariectomizadas tratadas com metoclopramida; 5) OME ovariectomizadas tratadas com metoclopramida e 17-estradiol; 6) OMP ovariectomizadas tratadas com metoclopramida e progesterona micronizada; 7) OMEP ovariectomizadas tratadas com metoclopramida, 17-estradiol e progesterona micronizada. Após 50 dias os animais foram sacrificados sendo retirados o útero e a hipófise de cada animal para extração do ácido ribonucleico total, que foi utilizado para a síntese de ácido desoxirribonucleico complementar e avaliação da expressão gênica da prolactina e das diferentes isoformas de seus receptores, por reação em cadeia da polimerase em tempo real. RESULTADOS: Na hipófise, em animais não ovariectomizados, o tratamento com metoclopramida aumentou a expressão do gene que codifica a prolactina em relação ao tratamento apenas com o veículo. Nos animais castrados, a progesterona isoladamente ou associada ao estrogênio determinou o incremento do RNA mensageiro da prolactina em relação aos outros animais castrados que receberam outras combinações de tratamento. Este efeito foi semelhante ao da metoclopramida em animais com os ovários intactos. Em relação ao receptor de prolactina, o estrogênio e a progesterona, isoladamente, foram responsáveis pelo incremento da isoforma S2. No útero houve aumento na expressão de RNA mensageiro de prolactina após tratamento com metoclopramida ou com tratamento isolado ou combinado de estrogênio e progesterona. A ovariectomia determinou a redução da expressão das isoformas S1 e S2 do receptor de prolactina de todas as isoformas estudadas. Já o tratamento estroprogestativo determinou elevação da formas S3 e L do receptor, enquanto com a progesterona isoladamente causou apenas o incremento da forma L do receptor da prolactina no útero dos animais castrados. CONCLUSÕES: Nossos dados sugerem que o tratamento com metoclopramida altera de forma diferente a expressão de prolactina e de seus receptores quando se compara o resultado da hipófise em relação ao útero em camundongos fêmeas castrados e tratados com esteróides sexuais INTRODUCTION: Prolactin is a polypeptide hormone with a recognized systemic action mainly on reproductive physiology. However, prolactin imbalance, particularly hyperprolactinemia, is increasingly more frequent in clinical practice. Although it is a comparatively common disorder, there are still doubts about the molecular effects of hyperprolactinemia on the genital tract especially in the uterus and the pituitary. The present study aimed at verifying the effects of metoclopramide-induced hyperprolactinemia on the gene expression of prolactin and its receptors in the uterus and pituitary of the female mouse. METHODS: Forty-nine female Wistar mice were randomized to 7 equal-sized groups as follows: 1) SS nonoophorectomized mice treated with saline solution (vehicle); 2) M nonoophorectomized mice treated with metoclopramide; 3) OSS oophorectomized mice treated with saline solution (vehicle); 4) OM oophorectomized mice treated with metoclopramide; 5) OME oophorectomized mice treated with metoclopramide and 17-estradiol; 6) OMP oophorectomized mice treated with metoclopramide and micronized progesterone; 7) OMEP oophorectomized mice treated with metoclopramide, 17-estradiol, and micronized progesterone. The animals were sacrificed 50 days after the end of the treatment, and the uterus and pituitary of each animal were removed for extraction of total ribonucleic acid, which was then used for synthesizing complementary deoxyribonucleic acid and for evaluating the gene expression of prolactin and the different isoforms of its receptors by the real-time polymerase chain reaction. RESULTS: In the pituitary of the nonoophorectomized mice, the treatment with metoclopramide against that with vehicle alone increased the expression of the prolactin-encoding gene. In the castrated animals, progesterone by itself or in conjunction with estrogen determined a raise in prolactin messenger RNA as opposed to the two other treatments with different combinations. This effect was similar to that produced by metoclopramide in animals with intact ovaries. Estrogen and progesterone, acting independently of each other, were responsible for the increase in the S2 isoform of the prolactin receptor. In the uterus, there was heightened expression of prolactin messenger RNA under the effect of the treatment with metoclopramide or with estrogen and/or progesterone. Oophorectomy caused a greater reduction in expression of the prolactin receptor S1 and S2 isoforms than in the other isoforms. However, the combined estrogen plus progesterone treatment led to an increase in the S3 and L forms of the receptor, while progesterone alone resulted solely in a higher expression of the L form of the prolactin receptor in the endometrium of the castrated mice. CONCLUSION: Our data suggest that metoclopramide treatment induces different changes in the expression of prolactin and its receptors according to whether the effect occurs in the pituitary or the uterus of castrated female mice treated with sex steroids
