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Biomedical subjects

Y Aoyagi

Publications and source records attributed to Y Aoyagi.

At least 91 records · Page 5Linked to original sources
PubMed1997

Antitumor activity of a novel quinoline derivative, TAS-103, with inhibitory effects on topoisomerases I and II.

A novel quinoline derivative, TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin -7-one dihydrochloride), was developed as an anticancer agent targeting topoisomerases (topo) I and II, with marked efficacy in solid tumors. TAS-103 inhibited topo I and II (IC50: 2 microM, 6.5 microM) at a concentration similar to or lower than those of previous agents, and had a strong cytotoxic effect on P388 and KB cells (IC50: 0.0011 microM, 0.0096 microM). TAS-103 stabilized topo I and II-DNA cleavable complexes in KB cells, generating a similar amount of topo II-DNA complex to that induced by etoposide (VP-16) but a smaller amount of topo I-DNA complex than that produced by camptothecin (CPT). In the in vivo study, intermittent i.v. administration was markedly effective against s.c.-implanted murine tumors. Furthermore, TAS-103 had marked efficacy against various lung metastatic tumors, and a broad antitumor spectrum in human tumor xenografts (derived from lung, colon, stomach, breast, and pancreatic cancer). The efficacy of TAS-103 was generally greater than that of irinotecan (CPT-11), VP-16, or cis-diamminedichloroplatinum (CDDP).

Adenocarcinoma↗
PubMed1997

Anti-platelet aggregation activity of some pyrazines.

This report describes the anti-platelet aggregation activity of 48 pyrazines. Among alkyl- and arylpyrazines tested, 2,3-diphenylpyrazines showed the strongest anti-platelet aggregation activity. Then, various substituents were introduced into the phenyl groups, and the 2,3-bis(p-methoxyphenyl)pyrazine derivatives were consequently found to possess considerably strong inhibitory activity.

Animals↗
PubMed1997

[Reactions and syntheses of pyrazines].

This review deals with syntheses and reactions of pyrazines, especially, of 2,5-disubstituted pyrazines. The description was made in due to order of 1) synthesis and properties of 2,5-disubstituted pyrazines, 2) synthesis of 2,5-disubstituted pyrazine N-oxides, 3) synthesis of pyrazinols, 4) synthesis and utilization of pyrazinethiols; preparation of aldehydes, utilization as an acyl carrier, and preparation of olefins via the elimination of pyrazinylsulfinyl group, 5) synthesis of aminopyrazines, 6) synthesis of azidopyrazines and their transformation to imidazoles, 7) palladium-catalyzed reactions of chloropyrazines; dechlorination, introduction of cyano, alkenyl, alkynyl, alkyl, and aryl groups to the pyrazine ring. The cross-coupling of chloropyrazines with aromatic heterocycles such as furan, thiophene, pyrroles, indoles, benzo[b]furan, benzo[b]thiophene, oxazole, thiazole, benz[b]oxazole, and benzo[b]thiazole is also described.

Pyrazines↗
PubMed1997

Interactions of physical training and heat acclimation. The thermophysiology of exercising in a hot climate.

