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Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 19 recordsLinked to original sources

Fine-scale deletion mapping of the distal long arm of chromosome 6 in 70 human ovarian cancers.

To define a small region on chromosome 6q containing a putative tumor suppressor gene for ovarian cancer, we examined loss of heterozygosity in 70 ovarian tumors of three histological types with nine restriction fragment length polymorphism markers located at 6q24-27. Among 33 cancers of serous type that were informative at one or more loci, 17 showed allelic loss at a few or all loci examined, whereas only 1 of 15 mucinous-type tumors and 2 of 12 clear-cell tumors revealed loss of heterozygosity. This result supported our earlier suggestion that alteration of a gene on chromosome 6q may play an important role during development of serous ovarian tumors (Sato et al., Cancer Res., 51: 5118-5122, 1991). Frequent losses were observed between loci defined by CI6-119 (D6S195) at 6q26 and CI6-49 (D6S161) at 6q27. A detailed deletion map indicated a commonly deleted region between loci defined by CI6-111 (D6S193) and CI6-24 (D6S149); these two markers are estimated to be 1.9 cM apart on the basis of linkage analysis. Our results further define a region containing a tumor suppressor gene involved in ovarian carcinoma within an approximately 2-megabase-long segment of chromosome 6q.

Blotting, Southern

Remodeling of large bone defects in the treatment of space-occupying lesions. Curettage without bone graft for treating benign bone tumors.

Curettage without bone graft was performed in 17 patients with benign bone tumors and tumor-like lesions. New bone formation with uniformly increased radiodensity appeared in serial plain radiographs within 3 months after the operation. The average period before full weight could be borne on the lower extremities was 14 weeks. Computed tomography revealed that the central part of the bone lesions persisted without bone formation. The thickening of cortical bone was predominant. These data indicate that enough mechanical strength for daily activity will be recovered by bone within 4 months after curettage without any filler, although remodeling continues for over a year. It is suggested that bone graft and implantation of "biomaterials" are not necessary in patients, especially younger ones, with benign bone tumors or tumorous conditions.

Adolescent

Peritoneal cytology in patients with uterine cervical carcinoma.

We studied the relationship between cytological diagnosis of peritoneal washing and pathohistological findings in 97 cases of stage Ib and 103 cases of stage IIa or b cervical carcinoma. No positive cytology was found in 24 cases classified as pT1 by pTNM classification. Positive cytology was found in 8 out of 40 cases with retroperitoneal lymph node metastasis, 2 out of 5 cases with uterine corpus infiltration, and 3 out of 4 cases with ovarian metastasis. Negative cytology was often found even in cases with metastasis to several retroperitoneal lymph nodes, while positive cytology was also found in cases without metastasis. The mechanism of cervical carcinoma metastasizing to retroperitoneal lymph nodes may not be the same as that of spreading into the abdominal cavity. Many cases with positive peritoneal cytology tended to recur with peritoneal carcinoma as compared to those with negative cytology. The above findings indicate that chemotherapy, including intraperitoneal administration, is necessary in addition to radiation therapy for patients with cervical carcinoma with positive peritoneal washings.

Adult

Twin umbilical cord blood gas values.

In vaginally delivered births (including a few cases where the mothers were under epidural anesthesia), differences between first and second born twins were compared according to presentation at delivery. Of twins with vertex/vertex presentation in 15 primipara cases and in 14 multipara cases, pO2 levels for the second born were significantly lower (both being p < 0.05) than for the first born. Of twins vertex/non-vertex presentation, the second born in 9 primipara cases showed significantly lower pH, pO2 and HCO3 levels (p < 0.05). Also for multipara twins, the second born had significantly lower pH (p < 0.05) and significantly higher pCO2 (p < 0.05) values. Umbilical cord blood gas value findings indicate unfavourable conditions for second born twins.

Bicarbonates

Perinatal management of twin pregnancy.