- Published
- 2012
330. Experimental transplantation, subcutaneous and intraperitoneal, ovary in pigs: immunohistochemical and histomorphometric study
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Lia Cruz Vaz da Costa Damásio, Edmund Chada Baracat, José Maria Soares Júnior, Tsutomu Aoki, Alexandre Guilherme Zabeu Rossi, and Manuel de Jesus Simoes
- Abstract
O transplante autólogo de tecido ovariano constitui alternativa relevante na preservação da fertilidade e da função hormonal ovariana em mulheres sujeitas à falência ovariana prematura e infertilidade, por causas malignas, tratamentos adjuvantes ou cirurgias. É a única opção para crianças, fase pré-puberal e para mulheres que não podem retardar a quimioterapia ou não podem ser submetidas à estimulação do ciclo. O transplante ovariano autólogo pode ser, quanto ao local de reimplantação, ortotópico ou heterotópico e, quanto à conservação, a fresco ou após o período de criopreservação. As várias etapas envolvidas neste transplante são estudadas mundialmente na atualidade, como a retirada e preservação do tecido ovariano, as técnicas de criopreservação, o local apropriado para o reimplante e as possibilidades de redução da perda folicular. A avaliação da apoptose - morte celular programada - é útil na avaliação da rejeição e viabilidade dos enxertos de transplantes estabelecidos na prática clínica, tanto autólogos como heterólogos. Com o intuito de utilizar animais de maior porte, conseguir seguimento de médio prazo e realizar os procedimentos cirúrgicos por via laparoscópica, padrão ouro em humanos, o presente estudo utilizou como modelo experimental fêmeas suínas, em idade reprodutiva, da raça Minipig. Este projeto teve como propósito avaliar a influência da criopreservação e do local de implante na qualidade e na viabilidade do transplante autólogo de ovário, a fresco e após criopreservação, no tecido celular subcutâneo e na região intraperitoneal peri-infundibular. Foram avaliados a quantidade e a densidade folicular dos implantes e os aspectos morfológicos e histomorfométricos, bem como a apoptose, por meio da imunoexpressão de proteínas proapoptóticas- Bax e antiapoptóticas-Bcl-2, além da Caspase 3-clivada, fase final das vias extrínseca e intrínseca dos mecanismos de apoptose.Quarenta animais foram divididos em cinco grupos: Controle com ooforectomia (Grupo I), ooforectomia e transplante a fresco subcutâneo (Grupo II), a ooforectomia e transplante fresco intraperitoneal (Grupo III), ooforectomia e transplante criopreservado subcutâneo (Grupo IV) e ooforectomia e transplante criopreservado intraperitoneal (GrupoV). Os resultados mostraram que independente da técnica empregada, havia folículos em desenvolvimento e corpos lúteos em todos os tecidos ovarianos transplantados; que a contagem de folículos antrais não degenerados foi menor nos grupos após criopreservação em relação ao grupo controle e que a imunoexpressão sugestiva de apoptose ocorreu em todos os grupos transplantados, sendo maior nos transplantes intraperitoneais. Concluiu-se que a técnica utilizada para o transplante de ovário e criopreservação foi viável no modelo suíno, em tecido celular subcutâneo e na região intraperitoneal peri-infundibular. O transplante autólogo heterotópico subcutâneo apresentou melhores taxas de apoptose que o transplante ortotópico. Autotransplantation of ovarian tissue is an important alternative to preserve fertility and hormonal ovarian function in women undergoing ovarian failure and premature infertilidade, because of cancer or surgery. It is the only option for infants, pre-pubertal patients and for women who can not delay chemotherapy or not may be subjected to stimulation of the cycle. The various steps involved in the transplant are studied worldwide today, as the removal and preservation of ovarian tissue, the techniques of cryopreservation, the appropriate site and mechanisms to reduce follicular loss. Assessment of apoptosis - programmed cell death-is useful in the study of the viability of the grafts and rejection of transplants established in clinical practice, both autologous and heterologous. In order to use larger animals, getting following medium term (over 21 days) and to perform surgical procedures by laparoscopy (gold standard in humans), this study used an experimental model sows, reproductive age, Minipig race. This project aims to evaluate the influence of cryopreservation and implantation site of the quality and viability of ovarian autografts, fresh and after cryopreservation, at subcutaneous site