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Biomedical subjects

M Wada

Publications and source records attributed to M Wada.

At least 91 records · Page 5Linked to original sources
PubMed2001

Simultaneous determination of phenolic xenoestrogens by solid-phase extraction and high-performance liquid chromatography with fluorescence detection.

A highly sensitive and selective method for simultaneous determination of some hydroxyl group-containing endocrine disruptors, including bisphenol A (BPA), bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF) and 4-nonylphenol (4-NP), was developed. The method consists of precolumn derivatization of the analytes, solid-phase extraction (SPE) and subsequent chromatographic analysis by high-performance liquid chromatography (HPLC) with fluorescence detection. 4,4'-Cyclohexylidenebisphenol (BPZ) was used as an internal standard. Derivatization was carried out using 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl) as a label. Parameters of the derivatization reaction (temperature, time, concentration of reagent, stability, etc.) and of the solid-phase extraction (recovery, solvent, etc.) were studied in detail. Detection limits of compounds studied in standard solutions ranged from 0.08-1.3 ppb (ng/ml). The proposed method was successfully applied to plastic samples; BPA was found in both polycarbonate and polyvinyl chloride plastics, while 4-NP was found in plastics made of polyvinyl chloride and another polymer.

Benzhydryl Compounds↗
PubMed2001

Autoimmune hepatitis concomitant with hypergammaglobulinemic purpura, immune thrombocytopenia, and Sjögren's syndrome.

Sjögren's syndrome occurs as an occasional complication of autoimmune hepatitis, and purpura or thrombocytopenia develops in some patients with this syndrome. This report describes a 62-year-old woman with a 6-year history of autoimmune hepatitis who concurrently had hypergammaglobulinemic purpura, immune thrombocytopenia and Sjögren's syndrome. Treatment with prednisolone resulted in marked improvement of biochemical, hematological and dermatological abnormalities. This case emphasizes the manifestation of purpura or thrombocytopenia as an associated disorder during the course of autoimmune hepatitis concomitant with Sjögren's syndrome.

Anti-Inflammatory Agents↗
PubMed2001

[Effects of gender and physical distance with an old friend on same-sex friendship].

This study examined the differences between interpersonal relationship of same-sex old friends (OF) and that of new friends (NF). It also investigated the effects of physical distance with an old friend and gender on the friendship. Respondents were 208 undergraduates, 86 men and 122 women, who chose one of most intimate person each from same-sex friends they had made before and after they entered a university, and answered questions to describe their relationship. Results showed that relationship satisfaction and tired feeling were higher for OF than NF. Spending time together and talking over telephone were more frequent for NF than OF, but for each occasion together or over telephone, OF spent longer time than NF. OF expected more self-disclosure between them than NF. Gender differences in friendship expectation were similar to previous findings (Wada, 1993, 1996). Furthermore, gender and physical distance both influenced the frequencies of OF spending time together and over telephone. These findings are discussed in terms of gender differences in friendship.

Adult↗
PubMed2001

[A male case of primary bilateral breast cancers during estrogen therapy for prostate cancer].

An 82-year old man received total androgen blockade therapy (bilateral orchiectomy and 375 mg/day flutamide) for the treatment of stage C prostate cancer. Serum PSA levels were undetectable for 13 months and thereafter increased gradually. We administered estramustine phosphate sodium (EPS) instead of flutamide under the diagnosis of hormone refractory prostate cancer. EPS therapy was discontinued after 9 months because serum PSA levels increased again. Then, the patient complained of bilateral breast nodules and pain. Bilateral mammectomies were performed due to bilateral breast cancers which had been diagnosed by aspiration biopsies and radiographic examinations, but he died four months after the operations. Final pathological diagnosis was ductal adenocarcinoma of the breasts. Immunohistochemical study revealed expressions of PSA in the breast cancers. We diagnosed double cancers of the prostate and the breast because of the different expression patterns of progesterone receptor between them. We review the literatures and discuss the differential diagnosis of prostate cancer and PSA-producing breast cancer.

Adenocarcinoma↗
PubMed2001

[Effectiveness and problems of PZA-containing 6-month regimen for the treatment of new pulmonary tuberculosis patients].

