Search PubMed⌕ Search

Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 145 records · Page 8Linked to original sources
PubMed2001

Effect of bile acids on absorption of nitrendipine in healthy subjects.

AIMS: To examine whether bile acids such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) can influence the absorption of nitrendipine, a highly lipophilic calcium channel blocker. METHODS: Six healthy subjects received nitrendipine (10 mg) with and without UDCA (50 mg) and CDCA (200 and 600 mg) with an interval of 1 approximately 2 weeks between study phases. RESULTS: Bile acids decreased the Cmax (ng ml(-1)) [control 10.9 +/- 5.8 (mean+/- s.d.), UDCA 5.0 +/- 4.7 (95% confidence interval for difference; 3.9, 7.8, P = 0.0006), CDCA (600 mg) 5.0 +/- 3.9 (2.6, 9.2, P = 0.0059)] and AUC (ng ml(-1) h) [(control; 60 +/- 36, UDCA 15 +/- 13 (20, 73, P = 0.0064), CDCA (600 mg) 19 +/- 19 (21, 63, P = 0.0038)] of nitrendipine, while elimination half-life remained unchanged. CONCLUSIONS: These results suggest that the amount of nitrendipine absorbed was decreased when the drug was administered with UDCA and CDCA.

Adult↗
PubMed2001

Glicentin, an active enteroglucagon, has a significant trophic role on the small intestine but not on the colon in the rat.

BACKGROUND: Many experiments have indicated that the gut glucagons (enteroglucagons) are associated with cell proliferation in the small intestine. However, recent studies have failed to show trophic effects of glicentin (enteroglucagon) on the intestine. AIMS: To examine the effects of glicentin on intestinal proliferation in vivo in the rat. METHODS: Rats were established on total parenteral nutrition for 6 days. Four experimental groups were given daily doses of 1, 4, 20 and 80 microg/rat of glicentin via the jugular vein. Rats fed by total parenteral nutrition and rats fed chow ad libitum were used as controls. Tissues taken from the duodenum, jejunum, ileum and colon were fixed in Carnoy's fluid and microdissected to determine the metaphase arrest scores and crypt fission ratios. RESULTS: The mean metaphase arrest scores per crypt of the small intestine were significantly increased in the rats given 4, 20 and 80 microg of glicentin. These responses were dose-dependent, and were most prominent in the ileum. Crypt fission of the ileum was significantly decreased in the 20 and 80 microg glicentin groups. Glicentin had no effects on proliferation or fission in the colon. CONCLUSIONS: Glicentin is trophic to the rat small intestine, but not the colon.

Animals↗
PubMed2001

Chicken pineal clock genes: implication of BMAL2 as a bidirectional regulator in circadian clock oscillation.

BACKGROUND: In a transcription/translation-based autoregulatory feedback loop of vertebrate circadian clock systems, a BMAL1-CLOCK heterodimer is a positive regulator for the transcription of the negative element gene Per. The chicken pineal gland represents a photosensitive clock tissue, but the pineal clock genes constituting the oscillator loop have been less well characterized. RESULTS: We identified expression of the Per2, Bmal1, Bmal2 and Clock genes in the chicken pineal gland. Messenger RNA levels of these genes exhibited overt circadian rhythms in the pineal cells, both in vivo and in culture. In vitro functional analyses revealed the formation of cBMAL1-cCLOCK and cBMAL2-cCLOCK heteromers. Both of the cBMAL-cCLOCK heteromers activated E-box element-dependent transcription, which was negatively regulated by cPER2 in luciferase assays. Co-expression of cCLOCK, cBMAL1 and cBMAL2 co-operatively activated E-box element-dependent transcription, and a greater level of expression of cBMAL2 inhibited the activation. In the cultured pineal cells, an over-expression of either cBMAL1 or cBMAL2 disrupted the circadian rhythm of melatonin production. CONCLUSION: The functional characterization of the chicken pineal clock molecules supports the key roles of BMAL1, BMAL2 and CLOCK which contribute to the E-box-dependent transcriptional regulation in the circadian clock system.

ARNTL Transcription Factors↗
PubMed2001

Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis.

