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Biomedical subjects

K Aoyama

Publications and source records attributed to K Aoyama.

At least 55 records · Page 3Linked to original sources
PubMed1999

Characterization of newly identified four isoforms for a putative cytosolic protein tyrosine phosphatase PTP36.

In the course of determining the expression profiles of protein tyrosine phosphatases in lactating mammary gland, we found the expression of an isoform for a putative cytosolic and cytoskeleton-associated protein tyrosine phosphatase PTP36. Further detailed RT-PCR and Northern blot analyses revealed the expression of several isoforms for PTP36 in a tissue-dependent manner. We have cloned the cDNAs encoding four truncated isoforms for PTP36 and designated PTP36-A, -B, -C, and -D, respectively. PTP36-A and -C had new sequences generated due to frameshift, whereas PTP36-B and -D were in-frame variants. Gly- and Glu-rich domains and a putative PTP domain were missing from PTP36-A, but the band 4.1 domain remained. PTP36-B retained the band 4.1 and PTP domains but lacked Pro-, Gly- and Glu-rich domains. Most domain structures were lacking in PTP36-C and -D. Interestingly, PTP36-C contained an incomplete band 4.1 domain, but the newly created sequence exhibited high homology to human nebulette, which was also suggested to associate with cytoskeletons. When transiently expressed in COS7 and HEK293 cells, not only the wild type but also all the isoforms were recovered in Triton X-100-insoluble cytoskeleton-associated fractions and this distribution was not affected by mechanical cell detachment and treatment with a kinase inhibitor staurosporine. Such cellular distribution of PTP36 was also observed in stable COS7 clones. Further studies using deletion mutants suggested that the first 30 amino acids as well as the band 4.1 domain of PTP36 were involved in association with Triton X-100 insoluble cytoskeletons. Tissue-dependent expression and deletion in domain structures might reflect the biological significance of the isoforms for PTP36 in certain physiological conditions.

Amino Acid Sequence↗
PubMed1999

Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cells.

CD9 belongs to the transmembrane 4 superfamily, and has been shown to influence cell proliferation, motility, and adhesion. We show here that ligation of CD9 modifies proliferation and/or differentiation of hematopoietic stem/progenitors. Pluripotent EML-C1 hematopoietic cells were cocultured with MS-5 stromal cells in the presence of KMC8.8, an anti-CD9 antibody. Numbers of recovered EML-C1 cells were slightly reduced and the antibody caused the hematopoietic cells to migrate beneath the adherent stromal cell layer. Of particular interest, EML-C1 cells recovered from CD9-ligated cultures had undifferentiated properties. Separate pretreatment of the two cell types with antibody showed that stromal-cell CD9 mediated these responses. Spontaneous expression of erythroid marker was completely blocked and there was a shift towards undifferentiated clonogenic progenitors. Immunoprecipitation studies showed that stromal-cell CD9 associates with the beta1 subunit of integrin, as well as a novel 100 kD protein. Antibody cross-linking of cell surface CD9 increased the amount of 100 kD protein that was subsequently coprecipitated with CD9. These observations show that stromal-cell CD9 influences physical interactions with hematopoietic cells and may be one factor that determines the degree of stem cell differentiation.

Animals↗
PubMed1999

S-form lipopolysaccharide (LPS), but not lipid A or R-chemo-type LPS, induces interleukin-6 production in vitamin D3-differentiated THP-1 cells.

Bacterial lipopolysaccharide (LPS) induces the production of various inflammatory cytokines and the inducibility is considered attributable to the glycolipid part of LPS called lipid A. We report an in vitro model in which lipid A is not necessarily a minimal structure for the LPS activity. Vitamin D3-differentiated THP-1 cells, cultured human monocytic leukemia cells, produced a high level of interleukin-6 (IL-6) by stimulating LPS from Escherichia coli O111:B4, but not by stimulating synthetic E. coli-type lipid A (compound 506), E. coli Re mutant LPS (ReLPS), or alkali-treated LPS. The induction by LPS was inhibited by the anti-CD14 antibodies or by the synthetic lipid A precursor (compound 406). An alkali-treated LPS or compound 506 partially inhibited the LPS-induced IL-6 production. These facts suggest that lipid A alone is not sufficient for the IL-6-inducing activity, but the polysaccharide part in LPS contributes or acts as a co-factor for activation of differentiated THP-1 cells.

