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Biomedical subjects

K Tani

Publications and source records attributed to K Tani.

414 records · Page 23Linked to original sources

Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.

Usual human livers contain two major ALDH isozymes, i.e., cytosolic ALDH1 and mitochondrial ALDH2, while approximately 50% of Orientals are "atypical" and have only the ALDH1 and are missing the ALDH2. Instead, the atypical livers contain an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH2 component. Some Orientals are found to be atypical also in the ALDH1 locus, i.e., they are missing the enzymatically active ALDH1 but contain a large amount of CRM corresponding to the ALDH1 component. cDNA for ALDH1 and that for ALDH2 were cloned and their nucleotide sequences were determined. The amino acid sequences of ALDH1 and ALDH2 were deduced from their cDNA sequences. The molecular abnormality of the inactive ALDH2(2) is found to be the substitution of Glu at the 14th position from the COOH-terminal of the protein by Lys which resulted from G----A transition in the gene.

Aldehyde Dehydrogenase↗

Effect of ultrafiltration on priming solution with preserved blood for extracorporeal circulation in infants.

In pediatric cardiac surgery, the initial priming solutions of the extracorporeal circulation include preserved blood. In an effort to eliminate unfavorable effects of preserved blood on the circulation, the authors introduced the preserved blood to ultrafiltration (UF). Seventeen infants with congenital heart defects were included in this study. UF was performed with a polysulfone ultrafiltrator before extracorporeal circulation. The 1600 ml of fluid, consisting of saline, 5% glucose, and maltose, were added to 400 ml of preserved blood, and the same amount of fluid was removed by UF. The concentrations of potassium, NH3, and bradykinin in the priming blood decreased significantly after UF. In the UF group, water balance during extracorporeal circulation and max. Creatinine-phosphokinase levels after surgery were better than controls. These data suggest that UF is able to remove some substances and result in reduction of an unfavorable effect on the circulation.

Blood Preservation↗

Comparative studies of glycoprotein Ib in heparin coated and nonheparin coated extracorporeal circulation circuits.

Contact between blood and artificial materials has various effects on blood. Impairment of platelet function is an especially important and well known effect, but its precise mechanism is not clearly understood. The authors constructed a circulation model to investigate the effect of extracorporeal circulation on platelet membrane glycoproteins (GPs), especially GP Ib, and to compare the changes in GP Ib in heparin coated (group C) and nonheparin coated (group N) circuits. As determined by flow cytometry, GP Ib in both groups decreased on initiating circulation, but the decrease in group N was significantly larger than that in group C. There was no observed change in GP IIb/IIIa levels in either group. The extent of shear stress induced platelet aggregation significantly decreased during circulation in both groups. Decreases in the extent of shear stress induced platelet aggregation were significantly less with the use of heparin coated circuits. In addition, the amount of GP Ib in the high speed pellet decreased progressively during circulation in both groups. In contrast, the amount of GP Ib in the Triton insoluble (low speed) pellet increased dramatically during circulation. However, expression of GP Ib in the Triton soluble platelet fraction was low in both groups. From the results, it was concluded that the cause of the decrease in platelet function during extracorporeal circulation is attributable to the internalization of GP Ib from the platelet surface inside the platelet. It also can be said that a heparin coated circuit is one effective means of controlling this change.

Blood Platelets↗

MR imaging of peripheral cholangiocarcinoma.

A prospective study was performed to compare MR spin-echo (SE) sequences [repetition time/echo time (TR/TE) 2,000/80, 500/44 ms], unenhanced CT, and rapid intravenous contrast enhanced CT in eight consecutive patients with peripheral cholangiocarcinoma. All the tumors (ranging from 5 to 9.6 cm in size) were detected with all four techniques. Tumor contrast, however, was qualitatively greatest on long TR/TE SE images. With long TR/TE SE images, tumors were demonstrated as well-demarcated homogeneous regions of high signal intensity, and the anatomic relations between tumors and intrahepatic blood vessels were easily perceived. Detection of small intrahepatic metastatic foci was best on long TR/TE images. Tumor invasion of the portal vein's branches was also best seen on long TR/TE SE images. These results indicate that long TR/TE SE sequence is the most effective initial screening method in demonstrating the presence and determining resectability of peripheral cholangiocarcinoma.

Adenoma, Bile Duct↗

Effect of interferon-alpha in patients with chronic myelogenous leukemia in the accelerated phase: cytogenetic and molecular studies.

