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Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 127 records · Page 7Linked to original sources

Effects of ageing on the oral absorption of D-xylose in rats: analysis of gastrointestinal disposition.

The effects of ageing on the oral (gastrointestinal) absorption of D-xylose were investigated by analysing the gastrointestinal disposition after oral administration to young (9 weeks) and old (53 weeks) rats. A linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction vs time profiles for the stomach and small intestine to estimate the gastric emptying rate constant (kg) and the intestinal absorption rate constant (ka). In young and old rats, Kg values were 0.087 +/- 0.008 and 0.070 +/- 0.007 min-1, respectively, and ka values were 0.020 +/- 0.002 and 0.018 +/- 0.002 min-1, suggesting an insignificant effect on ageing on the rate of oral absorption. The average intestinal lumen volume (Vav) was unchanged with ageing, and so was the apparent intestinal membrane permeability clearance (CLapp) as the product of Ka and Vav. However, the small intestinal transit time (Tsi) was suggested to be twice that in older rats (171 min) than in young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a non-absorbable marker. It was also shown that our preceding finding of an increase in the fraction absorbed of D-xylose with ageing can be solely ascribable to the delay in intestinal transit. Thus, among various determinants of oral absorption, only Tsi was found to be altered with ageing. The CLa,app and ka of passively absorbed drugs such as D-xylose may be generally unchanged, and the fraction absorbed may increase with ageing by the delay in intestinal transit.

Administration, Oral↗

Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus.

Familial central diabetes insipidus is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in a substitution of Ser for Gly57 in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu47 in the NPII moiety. In this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the polymerase chain reaction-amplified DNA and found two novel mutations in exon 2, which encodes the central part of the NPII moiety of the precursor. The mutation in one pedigree was a C to A transition at nucleotide position 1891, which replaces Cys67 (TGC) with stop codon (TGA). As the premature termination eliminates part of the COOH domain of the NPII moiety and the glycoprotein moiety, the conformation of the truncated protein is likely to be markedly different from that of normal precursor. In another pedigree, a G to T transversion was detected at nucleotide position 1874, which substitutes polar Trp (TGG) for hydrophobic Gly62 (GGG). It is possible that mutated NPII molecules, as a consequence of a conformational change, cannot bind AVP or self-associate to form higher oligomer complexes. Interestingly, all mutations we have identified to date, with the exception of the signal peptide mutation, are located in exon 2, suggesting the importance of the highly conserved central part of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis.

Adolescent↗

Uptake of low molecular weight fractionated [3H]heparin by rat hepatocytes in the primary culture.

The uptake of low molecular weight fractionated [3H]heparin (LMWFH: 7000 Da) was examined, for comparison with that of high molecular weight fractionated [3H]heparin (HMWFH:20000 Da), in a primary culture of rat hepatocytes. The uptake of LMWFH increased almost linearly with time up to 60 min (extended uptake), although a faster uptake was observed in the initial 2 min (initial uptake). Both the initial and extended uptake were saturable, and the maximum uptake velocity (Vmax) and the Michaelis constant (Km) were estimated to be 10.7 pmol/min/mg protein and 398 nM, respectively, for the initial uptake and 0.34 pmol/min/mg protein and 116 nM, respectively, for the extended uptake. The Km for the extended uptake was 5 times larger than that of 21 nM for HMWFH, but the other parameters were comparable with those for HMWFH. Thus, an increase in Km, or a decrease in the apparent affinity, with a decrease in molecular weight in the extended uptake may be responsible for the reported lower hepatic uptake of low molecular weight heparin, compared with unfractionated heparin. It was also shown that both the initial and the extended uptake of LMWFH were inhibited by several analogs of heparin, including HMWFH, and anionic compounds such as 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suggesting that LMWFH and HMWFH, in spite of a large difference in the molecular weight, share the same specialized uptake mechanism, in which an anionic moiety and/or heparin-like structure plays an important role.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Influence of anesthetic regimens on the intestinal absorption of 5-fluorouracil in rats.