Alkalies↗
PubMed1999

Both Stat3-activation and Stat3-independent BCL2 downregulation are important for interleukin-6-induced apoptosis of 1A9-M cells.

A unique subclone of a bone marrow-derived stromal cell line, BMS2.4, produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines. An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation. We used expression cloning to identify interleukin-6 (IL-6) as one factor that suppressed growth of a pre-B-cell variant line, 1A9-M. Moreover, IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells. During this process, IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression, but had no effect on p53, Bax, or Bak gene expression. Mechanisms for transduction of IL-6-induced signals were then evaluated in IL-6-stimulated 1A9-M cells. Whereas the signal transducer and activator of transcription 3 (Stat3) was phosphorylated and activated, there was no effect on either Stat1 or Stat5. The importance of BCL2 and Stat3 on IL-6-induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3, respectively. IL-6-induced apoptosis, but not macrophage-differentiation, was blocked by continuously expressed BCL2. A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6. However, diminished Stat3 activity did not prevent IL-6-induced downregulation of the BCL2 gene. Therefore, activation of Stat3 is essential for IL-6-induced macrophage-differentiation and programmed cell death in this model. Whereas overexpression of BCL2 abrogates the apoptotic response, Stat3-independent signals appear to downregulate expression of the BCL2 gene.

Apoptosis↗
PubMed1999

Fibreoptic assessment of laryngeal aperture in patients with difficult laryngoscopy.

PURPOSE: To determine the relationship between the area of the laryngeal aperture (LA) seen fibreoptically during laryngoscopy and the difficulty of tracheal intubation in patients with difficult laryngoscopy METHODS: In 587 adult patients after induction of general anesthesia and muscle relaxation, the best laryngoscopic view of the larynx using a Macintosh 3 blade was classified according to Cormack. When the LA could not be seen, with laryngoscope blade in place, the LA view provided by a fibreoptic bronchoscope (FOB)-camera passed nasally was photographed. Then, the laryngoscopist attempted to intubate the trachea using the Macintosh blade. Tracheal intubation requiring more than three attempts was defined as difficult. After the third attempt, the trachea was intubated orally aided by FOB. The LA view after jaw thrust during FOB-aided intubation was photographed. RESULTS: Laryngoscopy was difficult in 17 of 587 patients. In four, intubation was difficult. In the remaining 13 patients the trachea was easy to intubate. The LA area obtained by the FOB in the difficult group (median, 0.19; intra-quartile range, 0.14 to 0.39 cm2) was smaller than that in the easy group (2.43; 1.84 to 2.93 cm2)(P = 0.003). In contrast, the LA area provided by jaw thrust during the FOB-aided intubation in the difficult group (2.28; 1.99 to 2.73 cm2) was similar to that during laryngoscopy in the easy group. CONCLUSION: Inability of the laryngoscope to provide an adequate LA view is one cause of difficult intubation with the Macintosh laryngoscope in patients with difficult laryngoscopy.

Adult↗
PubMed1999

Development of rapid atrial fibrillation with a wide QRS complex after neostigmine in a patient with intermittent Wolff-Parkinson-White syndrome.

We report the case of a 67-yr-old man with intermittent Wolff-Parkinson-White (WPW) syndrome in whom neostigmine produced life-threatening tachyarrhythmias. The patient was scheduled for microsurgery for a laryngeal tumour. When he arrived in the operating room, the electrocardiogram showed normal sinus rhythm with a rate of 82 beat min-1 and a narrow QRS complex which remained normal throughout the operative period. On emergence from anaesthesia, the sinus rhythm (87 beat min-1) changed to atrial fibrillation with a rate of 80-120 beat min-1 and a normal QRS complex. We did not treat the atrial fibrillation because the patient was haemodynamically stable. Neostigmine 1 mg without atropine was then administered to antagonize residual neuromuscular block produced by vecuronium. Two minutes later, the narrow QRS complexes changed to a wide QRS complex tachycardia with a rate of 110-180 beat min-1, which was diagnosed as rapid atrial fibrillation. As the patient was hypotensive, two synchronized DC cardioversions of 100 J and 200 J were given, which restored sinus rhythm. No electrophysiological studies of anticholinesterase drugs have been performed in patients with WPW syndrome. We discuss the use of these drugs in this condition.

