Search PubMed⌕ Search

Biomedical subjects

K Yanagi

Publications and source records attributed to K Yanagi.

At least 91 records · Page 5Linked to original sources

[Patency of the ostium of the frontal sinus after endoscopic endonasal surgery for chronic sinusitis].

We examined the patency of the ostium of the frontal sinus after endoscopic endonasal surgery for chronic sinusitis. This study involved one hundred and seventy-two nasal sides of ninety cases who underwent surgery in this unit in the preceding three-year period by the designated three surgeons. All patients were followed up for more than one year after surgery. We obtained a high postoperative patent rate of 90.1%. However, communication between the frontal and ethmoidal sinus could not be confirmed in 9.9% of the cases due to the presence of polyp or adhesion in the middle meatus. Cases with preoperative severe lesion of the frontal sinus showed significantly lower rates of patent than cases with preoperative mild and/or no lesion. In cases where the opening of the ostium could not be sufficiently widened during surgery because the size around the ostium was already small, lower patent rates resulted. However, even in such cases, scraping or curetting of the surrounding bone should be avoided, because it may cause postoperative narrowing of the ostium due to new bone formation. Cases with unsatisfactory results caused by pathological changes in the middle meatus showed significantly lower patent rates than cases with satisfactory postoperative results. It is recommended that accurate cleaning of the ethmoid sinus and adequate postoperative treatment be considered important. Endoscopic endonasal opening of the ostium of the frontal sinus is shown to be a safe and reliable procedure, which can be performed with clear visualization.

Adolescent↗

Antiplatelet and antithrombotic effects of YM337, the Fab fragment of a humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.

The antiplatelet and antithrombotic effects of the Fab fragment of the humanized antiplatelet glycoprotein (GP) IIb/IIIa monoclonal antibody C4G1 (YM337) were investigated in monkeys. First, the relationship between the inhibition of platelet aggregation and the prolongation of bleeding time was studied in rhesus monkeys. YM337 dose-dependently inhibited ex vivo platelet aggregation, with complete inhibition at doses higher than 0.25 mg/kg intravenous injection or 1.5 micrograms/kg/min infusion. At 0.25 mg/kg bolus injection followed by 1.5 micrograms/kg/min infusion, YM337 immediately and continuously inhibited platelet aggregation during the 6-h infusion period with platelet aggregation rapidly returning to over 50% of baseline within 1 h after the cessation of infusion. Template-bleeding time was significantly prolonged during the period of complete inhibition of platelet aggregation. Second, the antithrombotic effects of YM337 were investigated in a photochemically-induced thrombosis model in squirrel monkeys. YM337 at a dose of 1 mg/kg intravenous injection followed by 6 micrograms/kg/min infusion for 60 min prevented occlusive thrombus formation in all 4 monkeys. In contrast, time to occlusive thrombus formation did not change on intravenous bolus injection of aspirin 17 mg/kg (11.3 +/- 5.2 min) or sodium ozagrel (9.4 +/- 3.0 min) compared with saline (13.3 +/- 4.0 min). YM337 but not aspirin or sodium ozagrel significantly inhibited ex vivo ADP-induced platelet aggregation, while all drugs completely inhibited arachidonic acid-induced platelet aggregation. However, while aspirin and sodium ozagrel inhibited the thromboxane B2 generation accompanying arachidonic acid-induced platelet aggregation, YM337 had no effect on this variable. Platelet counts and bleeding time showed no significant change in any group in this squirrel monkey model. These results indicate that YM337, with a short half-life, may be a useful therapeutic agent in patients with thrombotic disorders.

Animals↗

[HELP syndrome and anesthetic management].

From January 1990 to December 1994, 24 parturients were diagnosed as having HELLP syndrome alone or combined with preeclampsia/eclampsia among 8,224 patients who were delivered at our institution. They consisted of 14 primiparous and 10 multiparous patients. Mean maternal age was 28.9 +/- 3.3 and gestational age was 34.8 +/- 5.6 weeks. Of 24 parturients, 8 had vaginal delivery and the remaining 16 were delivered by caesarean section. Serious maternal morbidity included eclampsia (n = 3), preeclampsia (n = 18), renal failure (n = 5), hydrothorax (n = 4), and DIC (n = 1). There was no maternal death. There were 3 intrauterine fetal deaths and two neonatal deaths. Perinatal deaths were 2 (0.9%, 2/26). Three caesarean sections were performed under general anesthesia, and 13 under spinal anesthesia. In cases with apparent bleeding tendency, spinal and epidural anesthesia should be avoided. In providing general anesthesia, hypertension should be controlled, and the uterus is preferably dilated before the delivery and contracted there-after.

