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N Sato

Publications and source records attributed to N Sato.

At least 559 records · Page 31Linked to original sources

Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients.

OBJECTIVE: Troglitazone, which improves peripheral insulin resistance of experimental diabetic animals and diabetic patients, affects ob gene expression in the adipose tissue of rodents. The present study was undertaken to examine a hypothesis that clinical administration of troglitazone may reduce circulating leptin levels and affect eating behavior in NIDDM patients. RESEARCH DESIGN AND METHODS: Troglitazone was administered at a dosage of 200 mg twice daily for 12 weeks in 20 poorly controlled NIDDM patients. Chronological changes in glycemic control, serum lipids, immunoreactive leptin (IRL) levels, and BMI were measured. Body fat weight was also assessed by bioelectric impedance. RESULTS: Troglitazone significantly decreased fasting plasma glucose, serum immunoreactive insulin, and HbA1c levels. Serum levels of IRL and triglyceride were significantly reduced by troglitazone administered for 4, 8, and 12 weeks. Troglitazone administration significantly increased the BMI in NIDDM patients, and two-thirds of the patients complained of increased hunger after the start of troglitazone administration. CONCLUSIONS: Troglitazone significantly reduces circulating leptin levels at clinical doses. It may affect the eating behavior of poorly controlled NIDDM patients through the improvement of glycemic control and/or the reduction of circulating leptin.

Blood Glucose↗

Cellular characterization of the 91kDa-ectopic ascitic antigen sharing antigenicity with MRP8 in the human placenta as revealed by immunoelectron microscopical colloidal-gold techniques.

Cellular characterization of the 91kDa-ectopic ascitic protein that exhibits pregnancy-associated and tumour-related dynamics has been examined in the human placenta using an electron microscopic immunocolloidal-gold technique. This protein was initially isolated from the ascitic fluids of a patient suffered from ovarian and uterine cancers with mixed mesodermal tumours, and determined to be sharing antigenicity with the 28kDa-oncodevelopmental protein and a calcium-binding protein; MRP8/CFA, respectively. Placentas obtained were divided into three groups by their gestational periods. Small chorionic villous tissues were embedded in Lowicryl K4M resin or Epon 812 resin. Specific and higher labelings by gold-particles were obtained in sections of Lowicryl resin and, then, recognized in mesenchyme-derived cells and/or myeloid lineages; such as placental tissue macrophages (Hofbauer cells), fibroblasts, foetal myelomonocytic cells including endothelial cells, etc., in the first and second trimesters. So far, the pattern of antigenic appearances changed depending on the stage of gestation. On the other hand, 91kDa-protein was also determined in the syncytiotrophoblast, but not in cytotrophoblasts at whenever been examined. It is assumed that the antigenic expression in syncytiotrophoblasts might be reflected to be absorbed or incorporated from those of foetal or maternal origins, and the antibody used in this study should be sensitive to the antigenic epitope derived from those of myeloid lineages. In the light of these results, hypotheses concerning mechanisms of both transplacental permeability of substances by the placental barrier and cell/tissue differentiation by calcium-binding (and/or -depending) proteins such as 91kDa-protein, MRP8, etc.; presumable the S-100 protein family, are discussed further.

Antibody Specificity↗

Expressions of a 68kDa-glycoprotein (GP68) and laminin in the mesodermal tissue of the developing mouse embryo.

Immunohistochemistry revealed initial expression of the stage-specific glycoprotein, GP68, in various mesenchymal tissue substructures of mouse embryos. During the 11-15th days of gestation, GP68 was localized in the primitive meninges, chondroblasts and perichondrium of pre-cartilaginous vertebral bodies and ribs, connective tissue cells of the dermis, the epicardium and endocardium of the heart, the epimysium and perimysium of skeleton musclature, and the basement membranes of splanchnic organs. Double staining for laminin expression indicated coincidental expression in identical tissue substructures. However, laminin was expressed in days 10-18 embryos and the neonate. Therefore, GP68 is coincidentally expressed with laminin in mesenchymal tissues between the 11th and 15th day of gestation, and may play a role as a laminin-associated protein. In the light of these results, a hypothesis concerning the relationship between these two proteins and the mechanisms of non-integrin laminin-associated proteins during normal embryogenesis is discussed further.