Of 104 cases, 38 (ie, 36.53%) experienced premature delivery (controls: 4.32%). In instances of threatened premature delivery, 28 cases (26.92%) underwent ligation of the cervix. EPH gestosis occurred in 62 cases--a high incidence rate of 59.61% (controls: 12.9%). Forty-nine cases (47.11%) were complicated by anemia (controls: 8.36%). There were 57 cases of SFD infants, again a high 27.40% incidence rate (controls: 5.94%). Apgar scores of 7 or less at 1 minute after birth indicated that of the 208 neonates, the second-born twin only in 20 cases (9.61%); both infants in 14 cases (6.73%); and, the first-born only in 3 cases (1.44%), developed asphyxia neonatorum. Given the high incidence of premature and immature infants in cases of twins, caution should be employed against threatened premature delivery from around the 28th week of gestation onwards. Ligation of the cervix with ritodrine administration should be performed following admission to hospital, and EPH gestosis, anemia and IUGR should be carefully monitored.

Anemia

Metabolism and disposition of erythritol after oral administration to rats.

The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes.

Administration, Oral

Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.

The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-beta-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.

Administration, Cutaneous

[Bacteriological study of traveller's diarrhoea. 4) Isolation of enteropathogenic bacteria from patients with traveller's diarrhoea at Osaka Airport Quarantine Station during 1984-1991].

During the last 8 years (1984 to 1991), 16,639,233 overseas travellers were quarantined at Osaka Airport Quarantine Station and 38,326 travellers reported that they were (or had been) suffering from diarrhoea. Bacteriological examination of stools from 12,573 persons revealed the following results. 1) Various enteropathogenic bacteria were isolated from 3,669 cases (29.2%) examined. The predominant species of bacteria isolated were as follows: Salmonella, 1049 cases; Plesiomonas shigelloides, 1030 cases; Vibrio parahaemolyticus, 789 cases; Shigella, 607 cases; enterotoxigenic Escherichia coli, 422 cases; Vibrio cholerae non-O1, 212 cases. 2) There were no apparent seasonal variations in the isolation rate of these pathogens. 3) The suspected regions for infection with these pathogens were as follows: a) Salmonella, Enterotoxigenic E. coli and Plesiomonas, mainly South-East and South-West Asia. b) Shigella, South-West Asia, especially India (59.8%). c) V. parahaemolyticus and V. fluvialis, mainly South-East and East Asia. d) V. cholerae non-O1, V. mimicus, almost restricted to Asia, mainly South-East Asia. 4) 22 strains of V. cholerae O1 were isolated and 19 were Ogawa, E1 Tor. Of these strains, 13 were cholera toxin-producing strains and 9 were non-toxigenic strains. 5) Several pathogens (mixed infection) were isolated simultaneously from 670 cases. 6) The 1247 Salmonella strains were identified into 98 serovars. 7) Of 624 Shigella strains isolated, 57.9% were S. sonnei, 29.2% were S. flexneri, 8.6% were S. boydii, 4.3% were S. dysenteriae. 8) The most predominant serovar of V. parahaemolyticus was O4:K8. Of 1,247 strains isolated, 9.8% were not producing thermostable direct hemolysin (TDH). 9) 570 (91.3%) of 624 Shigella strains and 409 (32.8%) of 1,247 Salmonella strains isolated were resistant to any one of the drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). The resistance rate and the number of multiple drug-resistance strains increased year by year. 10) Enterotoxigenic E. coli was isolated from 422 cases (10.7%) of 3,939 cases. Cases with enterotoxigenic E. coli strains producing ST (heat-stable), LT (heat-labile) or both ST and LT were 53.8%, 24.2% and 14.2% respectively. The others were cases with mixed types of enterotoxin production.

Asia, Southeastern

[The first cholera case diagnosed early in the clinical laboratory by DNA probe method].

An alkaline-phosphatase-labelled synthetic oligonucleotide probe was applied to detect the structural gene of cholera enterotoxin (ctx). This DNA probe has a complementary base sequence to 30 base of the CT-A subunit. This method was, for the first time, applied to diagnosis of a diarrheal patient. The probe detected ctx rapidly and simply as compared with reversed passive latex agglutination (RPLA) and Beads-ELISA. The cfu minimal dose for detection with the probe was about 10(6-7)/ml. This method can be easily performed in any clinical laboratory because the procedure is safe, simple and rapid (it can be completed within about 3 hours).

Adult

Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101).