One third of the world population has been infected with Mycobacterium tuberculosis, and the number of tuberculosis will increase worldwide without more effective programs of tuberculosis control. Despite of the presence of very potent anti-tuberculosis drugs the global tuberculosis situation is still very serious, and such gloomy feature are caused, at least partly, by the failures in the treatment of tuberculosis. The most important factor for the failure in chemotherapy is incompliance of the patients to the regimens. History of the chemotherapy of tuberculosis can be said as the history of the efforts to reduce such defaulters. Modern chemotherapy of tuberculosis has started from the discovery of streptomycin. Streptomycin monotherapy could improve temporally symptoms and bacteriological status, but could not cure the patients with moderately advanced pulmonary tuberculosis because of the emerge of drug-resistant tuberculosis. This problem was overcome by combining use of para-aminosalicylate and/or isoniazid developed later on. About 97% of patients with pulmonary tuberculosis became bacteriologically quiescent by the 12 months of streptomycin, para-aminosalicylate and isoniazid. Since 1950s through 1970s three drug combination of streptomycin, para-aminosalicylate and isoniazid had been the standard regimen for the treatment of tuberculosis. By the introduction of rifampicin, the duration of chemotherapy could be shortened to 9 months. Subsequent to the successful animal experiments carried out by Grosset which demonstrated that the addition of pyrazinamide for initial 2 months to the standard two-drug combination (isoniazid and rifampicin) could remarkably shorten the duration of chemotherapy, many clinical trials have been done all over the world to compare the efficacy and safety of pyrazinamide-containing intensified short-course regimen with those of standard regimen without pyrazinamide. Sputum negative conversion rates after 2 months of treatment with PZA-regimen was 70-95%, and the relapse rates after the completion of the treatment course were less than 4%. The incidence of adverse events was less than 4%. The pyrazinamide-containing 6 months short-course regimens has been established as a new standard regimen for the initial treatment of pulmonary tuberculosis worldwide. But, in Japan, this regimen had not been adapted as the standard until April 1996 because of undue fear for high incidence of liver toxicity induced by pyrazinamide. However, in many clinical trials carried out in various parts of the world did not show any causative relationship between the higher incidence of liver toxicity and pyrazinamide. According to our own experience in Fukujuji Hospital, Japan Anti-tuberculosis Association, the frequency of drug induced hepatitis among 632 patients with normal liver function at the onset of chemotherapy was 7.9 percent (50/632) when treated with pyrazinamide-containing regimens, and was similar to that among 412 patients treated with other regimens without pyrazinamide (7.3 percent 30/412). These figures were higher than those reported in the literatures. The risk factors of drug-induced hepatitis so far reported included elderly, positive hepatitis C virus antibody, low serum albumin and so on. Such known risk factors could not wholly explain the higher rate of liver dysfunction observed among our Japanese patients. We have examined additional factors affecting the frequency of drug-induced hepatitis in our hospital, and noticed that the past history of gastrectomy and over-dosing of isoniazid (> or = 7.5 mg/kg) and/or pyrazinamide (> or = 30 mg) were relating to the higher incidence of drug-induced hepatitis. Another important finding is that the relapse rate among patients complicated with diabetes mellitus is significantly higher than that of the patients without diabetes mellitus (6.31/100 person-years vs 0.90/100 person-years, P < 0.001). Further research will need whether the patients complicated with diabetes mellitus have any immunological deficient to kill Mycobacterium tuberculosis. WHO, CDC and ATS recommended that 4-drug regimen including pyrazinamide for the initial treatment of all cases of tuberculosis. Considering that the incidence of initial resistance to isoniazid is 4.4% in Japan, we should start to treat all cases of newly diagnosed tuberculosis with pyrazinamide-containing regimen (isoniazid, rifampicin, pyrazinamide, plus streptomycin or ethambutol). To do this, further studies on the risk factors of drug-induced hepatitis are urgently needed.

Animals↗
PubMed2001

Resistance of Mycobacterium tuberculosis to four first-line anti-tuberculosis drugs in Japan, 1997.