Physical training and heat acclimation are both commonly adopted tactics to improve performance and/or tolerance times when individuals must compete or work in the heat. Potential benefits include: (i) improved aerobic fitness and thus a greater cardiovascular reserve (probably seen mainly after training); (ii) a lower resting body temperature that allows greater heat storage (probably seen mainly after acclimation); (iii) a decreased energy cost of a given intensity of exercise (seen after acclimation and also as the learning component of training); (iv) an enhanced sweating response at a given percentage of maximal effort (probably developed by both treatments); (v) a slower increase in body temperature owing to (iii) and/or (iv) [seen after both treatments]; (vi) a reduced cardiovascular stress because of changes in the autonomic nervous system (probably realised mainly by training), expansion of blood volume (seen after both treatments) and/or a decreased peripheral pooling of blood (probably found after both treatments); and (vii) improved subjective tolerance reflecting a decrease in the relative intensity of a given activity (probably seen mainly after training), a reduction in the physiological strain (found after both treatments) and/or habituation to heat-exercise stress (probably developed by both treatments). Factors affecting improvements in physiological and psychological responses to a given set of conditions include: (i) the individual's initial fitness and acclimatisation to heat; (ii) age, gender, hydration, sleep deprivation, circadian rhythms and in women the menstrual cycle: (iii) use of ergogenic aids such as fluid ingestion, carbohydrate and/or electrolyte replacement and blood doping; (iv) event or test conditions such as the mode of exercise, the severity of environmental heat stress and the type of clothing worn; and (v) treatment conditions such as the intensity, duration and frequency of exercise and/or heat exposure, the length of any rest intervals and cumulative depletion of body water and minerals.

Acclimatization↗
PubMed1996

Clinical significance of simultaneous determinations of alpha-fetoprotein and des-gamma-carboxy prothrombin in monitoring recurrence in patients with hepatocellular carcinoma.

BACKGROUND: Measurements of serum alpha-fetoprotein (AFP) concentration and plasma concentration of des-gamma-carboxy prothrombin (DCP) have been widely used for the early diagnosis of hepatocellular carcinoma (HCC). The two markers generally run parallel to each other. However, in our study, they sometimes fluctuated independently in response to tumor regression or recurrence. METHODS: A longitudinal series of concentrations of serum AFP and plasma DCP were determined simultaneously for 245 patients with HCC from the time of diagnosis to tumor recurrence after treatment. RESULTS: Positive reactions for AFP were noted in 168 patients (69%) and for DCP in 126 patients (51%). One hundred and ten of 245 patients with HCC (45%) were positive for both AFP and DCP. In 35 patients (14%), these 2 tumor markers fluctuated independently in response to tumor regression and recurrence. These patients were categorized into four groups as follows: Group 1 had elevated AFP only at diagnosis; it then decreased after treatment, but DCP was elevated at the time of tumor recurrence without AFP elevation (3 patients); Group 2 had elevated DCP at diagnosis and elevated AFP at tumor recurrence (4 patients); Group 3 had elevated AFP and DCP at diagnosis, but only AFP (8 patients) or DCP (7 patients) was elevated at tumor recurrence; Group 4 had only elevated AFP (2 patients) or DCP (11 patients) at diagnosis, but both AFP and DCP were elevated at tumor recurrence. CONCLUSIONS: The results of this study indicate that simultaneous determinations of AFP and DCP are useful for monitoring recurrence in patients with HCC after treatment, and that the decrease to normal levels of a single marker does not always indicate the absence of tumor recurrence.

Adolescent↗
PubMed1996

Determination of body heat storage: how to select the weighting of rectal and skin temperatures for clothed subjects.

Two methods of estimating body heat storage were compared under differing conditions of clothing and acclimation to heat. Sixteen male subjects underwent 6 consecutive days or two 6-day periods, separated by a 1-day rest period of heat acclimation, exercising 60 min.day-1 at 45%-55% of maximal aerobic power in a hot, dry environment (dry bulb temperature 40 degrees C; relative humidity 30%; and wind speed 0.3 m.s-1). Before and after acclimation, the subjects entered the same environment, wearing either normal light combat clothing or clothing protective against nuclear, biological, and chemical agents; they walked on a treadmill at 1.34 m.s-1, 0% slope continuously (n = 11 for normal clothing) or as repeated 15-min bouts of exercise followed by 15-min sitting rest (n = 5 for normal clothing and n = 16 for protective clothing). Average exposure times were 147 min (preacclimation) and 150 min (postacclimation) for continuous exercise and 150 min (both pre- and postacclimation) for intermittent exercise while wearing normal clothing, and 103 min (preacclimation) and 116 min (postacclimation) for intermittent exercise while wearing protective clothing. Heat storage was determined calorimetrically (from heat gains and heat losses) and thermometrically [using various weightings of rectal temperature (Tre) and mean skin temperature (Tsk)]. There were only minor (<5%) differences in estimated heat storage, whether calculations used a single specific heat (3.47 kJ.kg-1.degree C-1) or a value computed according to the subject's body composition. When wearing normal clothing, a formula with an invariant relative weighting for Tre to Tsk of 4:1 provided the best thermometric estimate of heat storage. When wearing protective clothing, the invariant relative weighting of 4:1 underestimated heat storage by 2%-12%; underestimation was attenuated by using respective relative weightings for a thermoneutral and hot environment of 2:1 and 2:1 or 4:1 and 9:1 before acclimation and 4:1 and 9:1 after acclimation. We conclude that the accuracy of thermometric estimates of heat storage can be improved by modifying the weighting factors according to environment, acclimation, and type of clothing.

