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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 343 records · Page 19Linked to original sources

[The role of surgery for advanced epithelial ovarian cancer].

Advanced epithelial ovarian cancer means. A unique approach to the treatment because almost always the chemotherapy challenge begins in the disseminated condition in the whole abdomen. This aggressive challenge is dependent on a 60-70 % response rate of cisplatin containing regimen for this tumor. The chemotherapy combined with maximum cytoreductive effort can expect long term survival, since the less the residual tumor diameter, the longer the expected. Unless surgery is successful at the beginning, secondary optimal surgery after the effective chemotherapy contributes to the survival. Suboptimal secondary cytoreduction, however, has no benefit for the subsequent course. Several studies documented primary bulky tumor affected the prognosis even after successful debulking surgery and chemotherapy. No prospective study clarified the advantage of neoadjuvant chemotherapy for long term survival in advanced ovarian cancer. Comprehensive combination study for initial debulking surgery, chemotherapy and secondary cytoreduction will help verify the optimal schedule. Systematic pelvic and paraaortic lymph node dissection is controversial to date. A metastatic lymph node is one of prognostic factors, but the removal of it may be not necessarily associated with improvement of survival. We must clarify the clinical advantage for systemic lymph node dissection in well-designed prospective random study. We have to perform the second look operation when this procedure contributes the subsequent outcome.

Antineoplastic Agents↗

[Carotid blood flow volume measurement using an ultrasonic Doppler flowmeter--predictive diagnosis of ischemic cerebrovascular diseases].

BACKGROUND: It is difficult to predict ischemic cerebrovascular diseases by noninvasive methods before overt symptoms develop. Advanced carotid and cerebral atherosclerosis reduce common carotid blood flow volume due to increased resistance of peripheral circulation. According to a study in which clinical and pathological specimens were compared, the lower threshold for the flow volume in normal individuals has been confirmed to be 6.5 ml/s. We investigated the possibility that the development of ischemic cerebrovascular diseases can be predicted based on blood flow volume. METHOD: We conducted a retrospective study on 314 patients who were available for determination of common carotid blood flow volume with an ultrasonic quantitative flowmeter. RESULTS: Thirty-three patients developed ischemic cerebrovascular attacks during the observation period (onset group), while the remaining 281 did not develop attacks (non-onset group). The discriminating value for common carotid blood flow volume between the onset and non-onset groups was 6.8 ml/s. Based on an odds ratio of 6.7, it was concluded that a common carotid blood flow volume of less than 6.8 ml/s is highly likely to predict the onset of ischemic cerebrovascular accidents.

Aged↗

[Three Japanese children with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X)].

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X), which was first reported by Wilkie, et al. in 1991, is a disorder with severe mental retardation, characteristic facial appearance, genital abnormalities, and mild form of alpha-thalassemia. At present, about 50 cases have been reported in the world, but few in Japan. We report 3 cases of this disorder in 2 families. All cases prefer a peculiar posture and show unique movements, such as self-induced vomiting or self-hanging, which can be diagnostic. ATR-X should be considered as a differential diagnosis in all male patients with severe mental retardation.

Child↗

[Effects of nitric oxide synthase inhibitor on skin blood flow responses to acute isovolemic hemodilution during halothane and isoflurane anesthesia].

Eighteen dogs under halothane or isoflurane anesthesia were subjected for a study in skin blood flow of the forearm under acute isovolemic hemodilution. Hematocrit was intentionally reduced to about 50% of baseline in ten minutes and hematocrit changes were induced by exchange of blood with hydroxyethyl starch. The skin blood flow increase response, measured by laser Doppler flowmetry, to hemodilution was abolished after inhibition of endogenous nitric oxide synthesis by N omega-nitro-L-arginine methyl ester. Skin blood flow responses to hemodilution and N omega-nitro-L-arginine methyl ester were different between halothane group and isoflurane group. Nitric oxide may have an important part to play in vasodilation during acute isovolemic hemodilution, and it may be affected differently by halothane and isoflurane.

Anesthesia, Inhalation↗

Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after a weight control program.

OBJECTIVE: To determine the variable most closely related to symptomatic relief of osteoarthritis (OA) of the knee in response to a weight control program. METHODS: Twenty-two patients diagnosed with knee OA whose body mass index (BMI) was more than 26.4 were treated with a low calorie diet, an appetite suppressant, and nonsteroidal antiinflammatory drugs for 6 weeks. The patients were instructed to follow a walking program. We analyzed BMI, percent body fat, the average number of steps per day by pedometer, and the metabolic correlates of obesity (blood pressure, fasting blood serum glucose, total cholesterol, triglycerides, and serum insulin) at the beginning and end of therapy. The correlation between the change in each variable and the remission score (delta score) using the Severity Index of Lequesne, et al was evaluated. RESULTS: Delta score of knee OA was more strongly associated with reduction in percent body fat (p= 0.0013, r=0.62) than other variables. Significant correlation was also observed between the number of steps per day and delta score (p=0.0031, r=-0.58). No other variable, including weight loss, was significantly correlated with delta score. There was a significant correlation between delta percent body fat and the number of steps per day (p=0.012, r=-0.62). CONCLUSION: In a weight control program, decreasing body fat and increasing physical activity are more important than body weight loss or decreasing other indices of obesity in producing symptomatic relief of knee OA, although there is not necessarily a cause and effect relationship between body fat and OA score.

