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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 379 records · Page 21Linked to original sources

Tracheal stenosis treated with self-expanding nitinol stent.

A self-expanding nitinol stent was used in 2 patients with inoperable tracheal stenosis due to invasive malignant tumor of the trachea. One was a 70-year-old man with recurrent tumor from adenocarcinoma of the left lung, and the other was a 63-year-old man with recurrent tumor in mediastinal lymph nodes from esophageal cancer. The self-expanding nitinol stent is very useful and effective in inoperable tracheal stenosis due to intraluminal tumor invasion.

Adenocarcinoma↗

Dibutyryl cyclic adenosine monophosphate attenuates lung injury caused by cold preservation and ischemia-reperfusion.

OBJECTIVE: Dibutyryl adenosine 3',5'cyclic monophosphate (db-cAMP) is a membrane-permeable analog of adenosine 3',5'cyclic monophosphate (cAMP). We examined the effect of db-cAMP against lung injury caused by cold preservation and ischemia-reperfusion. METHODS: Rats were divided into three groups (each n = 6) according to the presence or absence of db-cAMP in the preservative solution and cold ischemia (4 degrees C for 15 hours). In the fresh group, the lung was flushed with the preservative solution and reperfusion was performed immediately. In the control group and the db-cAMP group, the lung was flushed either with the solution or with a combination of the solution plus db-cAMP, respectively, and preserved at 4 degrees C for 15 hours. The lung was reperfused for 60 minutes in an ex vivo rat lung perfusion model. RESULTS: The shunt ratios of the reperfused lung in the db-cAMP group were 4.0% +/- 1.6% and 3.4% +/- 1.2% 10 and 60 minutes, respectively, after the initiation of reperfusion, being as low as those in the fresh group and significantly lower than those in the control group (p < 0.01). The wet/dry weight ratio of the lung tissue after reperfusion was 5.99 +/- 1.50 in the db-cAMP group, which was similar to that in the fresh group (5.45 +/- 0.23) and significantly lower than that in the control group (14.20 +/- 3.43) (p < 0.01). Electron microscopic examination showed less damage in the pulmonary arterial endothelium in the db-cAMP group. CONCLUSIONS: We conclude that db-cAMP attenuates the lung injury by cold preservation and ischemia-reperfusion, at least partly by protection of the vascular endothelium.

Animals↗

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung.

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Acetylcysteine↗

Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo.

Cilostazol(6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4- dihydro-2(1H)-quinolinone) selectively inhibits cGMP-inhibited phosphodiesterase (PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation (SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE1 and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg cilostazol to healthy volunteers produced a significant inhibition of SIPA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment of arterial occlusive diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗

Acute effects of phorbol ester and insulin on insulin-induced glucose uptake and protein kinase C activation in rat adipocytes.

We examined the acute effect of pretreatment with phorbol ester and insulin on insulin-induced glucose uptake and protein kinase C (PKC) translocation from cytosol to the membrane in rat adipocytes. Adipocytes were preincubated with 1 microM tetradecanoylphorbol 13-acetate (TPA) and 10 nM insulin for 60 min and then stimulated with 10 nM insulin for 10 and 30 min to measure PKC activity in cytosol and membrane fractions using a Mono Q column connected onto an HPLC system and [3H]2-deoxyglucose (DOG) uptake, respectively. Pretreatment with 1 microM TPA and 10 nM insulin for 60 min resulted in the marked decreases of insulin-induced [3H]2-DOG uptake. Translocation of Mono Q column-purified cytosolic PKC enzyme activity and PKC beta immunoreactivity from cytosol to the membrane was suppressed by pretreatment with TPA and insulin for 60 min. These results indicate that acute treatment with TPA and insulin which are PKC activators suppress translocation/activation of PKC, and accordingly inhibit insulin-induced glucose uptake. We suggest that a decrease of cytosolic PKC activity may mainly-contribute to the impaired responsiveness of the glucose transport system after acute TPA and insulin treatment.

Adipocytes↗

Effect of anesthetic agents and middle ear pressure application on distortion product otoacoustic emissions in the gerbil.