Aged↗
PubMed1999

Malposition of the epiglottis after tracheal intubation via the intubating laryngeal mask.

The intubating laryngeal mask has been reported to be a successful method of tracheal intubation although advancement of the tracheal tube via the laryngeal inlet into the trachea cannot be seen. Damage to the larynx or other tissues may occur during blind passage of a tracheal tube. We report a case in which the tracheal tube, advanced blindly, tucked the epiglottis into the laryngeal inlet, resulting in oedema of the epiglottis. This case illustrates the potential for airway obstruction after extubation when using the intubating laryngeal mask as a blind intubation guide.

Epiglottis↗
PubMed1999

[A case of sleeve resection of the left main bronchus for tuberculous bronchial lesion].

A 31-year-old woman was admitted to our center with left chest pain and dyspnea after treatment of pulmonary tuberculosis. Chest X-ray film showed atelectasis of left lower lobe and left deviation of the mediastium. Bronchofiberscopy revealed obstruction of the left main bronchus. Chest MRI showed intermediate intensity at the left main bronchus and very high intensity at the peripheral bronchus. We performed sleeve resection of the left main bronchus and anastomosed end to end with absorbable monofilament sutures. Postoperative course was uneventful. Bronchoplasty for tuberculous obstructive lesion is a useful procedure.

Adult↗
PubMed1999

[Light-guided tracheal intubation using a Trachlight: causes of difficulty and skill acquisition].

We studied the reasons why tracheal intubation using a lighted stylet (Trachlight) was sometimes difficult for unexperienced intubators. We also examined light-guided intubation skill acquisition in inexperienced anesthesiologists. Two anesthesiologists, with no prior experience in using a Trachlight, performed orotracheal intubation using a Trachlight in 60 anesthetized patients (30 patients each). During intubation, an assistant observed the advancement of the tracheal tube using a fiberscope passed nasally and recorded the reason for difficulty in intubation. The time to successful intubation was also measured. Data were divided into epochs of 10 cases, and the intubation time and the incidence of difficult cases were compared between the groups. Tracheal intubation was successful using the Trachlight in 59 of 60 patients. The incidence of difficult cases, defined as cases requiring two or more attempts, was 31.7%. Fiberscopy showed that when the tube tip was located in the vallecula or in the esophagus, it was sometimes difficult to determine the position of the tube tip by transillumination of the soft tissues of the neck, and this results in the need for multiple attempts. Both the intubation time and the incidence of difficult cases decreased significantly between the first and last epoch. The present study confirms that light-guided intubation is sometimes difficult when the tube tip is advanced to the vallecula or to the esophagus. An acceptable level of skill in light-guided intubation is achieved within 30 uses.

Adult↗
PubMed1999

[Patil-Syracuse mask for fiberoptic intubation].

Patil-Syracuse mask, recently introduced in Japan, has a port for fiberscopy. A fiberoptic bronchoscope and an endotracheal tube can be passed through the port with little air leakage. Positive pressure ventilation can be continuously maintained using this mask during fiberoptic intubation. This mask is particularly useful when a patient can be easily ventilated through a face mask but the trachea is unexpectedly difficult to intubate. With a modified endoscopy mask technique, the mean expiratory tidal volume of 10 ml.kg-1 could be obtained during fiberoptic orotracheal intubation. We describe a fiberoptic intubation technique using this mask, and discuss the complications and limitations of this method.

Anesthesia, General↗
PubMed1998

Growth-supporting activities of fibronectin on hematopoietic stem/progenitor cells in vitro and in vivo: structural requirement for fibronectin activities of CS1 and cell-binding domains.

