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Biomedical subjects

T Kawano

Publications and source records attributed to T Kawano.

At least 145 records · Page 8Linked to original sources

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis.

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.

Animals↗

Treatment of esophageal and gastric tumors.

Endoscopic mucosal resection (EMR) has gained increasing popularity in the treatment of esophageal and gastric mucosal cancers in Japan, for complete local resection of the cancer-bearing mucosa. In Western countries, the concept of mucosal cancer and the necessity of treating it are gradually but steadily coming to be accepted. As a treatment for inoperable cases of advanced cancer, on the other hand, intubation with self-expanding metal stents has been widely accepted as a less invasive form of palliation for malignant obstruction of the upper gastrointestinal tract. Tumor ingrowth into the stent can be mechanically avoided by adding a membrane coating to it. In the last two years, applications for therapeutic endoscopy in the treatment of esophageal and gastric tumors have continued to widen.

Adenocarcinoma↗

The ultrasonic tactile sensor: in vivo clinical application for evaluation of depth of invasion in esophageal squamous cell carcinomas.

BACKGROUND AND STUDY AIMS: We have previously demonstrated that an ultrasonic tactile sensor (UTS) could be used to distinguish between mucosal and submucosal cancer in surgically resected specimens, by providing a measurement of tissue stiffness which could be less prone to subjective errors. In the current study, we evaluated the potential of a newly developed, thin UTS to differentiate in vivo between mucosal and submucosal invasion during clinical endoscopic examination. PATIENTS AND METHODS: Between March and July 1997, 15 patients with esophageal cancer who were not receiving special treatment, underwent preoperative UTS examination during endoscopy. The thin UTS probe was inserted through the biopsy channel of the endoscope. A transparent cap was placed on the distal end of the endoscope in order to facilitate vertical placement of the probe on the tumor. RESULTS: Although the probe used in this study was a prototype, the results of the current in vivo study were in agreement with our previous in vitro study on surgically resected specimens. The mean delta(f) value of the mucosal cancers, which means the magnitude of the frequency shift recorded by the UTS, was -5356.23 Hz, and the corresponding value for submucosal cancers was -4126.56 Hz; this difference was significant. CONCLUSION: The UTS is potentially an essential tool for preoperative evaluation of esophageal cancers. The ability to differentiate between mucosal and submucosal cancers is important because of the differences in surgical management of these tumors, i.e. endoscopic mucosal resection or conventional open esophagectomy.

Carcinoma, Squamous Cell↗

Management of prenatally diagnosed congenital cystic adenomatoid malformation of the lung.

We have treated four prenatally diagnosed cases of extensive congenital cystic adenomatoid malformation (CCAM) of the lung. The first case in 1982 was associated with severe fetal hydrops. After thoracentesis at 31 weeks of gestation abruptio placentae occurred, and a female baby was delivered by cesarean section. She underwent a right lower lobectomy, but soon died. The second baby without hydrops, diagnosed as having CCAM at 26 weeks of gestation, was followed conservatively until full term. After birth, it was necessary to treat the baby boy with extracorporeal membrane oxygenation (ECMO), but he survived. The third baby with fetal hydrops had an indwelling drainage catheter inserted into the CCAM at 27 weeks of gestation. The hydrops subsided and the baby was delivered at 37 weeks of gestation. He was allowed to breathe spontaneously, but was intubated 16 hours after birth. A right lower lobectomy was successfully performed 24 hours after delivery. The fourth baby without fetal hydrops was followed conservatively until delivery. He underwent left lower lobectomy successfully on the 4th day of life. Although management of prenatally diagnosed CCAM varies among patients, insertion of an indwelling catheter into the cyst appears to be the treatment of choice if indicated; the catheter can be maintained for as long as 10 weeks, as shown in Case 3. Cases of CCAM without fetal hydrops should also be treated carefully, because persistent fetal circulation may occur postnatally.

Catheters, Indwelling↗

A novel recognition motif of human NKT antigen receptor for a glycolipid ligand.

