Search PubMed⌕ Search

Biomedical subjects

M Ohtani

Publications and source records attributed to M Ohtani.

At least 55 records · Page 3Linked to original sources
PubMed2000

Stereoselective high-performance liquid chromatographic determination of ketamine and its active metabolite, norketamine, in human plasma.

A stereoselective high-performance liquid chromatographic method for the determination of the enantiomers of ketamine and its active metabolite, norketamine, in human plasma is described. The compounds were extracted from plasma by liquid-liquid extraction three times in a combination of cyclohexane with 2.5 M NaOH, 1 mM HCl and 1 M carbonate buffer. Stereoselective separation was achieved on a Chiralcel OD column with a mobile phase of n-hexane-2-propanol (98:2, v/v). The detection wavelength was 215 nm. The lower limits of the determination of the method were 5 ng/ml for ketamine and 10 ng/ml for norketamine. The intra- and inter-day coefficients of variation ranged from 2.9 to 9.8% and from 3.4 to 10.7% for all compounds, respectively. The method was sensitive and sufficiently reproducible for stereoselective monitoring of ketamine and norketamine in human plasma during pharmacokinetic studies after the administration of ketamine for analgesia.

Adult↗
PubMed2000

A CAG trinucleotide repeat expansion and familial schizophrenia.

Studies which showed anticipation in families with schizophrenia suggested that a trinucleotide repeat expansion mechanism may be involved in the pathogenesis of familial schizophrenia. Furthermore, some studies involving the repeat expansion detection (RED) method showed the median length of CAG repeats to be longer in probands with schizophrenia than that in control subjects. We screened for a possible expanded CAG repeat by means of the direct identification of repeat expansion and cloning technique in 23 subjects (affected, 14; unaffected, 9) from six families with schizophrenia which showed anticipation. The polymorphism of a long and unstable CAG/CTG trinucleotide repeat, Dir1, was studied by PCR. No unusual expanded CAG/CTG trinucleotide repeat was detected in the subjects with familial schizophrenia. There was no significant difference between the affected and unaffected subjects in the allele frequency of Dir1. Our results suggest that a CAG expansion is not the mechanism underlying familial schizophrenia.

Adult↗
PubMed2000

Direct colorimetric method for determination of organophosphates in human urine.

A simple and sensitive method for determination of organophosphorus pesticides in human urine was developed by detecting the color complexes which resulted from reactions of organophosphorus pesticides and 4-(4-nitrobenzyl)pyridine (NBP) in urine. Based on studies of reaction conditions, e.g. reaction temperature and time, and reagent concentration, a colorimetric method was established. A 0.1-ml volume of NBP (45% in acetone) was added to a 1.0-ml volume of a urine sample, and the mixture was heated at 100 degrees C for 20 min. After cooling, 0.1 ml of tetraethylenepentamine was added. The organophosphorus pesticides showed a characteristic purplish blue color and the coloring complexes which were produced were stable for several hours. Furthermore, these complexes could be determined spectrophotometrically. The detection limits were 0.10-10 microg/ml in urine. The required time for analysis was approximately 30 min for one sample. Comparing the result of the proposed method with those of the GC-MS method, the results were similar for the 12 poisoning cases studied. Thus, the proposed method is useful for detection of these pesticides in critical care practices.

Chelating Agents↗
PubMed2000

Development of an antagonist of molluscan neuropeptide APGWamide with a peptide library.

Fifty-seven kinds of APGWamide-related peptides and a peptide library consisting of 38 peptide mixtures, each of which contained 19 kinds of APGWamide-related peptides, were synthesized with a multipeptide synthesizer, and their APGWamide-agonistic or -antagonistic effects were examined on the anterior byssus retractor muscle of the bivalve Mytilus edulis and the crop of the land snail Euhadra congenita. The peptide mixtures having agonistic or antagonistic effects were subjected to HPLC purification to isolate the active peptides using the muscles as bioassay systems. Many peptides having agonistic or antagonistic effects were obtained. Of the antagonists, APGWGNamide, isolated from the peptide mixture of APGWGXamide, was the most potent. At 10(-4) M, APGWGNamide almost completely blocked the actions of 10(-6) M APGWamide on the anterior byssus retractor muscle of M. edulis and the crop of E. congenita.