AIM: Biliary papillomatosis is characterized by papillary proliferations of biliary lining cells without invasion or metastasis. The neoplastic character and biological behaviour of this disease remain still speculative. These issues were examined in this study. METHODS AND RESULTS: Mucin core protein MUC1, MUC2, MUC3, MUC5AC and carbohydrate antigens (T, Tn and sialosyl Tn) were immunohistochemically examined, using 11 lesions of biliary papillomatosis from seven patients, and five lesions of biliary papillomatosis with foci of carcinoma from four patients. Five cases of papillary intrahepatic cholangiocarcinoma and 12 histologically normal livers were used as a control. Patients with biliary papillomatosis alone or with carcinoma were middle-aged or elderly (five men and six women). Microscopically, biliary papillomatosis showed a villous, papillo-tubular, papillary, or papillo-villous pattern with a thin fibrovascular core. Cytologically, they were classifiable into biliary epithelial or pyloric gland-like type. The former was frequent in the cases associated with carcinoma. Expression of MUC1, Tn antigen and sialosyl Tn antigen was frequent and marked in biliary papillomatosis alone and with carcinoma and also intrahepatic papillary carcinoma. In addition, marked expression of MUC1 and Tn antigen were rather frequent in biliary papillomatosis with carcinoma and intrahepatic biliary papillary carcinoma compared with biliary papillomatosis. MUC2 was rather frequent and marked in biliary papillomatosis alone compared to other two disease groups. Focal expression of MUC5AC and MUC2 was rather frequent and infrequent irrespective of disease group, respectively. Focal expression of T antigen was frequent in papillary ICC. CONCLUSION: Biliary papillomatosis could undergo overt malignant transformation along with altered phenotypic expression of MUC proteins and mucin carbohydrate antigens.

Aged↗
PubMed2001

A case of toxic shock-like syndrome presenting with serious hypoproteinaemia because of a protein-losing gastroenteropathy.

A 37-year-old man was admitted to our hospital because of toxic shock-like syndrome (TSLS) induced by Streptococcus pyogenes. After the pathogenic bacteria had been eradicated, serious diarrhoea appeared and a protein-losing gastroenteropathy developed. An immunohistochemical study of the biopsy specimens of both small and large intestines revealed the infiltration of T-lymphocytes, predominantly CD8+ cells, into the lamina propria of affected mucosa, villus atrophy and crypt hyperplasia. Considering these histological findings, some immunological mechanism which lead the activation of cytotoxic T-lymphocytes may play an important role in the pathogenesis of this rare intestinal manifestation of TSLS.

Adult↗
PubMed2001

Immunohistochemical study of the ontogeny of prochymosin--and pepsinogen-producing cells in the abomasum of sheep.

The appearance and development of prochymosin- and pepsinogen-producing cells were investigated in the ovine abomasum from fetus to adult using immunohistochemistry. Prochymosin immunoreactivity appeared first in the proper gastric glands of the 100-day-old fetus. The intensity and distribution of prochymosin-immunoreactive cells increased gradually with the progress of gestation, and their most intense immunoreactivities and widest distribution were observed in 3-day-old lambs. They were subsequently reduced throughout postnatal growth. A few prochymosin-immunoreactive cells were scattered in the glands of adult sheep. Pepsinogen immunoreactivity appeared at first in a small number of cells in the base of some proper gastric glands of 120-day-old fetuses. After 130 days, pepsinogen-immunoreactive cells increased their staining intensities and distribution. They reached a peak in area at 21 days, which is comparable to adult sheep. In the pyloric glands, prochymosin- and pepsinogen-immunoreactive cells appeared from 100 and 130 days, respectively. Numbers were reduced in comparison to gastric glands and their occurrence was capricious. The results demonstrated that the ontogeny of prochymosin- and pepsinogen-immunoreactive cells in the abomasum of sheep is more similar to that in cattle than to that in the goat. The present data will contribute to the overall understanding of the development of ruminant gastric proteases.

Abomasum↗
PubMed2001

The structure of the masseter muscle in the giraffe (Giraffa camelopardalis).