SETTING: Five years after the last survey of drug-resistant tuberculosis in Japan, a nationwide survey was conducted by the Tuberculosis Research Committee. OBJECTIVE: To determine the prevalence of and risk factors for resistance to four first-line anti-tuberculosis drugs. DESIGN: Cultures were obtained from patients hospitalized at 78 hospitals in different districts of Japan throughout a 6-month period, 1 June-30 November 1997. Drug susceptibility testing was carried out at the Research Institute of Tuberculosis, Tokyo, one of the supranational reference laboratories of the WHO/IUATLD global project. RESULTS AND CONCLUSION: Among patients with no prior treatment, resistance to any of the four drugs was found in 10.3%, and the prevalence of primary multidrug resistance (MDR) was 0.8%. The prevalence of acquired resistance was 42.4% for any of the four drugs and 19.7% for MDR, indicating a high prevalence rate compared with those reported in the WHO/IUATLD global project. About 73% of resistant isolates from new cases were resistant to one drug, while 64.3% of resistant isolates from the re-treatment cases were resistant to two or more drugs (P < 0.0001). No significant differences in resistance rates by sex, age group, nationality, district, and/or accompanying diseases were observed in any of the new or re-treatment cases. Other factors associated with the high prevalence in re-treatment cases remain to be determined.

Antitubercular Agents↗
PubMed2001

[A study on resistance of Mycobacterium tuberculosis to four first-line anti-tuberculosis drugs in Japan: comparison of results in the local facilities and in the reference laboratory, in 1997].

Five years after the last survey of drug-resistant tuberculosis in Japan, a nationwide survey was conducted by the Tuberculosis Research Committee (Ryoken). A total of 78 hospitals in various districts of Japan participated in this cooperative study. Each collaborating laboratory sent all the isolated mycobacterial cultures during June 1 to November 30, 1997 to the Research Institute of Tuberculosis (RIT), which is one of the Supranational Reference Laboratories of the WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. At RIT identification and drug susceptibility of Mycobacterium tuberculosis isolates were reexamined. The RIT received a total of 2,167 cultures. Among them, 523 cultures were excluded from further examinations because of various reasons, such as growth of mycobacteria other than tubercle bacilli (MOTT, 453), mixed cultures of M. tuberculosis and MOTT (16), and contamination or non-viability (54). Thus drug susceptibility test results were available for 1,644 cultures, including 47 from foreign-born people. In the local laboratories, the absolute concentration method using 1% Ogawa egg slant (standard method, 26 hospitals), its modified methods using a 48-well plate (Microtiter method, 29 hospitals) and a 16-well plate (Well-pack method, 7 hospitals), combination of above 2 or 3 methods (13 hospitals), and other method (3 hospitals) were used for drug susceptibility testing, and the proportion method using 1% Ogawa egg slant was used in the RIT. The results in the local laboratories were compared with those in the RIT. A high concordance rate (over 90%) was seen in the testing for 1 microgram/ml of isoniazid (INH), rifampin (RFP) and streptomycin (SM), but the rate was lower (under 90%) in the testing for 0.1 microgram/ml of INH and ethambutol (EMB). However, there was no significant difference in the concordance rates according to the test drugs among methods for drug susceptibility testing used in the local laboratories. Median concordance rates between the results with the standard method, Microtiter method and Well-pack method in the local laboratories, and those in the RIT were 95.9%, 93.2% and 96.4% respectively. Relatively lower concordance rates were seen in the laboratories using the Microtiter method related to high overestimation rates (median overestimation rate of 5.3%), compared with 1.2% and 2.3% in the laboratories using the standard method and Well-pack method, respectively. However, relatively lower concordance rates (less than 90%) were seen in the laboratories using any of the three methods, indicating that there are variations among facilities. Part of the results concerning the resistance patterns to four first-line anti-tuberculosis drugs were reported elsewhere.

Ethambutol↗
PubMed2001

Downregulation of differentiation specific gene expression by oxidative stress in ARPE-19 cells.

PURPOSE: To investigate how the differentiation of ARPE-19 cells affects the relative expression of the FGFR genes in response to oxidative stress. METHODS: After differentiation in vitro, APRE-19 cells were treated with t-butyl hydroperoxide (tBH) or hydrogen peroxide (H2O2) to induce oxidative stress. Viability and reactive oxygen intermediate (ROI) production were measured using standard assays. The mRNA expression of FGFR1, FGFR2, cellular retinaldehyde-binding protein (CRALBP), RPE65, and heme oxygenase-1 (HO-1) were measured by Northern blot analysis as a function of treatment with tBH and H2O2. RESULTS: ARPE-19 cells were viable at all tBH concentrations tested but showed progressive loss of viability at concentrations greater than 300 microM H2O2. Differentiated ARPE-19 cells treated with tBH or H2O2 resulted in upregulation of the HO-1 and FGFR1 transcripts. The expression of RPE-differentiated specific genes, including FGFR2, CRALBP, and RPE65 mRNAs, was downregulated with tBH or H2O2 treatment. CONCLUSIONS: Oxidative stress in differentiated ARPE-19 cells alters the expression of FGFR1, FGFR2, CRALBP, and RPE65 toward levels characteristic of the undifferentiated state. If similar changes take place in vivo, these events could alter the proliferative potential, viability, and even the function of the RPE.