and at intraperitoneal site. We analyzed the quantity and density of follicular implants and the morphological and histomorphometric as well as apoptosis, by proteins immunoexpression antiapoptotic and proapoptotic. Forty animals were divided into five groups: Control with oophorectomy (Group I), oophorectomy and fresh transplantation to subcutaneous site (Group II), oophorectomy and fresh transplantation to intraperitoneal site (Group III), oophorectomy and transplantation of cryopreserved ovarian tissue to subcutaneous site (Group IV) and oophorectomy and transplantation of cryopreserved ovarian tissue to intraperitoneal site (Group V). We concluded that the autologous ovarian transplantation was feasible in the technical proposals, in subcutaneous and intraperitoneal site in the porcine model; that regardless of the technique, there was developing follicles and corpora lutea in all ovarian tissue transplanted; that antral non-degenerate follicle count was lower in groups after cryopreservation that in the control group and that the immunoexpression of apotposis occurred in all transplanted groups, more evident in intraperitoneal transplants
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- 2011
331. Evaluation of markers of cell proliferation and apoptosis in eutopic and ectopic endometrial tissue in an experimental model of endometriosis in rabbits
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Júlio César Rosa e Silva, Antonio Alberto Nogueira, Tsutomu Aoki, Rui Alberto Ferriani, Sergio Britto Garcia, and Carlos Alberto Petta
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Gynecology ,medicine.medical_specialty ,Pathology ,business.industry ,Apoptosis ,Cell growth ,Experimental model ,medicine ,Endometriosis ,Obstetrics and Gynecology ,business ,medicine.disease ,Ectopic endometrial tissue - Abstract
Objetivo:Caracterizar o padrão de homeostase (proliferação celular e apoptose) de tecido endometrial eutópico e ectópico de coelhas submetidas à indução de lesões de endometriose por modelo experimental já conhecido, quatro e oito semanas após o procedimento de implantação endometrial. Material e Métodos:Estudo experimental animal sendo utilizado 20 coelhas adultas Nova Zelândia, fêmeas e virgens, submetidas à laparotomia para indução da lesão de endometriose, através da ressecção de um corno uterino e fixação no peritônio pélvico de fragmento de 5mm. As coelhas foram divididas em dois grupos de 10 animais, sendo os animais do grupo 1, sacrificados após 4 semanas da indução da lesão endometrial ectópica e os do grupo 2 após 8 semanas. A lesão foi excisada para análise histológica juntamentecom o corno uterino contralateral, comprovando a presença de tecido endometrial glandular e estromal. Reações de imunohistoquímica foram realizadas, no tecido endometrial eutópico e ectópico, para proliferação celular através do PCNA e para apoptose através do fas, na glândula e estroma, sendo obtido o índice de proliferação celular (IPC) e de apoptose (IA) através do número de células marcadas por 1000 contadas, e o índice dehomeostase tecidual através do coeficiente entre o IPC e IA. Resultados:Observou-se maior índice de proliferação no tecido ectópico, tanto glandular como estromal, quando comparado com o endométrio eutópico, com 4 e 8 semanas após a indução da lesão. Contudo, quando as lesões ectópicas foram comparadas entre si, com 4 e 8 semanas, não foi observada diferença significativa. Quando comparamos o índice de apoptose, observamos que não houve diferença entre o tecido ectópico e o eutópico, tanto glandular como estromal nas lesões induzidas e analisadas com 4 semanas, porém no tecido glandular das lesões analisadas com 8 semanas houve diferença significativa entre a lesão ectópica e o tecido endometrialeutópico 0,0819 ± 0,0213 e 0,0995 ± 0,01336, respectivamente (p=0,04). A homeostase tecidual foi calculada e observou-se uma tendência destes tecidos a proliferação, sempre com índicesde homeostase tecidual (IPC/IA) acima de 1. Conclusão:As lesões ectópicas parecem ter uma proliferação celular maior que o endométrio eutópico levando a uma tendência ao crescimento tecidual descontrolado nas lesões de endometriose induzidas. Objective: To characterize the pattern of tissue homeostasis (cell proliferation and apoptosis) of eutopic and ectopic endometrium in rabbitsfour and eight weeks after endometrium implantation for induction of endometriotic lesions by experimental standardized method. Material and methods: Animal experimental study with 20 female, virgins and adult New Zeland rabbits, submitted to laparotomy for endometriosis induction by resection of one uterine horn, isolation of the correspondent endometrium and fixation of a 5mm tissue segment to the pelvic peritoneum. The animals were divided in two groups of 