Adult↗

Flow visualization of microcirculation in solid tumor tissues: intravital microscopic observation of blood circulation by use of a confocal laser scanning microscope.

To visualize the blood flow in the neovasculature of a solid tumor tissue, we utilized an intravital microscope system equipped with real-time confocal laser scanning optics. Fluorescent labeling of the blood cells and blood plasma enabled quantitative measurements of microhemodynamic parameters such as flow velocity, blood cell flux and vessel diameter in both the normal and tumor microvasculature.

Animals↗

Antithrombotic activity of a symmetrical triglyceride with eicosapentaenoic acid and gamma-linolenic acid in guinea pig mesenteric microvasculature.

The antithrombotic effect of a synthetic symmetrical triglyceride having eicosapentaenoic acid (EPA) at positions 1 and 3, and gamma-linolenic acid (GLA) at position 2 was investigated. Administration of the triglyceride significantly increased thrombus formation time and thrombotic occlusion time induced by light irradiation and a fluorescent dye in guinea pigs after 14 days administration compared to that of soybean oil. The antithrombotic effect of the triglyceride was similar to that of EPA ethyl ester. Administration of the triglyceride increased GLA, dihomo-gamma-linolenic acid (DGLA) and EPA contents in plasma and the liver, and the ratio of DGLA to arachidonic acid. These results might be responsible for this antithrombotic effect.

8,11,14-Eicosatrienoic Acid↗

Biased T cell receptor V beta gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjögren's syndrome.

OBJECTIVE: To analyze the repertoire of T cell receptor (TCR) V beta gene transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome. METHODS: Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and single-strand conformational polymorphism (SSCP) analyses. RESULTS: A predominance of V beta 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT-PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the V beta 8 gene segment began in the early stages of disease (2-month-old mice) and increased over time. Extensive age-related diversity of TCR V beta gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the V beta 8 gene PCR product from the cell infiltrates during the course of the disease. CONCLUSION: Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR V beta elements according to the stage of the disease, and that V beta 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.

Age Factors↗

Prevention of adoptive transfer of murine Sjögren's syndrome into severe combined immunodeficient (SCID) mice by antibodies against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1).

We have analysed the role of ICAM-1 and LFA-1 during development of autoimmune sialadenitis in MRL/lpr mice by direct analysis of RNA obtained from the salivary gland tissues, and the therapeutic effects with antibody administration on adoptive transfer system into SCID mice. The expression of cell adhesion molecules was assessed by using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, and immunohistochemical analysis. Up-regulated expression of ICAM-1 mRNA was observed before the onset of inflammatory lesions in the salivary glands at 1 month and 2 months old, and thereafter LFA-1 mRNA was expressed within the typical inflammatory lesions, resembling human Sjögren's syndrome in MRL/lpr mice. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of varying sized blood vessels before the onset of disease, and LFA-1 expressing inflammatory cells were found within these lesions. When the therapeutic effects in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented adoptive transfer of Sjögren's syndrome in MRL/lpr mice into SCID mice, while no significant effect was found when treated with either antibody. These findings indicate that in Sjögren's syndrome-like autoimmune lesions in MRL/lpr mice the ICAM-1/LFA-1 pathway may play a crucial role in the initiation and subsequent progression of T cell-mediated autoimmunity in the salivary and lacrimal glands of MRL/lpr mice.

Animals↗

Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase.

Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. The patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD.

Adult↗

[Improvement of olfactory disturbance by endoscopic endonasal surgery for chronic sinusitis].

Olfactory disturbance is the one of the most important symptoms of chronic sinusitis. In the present study, we followed up the postoperative clinical course of olfactory disturbance in patients who underwent surgery for chronic sinusitis. Ninety patients with severe olfactory disturbance or anosmia who underwent endoscopic endonasal surgery for chronic sinusitis with severe olfactory disturbance or anosmia in the preceding three-year period were enrolled in this study. We obtained a high postoperative improvement rate of 78.8%. We compared and examined our cases' postoperative clinical course concerning their olfactory disturbance and various factors in other patients before and after surgery, and obtained the following results: a) Young patients, 30 years old or under at the time of surgery, showed significantly higher rates of improvement than patients who were 50 years old or more at the time of surgery. b) Even though revision surgery was performed, the improvement rates were almost the same as after the initial surgery. c) Although the Alinamin intravenous olfaction test is regarded as an olfaction threshold test, we have seen quite a few cases in which improvement was achieved despite the absence of a preoperative response to the Alinamin intravenous olfaction test. d) There was no clear correlation between the presence of preoperative lesions of the ethmoid sinus and the olfactory cleft and the improvement rates. e) The cases with unsatisfactory results concerning the paranasal sinuses and nasal cavity--those accompanied by postoperative adhesions of the olfactory cleft, recurrence of polyps, etc.,--showed significantly lower improvement rates than cases with satisfactory postoperative results. During surgery in patients with severe olfactory disturbance, we conclude that it is particularly important to adequately clean the lesions of the olfactory cleft and the anterior and posterior ethmoid sinus endoscopically. This ensures leaving clear the olfactory cleft.