Animals↗
PubMed2000

New gamma-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immunosuppressive activity.

Our continuing program to develop new antifolate drugs useful against rheumatoid arthritis led us to modify the pteridine ring of gamma-fluoromethotrexate. Pyrrolopyrimidine derivatives 1e and 1t were found to exhibit potent suppressive effects on the responses of both T and B cells to mitogens, although tetrahydropyridopyrimidine derivatives 2e and 2t and quinazoline derivatives 3e, 3t and 4e showed very weak suppressive activities. Thus, conversion of the pteridine ring of gamma-fluoromethotrexate to a pyrrolopyrimidine ring led to a new potential antirheumatic compound.

Antirheumatic Agents↗
PubMed2000

Periovulatory changes in the local release of vasoactive peptides, prostaglandin f(2alpha), and steroid hormones from bovine mature follicles in vivo.

We previously proposed that an endothelin-angiotensin-atrial natriuretic peptide system may contribute to inducing ovulation of mature bovine follicles by modulating follicular secretion of steroids and prostaglandins (PGs). Thus, this study aimed to determine the real-time changes in the local release of angiotensin II (Ang II), endothelin (ET), atrial natriuretic peptide (ANP), PGF(2alpha), and steroid hormones from bovine mature follicles during the periovulatory period in vivo. Seven cows were treated for superovulation using FSH and PGF(2alpha) injections. Two dialysis capillary membranes per follicle were surgically implanted into the theca layer of mature follicles and connected to a microdialysis system (MDS). Fractions of the perfusate were collected from Day -1 (Day 0 = LH surge) to Day 3. Five out of seven treated cows were normally ovulated, and the newly formed corpora lutea were observed at the end of the experiment. In these five ovulated cows, the release of estradiol, androstenedione, and progesterone in the theca layer increased (P < 0.05) synchronously with the LH surge. Acute increases in PGF(2alpha) and Ang II concentrations in the ovarian venous plasma (OVP) were observed at 24-48 h after the peak of the LH surge, when multiple ovulations were expected to occur. The follicular Ang II release was low during the pre-LH surge period and rose (P < 0.05) at the beginning of the increase in the LH surge. On the other hand, ET-1 release dropped (P < 0.05) when plasma LH started to increase. However, no clear changes in ANP concentration in the MDS perfusate and plasma were observed. The above local changes in Ang II, PGF(2alpha), as well as steroid hormones were not observed in cows (n = 2) that did not show an LH surge and ovulation. The present results demonstrate for the first time the local release of Ang II, ET-1, and ANP from the bovine mature follicle in real-time in vivo and show that Ang II and PGF(2alpha) concentrations in the OVP acutely increase around the time of ovulation. The overall results support the concept of a local functional ET-Ang-ANP system in the bovine mature follicle that may be involved in the ovulatory process.

Angiotensin II↗
PubMed2000

Prognostic significance of p27(kip1) protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas.

Tumor cell apoptosis, proliferation and p27 expression using an in situ apoptosis detection kit, anti-Ki67 antibody and anti-p27 antibody were investigated in 171 colorectal adenocarcinoma specimens, together with the assessment of mutated p53 expression. No apparent association was observed among p27 expression, mutated p53 accumulation, the Ki67 labeling index and the apoptotic index (AI). In the multivariate analysis using the median values as the cut-off points (46.8% for p27 expression and 0.89% for AI), p27 expression was identified as an independent and significant predictor for overall survival. When the present series of patients were dichotomized by these cut-off points to categorize the cases into 4 subgroups, the patients in the group with low p27 expression and a low AI had the poorest prognosis. The assessment of p27 expression and AI therefore may prove valuable in identifying patients with colorectal adenocarcinoma who may have a poor prognosis.