Fibronectin (FN) is supposed to play important roles in various aspects of hematopoiesis through binding to very late antigen 4 (VLA4) and VLA5. However, effects of FN on hematopoietic stem cells are largely unknown. In an effort to determine if FN had a growth-supporting activity on hematopoietic stem cells, human CD34(+)/VLA4(bright)/VLA5(dull) hematopoietic stem cells and a murine stem cell factor (SCF)-dependent multipotent cell line, EML-C1, were treated with or without FN in a serum and growth-factor-deprived medium, and then subjected to clonogenic assay in the presence of hematopoietic growth factors. The pretreatment of the CD34(+) cells with FN gave rise to significantly increased numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst colony-forming units, and mixed erythroid-myeloid colony-forming units. In addition, the numbers of blast colony-forming units and CFU-GM that developed after culture of EML-C1 cells with SCF and the combination of SCF and interleukin-3, respectively, were augmented by the pretreatment with FN. The augmented colony formation by FN was completely abrogated by the addition of CS1 fragment, but not of GRGDSP peptide, suggesting an essential role of FN-VLA4 interaction in the FN effects. Furthermore, the effects of various FN fragments consisting of RGDS-containing cell-binding domain (CBD), heparin-binding domain (HBD), and/or CS1 portion were tested on clonogenic growth of CD34(+) cells. Increased colony formation was induced by CBD-CS1 and CBD-HBD-CS1 fragments, but not with other fragments lacking CBD or CS1 domains, suggesting that both CS1 and CBD of FN were required for the augmentation of clonogenic growth of hematopoietic stem/progenitor cells in vitro. In addition to the in vitro effects, the in vivo administration of CBD-CS1 fragment into mice was found to increase the numbers of hematopoietic progenitor cells in bone marrow and spleen in a dose-dependent manner. Thus, FN may function on hematopoietic stem/progenitor cells as a growth-supporting factor in vitro and in vivo.

Amino Acid Sequence↗
PubMed1998

Neuroblastoma in an adult with a high serum level of carbohydrate antigen, CA125: report of a case.

We report herein the case of a 56-year-old woman with a neuroblastoma associated with a high serum level of carbohydrate antigen, CA125. The patient presented with massive ascites and a firm mass in her upper abdomen for which a laparotomy was performed. However, a recurrent tumor was found 6 months later and she died of the disease within 1 year of surgery despite several courses of adjuvant chemotherapy. Neuroblastoma rarely occurs in adults, and the features of 58 adult cases described in the world literature is summarized following the presentation of the clinical data on this case. The distribution of primary sites in adults is dispersed compared to that seen in pediatric cases, while the natural history of the disease in adults may be longer and less sensitive to chemotherapy than in children. The survival rate of adults with this disease is poor. We conclude that aggressive surgical intervention combined with appropriate chemotherapy protocols as applied in children should be performed in an attempt to achieve complete remission and improve the survival rate of adults with neuroblastoma.

Abdominal Neoplasms↗
PubMed1998

Relationship between bioavailability and hypocholesterolemic activity of YM17E, an inhibitor of ACAT, in cholesterol-fed rats.

The relationship between bioavailability and the serum cholesterol-lowering effect of YM17E, an ACAT inhibitor was investigated. Serum cholesterol levels in cholesterol-fed rats decreased after both oral and intravenous administration of YM17E. Marked inhibition of cholesterol absorption was observed after oral administration, but not after intravenous administration. YM17E and its five active metabolites were primarily distributed in the liver after intravenous administration, but in small intestine and liver after oral administration. Hepatic ACAT activity in cholesterol-fed rats was inhibited by intravenous administration. Cholesteryl ester input into plasma by Triton WR-1339 treatment to the rats was inhibited by intravenous administration of YM17E. Plasma clearance of 125I-LDL in cholesterol-fed rats increased after YM17E treatment suggesting a decrease in LDL production. These results indicate that the hypocholesterolemic effect of intravenous YM17E was due to hepatic ACAT inhibition, not an inhibition of intestinal cholesterol absorption. The contribution of ACAT inhibition in small intestine and liver on the pharmacological effect could be explained by plasma inhibitor concentration after oral or intravenous administration of YM17E. From these results, it is concluded that the change in bioavailability of ACAT inhibitors change the mechanism of hypocholesterolemic effects, shifting the relative contributions of small intestinal and hepatic ACAT inhibition.

Animals↗