Adult↗

Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.

To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB-100 and apoB-48 levels and apoB mRNA editing efficiency in the liver and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.

Animals↗

[Measurement of total body and leg bone mineral densities by dual energy X-ray absorptiometry in severely handicapped children and adults].

Total body and leg bone mineral densities (BMD) were measured in 42 severely handicapped children and adults using a dual energy X-ray absorptiometry (DEXA) (LUNAR Radiation Corp., DPX). Despite the differences in motor ability and nursing history, about 95% of patients, except for 2 cases, were diagnosed as having osteopenia. The degree of osteopenia was dependent on the motor disabilities of their original disease. Therefore we should bear in mind a precaution and therapy from early period. Because BMD of the legs in females were less than -3 SD of the age-matched control values, we should be careful for a possible fracture of femur. Since X-ray hazard of DEXA for patients is considerable to be negligible, this will provide an effective means for quantifying bone mineral in severely handicapped patients.

Absorptiometry, Photon↗

[Indications for endoscopic sinus surgery. A clinical study on patients with a poor post-operative course].

One hundred and fifty-three patients with chronic sinusitis underwent endoscopic endonasal sinus surgery. They were preoperatively evaluated on the basis of their complaints, the severity of nasal polyps, X-ray findings, and axial and/or coronal CT scans. Postoperative degree of improvement in their complaints and endoscopic findings in the nasal cavity and sinus cavities were assessed. Most patients, including those with severe maxillary sinusitis, had a good postoperative course. The percentage of improvement in their complaints was 99.3%. Even in the case of olfactory disturbance, which is the most difficult symptom to treat, the percentage of improvement was 81.0%. There were only 8 patients with complaints and pathological findings in their nose or sinuses after the operation, 4 with allergic rhinitis and/or asthma, 1 with severe inflammation of the olfactory cleft, 1 with thickening of the bone in the sinuses after a 25-year history of sinusitis without treatment, and 2 with narrowing of the antrostoma at the middle meatus after the operation.

Adolescent↗

Evaluation of endoscopic sinus surgery for chronic sinusitis: post-operative erythromycin therapy.

We discuss the results of endoscopic endonasal sinus surgery for chronic pan-sinusitis characterized by nasal polyposis, especially the effects of post-operative long-term administration of low-dose erythromycin (EM) therapy. The subjects analysed in this retrospective study are surgical cases who had initially been operated for chronic pan-sinusitis. They are classified into one group who has received a post-operative long-term, low-dose EM regimen and into another group who has not received this treatment. The groups have been compared with respect to: (1) the degree of improvement in the post-operative subjective symptoms; (2) postoperative objective findings of the ethmoidal sinus and the ostium of the frontal sinus; and (3) the degree of improvement in the maxillary sinus lesion. Better improvement is achieved in subjective symptoms and objective findings in the EM group than in the non-EM group.

Adolescent↗

A new animal model for primary Sjögren's syndrome in NFS/sld mutant mice.

In this study, we report an established and characterized animal model for primary Sjögren's syndrome in NFS/sld mutant mice bearing an autosomal recessive gene with sublingual gland differentiation arrest. Significant inflammatory changes develop spontaneously in both the salivary and lacrimal glands of NFS/sld mutant mice thymectomized 3 days after birth without any immunization, whereas no significant inflammatory lesions were found in other organs or in nonthymectomized mice. This pathology resembles primary Sjögren's syndrome in humans, which involves the parotid, submandibular salivary, and lacrimal glands. A significantly higher incidence of autoimmune lesions was found in female mice, and the anti-salivary duct autoantibodies were detected in sera from mice with autoimmune lesions but not in control mice. The inflammatory infiltration into the salivary and lacrimal glands consisted mainly of CD3+ and CD4+ T cells, and a lesser proportion of CD8+ T cells and B220+ B cells during the course of disease. When the repertoire of TCR V beta genes transcribed and expressed within the inflammatory infiltrates was analyzed in mice with autoimmune lesions, a considerable preferential use of TCR V beta gene (V beta 8 predominant) was detected in these lesions from the onset of disease. Thus, we can propose a newly established animal model for primary Sjögren's syndrome developing in this mutant strain of mice. Moreover, the predominant patterns of TCR transcript expression in an animal model may be somewhat restricted, suggesting that TCR-based immunotherapy of Sjögren's syndrome is possible.