Adult↗
PubMed1996

Residual analysis in the determination of factors affecting the estimates of body heat storage in clothed subjects.

Body heat storage can be estimated by calorimetry (from heat gains and losses) or by thermometry [from changes (delta) in mean body temperature (T b) calculated as a weighted combination of rectal (Tre) and mean skin temperatures (T sk)]. If an invariant weighting factor of Tre and T sk were to be used (for instance, delta T b = 0.8.delta Tre + 0.2 delta T sk under hot conditions), body heat storage could be over- or underestimated substantially relative to calorimetry, depending on whether the subject was wearing light or protective clothing. This study investigated whether discrepancies between calorimetry and thermometry arise from methodological errors in the calorimetric estimate of heat storage, from inappropriate weightings in the thermometric estimate, or from both. Residuals of calorimetry versus thermometric estimates were plotted against individual variables in the standard heat balance equation, applying various weighting factors to Tre and T sk. Whether light or protective clothing was worn, the calorimetric approach generally gave appropriate estimates of heat exchange components and thus heat storage. One exception was in estimating latent heat loss from sweat evaporation. If sweat evaporation exceeded 650 g.h-1 when wearing normal clothing, evaporative heat loss was overestimated and thus body heat storage was underestimated. Nevertheless, if data beyond this ceiling were excluded from the analyses, the standard 4:1 weighting matched calorimetric heat storage estimates quite well. When wearing protective clothing, the same 4:1 weighting approximated calorimetric heat storage with errors of less than approximately 10%, but only if environmental conditions allowed a subject to exercise for more than 90 min. The best thermometric estimates of heat storage were provided by using two sets of relative weightings, based upon the individual's metabolic heat production (M in kilojoules per meter squared per hour): (4 - [(M - x).x-1].2): 1 for an initial, thermoneutral environment and (4 + [(M - x).x-1].5):1 for a final, hot environment, the optimal value of x lay between 450 and 500 kJ.m-2.h-1. We concluded that the accuracy of thermometric estimates of heat storage can be improved by modifying weighting factors of Tre and T sk according to the environment, type of clothing, and metabolic rate.

Adult↗
PubMed1996

Presence of granulosa cells during oocyte maturation improved in vitro development of IVM-IVF bovine oocytes that were collected by ultrasound-guided transvaginal aspiration.