Human interferon-alpha (IFN-alpha) has been shown to be effective in the treatment of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in the benign stable phase. The present study indicates that IFN-alpha may have a suppressive effect on Ph1-positive clones not only in the early stable phase but also in the accelerated phase with additional chromosomal abnormalities in some patients. In this study, in addition to 5 benign-phase patients, 3 patients with CML in the accelerated phase who had additional chromosomal abnormalities were treated with IFN-alpha. The presence of the Ph1-positive clone was estimated by chromosomal analysis and by Southern analysis at the DNA level using a 3' breakpoint cluster region (bcr) probe. Hematological remission and the suppression of proliferation of Ph1-positive clone to various extents were achieved by IFN-alpha treatment in 2 benign-phase patients and 3 patients with additional chromosomal abnormalities. Interestingly, in one of the latter three patients, Ph1-positive clones with or without additional chromosomal abnormalities were completely suppressed judging from chromosomal analysis and from the disappearance of bcr gene rearrangements.

Adult↗

Role of endogenous platelet-activating factor in caerulein-induced acute pancreatitis in rats: protective effects of a PAF-antagonist.

The role of endogenous platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis was investigated by determining whether CV-6209, a selective PAF antagonist, confers protection against caerulein-induced acute pancreatitis in rats. Continuous intravenous infusion of caerulein (5 micrograms/kg x h) induced time-dependent increase in serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas, and produced histologic evidence of acute pancreatitis. Pretreatment with CV-6209 (1 mg/kg) significantly inhibited the elevation of serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas. Caerulein-induced tissue oedema and recruitment of leucocytic cells were markedly ameliorated with CV-6209. Platelet-activating factor may be released endogenously and may play a role during acute pancreatitis.

Acute Disease↗

Role of endogenous platelet-activating factor (PAF) in endotoxin-induced portal hypertension in rats.

To determine the role of platelet-activating factor (PAF) in endotoxin-induced portal hypertension, we performed continuous recording of both blood pressure (BP) and portal venous pressure (PVP) in rats following the administration of intravenous PAF (25 ng/kg), intraportal PAF (25 ng/kg), intraportal endotoxin (2 mg/kg), and intraportal endotoxin (2 mg/kg) for 1 min subsequent to pretreatment with a specific PAF-antagonist (CV-6209, 1 mg/kg, i.v.). Basal resting values of both BP (102.3 +/- 9.3 mmHg) and PVP (7.7 +/- 1.2 mmHg) fell rapidly after intravenous infusion of PAF (BP: 36.7 +/- 5.8 mmHg; PVP: 5.7 +/- 0.8 mmHg) and followed by gradual return. Intraportal PAF infusion elicited a rapid but less severe depression of BP (57.2 +/- 9.4 mmHg) as compared with intravenous PAF infusion, whereas PVP was increased transiently around 4 min after treatment (11.0 +/- 5.3 mmHg). A similar degree of PVP elevation (10.7 +/- 2.0 mmHg) was observed between 8 and 20 min after intraportal administration of endotoxin. Depression of BP was initiated 12 min after endotoxin administration but was not severe (76.6 +/- 12.8 mmHg). CV-6209 significantly alleviated the endotoxin-induced elevation of PVP and completely inhibited the hypotension. These observations suggest that: (i) PAF-induced elevation of PVP is a direct response of the liver to PAF; and (ii) endogenous PAF plays an important role in the endotoxin-induced portal hypertension.

Animals↗

Heterogeneous distribution of microcirculatory disturbance in the gastric mucosa during gastric hypercontraction in rats.

Gastric mucosal lesions induced by gastric hypermotility are characteristically observed along the gastric mucosal folds. To determine the role of microcirculatory disturbance in this particular condition, we measured the gastric mucosal haemodynamics after vagal stimulation and also examined histologically the transparent specimens of the transverse section of the contracted stomach in rats. Gastric mucosal haemodynamics measured with a reflectance spectrophotometer showed the repetition of ischaemia-reperfusion during gastric hypermotility. The rapidly frozen and transparent specimen of the corpus showed that gastric mucosa was stretched at the crest and compressed at the base of the mucosal folds. Characteristic distribution of red blood cells was observed; it was dense at the crest of the mucosal folds and sparse at the base. These results suggest that gastric hypermotility may induce the distinctive heterogeneous microcirculatory disturbance in the folds and may contribute to the characteristic localization of mucosal lesions.

Animals↗

Secretory IgA(S-IgA) levels in sera from patients with diffuse panbronchiolitis.

The serum S-IgA levels of 33 patients with diffuse panbronchiolitis (DPB) were compared with those of 13 patients with chronic bronchitis (CB) and 24 patients with bronchiectasis (BE), to obtain information on differences in the pathologic states in DPB and other chronic bronchial diseases. The S-IgA levelw as elevated in all three bronchial diseases, being significantly higher in DPB than in CB, and intermediate in BE. Persistent bacterial infections developed in most of the patients with DPB and two-thirds of those with BE, but in few of those with CB. Serum S-IgA levels were especially high in patients expectorating Pseudomonas aeruginosa-positive sputum, who constituted two-thirds of the patients with DPB and about one-third of those with BE. The highest levels over (100 micrograms/ml) were observed in far-advanced patients with DPB who expectorated P. aeruginosa-positive sputum. The increase in the serum level of IgA was less than that of S-IgA in all three diseases. These results indicate that the marked elevation of the serum S-IgA level in patients with DPB is due to extensive, chronic infection of the airways of the lungs, especially the peripheral airways, and that serum S-IgA is a useful marker for determining the clinical stage and the pathologic state of patients with diffuse peripheral airway diseases.