Murine NKT cells can recognize alpha-galactosylceramide (alpha-GalCer) in the context of a class Ib CD1d molecule. Here we show that alpha-GalCer can selectively activate freshly isolated human Valpha24(+)Vbeta11(+) cells, functionally defining the human NKT cells. The naive human NKT cell repertoire consisted of cells expressing an invariant Valpha24JalphaQ chain and a diverse array of beta chains derived from a single Vbeta11 gene segment. Stimulation with alpha-GalCer expanded a polyclonal subset of the human NKT cell repertoire carrying a novel complementarity-determining region (CDR) 3beta consensus motif that may directly interact with the sugar moiety of alpha-GalCer. Our data suggest that certain redundancy is allowed for CDR3beta of NKT antigen receptor to interact with the ligand and provide a first clue to understand the novel protein-carbohydrate interaction mechanisms.

Adult↗

Target cells for an immunosuppressive cytokine, glycosylation-inhibiting factor.

Receptors for bioactive glycosylation-inhibiting factor (GIF) were demonstrated using a bioactive mutant of recombinant human (rh) GIF, which is comparable to the suppressor T (Ts) cell-derived bioactive GIF in its affinity for the receptors on helper T (Th) hybridoma cells. Both naive T and B cells in normal mouse spleen lacked GIF receptors. However, presentation of specific antigen to naive T cells resulted in the expression of the receptors on activated T cells. Furthermore, activation of small resting B cells with F(ab')2 fragments of anti-mouse IgM plus IL-4, lipopolysaccharide (LPS) plus IL-4 or LPS plus dextran sulfate induced the expression of the receptors within 48 h of B cell stimulation. It was also found that NK T cells freshly isolated from mouse spleen, but not conventional NK cells, expressed receptors for GIF. CD4(+) and CD4(-) subpopulations of NK T cells showed a similar binding capability. Mature dendritic cells derived from bone marrow did not bear the receptors. The dissociation constant (Kd) of the interaction between the bioactive rhGIF mutant and the high-affinity receptors was 10-100 pM, whereas inactive wild-type rhGIF failed to bind to the receptors. A bioactive derivative of rhGIF suppressed both IgG1 and IgE synthesis by purified B cells activated by LPS and IL-4, indicating that the binding of bioactive GIF to its receptors on activated B cells results in suppression of their differentiation.

Animals↗

Natural killer T cell ligand alpha-galactosylceramide inhibited lymph node metastasis of highly metastatic melanoma cells.

The role of natural killer T (NKT) cells in the prevention of multiple tumor metastasis was examined. The i.v. inoculation of a highly metastatic subline of B16-BL6 (B16-BL6-HM) melanoma cells resulted in the formation of metastatic nodules in lymph nodes in addition to lung, intrapleural cavity, and ovary. However, treatment of the mice with the NKT cell ligand alpha-galactosylceramide (alpha-GalCer) three times from 1 day after B16-BL6-HM melanoma inoculation caused a significant inhibition of multiple metastasis. Lymph node metastasis of B16-BL6-HM was almost completely blocked by alpha-GalCer treatment. This antimetastatic effect of alpha-GalCer was abolished in NKT cell-deficient mice. These results suggest that alpha-GalCer-activated NKT cells played a critical role in the prevention of lymph node metastasis of melanoma cells.

Adjuvants, Immunologic↗

Intestinal metaplasia at the esophagogastric junction in Japanese patients without clinical Barrett's esophagus.

OBJECTIVE: The significance of intestinal metaplasia found in biopsy specimens taken from healthy appearing squamocolumnar junction is unclear. The aim of the present study was to investigate the prevalence of intestinal metaplasia at the esophagogastric junction in Japanese patients with no clinical diagnosis of Barrett's esophagus. METHODS: A total of 103 specimens from consecutive surgeries were studied. All subjects underwent surgical resection for squamous carcinoma of the esophagus. Microscopic examination was performed from the squamocolumnar junction to 4 cm distal to the squamocolumnar junction. The extent of intestinal metaplasia was investigated in detail. Microscopic columnar-lined esophagus was defined as columnar epithelium with esophageal-type submucosal glands. RESULTS: The extent of intestinal metaplasia varied and was usually identified at intervals. Intestinal metaplasia exactly at the squamocolumnar junction was identified in 29 of 103 specimens (28%). Microscopic columnar-lined esophagus was identified in five of the 103 (5%), four of which had intestinal metaplasia in the columnar-lined esophagus. CONCLUSION: Intestinal metaplasia occurs frequently in the region of the esophagogastric junction in Japanese patients with squamous cell cancer of the esophagus.

Adult↗

Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits.