The functional status of the middle ear system has a crucial importance in the measurements of distortion product otoacoustic emissions (DPOAEs), because each emission signal has to be detected indirectly in the external canal. It was observed that DPOAEs were scarcely detectable in the gerbil anesthetized with pentobarbital. On the other hand, when ketamine was used as an anesthetic, the DPOAE levels were generally high. The differences in the effects of these anesthetic agents on the DPOAEs became less clear when the tympanic bulla was opened. This strongly suggests that the effects might be due to a modification of the middle ear pressure. This study was designed to elucidate the mechanisms of the effects of these anesthetics on the DPOAEs. Comparing the effects of pentobarbital and those of pressure application to the middle ear on the frequency characteristics of DPOAEs, the following conclusions emerged: (1) pentobarbital administration causes negative middle ear pressure in the gerbil; (2) the generated pressure strongly reduces DPOAE conduction through the middle ear; and thus (3) proper selection of anesthetic agents is very important in gerbil experiments that involve OAE measurements.

Anesthetics↗

Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients.

Immunological abnormalities (IA) are frequently observed in patients with myelodysplastic syndromes (MDS). Although there have been a number of analyses of the prognostic factors, there have been few studies, if any, to determine whether IA affects prognosis. We investigated the prognosis of 153 MDS patients with or without IA who were treated at a single Japanese institute for 10 years. Nineteen of 153 patients (12%) developed autoimmune disorders. One hundred of 153 patients (63%) had an abnormality in at least one immunological laboratory test. Hypergammaglobulinemia was found in 50 of 128 (39%) patients tested, hypogammaglobulinemia was observed in 10 of 128 (8%), positivities of antinuclear antibody, RA factor. DNA antibody, and direct antiglobulin test were observed in 30%, 14%, 7% and 12%, respectively, and a CD4/CD8 ratio < 1 was observed in 20%. There was no significance in the distribution of age, MDS subtype, or sex between patients with and without IA. The survival of MDS patients without IA was significantly better than that of patients with IA, and the survival of patients with a CD4/CD8 ratio > 1 was also significantly superior to the survival of those with an inverted CD4/CD8 ratio. Patients with IA tended to die of infection or leukemic progression in comparison with those without IA, suggesting that IA may be associated with susceptibility to opportunistic infection and disease progression.

Adult↗

Extended operation for non-small cell lung cancer invading great vessels and left atrium.

OBJECTIVE: We analyzed the results of surgical treatment in patients with non-small cell lung cancer invading the great vessels (GV) and left atrium (LA) by direct extension and without distant metastases. METHODS: From 1976 to 1993, 42 patients (37/male, 5/female) with lung cancer invading the GV and LA were treated surgically, 13 had invasion of the superior vena cava and innominate vein, 15 of the aorta and subclavian artery, and 14 of the left atrium. In all 42 the diagnosis was confirmed by pathological examination. Surgical resection included pneumonectomy (16 patients) and lobectomy (26 patients). The histologic type was squamous cell carcinoma in 27 patients, adenocarcinoma in 12, and large cell carcinoma in 3. Preoperatively, 13 patients were treated with radiation and chemotherapy. Postoperatively, further treatment was given to 22 patients. All were staged according to the international TNM staging system. Survival was calculated by the Kaplan-Meler method. RESULTS: A total of 15 patients underwent complete resection. Reliability of clinical N factor was 80%. The overall survival was 17% at 3 years (median survival time (MST), 14 months). The operative mortality was 2.4%. Patients with lung cancer invading GV (MST, 19 months) had significantly longer survival than did those with cancer invading LA (MST, 10 months, P = 0.036). There were significant prognostic differences between N0-1 and N2-3 (MST, 22 months; MST, 9 months, respectively, P = 0.0013). Cox regression analysis identified pathological N factor, completeness of resection, and pre- and postoperative radiotherapy as important in affecting survival. CONCLUSIONS: We conclude that patients with pathological N0-1 non-small cell lung cancer invading great vessels can achieve long-term survival with adequate surgical treatment.

Aged↗

Prognosis of ipsilateral intrapulmonary metastases in resected nonsmall cell lung cancer.

OBJECTIVE: According to the new classification of intrapulmonary metastasis (pm) of lung cancer by the American Joint Committee on Cancer (AJCC), ipsilateral pm is classified as a T factor. We evaluated the prognostic factors of ipsilateral pm after surgical treatment, and validity of the new classification. METHODS: From January 1977 to December 1994, 41 patients (24 males and 17 females) with lung cancer had a postoperative diagnosis of intrapulmonary pm. The histologic type consisted of 27 adenocarcinoma. 12 squamous cell carcinoma, and 1 large cell carcinoma. Twenty patients had pm in the same lobe in which the primary lesion was located, and 21 patients had pm in ipsilateral different lobe(s). Thirty patients underwent lobectomy, 5 bilobectomy and 6 pneumonectomy. Survival was calculated by the Kaplan Meier method, and Cox proportional hazards model was used for multivariate analysis. RESULTS: The overall survival was 25.8% at 5 years (median survival time (MST), 26 months). The 3-year survival of patients with pm in the same lobe was 49% (MST, 33 months), and that of patients with different lobe was 21% (MST, 16 months) (P = 0.237). There were no significant differences in survival in relation to age, sex, histology, pathological N factor, or number of pm. Multivariate analysis identified a significant correlation between survival and T factor proposed by AJCC (P = 0.022). CONCLUSIONS: The new classification seems useful for estimating postoperative prognosis of the resected patients with lung cancer accompanied by ipsilateral pm.