Adipose Tissue↗

Sound lateralization and speech discrimination in patients with sensorineural hearing loss.

Sound lateralization and speech discrimination abilities are both closely related to central auditory system function. In this study, we investigated the relationship between sound lateralization and speech discrimination in patients with sensorineural hearing loss (SNHL) of unknown aetiology or presbycusis. Interaural intensity difference (IID) and interaural time difference (ITD) discriminations were measured using a self-recording apparatus for dichotic sound presentation, and the means of bilateral maximum scores in speech discrimination tests were calculated. Subjects with normal sound lateralization had good speech discrimination scores above 70%, while those with abnormal sound lateralization had poor scores below 70%. Some patients, however, had good speech discrimination but abnormal sound lateralization. These findings were obtained in both IID and ITD discrimination tests. Furthermore, some subjects could not discriminate ITD, although all could discriminate IID. These findings suggest that sound lateralization ability may be affected more than speech discrimination in SNHL of unknown aetiology or in presbycusis.

Adult↗

Patterns of change in growth function of distortion product otoacoustic emissions in Menière's disease.

The patterns of change in the growth function of distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in six patients with Menière's disease were investigated. The growth functions of 2F1-F2 DPOAEs at F2 frequencies of 1001, 2002 and 4004 Hz (DP-1, DP-2 and DP-4, respectively) were measured with F2 intensities ranging from 70 to 37 dBSPL in 3-dB steps. The F1 intensity was maintained 10 dB higher than the F2 intensity. The growth function was paired with the hearing threshold at the corresponding F2 frequency, and the relationships between changes in DP-1, DP-2 and DP-4 and those in hearing thresholds at 1, 2 and 4 kHz, respectively, were also investigated. The patterns of change in the growth function associated with hearing improvement could be classified into five types. In the first type, the DPOAE growth function became detectable, while the remaining four types were distinguished by combinations of changes in DPOAE amplitudes for lower and higher primary intensities. Multiple parameters, such as maximum amplitude and detection threshold of the growth function, appeared to be required for simple detection and discrimination of these patterns of change. It was also found that the DPOAE growth functions clearly changed in some cases even though the hearing thresholds did not change significantly at the corresponding F2 frequencies. This finding suggests that DPOAE growth function measurement can detect small changes in cochlear function which do not lead to changes in hearing threshold, and has higher sensitivity than pure tone audiometry in monitoring of cochlear function. In conclusion, our findings suggest that measurement of the DPOAE growth function is useful for monitoring cochlear function, and that information on its patterns of change is clinically important and useful.

Adult↗

Changes in distortion product otoacoustic emissions from ears with Menière's disease.

To investigate changes in distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in ears with Menière's disease, four parameters were studied. These were: DPOAE amplitudes for a moderate (L1/L2 = 65/55 dBSPL) and a high (L1/L2 = 74/64 dBSPL) primary level (65/55-DP and 74/64-DP amplitudes, respectively); maximum level of DPOAE amplitudes in the growth function (maximum DP level); and DPOAE detection threshold (DP threshold) of the growth function. Significant correlations were found between all four parameters and hearing threshold, except for the 65/55-DP amplitude at 1 kHz, and each parameter appeared to reflect the hearing threshold to some extent. However, the changes in the four parameters associated with hearing improvement were somewhat complicated. Changes could not be evaluated due to lack of detection of responses when the hearing thresholds exceeded 50 dBHL. Findings that parameters became detectable, the DP amplitude or the maximum DP level increased significantly, or the DP threshold lowered significantly were classified as "improved" findings. The number of ears with "improved" findings was larger for the maximum DP level or the DP threshold than for the 65/55-DP and 74/64-DP amplitudes in ears with a 10 dB or greater improvement in hearing threshold at the corresponding F2 frequency. Furthermore, a significant decrease in amplitude was found in some ears, although the hearing threshold was not elevated when the 65/55- or 74/64-DP amplitude was used as a parameter. On the other hand, "improved" findings for the maximum DP level or the DP threshold were observed for a relatively large number of ears without a significant change in hearing threshold, and it was thought that small changes in cochlear function which did not lead to changes in hearing threshold were detected by changes in DPOAEs. These findings suggest that parameters determined from the growth function, such as maximum DP level and DP threshold are better indicators for monitoring cochlear function than is DPOAE amplitude for a single primary level, and demonstrate the usefulness of the growth function measurement for monitoring purposes. Furthermore, evaluation by changes in the overall growth function using combined parameters appeared to increase sensitivity in detection of subtle changes in cochlear function. In conclusion, DPOAE measurement can be a useful examination for clinical monitoring of cochlear function in Menière's disease when the growth function is measured.