10, group 1 was sacrificed after 4 weeks of endometriosis induction and group 2 eight weeks after the procedure. The lesion was excised for later histological analysis together with the opposite uterine horn, just to verify the presence of endometrial gland and stroma. Immunohistochemistry reactions were performed in order to study cell proliferation (by PCNA technique) and apoptosis (by fastechnique) in the eutopic and ectopic endometrium, and a Cell Proliferation Index (CPI) and an Apoptotic Index (AI) werecalculated based on these findings, considering the number of marked cellsper 1000 counted cells. The Homeostatic Tissue Index (HTI) was considered to be the relation between CPI and AI (CPI/AI). Gland and stroma were analyzed separately. Results: There was an increase in the CPI of the ectopic tissue, considering gland and stroma, after four and eight weeks of endometriosis induction when comparing to the eutopic one. However, when comparing the ectopic lesions, there was no difference between four and eight weeks of induction. Analyzing the only the AI, there was no difference between the eutopic and the ectopic endometrium with four weeks,nevertheless there was a significant difference in the glandular tissue of the lesions with eight weeks when comparing eutopic and ectopic tissues (0.0819 ± 0.0213 e 0.0995 ± 0.01336, respectively (p=0,04)). Based on HTI there was a tendency to cell proliferation on these tissues, always with and HTI (CPI/AI) higher than 1. Conclusions: Ectopic lesions seem to have a higher cell proliferation than the eutopic endometrium, tending to present an uncontrolled tissue growth in the endometriotic inducted lesions.
- Published
- 2007
332. Transvaginal ultrasound with Doppler velocimetry to study stromal volume and thickness and vascularization of the ovaries in polycystic ovary syndrome
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Marcelo Afonso Gonçalves, Hans Wolfgang Halbe, Tsutomu Aoki, Angela Maggio da Fonseca, Ceci Mendes Carvalho Lopes, and Ayrton Roberto Pastore
- Abstract
INTRODUÇÃO - A síndrome dos ovários policísticos (SOP) é uma das mais controversas entidades da endocrinologia ginecológica. Após o simpósio de Rotterdam, em 2003, ficou evidente a importância da morfologia ovariana para o diagnóstico e para a composição dos fenótipos. A ultra-sonografia transvaginal com dopplervelocimetria pode ajudar a analisar as variáveis implicadas na vascularização e a monitorar os ovários. OBJETIVO - Avaliar o volume, a espessura do estroma e a vascularização dos ovários de mulheres com SOP. MÉTODO - Estudo prospectivo com cinqüenta mulheres que foram divididas em dois grupos (grupo SOP: n=30 e grupo Normal: n=20) e submetidas à ultra-sonografia transvaginal com Dopplervelocimetria, entre o terceiro e sexto dias do ciclo menstrual, para a avaliação do volume e da espessura do estroma do ovário e dos índices de resistência (IR) e pulsatilidade (IP) nas artérias uterinas, artérias ovarianas e vasos do estroma. RESULTADOS - No grupo SOP, o volume ovariano e a espessura do estroma ovariano foram significativamente maiores. Também o IR e o IP das artérias uterinas e ovarianas foram significativamente maiores. Já o IR e o IP dos vasos do estroma foram significativamente menores no grupo SOP, em comparação com o grupo Normal. CONCLUSÃO - As mulheres com SOP, em relação às mulheres normais, têm aumento do volume e da espessura do estroma dos ovários. Também apresentam diminuição do fluxo ovariano; porém, com aumento da vascularização do estroma. INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most controversial conditions in gynecological endocrinology. After the symposium in Rotterdam in 2003, the importance of ovary morphology has become evident for the diagnosis and the composition of phenotypes. Transvaginal ultrasound with Doppler velocimetry can help us analyze the variables implied in vascularization and monitor the ovaries of women with PCOS. METHOD: Prospective study with 50 women who were divided into 2 groups (PCOS group: n=30 and Normal group = 20), submitted to transvaginal ultrasound with doppler velocimetry between the third and sixth day of the monthly period to assess size and thickness of ovarian stroma and index of resistance (IR) and pulsatility (IP) of uterine arteries, ovarian arteries and stromal vessels. RESULTS: In the PCOS group, ovarian size and thickness of ovarian stroma were significantly greater. Uterine and ovarian arteries IR and IP were significantly higher. IR and IP of stromal vessels were significantly lower in the PCOS group relative to the Normal group. CONCLUSION: PCOS female patients compared to normal women have increase size and thickness of ovarian stroma. They also present reduced ovarian flow, but there is increased vascularization of the stroma.