We investigated the influence of anesthetic regimens on the intestinal absorption of 5-fluorouracil (5-FU), which is known to be absorbed by concurrent Na(+)-dependent, carrier-mediated transport and passive transport, in single-pass perfusion experiments in rats. Compared with the absorption in unanesthetized rats, the regular dose of urethane (1.13g/kg) reduced the maximum transport rate (Jmax), the Michaelis constant (Km) and the membrane permeability coefficient of passive transport (P m,d); a low dose of urethane (0.7g/kg) reduced Jmax and Kmax, but did not affect Pm,d; pentobarbital sodium (50 mg/kg) increased Jmax without affecting Km, and reduced Pm,d. The reductions in Jmax and Km were comparable for the regular and low doses of urethane. Thus, urethane and pentobarbital, which have been most commonly used in laboratory animal experiments, exerted qualitatively different effects on the carrier-mediated transport of 5-FU, although they similarly inhibited the passive transport. For urethane, the effect on the passive transport was avoided by reducing the dose, but the effect on the carrier-mediated transport was not. This influence of anesthetic regimens on intestinal drug absorption may not be easily scaled for normalizing absorption data. When compiling them for such purposes as establishing in situ-in vivo quantitative correlation, the absorption data in perfusion (in situ) should be categorized on the basis of anesthetic regimens, to avoid ending up with poor outcomes. We also examined the effect of urethane on the exsorption of Na+ in the intestinal loop where Na+-free buffer was introduced, and found a minimal effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Studies on dissolution tests for soft gelatin capsules by the rotating dialysis cell (RDC) method. VI. Preparation and evaluation of ibuprofen soft gelatin capsule.

We prepared soft gelatin capsules (SC) containing ibuprofen (IB), a widely used phenylpropionic acid-derived antiphlogistic-analgesic drug. To evaluate the SC, in vitro dissolution tests were performed both by the paddle (PD) method described in the Japanese Pharmacopoeia (JPXII) and by the rotating dialysis cell (RDC) method which we previously developed and evaluated for application. In vivo, the blood IB concentration was determined after administration to beagles. Higher bioavailability was observed after administration of the SC containing IB than after administration of the bulk IB powder. A higher correlation was observed between the in vitro dissolution behavior and in vivo results by the RDC method than by the PD method, suggesting the usefulness of the RDC method in the dissolution test of SC.

Animals↗

Eosinophils infiltration in the rat seminal vesicle associated with estradiol-17-beta-related stromal proliferation.

We performed a histological quantitative analysis of collagen and smooth muscle in seminal vesicle (SV) stroma after Estradiol-17 beta (E2) administration to the immature castrated rat. On day 14 after E2 administration, collagen and smooth muscle had increased approximately five and fifteen times, respectively, over the baseline of day 0. On day 28 (14 days after the cessation of E2 administration), smooth muscle decreased to the same level as that on day 7, but collagen did not decrease during the 14 days after the cessation of E2 administration. As the proliferation of stroma, the infiltration of eosinophils was seen in the perigrandular stroma that consisted of rich collagen. The number of infiltrated eosinophils increased exponentially in the period in which collagen proliferated. But in the peripheral stroma which consists of rich smooth muscle, no eosinophil infiltration was seen. These results suggest that eosinophil infiltration into SV is related to E2 administration and to stromal proliferation, especially to collagen proliferation in this condition.

Animals↗

[A resected case with lung cancer rapidly progressed to the mediastinum].

A 66-year-old man was revealed an abnormal shadow in the chest roentgenogram. Definitive diagnosis was not obtained by chest CT and bronchofiberscopy. Three months later, the shadow showed a rapid increase. We made a diagnosis of lung cancer by needle biopsy. Extended radical operation for the tumor was performed. The tumor with invasion to the chest wall and the mediastinum was completely resected with reconstruction of the chest wall and SVC. Postoperative pneumonia and respiratory failure were occurred, and patient died four months later.

Aged↗

[A case of spontaneous hemopneumothorax occurred after thoracocentesis].

A 41-year-old man was admitted to our hospital complaining of severe right chest pain and dyspnea. Soon after, right thoracocentesis was done and pleural free air was aspirated. Twenty minutes later he fell into a shock status. Chest roentgenogram showed massive right pleural fluid collection. Chest drainage revealed that massive bleeding continued. Therefore, emergent thoracotomy was performed. Bleeding point was a ruptured stump of pleural adhesion of the apical parietal pleura. His postoperative course was almost good, and discharged on the tenth postoperative day. Careful observation after thoracic aspiration is necessary in the treatment of spontaneous pneumothorax.

Adult↗

Kinetic analysis of plasminogen activation by staphylokinase/plasminogen complex in the presence of fibrin.