To evaluate the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of ventilator-induced lung injury, we 1) measured TNF-alpha production in the lung caused by conventional mechanical ventilation (CMV) and 2) evaluated the protective effect of anti-TNF-alpha antibody (Ab) in saline-lavaged rabbit lungs. After they received saline lung lavage, rabbits were intratracheally instilled with 1 mg/kg of polyclonal anti-TNF-alpha Ab in the high-dose group (n = 6), 0.2 mg/kg of anti-TNF-alpha Ab in the low-dose group (n = 6), serum IgG fraction in the Ab control group (n = 6), and saline in the saline control group (n = 7). Animals then underwent CMV for 4 h. Levels of TNF-alpha in lung lavage fluid were significantly higher after CMV than before in both control groups. Pretreatment with intratracheal instillation of high and low doses of anti-TNF-alpha Ab improved oxygenation and respiratory compliance, reduced the infiltration of leukocytes, and ameliorated pathological findings. CMV led to TNF-alpha production in the lungs, and intratracheal instillation of anti-TNF-alpha Ab attenuated CMV-induced lung injury in this model.

Acute-Phase Reaction↗

Cloning and characterization of a Drosophila melanogaster cDNA encoding a glutamate transporter.

A Drosophila cDNA encoding a glutamate transporter was cloned and examined. The predicted protein (479 amino acid residues) shows significant sequence identity with mammalian counterparts. The protein expressed in Xenopus oocytes had a glutamate transport activity. Northern blot analysis showed that the transcript increased in amount developmentally. This expression pattern is different from those of Drosophila glutamate receptors.

ATP-Binding Cassette Transporters↗

Comparison of precursor structures of the GGNG peptides derived from the earthworm Eisenia foetida and the leech Hirudo nipponia.

Earthworm and leech cDNAs encoding the GGNG peptides, a family of myotropic peptides, were cloned and examined in this study. Both of the predicted precursor proteins are of polyprotein structure and contain several putative peptides distinct from the GGNG peptides. However, the precursors show organizations distinct from each other and no sequence similarity except for the GGNG peptides.

Amino Acid Sequence↗

[A case of aggressive myeloma with abnormal plasmocytes in pleural effusion and cerebrospinal fluid].

Extramedullary involvement of myelomas is common but invasion of myeloma cells into the pleural cavity and cerebrospinal fluid (CSF) is rare. We report an aggressive case of multiple myelomas (Bence Jones lambda type) with pleural and meningeal infiltration. A 66-year-old man was referred to our hospital because of anemia, thrombocytopenia, and dyspnea. His peripheral blood contained 2% bizarre plasma cells. Bone marrow biopsy specimens and immunoelectrophoresis confirmed the diagnosis. A chest radiograph disclosed pleural effusion in both lungs containing M-protein and numerous abnormal cells. The patient also suffered from disorientation, speech disorder, and muscle weakness. A lumbar puncture revealed atypical plasma cells in CSF. Four courses of chemotherapy (cyclophosphamide, doxorubicin, and prednisolone) and the intrathecal administration of methotrexate and cytarabine at 3-week intervals were effective in decreasing the pleural effusions and eliminating plasma cells from CSF. Nonetheless a chest wall tumor, pelvic mass, and pneumonia developed, and the patient died 5 months after initial presentation. Pleural infiltration of myeloma cells and multiple lesions with plasma cell involvement were discovered at autopsy.

Aged↗

[Comparison of the effect of rapid infusion of lactated and that of acetated Ringer's solutions on maternal and fetal metabolism and acid-base balance].

The maternal and neonatal metabolism and acid-base balance were investigated in 20 parturients undergoing combined spinal and epidural anesthesia for cesarean delivery. Patients received intravenous infusion at a rate of either 25 ml.kg-1.h-1 of lactated (LR group, n = 10) or acetated (AR group, n = 10) Ringer's solution before anesthesia, to prevent hypotension during anesthesia. We obtained venous blood samples as follows; maternal control before anesthesia, maternal sample A after the infusion, umbilical sample B, and neonatal pedal sample C 5 h after birth, and determined lactate, pyruvate, bicarbonate, and base excess concentrations, and pH in each sample. In sample A, the lactate level was significantly higher and base excess level was significantly lower in the LR group than in the AR group. The pH of sample A and B was significantly higher in the AR group than in the LR group. However, no differences in all parameters of sample C between the two groups were observed. These results demonstrated that acetated Ringer's solution is better than lactated Ringer's solution in rapid infusion before cesarean section because of the correction of neonatal lactic acidosis.

