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Biomedical subjects

S Iseki

Publications and source records attributed to S Iseki.

At least 37 records · Page 2Linked to original sources

[Specific inhibitory effects of hybrid liposomes on the growth of various tumor cells].

The inhibitory effects of hybrid liposomes composed of lipids having a variety of head groups (zwitterionic L-alpha-dimyristoylphosphatidylcholine (DMPC), anionic L-alpha-dimyristoylphosphatidylglycerol (DMPG), and cationic 1,2-dimyristoyl-3-trimethylammonium propane (DMTAP)) and polyoxyethylene (10) dodecyl ether (C12(EO)10) on the growth of tumor cells (human lung carcinoma (RERF-LC-OK), human hepatoma (Hep-G2), human stomach tumor (GT3TKB)) in vitro were examined. The hybrid liposomes of DMPC/10 mol% C12(EO)10 and DMPG/10 mol% C12(EO)10 were fairly more effective for inhibiting the growth of all tumor cells employed in this study as compared with liposomes (DMPC and DMPG) or micelles (C12(EO)10). Especially, it is attractive that the highly specific inhibitory effect of the hybrid liposomes of DMPG/10 mol% C12(EO)10 without any antitumor drugs on the growth of RERF-LC-OK and GT3TKB was obtained for the first time.

Animals↗

[Clinical outcome of catheter fragmentation and aspiration therapy in patients with acute pulmonary embolism].

The clinical usefulness of catheter fragmentation and aspiration therapy was studied in 8 patients with acute pulmonary embolism who received thrombolytic therapy using urokinase or tissue-type plasminogen activator (t-PA) (thrombolysis group) and 8 patients who underwent catheter fragmentation and aspiration therapy using a percutaneous transluminal coronary angioplasty (PTCA) guide catheter (catheter group). The patients were selected from 20 patients with a definite diagnosis of acute pulmonary embolism based on pulmonary arteriography and nuclear imaging. Urokinase (48 x 10(4) to 96 x 10(4) unit/day) or t-PA (12 x 10(6) unit/day) was administered intravenously for mean 4 days in the thrombolysis group. Pulmonary artery pressure was first measured using a Swan-Ganz catheter via the jugular vein or the femoral vein in the catheter group. Then, a PTCA guide catheter was advanced into the pulmonary artery, and the thrombus was disrupted repeatedly using a Radifocus wire, followed by manual aspiration. Subsequent treatment consisted of intravenous infusion of heparin (10,000 to 15,000 unit/day) and urokinase (24 x 10(4) to 48 x 10(4) unit/day) for mean 6 days. Partial revascularization was achieved in all patients in both groups. Five patients in the thrombolysis group died within 1 month due to respiratory failure, re-embolization, and/or hemorrhagic complications. One patient in the catheter group died of hemorrhagic shock. Pulmonary artery systolic pressure in the catheter group was significantly reduced from 47.4 to 26.5 mmHg (p < 0.01). Catheter treatment of acute pulmonary embolism associated with acute circulatory failure such as shock can lead to rapid hemodynamic improvement. In contrast, thrombolysis is an effective treatment, but bleeding problems are common and caution is required. Catheter fragmentation and aspiration therapy is effective for acute pulmonary embolism, is minimally invasive, and should be considered the treatment of first choice.

Acute Disease↗

Expression and cellular localization of the mRNA for the 25-kDa heat-shock protein in the mouse.

The 25-kDa heat-shock protein (Hsp25) is a member of the small heat-shock protein family but its function remains largely unknown. In the present study we examined the expression and cellular localization of Hsp25 mRNA in mice under physiological, unstressed conditions using Northern blot and in situ hybridization analyses with specific oligonucleotide probes. At the organ level, high amounts of Hsp25 mRNA were detected in the oesophagus, skin,eye, stomach, lung and urinary bladder, with moderate amounts in the heart, skeletal muscle, aorta, adrenal gland, ovary, testis, uterus, large intestine, and thymus. At the cellular level, intense to moderate signals for Hsp25 mRNA were localized in the muscle cells of smooth, heart and skeletal types, in the epithelial cells of stratified squamous and transitional types and of the oviduct, in the steroid endocrine cells of the adrenal cortex and corpus luteum, as well as in the spermatocytes of the testis. In contrast, the signal was scarcely detectable in the nervous tissues, lymphatic tissues, the columnar epithelial cells of the digestive tract, or the parenchymal cells of the liver, pancreas and kidney. These results suggest some significant role for Hsp25 in distinct populations of mouse cells under physiological conditions.