The effects of granulosa cells in maturation media on male pronuclear formation and in vitro development of in vitro-matured and fertilized (IVM-IVF) bovine oocytes were examined. In Experiment 1, cumulus-oocyte complexes (COCs) were aspirated from follicles of slaughterhouse ovaries and classified into 4 morphological categories according to the surrounding cumulus cells: Grade 1 (> 4 layers), Grade 2 (3 to 4 layers), Grade 3 (1 to 2 layers) and Grade 4 (denuded). Oocytes were co-cultured with or without granulosa cells (1 x 10(6) cells/ml) for 21 to 22 h. At 18 and 192 h after insemination, the abilities of oocytes to form a male pronucleus and develop up to the blastocyst stage in vitro were determined, respectively. The presence of granulosa cells during maturation did not affect (P < 0.05) the ability of oocytes in Grades 1 and 2 to form a male pronucleus and to develop to the blastocyst stage in Grades 1 and 4. However, the incidence of male pronuclear formation in Grades 3 and 4 and in vitro development to the blastocyst stage in Grades 2 and 3 was higher (P < 0.05) when COCs were cultured in the presence of granulosa cells than when cultured in the absence of granulosa cells. In Experiment 2, COCs collected by ultrasound-guided aspiration were co-cultured with or without granulosa cells, fertilized and cultured as described above. The incidence of blastocysts at 192 h after insemination was higher (P < 0.05) when COCs were cultured for maturation in the presence of granulosa cells (24%) than in the absence of granulosa cells (12%). These results demonstrate that supplementation of maturation medium with granulosa cells improves the quality of oocytes with relatively few cumulus cell layers, as determined by male pronuclear formation and in vitro development. We also conclude that this supplementation effectively improves the developmental ability of bovine IVM-IVF oocytes that were collected by ultrasound-guided transvaginal aspiration.

Journal Article↗
PubMed1996

Microheterogeneity of serum transferrin in the diagnosis of hepatocellular carcinoma.

Heterogeneous reactivity of human serum transferrin (Tf) with lectins was analysed using patient sera to determine whether it can be used to distinguish patients with hepatocellular carcinoma (HCC) from those with liver cirrhosis (LC). Microheterogeneity of Tf was analysed by crossed immunoaffinity electrophoresis (CIAE) with concanavalin A (Con A) and Lens culinaris agglutinin (LCA). Sample sera from 58 patients with HCC, 43 patients with LC and 10 normal controls were used in this study and the results were evaluated statistically. The increments of Con A-non-reactive (C1) and -weakly reactive (C2) species of Tf were observed in HCC compared with those of LC and Norm. Significant increase in the combined percentage of Con A- C1 + C2 species was also revealed in HCC (35.5 +/- 8.5%, mean+/-s.d.) compared with those of LC (29.1 +/- 6.8%; P < 0.001) and normal controls (17.1 +/- 2.3%; P < 0.001). The elevation of LCA-reactive (L2) species of Tf was recognized in HCC (8.2 +/- 3.8%) in comparison with those of LC (4.8 +/- 3.1%; P < 0.001) and normal controls (1.3 +/- 1.7%; P < 0.001). The increment of C1 + C2 species and/or L2 species of Tf was observed in 78% (sensitivity) of patients with HCC. The specificity, the positive predictive value and the overall accuracy were 81, 88 and 72%, respectively. Positive ratio of C1 + C2 and/or L2 species was 77 and 70% in alpha-fetoprotein low and -high producing HCC patients, respectively. These results indicate that the microheterogeneity analysis of human serum Tf is useful for distinguishing patients with HCC from those with LC and normal controls.

Aged↗
PubMed1996

Heat strain in protective clothing following hot-wet or hot-dry heat acclimation.

The purpose of the present study was to compare the heat strain while wearing nuclear, biological, and chemical (NBC) protective clothing following a hot-wet (HW) or hot-dry (HD) heat acclimation protocol. Twenty-two males were assigned to groups HW (n = 7), HD (n = 8), or control (C, n = 7). Subjects were evaluated during continuous treadmill walking while wearing lightweight combat clothing and during intermittent exercise while wearing the NBC protective clothing. While wearing Combat clothing, greater decreases in rectal temperature (Tre), mean skin temperature (Tsk), and heart rate were observed for both acclimation groups. For the NBC clothing trials, lower Tre, Tsk, and heart rates were observed only for group HW. The time required for Tre to increase 1.0 degrees C and 1.5 degrees C was significantly delayed for groups HW and HD. Sweat evaporation increased for HW, whereas no change was found for HD. The most significant changes in Tre, Tsk, and heart rate while wearing the NBC protective clothing occur following heat acclimation that involves wearing the clothing during exercise.