Aged↗

Time trends and survival after surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC).

OBJECTIVE: To evaluate the role of surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC), time trends and survival after surgery and the prognostic factors were investigated retrospectively. METHODS: Consecutive patients, 155, with p-stage IIIa, pN2 NSCLC who underwent thoracotomy at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between January 1976 and December 1990 were divided into three groups by the period of operation (the earlier period: 1976-1980, n = 49; the middle period: 1981-1985, n = 55; and the later period: 1986-1990, n = 51), and were reviewed. Of the 155 patients, 84 (54.2%) were preoperatively evaluated to have mediastinal lymph nodes metastases (cN2 disease). RESULTS: The 5 year survival rates in the earlier, middle and later periods were 12.1, 18.6, and 43.8%, respectively, showing significant improvement in the later period (P < 0.001, for the later period versus the earlier period or the middle period). The improvement was caused by decrease in the rate of operation-related death (4.1, 1.8, and 0.0%, in the earlier, the middle, and the later period, respectively), increase in the rate of complete tumor resection (59.1, 76.4, and 96.1%, respectively), and decrease in the ratio of pT3N2M0 patients (44.9, 34.5, and 17.6%, respectively) having poor prognosis compared with pT1-2N2M0 patients. Decrease in the ratio of cT3N2M0 patients and for increase in the rate of complete resection could be realized by accurate preoperative diagnosis with introduction of chest computed tomography (CT). Based on the preoperative evaluation, the 5 year survival rates of cT1N2M0, cT2N2M0, and cT3N2M0 patients were 39.4, 30.5, and 10.2%, respectively, showing significant poor prognosis in cT3N2M0 patients. CONCLUSION: In cT1-2N2M0 or pT1-2N2M0 patients, a good prognosis can be realized by complete tumor resection with mediastinal lymph nodes dissection. In contrast, surgical treatment should not be justified in cT3N2M0 or pT3N2M0 patients.

Adult↗

Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient.

A female patient with ALL received a bone marrow transplant (BMT) from an unrelated donor with a one locus HLA mismatch. The donor was heterozygous at the HLA-A locus, while the patient was homozygous at this locus. The patient had cytomegalovirus (CMV) antigenemia on day 42 following an intensive preparative regimen that included anti-thymocyte globulin and BU+CY+TBI to prevent graft rejection. Ganciclovir was given initially for the treatment of CMV antigenemia, although the patient soon developed severe myelosuppression. The patient's hematopoietic recovery was poor, and CMV and human herpesvirus-6 (HHV-6) were detectable in the peripheral blood. Severe CMV retinitis was treated with foscarnet and the intraocular injection of ganciclovir. The CMV retinitis improved and the marrow gradually recovered. CMV and HHV-6 were no longer detectable in the peripheral blood. Foscarnet and intraocular injection of ganciclovir appeared to be an effective treatment for CMV retinitis in this myelosuppressed BMT patient.

Adult↗

Granulocyte-macrophage colony-stimulating factor abrogates transforming growth factor-beta 1-mediated cell cycle arrest by up-regulating cyclin D2/Cdk6.

The role of positive and negative cytokine interactions in G1 cell cycle regulation of haemopoietic cells was analysed by determination of the expression patterns of D-type cyclins and cyclin-dependent kinases (cdks) in SKM-1 myelodysplastic syndrome (MDS) cells incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or transforming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 inhibited SKM-1 cell proliferation due to the cell cycle arrest in G1 phase. GM-CSF abrogated the TGF-beta 1-mediated G1 arrest in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 1-mediated G1 arrest correlated with the down-regulation of cdk4, cdk6 and cyclin D2, and that abrogation of TGF-beta 1-mediated G1 arrest by GM-CSF correlated with the constitutive over-expression of cyclin D2 and cdk6 but not cdk4. These results suggest the importance of cyclin D2/cdk6 levels in abrogating G1 arrest in cells exposed to TGF-beta 1, and raise the possibility that the GM-CSF-mediated up-regulatory pathway of signal transduction through cyclin D2/cdk6 differs from the TGF-beta 1-cdk4-mediated pathway in SKM-1 cells. This signal transduction pathway through cyclin D2/cdk6 might play an important role in haemopoietic regulation by the cytokine network.