Adrenal Glands↗

Occurrence and nuclear localization of cAMP response element-binding protein in the post-natal development of the rat submandibular gland.

Cyclic AMP response element-binding protein (CREB) is a 43-kDa polypeptide that binds a cAMP response element located at the 5' promoter region of cAMP regulatory genes. The spatial and temporal distribution of CREB in the postnatal development of the rat submandibular gland was investigated using immunohistochemistry with a specific antibody. At birth, cells of the terminal tubules and ducts in the submandibular gland showed a nuclear CREB immunoreactivity of moderate intensity. At 1-2 weeks after birth, an intense CREB immunoreactivity was localized primarily to acinar cells. When the beta-adrenergic agonist isoproterenol was administered to 2-week-old rats, a twofold transient increase in the number of immunoreactive acinar cells was induced. Beginning 3 weeks after birth, CREB immunoreactivity shifted from acini to the duct system and showed a clear localization in the cells of the intercalated ducts and distal portions of striated ducts, where the granular convoluted tubule develops after 4 weeks. Immunopositive materials were localized exclusively in the nuclei of both acinar and ductal immunoreactive cells. After the development of the granular convoluted tubules, CREB immunoreactivity was absent in the tubule cells and was gradually reduced in intensity over the entire gland. In order to examine a hypothesis that CREB is involved in the initial differentiation of the granular convoluted tubular cells, testosterone was administered to hypophysectomized adult rats. Whereas the tubular cells of hypophysectomized rats showed a complete regression, and no CREB immunoreactivity was found in any acinar or duct cells, administration of testosterone for a few days induced an intense CREB immunoreactivity in the nuclei of duct cells, followed by their differentiation into the granular convoluted tubular cells. These results suggested that CREB is involved not only in the growth and differentiation of acinar cells that are regulated by beta-adrenergic nerves but also in those of the duct system, and especially in the androgen-regulated differentiation of the granular convoluted tubular cells, during the post-natal development of the rat submandibular gland.

Adrenergic beta-Agonists↗

Immunohistochemical localization of vascular endothelial growth factor in the endocrine glands of the rat.

Vascular endothelial growth factor (VEGF) is a secreted polypeptide with specific effects on endothelial cell growth and vascular permeability. While previous studies have focused on the expression of VEGF associated with angiogenesis in tumor and embryonal tissues, little is known about the role of VEGF in normal adult tissues. In the present study, a specific antibody was used to study the immunohistochemical localization of VEGF in the entire body of normal adult rats. Intense to moderate immunoreactivities for VEGF were detected in some endocrine cell types, namely, the parafollicular cell of thyroid gland, B cell of endocrine pancreas, N cell of adrenal medulla and a minority of the thyrotrophs of the pituitary gland. A certain exocrine cell type, i.e., the surface mucous cell of stomach, was also immunoreactive for VEGF. At the ultrastructural level, VEGF immunoreactivity was localized exclusively in the secretory granules of all immunopositive endocrine and exocrine cells examined. The present study provided immunohistochemical evidence for the occurrence of VEGF in subsets of endocrine and exocrine cells of normal adult rats, suggesting that these secretory cells regulate local vascular permeability through a paracrine action of VEGF.

Adrenal Glands↗

Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells.