Adolescent↗

[Augmented antitumor efficacy of combination chemotherapy of nedaplatin with 5-fluorouracil in in vivo murine and human tumor model].

Augmented antitumor activity was demonstrated in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with 5-fluorouracil (5-FU) against murine lung carcinoma and human squamous carcinoma from head and neck. Either NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) was injected once and 5-FU (1/16 MTD) was injected daily for five days via tail vein to tumor-implanted mice. The sequential administration of either NDP or CDDP prior to 5-FU (NF or CF therapy) showed severe body weight loss followed by the toxic death of tumor-bearing mice at the MTD of NDP or CDDP. In contrast, the reverse sequence of the treatment, that is, 5-FU prior to NDP or CDDP (FN or FC therapy), resulted in the synergistically enhanced inhibition of tumor growth and the prolonged survival in comparison with NDP, CDDP or 5-FU monotherapy. The antitumor activities of the combinations of CDDP with 5-FU was less than those of the combination of NDP with 5-FU. Especially, at the MTD of NDP in FN therapy, long-term tumor-free survival was frequently observed. Thus, FN therapy was thought to be the most efficient regimen in combination of NDP with 5-FU as a clinical therapy.

Animals↗

A fine physical map of Arabidopsis thaliana chromosome 5: construction of a sequence-ready contig map.

A fine physical map of Arabidopsis thaliana chromosome 5 was constructed by ordering the clones from YAC, P1, TAC and BAC libraries of the genome using the sequences of a variety of genetic and EST markers and terminal sequences of clones. The markers used were 88 genetic markers, 13 EST markers, 87 YAC end probes, 100 YAC subclone end probes, and 390 end probes of P1, TAC and BAC clones. The entire genome of chromosome 5, except for the centromeric and telomeric regions, was covered by two large contigs 11.6 Mb and 14.2 Mb long separated by the centromeric region. The minimum tiling path of the chromosome was constituted by a total of 430 P1, TAC and BAC clones. The map information is available at the Web site http://www.kazusa.or.jp/arabi/.

Arabidopsis↗

Characterization of alpha1-adrenoceptor subtypes in facilitation of rat spinal motoneuron activity.

The subtypes of alpha1-adrenoceptor mediating facilitation of alpha-motoneuron activity in adult rat spinal cord were examined. The potencies of agonists and antagonists were compared, using extracellular single unit recordings made in spinal cord slices isolated from adult rats. Catecholamines (epinephrine, norepinephrine), phenylethylamines (phenylephrine, methoxamine) and imidazolines (clonidine, oxymetazoline, St587 (2-(2-chloro-5-trifluoromethyl-phenylimino)-imidazoline)) enhanced motoneuron activity. Catecholamines and phenylethylamines elicited maximal responses but imidazolines elicited submaximal responses. The potencies of the agonists were similar to their affinities for alpha1A-adrenoceptors. The alpha1A-adrenoceptor agonist SDZ NVI 085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2H-naphth[2,3b]-1,4-oxazine) behaved as a partial agonist with a maximal response of about 75% and this response was not inhibited by chloroethylclonidine. Pretreatment with chloroethylclonidine produced a rightward shift of the phenylephrine response curve but caused little reduction in the maximal response. Prazosin, 5-methyl-urapidil, WB4101 (2-([2,6-dimethoxyphenoxyethyl] aminomethyl)-1,4-benzodioxane) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8azaspiro[4.5]decane-7,9-dione dihydrochloride) concentration dependently inhibited the facilitation of alpha-motoneuron activity produced by phenylephrine. The order of inhibitory potency was similar to that for their alpha1A-adrenoceptor binding site affinity. Therefore, it seems that alpha1A-adrenoceptors may be functionally predominant in the facilitation of rat spinal motoneuron activity.

Adrenergic alpha-1 Receptor Agonists↗

Epidermal cell differentiation in Arabidopsis determined by a Myb homolog, CPC.

The roots of plants normally carry small hairs arranged in a regular pattern. Transfer DNA-tagged lines of Arabidopsis thaliana included a mutant with few, randomly distributed root hairs. The mutated gene CAPRICE (CPC) encoded a protein with a Myb-like DNA binding domain typical of transcription factors involved in animal and plant development. Analysis in combination with other root hair mutations showed that CPC may work together with the TTG gene and upstream of the GL2 gene. Transgenic plants overexpressing CPC had more root hairs and fewer trichomes than normal. Thus, the CPC gene determines the fate of epidermal cell differentiation in Arabidopsis.