Adenocarcinoma↗
PubMed2000

Comparative aspects of invertebrate neuropeptides.

1. We searched for bioactive peptides, most of which were considered to be neuropeptides, in various animals of several phyla. These peptides were compared with each other and with peptides identified by many other investigators. Consequently, we found that structures of neuropeptides are generally conserved in each phylum. 2. We also found some exceptional interesting aspects. First, there are a number of peptide groups whose members are distributed among several phyla. Second, there are many structural similarities between molluscan and annelidan peptides as if molluscs and annelids were the animals in a phylum. Third, certain toxic peptides of invertebrates are closely related to vertebrate neuropeptides. 3. In addition to the above phylogenetic aspects, we found some other interesting aspects. A wide structural variety of members of a peptide group is generally found in invertebrate species. Invertebrate muscles seem to be generally regulated not only by some or several classical non-peptidic neuromediators but also by various peptidic neuromediators. Peptides containing a D-amino acid residue are not rare.

Amino Acid Sequence↗
PubMed2000

Assessment of perioperative predictive factors influencing survival in patients with postinfarction ventricular septal perforation. Classified by the site of myocardial infarction.

BACKGROUND: The present study was designed to identify the perioperative factors and to consider a counterplan for the improvement of surgical results, based on the site of myocardial infarction. METHODS: Sixteen patients with postinfarction ventricular septal perforation underwent surgical repair. The operation was performed 5+/-3 days after the onset of ventricular septal perforation using the same method, an infarctectomy and reconstruction of the septum and right and left ventricular walls with a single Dacron patch. The ventricular septal perforation was anterior in 11 patients and posterior in 5. Preoperative hemodynamics between survivors and non-survivors were compared. Left ventricular wall motion was estimated using echocardiography by wall motion score (divided into 17 segments and each segment was graded on a fourpoint scale: normal, 0; hypokinetic, 1; severe hypokinetic, 2; a- or dyskinetic, 3) and summed up. RESULTS: The operative mortality was 36% in 11 patients with anterior ventricular septal perforation. In non-survivors compared to survivors, wall motion score was greater (25+/-4 vs 18+/-4, p<0.01) and all values were over 20. The value of the cardiac index divided by Qp/Qs was lower (0.98+/-0.09 vs 1.44+/-0.31, p<0.02) and all were under 1.1. In 5 patients with inferior ventricular septal perforation, the operative mortality was 40%. In non-survivors compared to survivors, wall motion score was greater (18, 18 vs 7, 2, 12) and the right atrial pressure was greater (18, 19 vs 10, 9, 9 mmHg) due to a right ventricular infarction. CONCLUSIONS: The patients with poor left ventricular wall motion were lost for reasons unrelated to the site of myocardial infarction. Moreover, a cardiac index over Qp/Qs in anterior ventricular septal perforation and the existence of a right ventricular infarction in inferior ventricular septal perforation was predictive of operative mortality.

Aged↗
PubMed2000

[A randomized long-term comparative study of clinical efficacy of alpha 1-blocker with or without antiandrogen therapy for benign prostatic hyperplasia: focusing on improvement of I-PSS].