Craniofacial development of vertebrates depends largely on neural crest contribution and each subdomain of the crest-derived ectomesenchyme follows its specific genetic control. The rat small eye (rSey) involves a mutation in the Pax-6 gene and the external feature of rSey homozygous embryos exhibits craniofacial defects in ocular and frontonasal regions. In order to identify the mechanism of craniofacial development, we examined the cranial morphology and migration of cephalic crest cells in rSey embryos. The chondrocranial defects of homozygous rSey embryos primarily consisted of spheno-orbital and ethmoidal anomalies. The former defects appeared to be brought about by the lack of the eye. In the ethmoid region, the nasal septum and the derivative of the medial nasal prominence were present, while the rest of the nasal capsule, as well as the nasal and lachrymal bones, were totally absent except for a pair of cartilaginous rods in place of the nasal capsule. This suggests that the primary cranial defect is restricted to the lateral nasal prominence derivatives. Dil labeling revealed the abnormal migration of crest cells specifically from the anterior midbrain to the lateral nasal prominence in homozygous rSey embryos. Pax-6 was not expressed in the crest cells but was strongly expressed in the frontonasal ectoderm. To determine whether or not this migratory defect actually resides in environmental cues, normal midbrain crest cells from wild-type embryos were labeled with Dil and were orthotopically injected into host rSey embryos. Migration of the donor crest cells into the lateral nasal prominence was abnormal in homozygous host embryos, while they migrated normally in wild-type or heterozygous embryos. Therefore, the cranial defects in rSey homozygous embryos are due to inappropriate substrate for crest cell migration towards the lateral nasal prominence, which consistently explains the cranial morphology of homozygous rSey embryos.

Animals↗

Three-dimensional arterial computed tomography and laparoscope-assisted splenectomy as a minimally invasive examination and treatment of splenic aneurysms.

For the purpose of prophylactic treatment of splenic aneurysms, both examinations and treatments should be minimally invasive. Here, we report a case of a patient who underwent three-dimensional arterial computed tomography (CT) and laparoscope-assisted splenectomy with aneurysm resection as a combination of minimally invasive examination and treatment.

Aneurysm↗

Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2.

Mutations in the human fibroblast growth factor receptor type 2 (FGFR2) gene cause craniosynostosis, particularly affecting the coronal suture. We show here that, in the fetal mouse skull vault, Fgfr2 transcripts are most abundant at the periphery of the membrane bones; they are mutually exclusive with those of osteopontin (an early marker of osteogenic differentiation) but coincide with sites of rapid cell proliferation. Fibroblast growth factor type 2 (FGF2) protein, which has a high affinity for the FGFR2 splice variant associated with craniosynostosis, is locally abundant; immunohistochemical detection showed it to be present at low levels in Fgfr2 expression domains and at high levels in differentiated areas. Implantation of FGF2-soaked beads onto the fetal coronal suture by ex utero surgery resulted in ectopic osteopontin expression, encircled by Fgfr2 expression, after 48 hours. We suggest that increased FGF/FGFR signalling in the developing skull, whether due to FGFR2 mutation or to ectopic FGF2, shifts the cell proliferation/differentiation balance towards differentiation by enhancing the normal paracrine down-regulation of Fgfr2.

Animals↗

Immunolocalization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of beta-lactam antibiotics.

A polyclonal antibody (anti-PepT1/C) was raised against the rabbit intestinal H(+)-coupled oligopeptide transporter, PepT1. Anti-PepT1/C detected 70-80-kDa protein in crude membranes obtained from rabbit duodenum, jejunum and ileum. PepT1 was localized in the brush-border of the absorptive epithelial cells by subcellular fractionation of membranes on a sucrose density gradient and by immunohistochemistry using light and electron microscopy. Transport activity for cephalosporins and dipeptide expressed in Xenopus laevis oocytes injected with total mRNA obtained from rabbit small intestine was eliminated completely by prehybridization of the mRNA with antisense oligonucleotide against the 5'-coding region of rabbit PepT1 cDNA.

Amino Acid Sequence↗

Sonic hedgehog is expressed in epithelial cells during development of whisker, hair, and tooth.

Sonic hedgehog (Shh) is a vertebrate gene homologous to a Drosophila segment polarity gene, hedgehog, and functions as a secreted signaling molecule in limb pattern formation, differentiation of motor neurons, and sclerotome induction. We found that Shh is also expressed in epithelia of the developing whisker, hair, tooth, rugae, and thyroid primordium of mouse embryos. In whisker and hair development, Shh is expressed in epithelial cells before condensation of the underlying mesenchymal cells and then in the placode. The expression of Shh continues in the hair bulb surrounding the dermal papilla. Shh is also expressed in epithelial cells of the tooth bud, then localized to the enamel knot. The Shh expression continues in developing ameloblasts. These results suggest that SHH is an essential epithelial signaling molecule in epithelio-mesenchymal interactions for the terminal differentiation.