Acclimatization↗
PubMed1996

Alpha-fetoprotein-producing renal cell carcinoma with increased activity of N-acetylglucosaminyl-transferase III.

N-acetylglucosaminyltransferase (GnT) III catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin-A-(ConA)-reactive glycan into the ConA-nonreactive one. In this study, we measured GnT III levels in serum, tumor, and surrounding normal tissues together with a glucosaminylation index of alpha-fetoprotein (AFP), which is defined as the percentage of the ConA-nonreactive species in total AFP, in a case of AFP-producing renal cell carcinoma. The glucosaminylation index was determined by affinoelectrophoresis in the presence of ConA. GnT III was measured by using a pyridylaminated asialoagalactobiantennary sugar chain as a substrate by high-performance liquid chromatography. The glucosaminylation index of serum AFP, the concentration of which was 68 ng/ml, was 60%. This value is much higher than observed in hepatocellular carcinomas. The tumor tissue level of GnT III was 55.34 pmol/mg/h which was about six fold higher (9.50 pmol/mg/h) than in normal surrounding tissues. The serum level of this enzyme before surgery was 27.65 pmol/ml/h and decreased to 5.38 pmol/ml/h thereafter in association with a depression of serum AFP from 68 to 5.4 ng/ml. Thus, an increased level of GnT III in tumor tissues could account for the elevated conversion of a biantennary complex type sugar chain of AFP into a bisecting glucosaminylated biantennary one resulting from the addition of an N-acetylglucosamine residue at the trimannosyl core. This is, to our knowledge, the first report explaining the change in the carbohydrate structure of AFP with different affinity to ConA on the enzymatic basis in a renal cell carcinoma.

Biomarkers, Tumor↗
PubMed1996

Production and transfer of IVF embryos from individual inhibin-immunized cows by ultrasound-guided transvaginal follicular aspiration.

Ultrasound-guided transvaginal follicular aspiration (UTA) was performed on 8 multiparous Japanese Black cows which had not been successful in a conventional superovulation program. These cows were actively immunized with a synthetic peptide replica of porcine inhibition alpha N1-26 (pINH) conjugated with rabbit serum albumin (RSA) using Freund's complete adjuvant. Booster injections of the peptide were given at 6, 10, 14 and 20 wk after the primary injection. Twelve follicular aspirations were performed between 10 and 33 wk after the primary injection. Cumulus-oocyte complexes (COCs) were aspirated from follicles > or = 2 mm in diameter. The recovered COCs were classified into 5 categories according to the surrounding cumulus cells: Grade 1 (> 4 layers), Grade 2 (3 to 4 layers), Grade 3 (1 to 2 layers), Grade 4 (denuded) and Grade 5 (expanded and fluffy cumulus cell mass or degenerated ooplasm). The recovered COCs available for in vitro fertilization (IVF; Grades 1, 2, 3 and 4) were matured with granulosa cells (1 x 10(6) cells/ml) for 20 to 23 hr, fertilized with frozen-thawed spermatozoa, and cultured in vitro. At day 7 after insemination, a portion of the embryos were transferred to Holstein heifers. There were great variations among donors in the number of recovered COCs in the numbers of COCs in each grade, and also in the developmental ability of fertilized COCs. IVF procedures were carried out on 685 oocytes and produced 120 embryos (17.5%). The transfer of 36 fresh IVF embryos resulted in 20 pregnancies (55.6%) at 60 days after the transfer. This study has demonstrated first, that the number of COCs collected from individual inhibin-immunized cows by UTA greatly varies among donors. Second, recovered COCs vary greatly in the classification of the morphological categories of surrounding cumulus cell mass among donors and had different developmental abilities when they were cultured after fertilization in vitro. Third, the production of pregnancy in previously nonproductive problem donors is possible using the UTA technique.

Animals↗