In the giraffe (Giraffa camelopardalis), the masseter muscle was divided into several layers. The superficial and more medial (second) tendinous sheets of the masseter muscle fused with each other at the dorso-caudal part and a fleshy portion was located between these tendinous sheets. In the rostral part, the most superficial tendinous sheet turned around as a compact tendon and attached to the facial crest (Crista facialis). The turned tendinous sheet, however, never fused with the second tendinous sheet and this layer of the masseter muscle, that originated from the facial crest with the turned sheet, was inserted into the mandible with its fleshy portion. In the cattle, goat, sheep and Sika deer, the rostral layer of the masseter muscle arises from the facial crest with its fleshy portion and is inserted into the tubercle on the mandible through the strong tendinous sheet. In this study, the takin also showed the same structure of the masseter muscle. In the giraffe, however, the rostral layer inserted into the mandible through the strong tendinous sheet could not be distinguished, thus, there was no conspicuous tubercle on the mandible. Moreover in the masseteric region of the skull.,the giraffe was similar to the Sika deer in several ways. However, it is suggested that the giraffe exerts smaller forces on the cheek teeth than does the Sika deer because of its longer Margo interalveolaris.

Animals↗
PubMed2001

Immunohistochemical localization of inhibin subunits in the testis of the bull.

The differential localization of the inhibin beta subunits betaA and betaB in the testis of adult bull was studied using specific monoclonal and polyclonal primary antibodies. Inhibin betaA- and betaB-subunits were localized only in the Sertoli cells. The inhibin betaA-subunit was observed in the cytoplasm while the betaB-subunit was localized in the nucleus. No specific findings depending on spermatogenic stages were observed among the seminiferous tubules. Moreover, the inhibin alpha-subunit was not detected in the testis of the bulls. In addition, no inhibin subunits were detected in the Leydig cells and spermatogenic cells. These findings indicate the presence of betaA- and betaB-subunits in the bull, which may suggest a possibility that activin is produced and/or stored in the Sertoli cells and regulates spermatogenesis in an autocrine/paracrine manner. Moreover, the inhibin betaB-subunit may be produced in the nucleus but the functional meaning of this is not yet clear.

Animals↗
PubMed2001

The effects of flumazenil on sleepiness, task performance and nocturnal sleep after anesthesia with midazolam.

The purpose of the present study was to clarify the changes in psychophysiological functions after anesthesia with midazolam (intravenous (i.v.) benzodiazepine anesthetic) and to examine the ability of flumazenil (benzodiazepine antagonist) to prevent the adverse effects of anesthesia with midazolam. Clinical dose of midazolam (0.1 mg/kg i.v.) was administered to seven healthy volunteers and either flumazenil (0.3 mg i.v.) or saline was injected at the end of the anesthesia. After anesthesia with midazolam, subjective sleepiness and euphoria increased significantly, but these changes were not observed when flumazenil was administered. In addition, sleep latency was prolonged and sleep efficiency decreased significantly after midazolam anesthesia with and without flumazenil. Slow wave sleep decreased significantly only by co-administration of flumazenil.

Adult↗
PubMed2001

Re-entrainment of the circadian rhythms of plasma melatonin in an 11-h eastward bound flight.

We investigated the re-entrainment of melatonin rhythm in an 11-h eastward-bound flight. Eight male subjects participated in the present study. Blood sampling was carried out once before the flight and twice after the flight. During the daytime the subjects were exposed to natural zeitgeber outdoors on the day except the blood sampling. Seven of eight subjects showed antidromic re-entrainment, and the other subject showed orthodromic re-entrainment. The intensity of natural day light in New York amounted to 20 000 lx. As for the direction of the re-entrainment in New York the antidromic re-entrainment is naturally dominant.

Adaptation, Physiological↗
PubMed2001

Carpal bone movements in gripping action of the giant panda (Ailuropoda melanoleuca).

The movement of the carpal bones in gripping was clarified in the giant panda (Ailuropoda melanoleuca) by means of macroscopic anatomy, computed tomography (CT) and related 3-dimensional (3-D) volume rendering techniques. In the gripping action, 3-D CT images demonstrated that the radial and 4th carpal bones largely rotate or flex to the radial and ulnar sides respectively. This indicates that these carpal bones on both sides enable the panda to flex the palm from the forearm and to grasp objects by the manipulation mechanism that includes the radial sesamoid. In the macroscopic observations, we found that the smooth articulation surfaces are enlarged between the radial carpal and the radius on the radial side, and between the 4th and ulnar carpals on the ulnar side. The panda skilfully grasps using a double pincer-like apparatus with the huge radial sesamoid and accessory carpal.