Animals↗

Polarizing activity, Sonic hedgehog, and tooth development in embryonic and postnatal mouse.

Tooth development involves reciprocal epithelial-mesenchymal interactions, polarized growth, mesenchyme condensation, and complex morphogenetic events. Because these processes bear similarities to those occurring in the developing limb, we asked whether morphogenetic signals found in the limb also occur in the developing tooth. We grafted mouse embryo tooth germs to the anterior margin of host chick embryo wing buds and determined whether the dental tissues had polarizing activity. Indeed, the grafts induced supernumerary digits. Activity of both molar and incisor tooth germs increased from bud to cap stages and was maximal at late bell stage in newborn. With further development the polarizing activity began to decrease, became undetectable in adult molar mesenchyme but persisted in incisor mesenchyme, correlating with the fact that incisors grow throughout postnatal life while molars do not. When different portions of neonatal incisors were assayed, a clear proximo-distal gradient of activity was apparent, with maximal activity restricted to the most proximal portion where undifferentiated mesenchyme and enamel organ reside. In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced expression in host tissue of Hoxd-12 and Hoxd-13. In addition, whole-mount in situ hybridizations and immunohistochemistry showed that developing tooth germs express Sonic hedgehog (Shh). Shh expression was first detected in bud stage tooth germs; at later stages Shh transcripts were prominent in enamel knot and differentiating ameloblasts at the cuspal region. We concluded that tooth germs possess polarizing activity and produce polarizing factors such as Shh. As in the limb, these factor(s) and activity probably play key roles in establishing polarity and regulating morphogenesis during early tooth development. Given its subsequent association with differentiating ameloblasts, Shh probably participates also in cytogenetic events during odontogenesis.

Aging↗

Expression of 16 kDa proteolipid of vacuolar-type H(+)-ATPase in human pancreatic cancer.

Recent studies have shown that bafilomycin A1-sensitive vacuolar-type H(+)-ATPase (V-ATPase) plays important roles in cell growth and differentiation. However, there is no published study that has focused on the expression of V-ATPase in human tumour tissues. This study was designed to examine the mRNA and protein levels for the 16 kilodalton (kDa) proteolipid of V-ATPase in human pancreatic carcinoma tissues. We first investigated the mRNA level for V-ATPase in six cases of invasive pancreatic cancers and two normal pancreases, using reverse transcription-polymerase chain reaction technique. Then, we examined immunohistochemically the level of V-ATPase protein in 49 pancreatic cancers and ten benign cystic neoplasms of the pancreas, using antisera raised against the 16 kDa proteolipid. There was a notable difference in the level of V-ATPase mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 42 out of 46 invasive ductal cancers (92%) displayed a mild to marked immunoreactivity for V-ATPase in the cytoplasm, whereas neither non-invasive ductal cancers nor benign cystic neoplasms expressed detectable immunoreactive proteins. These findings suggest that the overexpression of V-ATPase protein is characteristic of invasive pancreatic tumours. V-ATPase may play some crucial roles in tumour progression.

Adenocarcinoma↗

Microwave coagulation therapy for hepatocellular carcinoma.