This study was conducted to examine the efficacy of administration of tamsulosin hydrochloride alone or in combination with chlormadinone acetate (CMA) against lower urinary tract symptoms for a period of 52 weeks in 33 patients with benign prostatic hyperplasia. The patients were randomly allocated into a group administered tamsulosin alone and a group administered tamsulosin in combination with CMA. Based on the assessment of the total I-PSS (International Prostate Symptom Score), significant symptomatic improvement was noted 4 weeks after the commencement of drug administration in the tamsulosin + CMA group, whereas no significant improvement was observed in the tamsulosin group. Both irritative and obstructive bladder symptoms improved significantly at any time of assessment after 4 weeks of drug administration in the tamsulosin + CMA group; however, significant improvement was noted only at week 16 and week 52 for irritative symptoms and at week 16 for obstructive symptoms in the tamsulosin group. In particular, obstructive symptoms showed significant improvement at week 4 in the tamsulosin + CMA group, as compared with that in the tamsulosin group. The average value of peak urinary flow rate was significantly increased in the tamsulosin + CMA group (10.4 ml/s to 15.6 ml/s) as compared with that in the tamsulosin group (8.5 ml/s to 10.5 ml/s). These findings indicate that combined administration of tamsulosin and CMA resulted in early improvement of lower urinary tract symptoms in these patients. Long-term combined administration of tamsulosin and CMA thus appears to be a promising treatment strategy for the improvement of obstructive symptoms and peak urinary flow rate, particularly, 16 weeks onward after administration in patients with benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗
PubMed2000

[Poison elimination methods in acute poisoning].

This paper presents current ideas about the application of poison elimination methods in acute poisoning. The methods are divided into two groups: poison elimination before absorption; and enhancement of elimination after drug absorption. The former include washes, emesis, gastric lavage, and administration of activated charcoal and cathartics, while the latter include forced diuresis and extracorporeal toxin elimination such as hemodialysis or hemoperfusion. The indications, contraindications, techniques, and complications, associated with these elimination methods, except for extracorporeal toxin elimination, are discussed. In the treatment of poisoning, early and comprehensive poison elimination is important.

Acute Disease↗
PubMed1999

Homology modeling of gelatinase catalytic domains and docking simulations of novel sulfonamide inhibitors.

Three-dimensional models for the catalytic domain of gelatinases (MMP-9 and -2) have been constructed based on the X-ray crystal structure of MMP-3. Conformations of the loop segment which forms the bottom half of the S1' subsite but shows conformational diversity among the crystal structures of other MMPs have been explored by simulated annealing of each gelatinase model complexed with two highly potent "probe" inhibitors. Representative catalytic domain models have been selected for each gelatinase from the set of generated conformations based on shape complementarity of the loop to the probe inhibitors. The single model selected for MMP-9 was utilized to explain the structure-activity relationship of our novel sulfonamide inhibitors. Molecular dynamics (MD) simulations of the complex models revealed important features of the binding mechanism of our inhibitors: (i) the ligand carboxylate group coordinating to the catalytic zinc ion and hydrogen bonding to the Glu219 side chain, (ii) one of the sulfonyl oxygens forming hydrogen bonds with the main chain NHs (Leu181 and Ala182), (iii) the sulfonyl substituent making extensive hydrophobic contact with the S1' subsite. The gauche conformation exclusively adopted by the sulfonamide C-N-S-C torsion plays an important role in achieving the third binding feature by properly directing the substituent into the S1' subsite. Improvement of the inhibitory activity according to straight elongation of the sulfonyl substituent was attributed to an increase of the hydrophobic contact between the substituent and the S1' subsite. Structural modifications which alter the straight shape of the substituent lead to deterioration of the activity. On the other hand, the two candidate models selected for MMP-2 differ in the bottom shape of the S1' subsite: one with a channel-like subsite and the other with a pocket-like subsite resembling that of the MMP-9 model. The bottom shape was experimentally probed by chemical synthesis of inhibitors having elongated sulfonyl substituents whose terminal alkyl groups were shown by MD simulations to protrude from the S1' subsite bottom into the solvent. Gelatinase assays of these inhibitors showed that elongation of the substituent significantly reduces activity against MMP-9 while retaining activity against MMP-2, consequently increasing the selectivity between MMP-2 and -9. The results confirm that MMP-9 has a pocket-like S1' subsite with a floorboard and MMP-2 has a channel-like S1' subsite.

Amino Acid Sequence↗
PubMed1999

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma.