A new compound, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101) was synthesized, and its skin penetration enhancing activity was examined by using 14C-indomethacin as a penetrant. A solution of HPE-101 and indomethacin was applied to a cloth pad affixed onto an adhesive tape to give a HPE-101 patch, and the patch was applied to hairless mouse skin. The amount of percutaneously absorbed indomethacin was determined by measuring the radioactivity excreted in urine for 24 h after application. 1) Azone and decylmethyl sulfoxide, enhanced markedly the percutaneous absorption of indomethacin when the propylene glycol-ethanol (9:1 v/v) mixture was used as the solvent. 2) Among various penetration enhancers dissolved in the indomethacin solutions and applied to screen for penetration enhancing activity, HPE-101 was found to be the most prominent. 3) Solvents containing more than 3% (w/w) of HPE-101 produced a plateau level of the penetration enhancing activity. 4) Daily application of 1% (w/w) solutions of HPE-101 or Azone increased the daily excretion of indomethacin significantly above the level excreted on the previous day. However, repeated daily application beyond 3 d gave a steady state excretion of indomethacin. 5) The mouse skin was pretreated with 3% (w/w) solutions of HPE-101 or Azone for 24 h on the 1st day, and the indomethacin solution was applied for 24 h on the 3rd day and 7th day to examine the recovery of skin barrier function. Enhanced excretion of indomethacin was still noted on the 3rd day, but enhancement was not observed on the 7th day.

Animals

Laser diffraction estimation of particle size distribution of slightly water-soluble drugs coexisting with additives: application to solid dosage forms.

A simple and quantitative evaluation method for particle size distribution (fx(r)) of slightly water-soluble drugs dispersed in an aqueous medium together with other water-insoluble additives was developed using a laser diffraction method. The particle size distribution function of the powder mixture, (f(r)), was assumed as f(r) = phi x.fx(r) + phi a.fa(r), where phi is the volume fraction of each component dispersed in a measurement medium and fa(r) is the distribution function of another water-insoluble additive "a". In order to calculate fx(r) from f(r), it is necessary to know the density of drug and additive in the measurement medium, d(x) and d(a), but this is difficult to determine since particles usually swell in the medium. Thus, a method was developed to use their relative value, delta a (= da/dx). As a practical application, oxolinic acids (OA) of three sizes (OA-S (about 2 microns), OA-M (about 7 microns) and OA-L (about 24 microns)) were used as model drugs. delta a values were determined for various additives using the mixture of OA-S and each additive. Then, using delta as, fx(r) of OA-M or OA-L in the mixture containing OA-M or OA-L and additives was calculated from the f(r) experimentally determined for the mixture. They agreed well with their original distributions. The method was applied to some dosage forms, and the results obtained had good correlation with those from turbidity, wet sieving or dissolution test.

Algorithms

Enhancement of bioavailability of dopamine via nasal route in beagle dogs.

Dopamine (DA), which is ineffective by oral administration due to first pass metabolism and is usually injected, was administered to dogs via rectal, dermal, buccal and nasal routes. The nasal route had the highest bioavailability and best avoided first pass metabolism. The effects of the addition of hydroxypropyl cellulose (HPC), sodium deoxycholate, POE (6) hydrogenated caster oil (HCO-60) and Azone on the nasal absorption increased bioavailability from 11.7% (control) to about 20%, 35%, 25% and 68%, respectively. Further, with a combination of 2% HPC and 5% Azone, bioavailability was increased to almost the same level as with i.v. administration. At the same time, plasma concentrations were maintained at a high level for more than 7 h. The increase in bioavailability is presumed to be caused by an enhancement in absorption and prolongation of the time DA is retained in the nasal cavity due to Azone and HPC, respectively.

Administration, Intranasal

Design and preparation of pulsatile release tablet as a new oral drug delivery system.

To achieve time-controlled or site specific delivery of a drug in the gastrointestinal tract, an orally applicable pulsatile drug release system with the dry-coated tablet form was developed. The system consisted of a less water permeable outer shell and a swellable core tablet; from such a system, the drug was expected to be rapidly released after a certain period of time on the basis of time-controlled disintegration mechanism. Various model disks of outer shell, consisting of hydrogenated castor oil and polyethyleneglycol 6000, were tested for their water penetration rate. The experimental results showed that water penetration proceeded obeying the boundary retreating mechanism, so that the lag time of the system could be controlled by changing either the thickness or the composition of the outer shell. The swelling force of various commercially available disintegrants was quantitatively compared, and it was found that carboxymethylcellulose calcium was the preferable disintegrant to be used for the core tablet. On the basis of the results of a series of fundamental studies, various pulsatile release tablets of isoniazide with different lag times were designed. In the in vitro dissolution test, typical pulsatile release was achieved for all the tablets prepared, and a good correlation was found between the observed lag time and the estimated lag time calculated from an empirical equation deduced from the thickness and polyethyleneglycol 6000 content of the outer shell.