BACKGROUND & AIMS: Surgical resection is not always feasible in patients with hepatocellular carcinoma. Microwave coagulation therapy has been used as an alternative to resection, and its efficacy has been evaluated. METHODS: Nineteen patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy through laparotomy (n = 12), laparoscopy (n = 5), or thoracotomy (n = 2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 13 patients, tumor size ranged from 5 to 90 mm. Patient outcomes were studied. RESULTS: Microwave coagulation therapy created a reproducible regional necrosis. Fourteen patients underwent potentially curative treatment; the remaining 5 patients underwent palliative treatment (n = 4) or incomplete tumor coagulation (n = 1). Of the 31 nodules treated, 28 underwent complete tumor ablation. Only 2 patients undergoing laparoscopic microwave coagulation therapy developed local recurrence. The coagulated area subsequently shrank. Patients showed rapid recovery without hepatic dysfunction. Thirteen patients, including 2 long-term survivors, are alive either without tumor (n = 10; 14-64 months) or with tumor (n = 3; 17-22 months). Six patients died of hepatocellular carcinoma (n = 4) or liver insufficiency (n = 2). CONCLUSIONS: This preliminary study suggests the efficacy of microwave coagulation therapy, including safety and potential curability, in patients with hepatocellular carcinoma with advanced liver cirrhosis and multifocal or central tumors.

Adult↗

Preceding PTGBD decreases complications of laparoscopic cholecystectomy for patients with acute suppurative cholecystitis.

Laparoscopic cholecystectomy (LC) has become one of the options for the treatment of acute cholecystitis as surgeons gain facility with this procedure. However, acute suppurative cholecystitis is still a severe condition, because a high mortality rate still exists. In the early years (1991 to 1992), 4 patients were operated on without a preceding percutaneous transhepatic gallbladder drainage (PTGBD) at our hospital, however, one patient died of septic shock after a laparoscopic cholecystectomy. Conversion to open surgery was performed on two patients. However, in later years (1992 to 1995), 14 patients were operated on with preceding PTGBDs safely. Here, we report the safeness and significance of the combination therapy of PTGBD and LC for patients with severe acute suppurative cholecystitis.

Acute Disease↗

Expression of apolipoprotein A-1 mRNA in normal intrahepatic biliary tree.

Our previous study demonstrated that apolipoprotein A-1 (apo A-1) immunoreactive peptides were located diffusely in the cytoplasm, not only of human normal hepatocytes, but also of intrahepatic bile ducts and peribiliary glands. It is important to determine whether the presence of these immunoreactive peptides in intrahepatic biliary tree is caused by pinocytosis from the bile, or by intracellular protein synthesis. Thus, we investigated whether apo A-1 is synthesized by cells that line the biliary tree. Normal human liver samples obtained at surgery were used; and the expression and distribution of apo A-1 mRNA in normal human liver tissues were examined, using in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe specific for apo A-1. On the autoradiogram, many silver grains were found to be distributed uniformly in hepatocytes. In addition, an appreciable apo A-1 mRNA signal was also observed in both the surface epithelial lining of the bile ducts and the epithelial cells of the peribiliary glands. In conclusion, these findings suggest that the apo A-1 found in bile is secreted both by hepatocytes and by intrahepatic bile duct cells and peribiliary glands.

Aged↗

Duodenum-preserving resection of the head of the pancreas: the significance as a diagnostic therapy of the lesion in the pancreatic head.

A 75-year-old man who was diagnosed as having mucin-producing pancreatic cystic lesion of the main pancreatic duct by duodenoscopic examination was reported. Because of the low malignant potential of such lesions, duodenum-preserving resection of the head of the pancreas was performed, and the intra-operative histological examination showed no malignancy of the resected pancreatic head and no other surgical procedures, such as lymph-adenectomy nor pancreato-duodenectomy were necessary. The significance of this case report lies in that a less invasive operation should be selected at first to diagnose whether the lesion is malignant or not, and also that the selected operation itself must be sufficient to resect an adequate part of the pancreatic tissue involving the cystic lesion, if not malignant. Here, we report the process to select the procedure and the surgical technique.

Aged↗

Tissue-specific regulation of the expression of rat intestinal bile acid-binding protein.

A lipid-binding protein identical to the rat intestinal bile acid-binding protein, termed I-15P, was expressed in steroid hormone-producing tissues such as ovary and adrenal gland, but not testis. In immature rats, I-15P was expressed in intestine but not in ovaries. The expression of I-15P in the ovaries of immature rats was induced to the level in immature rats by gonadotropin treatment. This suggests that the expression of I-15P in the ovaries is controlled by the ovarian cycle. The present results indicate that the expression of I-15P is developmentally and hormonally controlled in a tissue-specific manner.

Adrenal Glands↗