Animals↗

Transfer of Sjögren's syndrome-like autoimmune lesions into SCID mice and prevention of lesions by anti-CD4 and anti-T cell receptor antibody treatment.

We describe the successful transfer of murine Sjögren's syndrome-like autoimmune lesions from MRL/lpr mice (H-2k) to severe combined immunodeficiency (SCID) mice (H-2d) and prevention of lesions by anti-CD4 and -T cell receptor V beta 8 antibody treatment. Mononuclear cells (1 x 10(6)) isolated from the inflamed submandibular salivary gland tissues of MRL/lpr mice were transferred intraperitoneally into SCID mice. Autoimmune lesions resembling those seen in Sjögren's syndrome developed in the salivary and lacrimal glands of SCID mice 8 weeks after the injection, whereas other organs did not show any lesion. This pathology resembles Sjögren's syndrome in humans involving both the salivary and lacrimal glands. Immunohistochemically, a major proportion of these infiltrating cells in transferred SCID mice were CD4+ and V beta 8+. When the spleen cells from MRL/lpr mice were injected, severe inflammatory lesions, probably resulting from a graft-versus host reaction, were observed in multiple organs of SCID mice. The disease could not be induced by intraperitoneal administration of the sera from MRL/lpr mice, or of the spleen cells from C3H/He (H-2k) and BALB/c (H-2d) mice. We detected autoantibody production specific for the salivary gland tissue in sera from transferred SCID mice. Moreover, we found that the lesions were prevented by administration of the isolated cells treated in vitro with anti-CD4 and anti-V beta 8 monoclonal antibodies. These results suggest that CD4- and V beta 8-bearing T cells are involved in recognizing an autopeptide and triggering autoimmunity in the salivary and lacrimal glands, and therapies designed with anti-CD4 and anti-V beta 8 antibodies may prove effective in treating the murine autoimmune disease.

Animals↗

A simple procedure for assigning a sequence motif with an obscure pattern: application to the basic/helix-loop-helix motif.

We have developed a simple method to assign a sequence motif with an obscure pattern. Given a multiple sequence alignment for a region of protein that is known or strongly believed to have the same secondary and tertiary structures, the quantification method by principal component analysis is designed to find the regions most likely to have the same structure in a protein outside of the original set. The potential of this newly developed method was evaluated with reference to the known basic/helix-loop-helix (bHLH) motifs, and its characteristics were discussed with four obscure but well-defined motifs and compared with the other methods for searching sequence motifs. The method was also applied to assign the bHLH motif in Epstein-Barr virus nuclear antigen 1 (EBNA-1). This application revealed one candidate for the basic/helix 1 region and two candidates for the helix 2 region in the bHLH motif, within the region from amino acid residues 460 to 600, which is in good agreement with our previous experimental studies on the DNA binding region of EBNA-1. The basic/helix-loop-helix-loop-helix structure thus assigned suggests a function of EBNA-1 which is associated with both replication and transcription.

Amino Acid Sequence↗

Thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, in a photochemically induced platelet-rich thrombosis model.

We compared the thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA; del 92-173, 275Arg-->Glu), YM866, with that of t-PA in a platelet-rich thrombosis model. Thrombus was induced in guinea pig mesenteric artery by irradiation with filtered light in combination with intravenous (i.v.) administration of fluorescent dye. When occlusion by the thrombus extended to 99% of the luminal area of the vessel, test drug (YM866, t-PA, or saline) was administered by i.v. bolus injection under heparinization. Both YM866 and t-PA exhibited dose-dependent thrombolytic activity; however, the improvement in occlusion rate and the incidence of successful thrombolysis induced by YM866 were three times higher than those induced by t-PA. With YM866 1 mg/kg, alpha 2-plasmin inhibitor levels decreased significantly to 58% of saline group values, but no change was noted in fibrinogen levels. YM866 antigen levels at this dose were seven times higher than those of t-PA. These results suggest that YM866 in single bolus injection is a thrombolytic agent superior to t-PA in platelet-rich thrombi without systemic fibrinolytic activation and that this efficacy is due to the prolonged half-life (t1/2) of the drug.

Animals↗