Blotting, Northern↗
PubMed2001

External Ca(2+) is essential for chloroplast movement induced by mechanical stimulation but not by light stimulation.

In the fern Adiantum capillus-veneris, chloroplast movement is induced by mechanical stimulation as well as by light stimulation. Directional movement of both types depends on an actin-based motile system. To investigate the physiological relationship between mechanical and light signaling in the regulation of chloroplast movement, we examined the mechano-response of chloroplasts whose motility had been already restricted after photo-relocation. Chloroplast mechano-avoidance movement was induced under all of the photo-relocation conditions tested, indicating that mechano-specific signals generated by mechanical stimulation dominate over the light signals and reactivate the motility of chloroplasts. When the effects of external Ca(2+) on the induction of mechano- and light responses were examined, strikingly different requirements of external Ca(2+) were found for each. In medium without Ca(2+), the mechano-response was suppressed but no effects were observed on photo-response. Mechano-relocation movement of chloroplasts was inhibited by 100 microM lanthanum (La(3+)), a plasma membrane calcium channel blocker, and by 10 microM gadolinium (Gd(3+)), a stretch-activated channel blocker. However, the same concentrations of these drugs did not affect the photo-relocation movement at all. These results suggest that the influx of external Ca(2+) is crucial for the early signaling step of chloroplast mechano-relocation but not for that of photo-relocation. This is the first report showing the separation of signaling pathways in mechano- and photo-relocation of chloroplasts.

Actins↗
PubMed2001

High trough levels of oral FK506 induced by loss of small intestine.

To establish a safe and effective usage of oral tacrolimus (FK506) in small bowel transplantation (SBTx) recipients, trough levels and area under the curve (AUC) values of FK506 were assessed using swine models of SBTx and short bowel. Thirty-eight Landrace male piglets were divided into four groups as follows: Group 1, controls (n=13); Group 2, a one-third small bowel model (n=5); Group 3, a short bowel model (n=10); and Group 4, a one-third small bowel allograft model (n=10; five donors and five recipients). Piglets of Groups 1 and 3 were further divided into two sub-groups, according to the route of drug administration: Groups 1a (n=10) and 3a (n=7) received FK506 orally, and Groups 1b (n=3) and 3b (n=3) received FK506 intravenously. Oral or intravenous FK506 was started on post-operative day 3 and continued until day 7 in each group. On day 7, trough levels and AUC values were measured. In Groups 1a, 2, 3a and 4, trough levels of FK506 were 2.1+/-1.2 (p<0.01 vs. Group 2, 3a or 4), 11.2+/-2.1, 23.3+/-4.8 (p<0.05 vs. Group 2 or 4) and 14.6+/-3.0 ng/mL, and AUC values were 101+/-90 (p<0.01 vs. Group 3a or 4), 319&+/-155, 808+/-200, and 531+/-113 ng.h/mL, respectively. Both trough levels and AUC values were lowest in Group 1a and highest in Group 3a. Between Groups 1b and 3b, there was no significant difference in the blood levels of intravenous FK506. The shorter the functioning residual small intestine was, the higher the trough level of oral FK506 was, while the presence or absence of small intestine did not affect blood levels of intravenous FK506. These results suggest that oral FK506 is metabolized in the functioning small intestine during its absorption. Therefore, events which cause intestinal malfunction, such as graft rejection in SBTx, inflammation and loss of small intestine, may adversely raise the trough level of oral FK506.

Animals↗
PubMed2000

High-performance liquid chromatography with peroxyoxalate chemiluminescence detection of bisphenol A migrated from polycarbonate baby bottles using 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride as a label.