Staphylokinase (SAK) expresses plasminogen activator activity by forming a complex with plasminogen. In order to elucidate the mechanism for the expression of enzymatic activity of the complex, a cross-linked staphylokinase/plasminogen (SAK/plg) complex was produced with disuccinimidyl suberate, and its enzymatic characteristics were compared with those of a streptokinase/plasminogen (SK/plg) complex. SAK/plg complex and SK/plg complex showed a band with a molecular weight of 110 kDa and 140 kDa by SDS-PAGE under non-reduced condition, respectively. Both complexes exhibited plasminogen activator activity in a concentration-dependent manner on fibrin film and synthetic chromogenic substrate assay. The kinetic analysis of enzymatic activity of both complexes was performed. The plasminogen activator activity of SAK/plg complex was enhanced about 5-fold in the presence of FCB-2. However, SK/plg complex showed only 1.7-fold increase in the presence of FCB-2. These findings indicate that the SAK/plg complex reacts with fibrin, and efficient plasminogen activation is induced on fibrin surface.

Amino Acid Sequence↗

Gastric and small intestinal lesions after partial stomach resection with Billroth II or Roux-en-Y reconstruction in the rat.

The evolution and phenotypic expression of mucosal lesions of the gastric stump were investigated in male rats submitted to gastric resection with reconstruction by the Billroth II technique (BII with biliopancreatic reflux, BPR) or by the Roux-en-Y procedure (without BPR). Animals were studied at 24, 36, 54 and 64 weeks after surgery and the phenotypic expression of lesions analysed using routine hematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff (GOS) and sialidase GOS reactions). BPR was found to be responsible for the formation of adenomatous hyperplasia (AH), increasing in incidence and size with time, since the Roux-en-Y procedure failed to induce the gastric stump lesions observed after BII reconstruction. AHs always occurred in the transition of the gastrojejunal junction, a site offering special conditions for BPR influence, and were classified as gastric (G), intestinal (I) and G+I types according to their phenotypic expression. No pure I type AH was diagnosed at any time point. The G and G+I types developed at approximately equal incidences (i.e., G type 7/17, G+I type 10/17 at the 64th week). It was suggested that both gastric and intestinal mucosal elements were stimulated to proliferate by BPR, with the gastric mucosa tending to demonstrate AH. Intestinal type components of AH were found adjacent to the jejunum and not at the stomach margin, indicating an origin from intestinal mucosa. No metaplasia of the gastric mucosa was observed in any animal after partial gastric resection. In 101 rats submitted to the BII procedure, 5 mucinous adenocarcinomas were eventually diagnosed, mostly located in the subserosa of the gastrojejunal junction. All carcinomas expressed the phenotype of cells of the small intestine. Evidence of malignant transformation within the gastric components of AH was not observed even at the 64th week. In conclusion, all lesions induced by BPR in the rat remnant stomach are benign, and the few true cancers that arise in association are derived from the small intestine.

Animals↗

Reticuloendothelial function following cardiopulmonary bypass: laboratory and electron microscopy findings.

Several studies on the effects of cardiopulmonary bypass (CPB) on the reticuloendothelial system (RES) function have been performed previously, but different results have been reported. This study was carried out to determine the effect of CPB on RES function in a canine model simulating clinical CPB. Nine dogs undergoing surgery with CPB were compared with an identical number of dogs subjected to thoracotomy without CPB. A lipid emulsion test was performed in all dogs before and after the surgical procedure to measure RES phagocytic index, i.e., phagocytic function. Kupffer cell iron uptake under conditions of iron loading following CPB was examined histologically, and any ultrastructural changes in the Kupffer cells were observed by electron microscopy. In both groups, the RES phagocytic index showed a significant decline after surgery. However, a comparison of the two groups revealed that there was a significantly greater decrease in the CPB group (P < 0.05). Moreover, histologic evidence of iron uptake in Kupffer cells was strongly suppressed in the CPB group. Electron microscopy of the Kupffer cells showed that the number of phagosomes, especially deformed erythrocytes, increased after CPB. These findings suggest that RES function is significantly impaired following CPB, and an increase in the amount of material, especially deformed erythrocytes, to be processed by the RES is responsible, in part, for the depressed RES phagocytic function. The prevention of hemolysis during CPB may preserve the RES function following CPB.

Animals↗

Increase of labeling indices in gastrointestinal mucosae of mice and rats by compounds of the okadaic acid type.