Amino Acid Sequence↗

Phosphorylation and high level expression of Fra-2 in v-src transformed cells: a pathway of activation of endogenous AP-1.

Chicken embryo fibroblasts (CEF) transformed with v-src were previously reported to revert to normal phenotype after the introduction of dominant-negative mutants of Fos or Jun, indicating that endogenous AP-1 activity is essential for the cellular transformation. The major changes in the expression levels of fos and jun family genes induced by v-src were the elevation of fra-2 and c-jun transcripts. We show here that extensive phosphorylation of the AP-1 component Fra-2 is a major qualitative change in v-src transformed CEF and that several Ser and Thr residues in a C-terminal region of Fra-2 (amino acids 266-323) are phosphorylated specifically. The induced kinase activity was detected at the position of 42 kDa by in gel kinase assay using the Fra-2 C-terminal region as a substrate, and it was identified as chicken ERK2. JNK1 and JNK2, other members of the MAP kinase family, were not significantly activated in v-src transformed CEF and Fra-2 was not a good substrate for JNKs. fra-2 promoter analysis indicated that this promoter activity is elevated in v-src transformed CEF via two AP-1 binding sites and CRE-like sequence. We propose that phosphorylation of Fra-2 by ERK2 converts it from an inefficient transcriptional activator to an active one and further that fra-2 expression is autoregulated in response to the phosphorylation status of its gene product.

Animals↗

Relationship between specific binding of 125I-omega-conotoxin GVIA and GTP binding protein: effects of the GTP analogues, mastoparan and A1F4-.

We investigated whether the specific binding or labeling of 125I-omega-CgTX on crude membranes from chick whole brain was affected when endogenous GTP binding protein (G protein) was activated by GTP analogues, mastoparan (MP) and aluminum fluoride (AIF4-; AICl3 + NaF). Both GTPgammaS and Gpp(NH)p attenuated the inhibitory effect of selective N-type Ca channel inhibitors such as aminoglycoside antibiotics (AGs) or dynorphine (1-13)(Dyn) on specific 125I-omega-CgTX binding in a dose-dependent manner. On the other hand, the inhibitory effects of the divalent metal cations Cd2+, Co2+, Mg2+ and Mn2- on such binding were not attenuated by GTPgammaS. MP and AIF4- also attenuated the inhibitory effect of Neo on this binding similar to GTPgammaS. The attenuating effect of MP was enhanced by the presence of Mg2+ in a dose-dependent manner. However, GTP analogues, MP and AIF4-, did not affect binding or labeling without AGs or Dyn. GTPgammaS, MP and AIF4- also attenuated the specific labeling of a 215-kDa band in crude membranes with 125I-omega-CgTX using the cross-linker DSS (non-reduced condition) in the presence of Neo. These results indicate that there are direct or indirect relationships between N-type Ca channels and G proteins via binding sites for AGs or MP.

Aluminum Compounds↗

Renal sympathetic nerve activity and the weight of the remaining kidney in unilateral nephrectomized rats.

To examine compensatory response of the kidney to reduction in renal mass, acute and chronic effects of unilateral nephrectomy on renal sympathetic nerve activity (RNA) and weight of the remaining kidney were analyzed in rats. Under acute nephrectomy, RNA decreased significantly due to ligation of the renal vessels, ureter and nerves. With acute unilateral renal denervation, basal mean RNA (MRNA) did not change but the reflex inhibition of RNA due to ligation disappeared. Chronic effects of nephrectomy were analyzed at 3, 7, 14 and 28 days after surgery. At 3, 7, 14 and 28 days after nephrectomy, MRNA were about two times larger than the values obtained in sham operation group (p < 0.01). Changes in arterial pressure and heart rate were not significant after unilateral nephrectomy. When the maximal MRNA due to dimethylphenylpiperazinium iodide (DMPP) administration was set as 100%, relative basal MRNA at 3, 7, 14 and 28 days were estimated in sham and nephrectomy groups. Also, relative basal MRNA increased about two times in nephrectomy group. After unilateral nephrectomy, the remaining kidney weight per unit body weight increased significantly by 18-35%. These findings indicate that the RNA in the remaining kidney was reflexly inhibited by the activation of afferent input due to ligation of renal vessels, ureter and nerves under acute nephrectomy. Under chronic unilateral nephrectomy, basal MRNA and the weight of the remaining kidney were increased significantly. The RNA per unit of kidney weight in unilateral nephrectomized rats was increased at 3 and 7 days and then it was relatively constant at 14 and 28 days.

Action Potentials↗