A highly sensitive and selective high-performance liquid chromatographic method with peroxyoxalate chemiluminescence detection for the determination of bisphenol A at sub-ppb levels is described. Bisphenol A was derivatized with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride and the excess unreacted reagent was removed by a simple solid-phase extraction procedure with recoveries of approximately 60%. The separation was carried out isocratically on an ODS column and the derivatized bisphenol A was detected by peroxyoxalate chemiluminescence. A mixture of bis[2-(3,6,9-trioxadecanyloxycarbonyl)-4-nitrophenyl]oxalate (0.6 mM) and hydrogen peroxide (25.0 mM) dissolved in acetonitrile was used as a chemiluminescence reagent solution with a mixture of imidazole-HNO3 buffer (40.0 mM, pH 7.0): acetonitrile (17:83, v/v) as a mobile phase. The linear standard curve was obtained over the range from 0.57 (2.5) to 22.8 (100) ppb (nM) (r=0.996) with a detection limit of 0.38 ppb (2.8 fmol on column) at a signal-to-noise ratio of 3. The method was successfully applied to the determination of bisphenol A in hot water in contact with commercially available baby bottle samples.

Benzhydryl Compounds↗
PubMed2000

Parkinson's disease associated with argyrophilic grains clinically resembling progressive supranuclear palsy: an autopsy case.

A 70-year-old male began to show akinesia, rigidity of extremities, finger tremor, disturbed vertical external ocular movement, and nuchal dystonia, which progressed slowly. Brain CT scan and magnetic resonance images showed slight atrophy of the frontal lobe and slight enlargement of the lateral ventricles. Hasegawa's dementia rating scale-revised version gave a moderate score of 11/30 points. He died of pneumonia at the age of 76. The clinical diagnosis was progressive supranuclear palsy (PSP). However, there were no neuropathological characteristics of PSP. Neuropathologically, Parkinson's disease was diagnosed. In addition, many argyrophilic grains (ArGs) in the gray matter were stained, especially in the insula, amygdala, hippocampus, parahippocampal gyrus, lateral occipitotemporal gyrus, and substantia nigra, by the Gallyas-Braak method. We consider that ArGs could modify the symptoms of Parkinson's disease and that Parkinson's disease with ArGs may show a PSP-like clinical course.

Aged↗
PubMed2000

Pleasant odors attenuate the blood pressure increase during rhythmic handgrip in humans.

We have investigated the effects of inhaling odors of preference on physiological responses to physical exercise in college students. Rhythmic handgrip, maintaining a mercurial pressure by repetitive compression, increased blood pressure. In the participants exercised with inhaling odors of their choice, such as rose, jasmine and lavender, the increase in diastolic blood pressure during exercise was reduced by 24%. In contrast, the blood pressure increase during static handgrip, maintaining the power 30-40% of maximum, was not affected by the existence of favorite odors. Since the blood pressure increase during static handgrip is a lower brainstem reflex, the present result shows that the inhalation of favorite odors suppresses the muscle sympathetic vasoconstrictor activity and attenuates the blood pressure increase by affecting the central nervous system higher than the midbrain.

Adolescent↗
PubMed2000

The binding between the stem regions of human growth hormone (GH) receptor compensates for the weaker site 1 binding of 20-kDa human GH (hGH) than that of 22-kDa hGH.

Despite the lower site 1 affinity of the 20-kDa human growth hormone (20K-hGH) for the hGH receptor (hGHR), 20K-hGH has the same hGHR-mediated activity as 22-kDa human GH (22K-hGH) at low hGH concentration and even higher activity at high hGH concentration. This study was performed to elucidate the reason why 20K-hGH can activate hGHR to the same level as 22K-hGH. To answer the question, we hypothesized that the binding between the stem regions of hGHR could compensate for the weaker site 1 binding of 20K-hGH than that of 22K-hGH in the sequential binding with hGHR. To demonstrate it, we prepared 15 types of alanine-substituted hGHR gene at the stem region and stably transfected them into Ba/F3 cells. Using these cells, we measured and compared the cell proliferation activities between 20K- and 22K-hGH. As a result, the activity of 20K-hGH was markedly reduced than that of 22K-hGH in three types of mutant hGHR (T147A, H150A, and Y200A). Regarding these mutants, the dissociation constant of hGH at the first and second step (KD1 and KD2) in the sequential binding with two hGHRs was predicted based on the mathematical cell proliferation model and computational simulation. Consequently, it was revealed that the reduction of the activity in 20K-hGH was attributed to the change of not KD1 but KD2. In conclusion, these findings support our hypothesis, which can account for the same potencies for activating hGHR between 20K- and 22K-hGH, although the site 1 affinity of 20K-hGH is lower than that of 22K-hGH.

Animals↗