Effects of compounds of the okadaic acid type (okadaic acid, dinophysistoxin-1, calyculin A and tautomycin) on proliferation by digestive-tract epithelial cells were investigated in mice and rats. In mice, a single oral administration of these agents caused significant enhancement of BrdU labeling indices in a dose/response manner. Exceptions showing no response were limited to the pyloric mucosa for okadaic acid, the pyloric and fundic mucosa for calyculin A and the pyloric mucosa for tautomycin. Sequential analysis of labeling indices after a single oral administration of dinophysistoxin-1 revealed two peaks of cell proliferation at 18 h and 36 h in the esophagus, ileum and colon. The labeling indices of the forestomach, fundus, pylorus and jejunum, on the other hand, continuously increased from 6 h after the administration. Elevated proliferation was also observed in the skin after 30 h or after, but no effects on the liver or kidney were evident. A single oral administration of the okadaic acid type of compounds also dose-dependently enhanced cell proliferation of the rat digestive tract. These results strongly suggest that the okadaic acid class of compounds may exert promoting potential for the gastrointestinal mucosa when administered orally.

Administration, Oral↗

Effects of inhaled nitric oxide in rats with chemically induced pulmonary hypertension.

To determine the model animal with pulmonary hypertension in which nitric oxide (NO) inhalation reduces pulmonary arterial pressure (PAP), we examined the inhalation of 20-100 ppm NO gas on normal rats and rats with monocrotaline induced pulmonary hypertension. In the control group, mean PAP showed no change after spontaneous breathing of NO at the concentration of 20 to 100 ppm for 5 min. On the contrary, in both the severe (mean PAP > 40 mmHg) and moderate (mean PAP < 40 mmHg) pulmonary hypertensive groups, NO inhalation produced a prompt reduction of the mean PAP which had been elevated by monocrotaline. 20 ppm NO inhalation reduced mean PAP from 64.4 +/- 3.7 mmHg to 56.2 +/- 4.4 mmHg (mean +/- SEM, P < 0.01) in the severe pulmonary hypertensive group, from 31.0 +/- 2.0 mmHg to 24.2 +/- 0.9 mmHg in the moderate pulmonary hypertensive group (mean +/- SEM, P < 0.05). The onset of the reduction of mean PAP occurred within 30 sec after the start of NO inhalation and maximum reduction occurred within 4 min. 20 ppm NO inhalation significantly reduced mean PAP, and mean PAP was reduced dose-dependently at the concentration of 20 to 60 ppm and reaction to NO was almost constant at the concentrations of over 60 ppm.

Administration, Inhalation↗

Immunohistochemical demonstration of intestinal-type alkaline phosphatase in stomach tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

A polyclonal antibody against rat intestinal-type alkaline phosphatase (I-ALP) was generated and proven to be applicable immunohistochemically to paraffin-embedded sections. Expression of I-ALP in normal tissues, intestinal metaplasia and stomach tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) animals were given drinking water containing 100 micrograms/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all stomach tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal-type tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I-ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I-ALP was also detected in the normal stomach, limited to the striated cell borders of absorptive cells of the upper one-fourth of intestinal metaplastic glands. I-ALP may thus be a useful marker for stomach tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No stomach tumors consisting mainly of intestinal-type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.

Adenocarcinoma↗

The effects of single lung transplantation in rats with monocrotaline-induced pulmonary hypertension.

Acute haemodynamic change after single lung transplantation for primary pulmonary hypertension was evaluated using a rat transplantation model. Inbred Fisher 344 rats were administered with 40 mg/kg monocrotaline in order to induce pulmonary hypertension. The rats whose mean pulmonary arterial pressure (PAP) was over 30.0 mm Hg received a left lung isograft from a normal donor after right heart catheterization. In the control group, PAP increased after single lung transplantation. On the other hand, in the pulmonary hypertensive group, PAP was significantly decreased 60 min after the transplantation, but 3 and 6 h after the transplantation, the PAP significantly increased again. On the day after the operation, it again decreased significantly. Left-to-right lung blood flow ratio was significantly increased in rats with pulmonary hypertension compared to rats with normal pulmonary pressure on both the 1st and 3rd postoperative days. The oedema of the grafted lung was more severe in the pulmonary hypertensive group than in the control group in the acute phase. In conclusion, single lung transplantation for pulmonary hypertension shifted pulmonary blood perfusion to the grafted lung and this shift made pulmonary oedema of the grafts more severe in the acute phase. These oedematous changes, which were more pronounced in the grafts in the pulmonary hypertensive rats, might have contributed to the transient rise in PAP in those rats after single lung transplantation.

Animals↗

Surgical treatment of primary lung cancer in patients less than 40 years of age.

PURPOSE AND METHODS: The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS: Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION: Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.

Adult↗

Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus.

Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A-->G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin.

Adolescent↗