Animals↗

Calcitonin gene-related peptide-, neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerve fibers in the human umbilical cord.

The distribution of nerve fibers positive for calcitonin gene-related peptide (CGRP), which is a vasodilator peptide, neuropeptide Y (NPY), which is a vasoconstrictor peptide, and tyrosine hydroxylase (TH), which is a key enzyme for the synthesis of the neurotransmitter of adrenergic nerves, was studied in the fetal side, middle part, and placental side of the human umbilical cord using immunohistochemistry. In the fetal side of the umbilical cord, CGRP-, NPY-, and TH-positive fibers were observed in the smooth muscle of the media of the umbilical artery and in the margins of the Wharton jelly. They were not observed around the umbilical vein or in the middle part or placental side of the umbilical cord. These results demonstrate the presence of the vasoactive peptides CGRP and NPY, as well as of the enzyme TH in the fetal side of the umbilical vessel. The presence of CGRP and NPY suggests the involvement of these peptides in the regulation of the umbilical and placental circulation.

Calcitonin Gene-Related Peptide↗

Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologous peripheral blood stem cell transplantation.

We monitored 30 laboratory hemostatic parameters in an attempt to better comprehend alterations in coagulation and fibrinolysis in 10 patients with hematological malignancies subjected to autologous peripheral blood stem cell transplantation (APBSCT). These parameters were assessed before and just after high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical manifestations associated with fibrino-coagulation disorders never occurred, including veno-occlusive disease, a statistically significant increase was seen in 7 of 30 parameters, compared to values seen before conditioning chemotherapy. These were subdivided into early and late phase parameters. The early phase parameters, which increased during the first day after the conditioning chemotherapy was given, then returned to baseline values, included protein C, plasma tissue factor and tissue-plasminogen activator. The late phase parameters, which increased over baseline values during days 7 to 28, included free-protein S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble-thrombomodulin. The increase of early phase parameters, as produced by the liver and by endothelial cells, may reflect tissue damage by conditioning chemotherapy. Late phase parameters increased in parallel with C-reactive protein, which suggests a correlation with the degree of inflammation, such as the presence of infective disease during neutropenia. These subclinical alterations in coagulation and fibrinolysis which take on a biphasic pattern during the course of APBSCT should be kept in mind by the attending physicians during therapy.

Adolescent↗

Improved intratumoral penetration of radiolabeled streptavidin in intraperitoneal tumors pretargeted with biotinylated antibody.

UNLABELLED: Inefficient intratumoral penetration of pharmaceuticals is one of the major limiting factors against effective tumor-targeting therapy. This study investigated the effect of the distribution pattern of the binding site in tumors on the penetration of target material. METHODS: In the first experiment, radiolabeled biotinylated monoclonal antibody, MLS128, was injected intraperitoneally or intravenously into nude mice bearing intraperitoneal human colon cancer xenografts. In the second experiment, radiolabeled streptavidin was injected intraperitoneally in the tumor-bearing mice after the pretargeting with the unlabeled biotinylated antibody. Intratumoral distribution of radioactivity was examined with quantitative autoradiography. RESULTS: There was no difference in the biodistribution of biotinylated antibody between intraperitoneal and intravenous administrations, but autoradiography showed a higher uptake in the margin and a lower uptake in the center of radioactivity in tumor nodules with intraperitoneal injection and a more uniform intratumoral radioactivity distribution with intravenous injection. In the two-step method, radioactivity in a low dose of streptavidin with intraperitoneal pretargeting primarily localized at the tumor margin. By increasing the dose, streptavidin penetrated more deeply. In tumors with intravenous pretargeting, a more uniform intratumoral distribution of streptavidin was obtained. The biodistribution of radiolabeled streptavidin was the same between different pretargeting routes. CONCLUSION: The better intratumoral penetration of radiolabeled streptavidin after intravenous pretargeting than intraperitoneal pretargeting with biotinylated antibody may be the result of different intratumoral distribution of the binding site for the radiolabel.

Animals↗

Lysophosphatidylcholine decreases the synthesis of tissue factor pathway inhibitor in human umbilical vein endothelial cells.

Thrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 microM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

Cells, Cultured↗

[Treatment of patients with recurrent esophageal carcinoma].

From 1987 to 1997, 211 patients with thoracic esophageal carcinoma underwent radical surgery. The 5 year survival rate was 87% in pTNM stage I, 64% in stage II A, 57% in stage II B, and 31% in stage III. The survival curve was improved by postoperative chemotherapy including CDDP/5-FU as compared with surgery alone. Relapse occurred in 59 of these patients (28%). Lymphatic recurrence was recognized in 32 patients, hematogenic recurrence in 19, mixed type in 4, and intramural or local recurrence in 4 patients. In spite of through lymph node dissection, postoperative lymphatic recurrence was most frequent at the upper mediastinum and neck. Among hematogenic metastases, pulmonary and hepatic metastases were observed at equal incidences. The 1 year survival rate and median survival period of the patients with recurrent carcinoma were 36% and 191 days (26-1,122), respectively. There was no significant difference in prognosis between lymphatic and hematogenic recurrence. The prognosis for patients who underwent active therapy for recurrence (42 cases) was significantly better than for those who underwent only palliative therapy (17 cases). Resection of the site of recurrence was performed in 4 cases. The combination therapy of resection or irradiation and combined chemotherapy with CDDP and 5-FU resulted in a better prognosis (median survival period was 504 days) than irradiation alone or chemotherapy alone. In conclusion, early diagnosis and active multimodality therapy were important to improve the prognosis of recurrent esophageal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Myeloperoxidase].

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Diabetes Mellitus↗

Mutations in the human homologue of the Drosophila patched gene in esophageal squamous cell carcinoma.

The human homologue (PTCH) of the Drosophila segment polarity gene patched has recently been identified as a tumor-suppressor gene for nevoid basal cell carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We analyzed 30 esophageal squamous cell carcinomas (ESCC) for intrageneic mutations of the PTCH gene by polymerase chain reaction-single-strand conformation polymorphism analysis followed by DNA sequencing. We identified two somatic PTCH mutations (7%) in 30 ESCC. These were a nonsense mutation (CAG to TAG at codon 361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of the PTCH gene. These results indicate that inactivation of the PTCH gene via a two-hit mechanism occurs in a subset of ESCC.

Amino Acid Substitution↗

Hypophysitis: endocrinologic and dynamic MR findings.

PURPOSE: Our purpose was to assess the worth of dynamic MR imaging in the evaluation of vascular changes of the pituitary in patients with lymphocytic hypophysitis. METHODS: Five patients (four males, one female; 9 to 53 years old) with lymphocytic hypophysitis or infundibuloneurohypophysitis were studied. All patients underwent endocrinologic studies and a series of two to five MR examinations performed over a period of 8 months to 5 years, including a total of nine dynamic imaging studies. RESULTS: Two patients had panhypopituitarism and three had partial hypopituitarism. Diabetes insipidus was present in four patients. Among the five patients, the pituitary was enlarged in three, of whom two showed improvement on follow-up MR studies. Three patients had a thickened stalk, which improved on subsequent examinations. In all nine dynamic studies, the enhancement time of the whole pituitary was delayed to over 90 seconds, even though five of the nine conventional, simultaneously performed MR studies showed a normal pituitary. The peak time of posterior pituitary enhancement in the first dynamic study was also delayed in all patients (from 60 to 120 seconds). In two patients, normal early enhancement of the posterior pituitary was identified on initial studies but not on subsequent studies. CONCLUSION: Dynamic MR imaging can display an abnormality of the hypophysial vasculature even if the pituitary disease is seen to regress on the conventional MR study. The delay or even the lack of early enhancement of the posterior pituitary in lymphocytic hypophysitis may be due to secondary inflammatory changes.

Adolescent↗

[Electrophysiological heterogeneity of rabbit atrioventricular node cells: possible relationship to fast and slow pathways].