- Published
- 2007
333. Seric and peritoneal assessment of interleukin 1ß, 6 and protein amyloid A concentrations in patients with pelvic endometriosis
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Dani Ejzenberg, Mauricio Simões Abrão, Tsutomu Aoki, and Angela Maggio da Fonseca
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business.industry ,Medicine ,business - Abstract
Objetivo: determinar as concentrações séricas e peritoneais das interleucinas 1ß (IL-1ß) e 6 (IL-6) e da proteína amilóide A (SAA) em pacientes com endometriose pélvica. Métodos: foram avaliadas 97 pacientes submetidas à videolaparoscopia, 57 com endometriose (A), 27 com sintomas sugestivos porém sem endometriose (B) e 13 sem sintomas e doenças (C). Foram coletados no ato cirúrgico líquido peritoneal e sangue. As concentrações dos mediadores foram determinadas em pg/ml (IL-1 e 6) e ng/ml (SAA) por método imunoenzimático e leitura óptica. Resultados: (líquido peritoneal e sangue medianas) IL-1ß: A- 11,22 and 1,83; B- 15,62 and 1,16; C- 1,92 and 0,80; IL-6: A- 6,80 and 3,70; B- 8,60 and 3,90; C- 3,40 and 2,0; SAA- A- 310,30 and 14,01; B- 306,20 and 10,39; C- 53,4 e 9,5. Conclusão: as concentrações dos mediadores de inflamação avaliados estão elevadas no líquido peritoneal e no soro das mulheres com endometriose. Estas concentrações foram semelhantes às das pacientes com sintomas sugestivos porém sem a doença. A fase do ciclo menstrual, o tipo histológico envolvido e o local de acometimento da doença não influíram de forma significante nas concentrações séricas ou peritoneais de IL-1ß, IL-6 e SAA. Objective: to assess peritoneal and seric interleukin-1ß (IL-1ß), 6 (IL-6), and protein amyloid A (SAA) concentrations in patients with pelvic endometriosis. Methods: 97 patients were submitted to video laparoscopic surgery, 57 with endometriosis (A), 27 with suggestive symptoms but no endometriosis (B), and 13 without symptoms and diseases (C). Peritoneal fluid and blood were collected during the procedure. Mediator s concentration was determined in pg/ml (IL-1ß and IL-6) and ng/ml (SAA) through immunoenzimatic test and optic measure. Results: (peritoneal fluid and blood -medians) IL-1ß: A- 11,22 and 1,83; B- 15,62 and 1,16; C- 1,92 and 0,80; IL-6: A- 6,80 and 3,70; B- 8,60 and 3,90; C- 3,40 and 2,0; SAA- A- 310,30 and 14,01; B- 306,20 and 10,39; C- 53,4 e 9,5. Conclusion: the inflammation mediators are increased in the peritoneal fluid and blood of women with pelvic endometriosis. The concentrations are similar to those found in patients with suggestive symptoms but no endometriosis. The place of the disease, the histological type and the day of the menstrual cycle didn t alter peritoneal or seric concentration of these cytokines.
- Published
- 2007
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