Animals↗
PubMed2001

Axonal transport of VR1 capsaicin receptor mRNA in primary afferents and its participation in inflammation-induced increase in capsaicin sensitivity.

Capsaicin receptors are expressed in primary sensory neurons and excited by heat and protons. We examined the inflammation-induced changes of the level of VR1 capsaicin receptor mRNA in sensory neurons and the sensitivity of primary afferents to capsaicin. Carrageenan treatment induced axonal transport of VR1 mRNA, but not that of preprotachykinin mRNA, from the dorsal root ganglia to central and peripheral axon terminals. The sensitivity of central terminals to capsaicin, which was estimated by measuring the capsaicin-evoked release of glutamate from the dorsal horn, was increased by peripheral inflammation, and such an increase was suppressed by inhibiting the RNA translation in the dorsal horn with cycloheximide and an intrathecal injection of VR1 antisense oligonucleotides. Thus, peripheral inflammation induces the axonal transport of VR1 mRNA, which may be involved in the hypersensitivity of primary afferents to capsaicin and the production of inflammatory hyperalgesia.

Afferent Pathways↗
PubMed2001

Immunoglobulin gene usage and immunohistochemical characteristics of human monoclonal antibodies to the mitochondrial autoantigens of primary biliary cirrhosis induced in the XenoMouse.

The immunodominant antimitochondrial antibody (AMA) response in primary biliary cirrhosis (PBC) is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). The nature of the clonal selection process is unclear, and to address this issue, we took advantage of a transgenic technology, XenoMouse, that contains 80% of the human immunoglobulin (Ig) variable gene repertoire and can produce high-affinity human antibodies to virtually any immunogen without evidence of clonal bias. We immunized mice with PDC-E2 to obtain 13 HmAbs, including 4 IgG(2) and 9 IgM isotypes. Immunoglobulin gene analysis was unique and demonstrated a clonal bias; the immunoglobulin gene usage was considerably different from other antibody responses analyzed in XenoMouse systems. Four of the 13 mAbs recognized the inner lipoyl domain of PDC-E2, 2 of 13 recognized the entire PDC-E2 molecule, 4 of 13 recognized PDC-E2 and OGDC-E2, 1 of 13 recognized OGDC only, 1 recognized BCOADC-E2 only, and 1 recognized an unidentified 100-kd mitochondrial protein. Immunohistochemical staining using these HmAbs produced mitochondrial staining of septal bile ducts in both PBC and control livers. Ig gene analysis showed that 7 of 13 HmAbs used the V(H)3 and 4 of 13 used VH4 gene repertoire, respectively. Three of 7 V(H)3 antibodies used the same Ig VH3-21 gene family found in human AMA from patients with PBC. The CDRs of these autoantibodies were slightly mutated when compared with the sequences present within the Ig germline genes. In conclusion, the XenoMouse not only recapitulates the unique specificity and restriction of PBC patients, but indicates that the autoantibodies are derived from a restricted clonal selection process. Such data suggest that the original immunogen leads to somatic mutation without subsequent development of determinant spreading.

Amino Acid Sequence↗
PubMed2001

Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes.

Roxatidine acetate hydrochloride (ROX, 2-acetoxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide hydrochloride, CAS 78273-80-0), a histamine 2 (H2)-receptor antagonist, has been clinically applied for the treatment of gastritis, gastric and duodenal ulcers. There is no report on the identification of the metabolic enzyme of M-1 (2-hydroxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide), the pharmacologically active metabolite, in humans. In this study, the Cytochrome P450 (CYP or P450) enzymes which participate in the metabolism of ROX were identified using human liver microsomes and S9 fractions. M-1 was converted to M-4 (3-[m-(1-piperidinyl-methyl)phenoxy]propylamine) by the enzyme reaction with the S9 but not with microsomes. M-4 was further metabolized to M-5 (3-[m-(1-piperidinylmethyl)phenoxy]propanol) by microsomes. The metabolism was inhibited by coumarin and anti-CYP2A1 serum. (3-[m-(1-piperidinylmethyl)-phenoxy]propionic acid) and M-3 (m-(1-piperidinylmethyl) phenol) formation from M-5 were inhibited by quinidine and anti-CYP2D6 serum. Moreover, M-5 was converted to M-2 and M-3 by cDNA-expressed CYP2D6. In conclusion, this study shows that microsomal enzymes do not participate in the clearance of the active metabolite M-1, CYP2A6 primarily catalyzes M-5 formation from M-4, and CYP2D6 primarily catalyzes M-2 and M-3 formation from M-5 in humans.