Catheter ablation has been applied for the therapy of atrioventricular nodal re-entrant tachycardia for several years. Although this procedure is quite successful, the cellular electrophysiological mechanisms underlying fast and slow conductions remain unknown. Therefore, the characteristics of the action potential waveform of rabbit atrioventricular node (AVN) cells obtained from different regions within Koch's triangle were studied using nystatin-permeabilized patch methods, and 64 AVN cells were used for this study. Based on gross morphology, AVN cells were classified into three groups: ovoid cells, rod shaped cells, and cells with an intermediate shape. Results obtained by measuring the maximum velocity dV/dt of action potentials fell into four subgroups: Group I (dV/dt < 5 V/sec, n = 23), Group II (dV/dt > 5 but < 10 V/sec, n = 20), Group III (dV/dt > 10 but < 20 V/sec, n = 13), and Group IV (dV/dt > 20 V/sec, n = 8). Ovoid cells had the smallest dV/dt, whereas the rod shaped cells had the highest dV/dt. The maximum diastolic potential was more negative in Groups III and IV than in Groups I and II. A notch in the phase II of the action potential was observed in 23% of Group III cells and 56% of those in Group IV, but was not present in Groups I and II. These findings provide further evidence that AVN cells are heterogeneous both in morphology and electrophysiological characteristics. Provided that values of dV/dt can be related to conduction velocity, our findings suggest that cells in Groups III and IV may contribute to fast conduction pathways whereas those in Groups I and II are responsible for slow conduction pathways.

Action Potentials↗

[Rapid tapering of cyclosporine for cytogenetic relapse shortly after bone marrow transplantation in a patient with chronic myeloid leukemia].

A 53-year-old female case of cytogenetically relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation (BMT) who achieved remission by withdrawal of immunosuppressant is reported. On day 690 of this presentation she is well and alive with performance status of 100%. She had episodes of cyclic oscillation of her neutrophil count during hydroxyurea therapy lasting 1 year before transplantation. Increase of the neutrophils at the time of BMT might have contributed to her early relapse on day 207. Withdrawal of immunosuppressant was successful at least in this case.

Bone Marrow Transplantation↗

[Successful removal of an infected pacemaker electrode adhered to the tricuspid valve].

A 77-year-old male suffered from pacemaker lead infection with pacing failure. Because he had a severe fever, we performed an interventional removal procedure with the help of a lead removal kit. However, the tip of the lead could not be withdrawn via the right internal jugular vein because it adhered tightly to the tricuspid valve. Two days later, we proceeded with an open removal procedure under cardiopulmonary bypass. The lead could be removed without any complication, and no inflammation was observed postoperatively. We report the case and discuss the indications and limitations of both the interventional and open methods.

Aged↗

[An experience of video-assisted thoracoscopic surgery for an intrapulmonary needle under CT-guided marking].

A 46-year-old female visited a near hospital, complaining of repeating skin eruption with spontaneous remission. A chest X-ray and CT examinations revealed a needle in the left S6, about 5 mm in length, which was suspected of causing the eruption. She was admitted to our hospital for operation. After CT-guided marking, video-assisted thoracoscopic surgery was performed. Because the needle was too small to be palpable, we decided to respect of it with the lung surrounding the marker and clamped the lung, followed by finding the needle finally. The analysis of the removed needle showed that it contained lead and tin besides iron, nickel and chromium, which are components of stainless steel. Although dermatological examination could not reveal the relation between the needle and the eruption, it has never recurred since the operation. It is thought that CT-guided marking is very useful for resection of an intrapulmonary needle and that a foreign body should be removed for the possibility of being harmful.

Endoscopy↗

Rebamipide prevented delay of wound repair induced by hydrogen peroxide and suppressed apoptosis of gastric epithelial cells in vitro.

The effects of rebamipide on the restoration process of gastric epithelial wounds were assessed using an in vitro wound-healing model and hydrogen peroxide treatment. Rebamipide (10 or 100 microM) was added to a complete monolayer cell sheet after artificial wounding. The restoration process was analyzed sequentially by a time-lapse video system, and cell migration, proliferation, and apoptosis were assessed. Hydrogen peroxide (1 or 3 mM) inhibited restoration after wounding by suppressing cell migration and proliferation. It also induced epithelial cell apoptosis around the wound. The addition of rebamipide abolished the H2O2-induced retardation and prevented apoptosis. Rebamipide might act as a radical scavenger and have favorable effects on peptic ulcer diseases.

Alanine↗