Administration, Oral

Absorption of diltiazem in beagle dog from pulsatile release tablet.

An orally applicable pulsatile drug delivery system in dry-coated tablet form was prepared using diltiazem hydrochloride as the model drug, and a polyvinyl chloride-hydrogenated castor oil-polyethyleneglycol mixture as the outer shell of the tablet. In vitro drug release from the prepared tablet exhibited a typical pulsatile pattern with a 7 h lag phase (non-drug release period). This dosage form was orally administered to three beagle dogs under non-fasting and fasting conditions, and the plasma concentration level of diltiazem was determined according to time after administration. The result of the in vivo study in non-fasting dogs suggested that the drug could be released in the gastrointestinal tract as in the in vitro test. However, under the fasting condition, a large difference in the plasma concentration profile was found, suggesting that the disintegration time of the tablet tended to be influenced by the feeding condition of subject.

Administration, Oral

Characterization of the triphenyltin-induced increase in intracellular Ca2+ of mouse thymocytes: comparison with the action of A23187.

The properties of triphenyltin (TPT) in increasing intracellular Ca2+ ([Ca2+]i) of thymocytes was studied, in comparison with those of A23187, by the use of fluorescent dyes to monitor membrane potential and [Ca2+]i. Both 1 microM TPT and 30 nM A23187 increased the [Ca2+]i associated with the hyperpolarization mediated by Ca(2+)-dependent K+ conductance. The time course for the TPT-induced increase in the [Ca2+]i was much slower than that of A23187. When the external Ca2+ ([Ca2+]o) was removed, TPT produced a slight, but persistent, increase in the [Ca2+]i while A23187 caused only a transient increase in the [Ca2+]i. Reintroduction of Ca2+ to the external solution produced an increase in [Ca2+]i in both cases. Therefore, these results suggested that the increase in the [Ca2+]i of thymocytes induced by TPT and A23187 was dependent on the presence of [Ca2+]o and an intracellular Ca store. The potency of TPT in increasing the [Ca2+]i was greater than those of diphenyltin and monophenyltin, suggesting an involvement of the lipophilic property of organotins in increasing [Ca2+]i. The TPT-induced increase in the [Ca2+]i may be partly responsible for the toxicity of TPT on organs and/or organ systems.

Animals

Flow cytometric estimation of the effect of Ginkgo biloba extract on the content of hydrogen peroxide in dissociated mammalian brain neurons.

The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide was estimated in cerebellar neurons dissociated from rats, by means of a flow-cytometer and 2',7'-dichlorofluorescein (DCF) diacetate, a fluorescent dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further increases in the GBE concentration (up to 3 micrograms/ml) produced a dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces the content of hydrogen peroxide or suppresses the reactive oxygen species (ROS) formation of cerebellar neurons. The present technique may be useful for preliminary evaluations of agents affecting the ROS formation in mammalian brain neurons.

Animals

Translation of rat ovarian mRNA to two 20 alpha-hydroxysteroid dehydrogenase isozymes in Xenopus oocytes.

20 alpha-Hydroxysteroid dehydrogenase (20 alpha-HSD) in rat luteal tissue catalyzes the conversion of progesterone into a biologically inactive steroid, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) and depletes the output of progesterone into the circulation. An increase in 20 alpha-HSD activity in luteal tissue is therefore a prerequisite for the regression of functional corpora lutea in rats. We have reported that ovarian 20 alpha-HSD is composed of two isoforms (HSD1 and HSD2). In this study, among batches of ovaries collected randomly during the estrous cycle, we selected two batches (batches A and B): the cytosol preparation from batch A contained both HSD1 and HSD2 activities, whereas that from batch B contained only HSD1 activity. From these 2 batches, we extracted mRNA, and each mRNA preparation was subjected to translation in Xenopus oocytes. The translation products of batch A exhibited both HSD1 and HSD2 activities, and those of batch B only HSD1 activity in accordance with the enzymatic activities observed in the respective cytosolic preparations. The results are compatible with the presence of two distinct mRNAs coding HSD1 and HSD2, and if so their transcription will be regulated separately according to the functional state of the ovary.

20-Hydroxysteroid Dehydrogenases