BACKGROUND: The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non-early stage gastric carcinoma. METHODS: Primary gastric tumor specimens from 225 patients were investigated by immunohistochemistry with anti-p27Kip1 and anti-Ki-67 antibodies, and their apoptotic indices were determined with the use of an Apop-Tag in situ detection kit. RESULTS: The median p27Kip1 labeling index (LI) was 48.4%. There was a significant association between the p27 LIs and the apoptotic indices (Als). However, there was no association between the p27 LIs and the Ki-67 LIs. p27 LI was demonstrated to be one of the most significant and independent prognostic factors in multivariate analysis. Although AI was found to be prognostically significant in univariate analysis, it failed to retain an independent and significant value regarding overall survival in multivariate analysis. CONCLUSIONS: Decreased expression of p27Kip1 and reduction of apoptotic potential were two of the most important factors in predicting a poor prognosis for patients with non-early stage gastric carcinoma. These findings support the hypothesis that decreased p27Kip1 expression, which may reflect a decreased rate of apoptosis, is closely related to the aggressiveness of gastric carcinoma. Therefore, the assessment of p27Kip1 expression and apoptotic potential may prove valuable in identifying patients with gastric carcinoma who are at high risk for recurrence and would benefit from adjuvant therapy.

Adenocarcinoma↗
PubMed1999

Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor.

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential.

Animals↗
PubMed1999

The efficiency of performing ultrasound-guided fine-needle aspiration biopsy following mass screening for thyroid tumors to avoid unnecessary surgery.

Thyroid masses are a common clinical finding, and their management remains controversial. The purpose of this study was to evaluate the clinical effect of performing routine ultrasound (US) examinations and US-guided fine-needle aspiration biopsy (US-FNAB) in the management of diffuse or nodular goiter diagnosed by mass screening. Mass screening carried out from 1993 to 1996 revealed 444 women with goiter, 322 of whom had diffuse goiter and 122 had nodular goiter. All of these patients underwent US examination, the results of which determined that 169 should undergo US-FNAB to confirm an accurate diagnosis of their thyroid tumors. Histological examinations after surgical resection revealed that 12 of the 322 patients with diffuse goiter (3.7%) and 23 of the 122 with nodular goiter (18.9%) had malignant tumors. Among the 61 thyroid tumors surgically verified, US-FNAB yielded a sensitivity rate of 93%, a specificity rate of 81%, and an accuracy rate of 90%. Insufficient aspiration was obtained from 5%. Performing US-FNAB-resulted in an elevation in the percentage of malignant tumors yielded at surgery of up to 72%. Thus, ultrasonography followed by US-guided-FNAB could be a useful routine method of evaluating thyroid tumors detected by mass screening. Moreover, a greater number of unnecessary thyroid operations can be avoided by performing US-FNAB rather than FNAB alone.

Biopsy, Needle↗
PubMed1999

Analysis of synovial fluid components of hydrarthrosis in long-term hemodialysis patients.

The synovial fluid components in long-term hemodialysis patients (HD; 43 knees in 43 patients) were investigated and compared with those in patients with osteoarthritis (OA; 21 knees in 21 patients) and rheumatoid arthritis (RA; 26 knees in 26 patients). The average ages in the three groups were, respectively, 60.7 years (range, 34-79 years), 63.2 years (range, 48-88 years), and 59.7 years (range, 37-76 years). The duration of hemodialysis in the HD group averaged 14.0 years (range, 4-24 years). The concentrations of hyaluronic acid, protein, and isomers of chondroitin sulfate (chondroitin 6-sulfate [C6S] and chondroitin 4-sulfate [C4S]) in the synovial fluid, and its viscosity were measured. Differences in each of the parameters were investigated according to disease clinical stage, roentgenological grade, and periods of dialysis in the HD group. The viscosity of the synovial fluid and the concentration of hyaluronic acid in HD patients were similar to those in OA patients; however, the C6S/C4S ratio in the synovial fluid of HD patients was similar to that in RA patients. The latter finding suggests that synovitis may be present in the hydrarthrosis of HD patients. The cause of this synovitis in HD patients remains to be elucidated.

Adult↗