Acid-Base Equilibrium↗

[Dural arteriovenous fistula of the transverse-sigmoid sinus with intraventricular hemorrhage: a case report].

We report a case of dural arteriovenous fistula of the transverse-sigmoid sinus (TS-DAVF) with intraventricular hemorrhage. An 83-year-old woman presented with headache and vomiting. Neurological examination showed no defects. CT scans demonstrated intraventricular hemorrhage. Left external carotid angiograms showed a dural arteriovenous fistula of the isolated transverse-sigmoid sinus fed by the occipital and middle meningeal arteries. The draining vein was the leptomeningeal vein. Left internal carotid angiograms demonstrated venous congestion in the left temporal and occipital lobes. This case was grade 4 according to Lalwani's classification. 123I-IMP SPECT revealed a low perfusion are in the left temporal and occipital regions. Dynamic CT scans revealed venous congestion in the left temporal and occipital regions. We considered that the venous congestion was the cause of intraventricular hemorrhage. Initially, we embolized the DAVF using a transarterial approach with liquid material. However, the embolization of the DAVF was not complete. Therefore, we treated the DAVF by sinus packing with coils using a small craniotomy. Angiographic cure was obtained and the postoperative course was uneventful. We discuss the clinical features, the hemodynamic findings and the management of this case.

Aged↗

[Dural arteriovenous fistula of the transverse sigmoid sinus after transvenous embolization of the carotid cavernous fistula].

We report a case of dural arteriovenous fistula of the transverse-sigmoid sinus after transvenous embolization of the carotid cavernous fistula. A 72-year-old woman presented with left exophthalmos, chemosis, bruit and left abducens nerve palsy in June 1996. Bilateral external and internal carotid angiograms revealed the dural arteriovenous fistula of the cavernous sinus. We embolized the dural arteriovenous fistula using a transvenous approach via the left inferior petrosal sinus. Angiograms demonstrated the complete disappearance of the dural arteriovenous fistula. Two years and six months later, she complained of tinnitus at the retroauricular region. Left external carotid angiograms showed a dural arteriovenous fistula of the transverse-sigmoid sinus fed by occipital, posterior auricular, middle meningeal and superficial temporal arteries. We embolized the dural arteriovenous fistula using a transarterial approach. Her symptoms disappeared but the dural arteriovenous fistula did not disappear completely. We discussed the clinical features and etiology of this case.

Aged↗

Serine/threonine phosphatase activity of calcineurin is inhibited by sodium orthovanadate and dithiothreitol reverses the inhibitory effect.

Orthovanadate is known to be an inhibitor of protein tyrosine phosphatases. However, we found that it inhibited calcineurin which has the activity of a serine/threonine protein phosphatase, using casein phosphorylated by cyclic AMP-dependent protein kinase as a substrate. Orthovanadate inhibits the Mn2+-activated activity of purified calcineurin to 20%; this is not the case without Mn2+. Furthermore, 10 mM dithiothreitol (DTT) reversed the inhibitory effects of orthovanadate. Orthovanadate showed the same inhibitory effect for calcineurin activity in homogenates as for the purified enzyme; the inhibitory effect was reversed by DTT. These results indicate that orthovanadate inhibits not only protein tyrosine phosphatases as reported, but also serine/threonine phosphatase activity of calcineurin.

Animals↗

Expression of spliceosome-associated protein 49 is required for early embryogenesis in Caenorhabditis elegans.

Spliceosome-associated protein 49 (SAP 49) is a subunit of the splicing factor SF3b, which is involved in 3' splice site recognition in pre-mRNA splicing. Here we show the Caenorhabditis elegans SAP 49 gene is located in a gene cluster that is transcribed polycistronically with three other upstream genes. Transgenic analysis of expression of the gene cluster under the control of its native promoter revealed that in spite of its predicted essential function for all cells, the C. elegans SAP 49 expression is limited to specific cells in both larval and adult stages. When the endogenous SAP 49 expression was inhibited by microinjection of an antisense RNA, embryos laid by the injected worms ceased to develop at a specific stage of early embryogenesis, indicating that SAP 49 plays an essential role in the development of C. elegans. These results raise the possibility that SAP 49 is a cell-specific, not constitutive, splicing factor.

Animals↗