Chromatography, High Pressure Liquid↗
PubMed2001

Improved survival and ammonia metabolism by intraperitoneal transplantation of microencapsulated hepatocytes in totally hepatectomized rats.

BACKGROUND: We evaluated the effects of intraperitoneal transplantation of microencapsulated hepatocytes in a 3-stage total hepatectomy rat model. METHODS: A new model of total hepatectomy was created as follows. First, the infrahepatic inferior vena cava was ligated just above the right renal vein. Seven days later, the portal vein was ligated and a portacaval shunt was established using a Teflon catheter over a venipuncture needle. Another 7 days later, total hepatectomy was completed by ligating and dividing the suprahepatic inferior vena cava, the hepatic artery, and the bile duct. Next, 4 x 10(7) hepatocytes (4% of the normal liver hepatocyte mass) isolated from male Wistar rats were microencapsulated within a collagen matrix enveloped by a 3-layer membrane of sodium alginate-poly-L-lysine-sodium alginate copolymer. Capsules containing hepatocytes (diameter, 500-800 microm) and empty capsules (control) were transplanted intraperitoneally 4 days before the total hepatectomy. Survival time and selected blood chemistry concentrations after the total hepatectomy were measured. The capsules were also examined histologically with hematoxylin and eosin staining and modified Gmelin's stain for bile pigments. RESULTS: The survival time was greater in the rats given the microencapsulated hepatocytes than in the control rats (17.3 +/- 3 vs 3.7 +/- 0.1 hours; P <.01). The blood ammonia concentrations increased soon after total hepatectomy but remained significantly lower in the rats with microencapsulated hepatocytes (P <.05). The microcapsules contained numerous viable hepatocytes with abundant bile pigments and no lymphocytic infiltration. CONCLUSIONS: Microencapsulated hepatocytes with an ultrathin polymer layer that protects them from inflammatory and lymphocytic reactions may facilitate their ability to function. In this study, 4 x 10(7) hepatocytes significantly prolonged the survival of rats that underwent hepatectomy and supported ammonia metabolism. Further development of this technique may permit its use in patients with hepatic failure.

Ammonia↗
PubMed2001

Intrahepatic cholangitis and arteritis after transcatheter arterial embolization in a patient with tumor-like lesion-associated autoimmune hepatitis.

Autoimmune hepatitis is a chronic liver disease characterized by immune-mediated, progressive hepatocellular damage, although the target autoantigen remains speculative. Intrahepatic biliary lesions are not a feature of this disease. We describe herein a female patient, 57 years, with autoimmune hepatitis who developed hepatic regenerative mass after acute exacerbation of hepatitis. This hepatic regenerative mass was clinically diagnosed as hepatocellular carcinoma and was surgically resected after transcatheter arterial embolization therapy. Widespread nonsuppurative destructive granulomatous cholangitis as well as necrotizing, granulomatous arteritis of the intrahepatic small arteries were found in the surgically resected hepatic regenerative mass. The bile duct lesions were histologically and immunohistochemically very similar to the granulomatous cholangitis of primary biliary cirrhosis. We would like to propose that these unusual lesions in the intrahepatic bile ducts and intrahepatic arteries represent a reaction of this patient to an anti-cancer drug included in chemoembolization. No such cases have been reported so far.

Arteritis↗
PubMed2001

Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report.

Anti-HLA antibodies reportedly exist in 31% of pregnant women. However, few ocurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibody have been reported. In this study, maternal anti-HLA B60 and B61 antibodies were identified in patient serum at birth, but no anti-platelet antibodies were present. No maternal anti-HLA A2, A24, B51, or B52 antibodies were detected in patient serum. Platelet transfusion from the third donor was effective because these platelets expressed HLA A24 and B52 but not B60 or B61. Cross-matching tests between patient leukocytes or platelets and maternal serum were strongly positive, indicating that maternal anti-HLA antibodies were responsible for NAIT. This report is the first to demonstrate NAIT probably caused by maternal anti-HLA A24 and B52.

Female↗