Cell Cycle↗

Total absence of protein 4.2 and partial deficiency of band 3 in hereditary spherocytosis.

Unlike previously reported cases with total protein 4.2 deficiency due to mutations in the EPB42 gene, we describe a total deficiency in protein 4.2 with normal EPB42 alleles. Hereditary spherocytosis (HS) was observed in a Japanese woman (unsplenectomized) and her daughter (splenectomized). The mother showed a partial deficiency in band 3 and a proportional reduction in protein 4.2. She was heterozygous for a novel allele of the EPB3 gene, allele Okinawa, which contains the two mutations that define the Memphis II polymorphism (K56E, AAG-->GAG, and P854L, CCG-->CTG) and, additionally, the mutation: G714R, GGG-->AGG, located in a highly conserved position of transmembrane segment 9. The latter change was responsible for HS. In trans to allele Okinawa, the daughter displayed allele Fukuoka: G130R, GGA-->AGA, an allele known to alter the binding of protein 4.2 to band 3. The daughter presented with a more pronounced decrease of band 3, and lacked protein 4.2, resulting in aggravated haemolytic features. Although the father was not available for study, heterozygosity for allele Fukuoka has been documented in another individual who showed no clinical or haematological signs, and a normal content of band 3. We suggest that band 3 Okinawa binds virtually all the protein 4.2 in red cell precursors, band 3 Fukuoka being unable to do so, and that the impossibility of band 3 Okinawa incorporation into the membrane leads to degradation of the band 3 Okinawa protein 4.2 complex. In contrast, band 3 Fukuoka, free of bound protein 4.2, could then incorporate normally into the bilayer. Thus, protein 4.2 would not appear in the daughter's red cell membrane.

Amino Acid Substitution↗

Unsuccessful omentopexy in thoracic surgery.

Omentopexy has improved the treatment of chronic empyema and postpneumonectomy bronchopleural fistula, which otherwise are difficult to manage. However, omentopexy is not effective in some patients. Four of 17 patients who underwent omentopexy in our institution between January 1978 and March 1994 did not respond to the treatment and died. In two patients, a dead space remained after surgery and there was insufficient sterilization. In one patient, a dead space appeared after surgery and it was impossible to control infection. The fourth patient had dehiscence of the anastomosis triggered by postoperative acute gastritis. All four patients in whom omentopexy was not successful died. When omentopexy is used for empyema, the space should first be sterilized. If sterilization is insufficient, muscle filling and thoracoplasty must be performed and no dead space left.

Adult↗

"Reversed" latissimus dorsi musculocutaneous flap for closure of large bronchopleural fistula.

The patient was a 54-year-old male with diabetes mellitus and liver abscess perforating into the right lung through the diaphragm. After right lower lobectomy of the lung, S3-segmentectomy of the liver, and debridement of the subdiaphragmatic abscess a bronchopleural fistula appeared. After open-drainage thoractomy, secondary operation for closure of a large bronchopleural fistula and obliteration of the empyema cavities was performed with a "reversed" latissimus dorsi musculocutaneous flap.

Bronchial Fistula↗

Increased soluble fibrin monomer and soluble thrombomodulin levels in non-insulin-dependent diabetes mellitus.

We measured the plasma levels of fibrinogen, D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (SFM), tissue-type plasminogen activator (t-PA) and thrombomodulin (TM) in patients with non-insulin-dependent diabetes mellitus (NIDDM). There were no significant differences in the hemostatic parameters between the 77 patients with NIDDM and healthy control subjects, although the plasma levels of fibrinogen, D-dimer, TAT, and PPIC in the NIDDM patients were slightly higher than those in the healthy controls. Among the NIDDM patients divided into three groups by the urinary albumin excretion (UAE) level, there was no significant difference in age or sex among the normo-, micro-, and macroalbuminuria groups, and the HbA1C level in the micro- and macroalbuminuria groups were slightly higher than those in the normoalbuminuria group. There was no significant difference in activated partial thromboplastin time, prothrombin time, fibrinogen, TAT, PPIC, D-dimer, or t-PA among these three groups. The plasma SFM and TM levels in the macroalbuminuria group were significantly higher than those in the normo- and microalbuminuria groups. The relationships between HbA1C and the hemostatic parameters were poor, but the plasma TM and SFM levels were significantly correlated with the urine albumin index.

Adult↗