Adult↗

Fibroblast growth-stimulating activity in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.

Increased fibroblast growth-stimulating activity (FGA) was found in bronchoalveolar lavage fluid (BALF) from sarcoidosis patients. For evaluation of the significance of FGA in disease activity and the pathophysiology of sarcoidosis, the FGA levels were compared with data on cellular analysis of BALF, serum angiotensin-converting enzyme (S-ACE) activity and chest radiograms. The FGA level was significantly higher in sarcoidosis patients with parenchymal involvement (radiological stages II and III) than in those without parenchymal involvement (radiological stage I). The FGA was positively correlated with albumin and fibronectin concentrations in BALF. However, it was not significantly correlated with the ratio of CD-4 + to CD-8 + T-lymphocytes in BALF or the S-ACE level, which are known to be useful in evaluating the disease activity of sarcoidosis. These results indicate that the diagnostic value of FGA is different from that of the lymphocyte subpopulations in BALF and S-ACE, and is useful in estimating the extent of parenchymal involvement in sarcoidosis.

Adult↗

Elevated level of soluble interleukin-2 receptor in bronchoalveolar lavage fluid from sarcoidosis patients.

Pulmonary sarcoidosis is a granulomatous disorder of unknown cause, characterized by an accumulation of active T lymphocytes in the lung. We measured the levels of soluble interleukin-2 receptor (IL-2R) in bronchoalveolar lavage fluid (BALF) of patients with active pulmonary sarcoidosis and normal subjects by a sensitive enzyme-linked immunosorbent assay. Soluble IL-2R was detectable in BALF from 6 of 11 patients with sarcoidosis but in only 1 of 8 normal control subjects, the mean levels of IL-2R in BALF of the two groups being 2.8 +/- 0.9 U/ml and 0.1 +/- 0.1 U/ml, respectively (p less than 0.01). A slight correlation was found between the soluble IL-2R level and the number of CD4-positive cells. Sarcoidosis patients were classified by radiographical staging. Soluble IL-2R was not detectable in the BALF of any stage I patients, but was found in the BALF of 6 of the 7 stage II and stage III patients. These results suggest that in the clinical management of patients with sarcoidosis, measurement of soluble IL-2R in BALF is useful for evaluating the activity of the lung disease is sarcoidosis.

Adult↗

Cytotoxic factor for fibroblasts in bronchoalveolar lavage fluid of bleomycin-treated rats.

The mechanisms of lung injury and fibrosis in diffuse interstitial lung diseases were studied by tests on the in vitro effect of bronchoalveolar lavage fluid (BALF) from bleomycin-treated rats on quiescent fibroblasts in culture. The BALF was obtained on days 2, 3, 6, 15, and 29 after intratracheal administration of bleomycin. Cytotoxic activity was detected in the BALF only on day 2. The factor responsible for the cytotoxic activity was detected in 50-70% ammonium sulfate fraction, and lost 10% of its activity after 30 min at 56 degrees C, 75% after 10 min at 80 degrees C, and all activity after 10 min at 100 degrees C. The factor was completely precipitated by 60% acetone and was not extractable with ether. In ion exchange chromatography, the factor was eluted with the main fraction of protein, and gel filtration indicated that it had a molecular weight of 60-70 kDa. Histological examination showed disappearance of the normal alveolar architecture on day 2, and pulmonary fibrosis on day 15. Thus the cytotoxic factor may be one of factors responsible for lung injury and may act as trigger for subsequent fibrosis in bleomycin-induced lung damage.

Ammonium Sulfate↗

Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method.

This study compared the results of annuloplastic repair of tricuspid regurgitation (TR) using Doppler echocardiography. Sixty-three patients who underwent tricuspid annuloplasty were studied. Thirty-four patients received Kay-Boyd annuloplasty and 29 Carpentier-Edwards ring annuloplasty. A new classification of TR based on the direction and area of regurgitation flow on Doppler echocardiogram was applied preoperatively. In the Kay-Boyd group, 10 cases showed massive TR and 24 cases showed localized TR preoperatively. Localized TR was well controlled in all cases, but 8 of 9 cases of massive TR showed grade III residual TR. In the C-E group, 21 cases showed massive TR and 8 cases showed localized TR. All cases were well controlled postoperatively. We conclude that (1) although the Kay-Boyd method is acceptable for localized TR, the C-E method should be employed for massive TR; (2) analyzing the regurgitant pattern of TR by Doppler echocardiogram is useful in selecting an appropriate surgical technique.

Adult↗

Clinical evaluation of a silicone coated hollow fiber oxygenator.

In this article, the clinical experience with a cardiopulmonary bypass (CPB) using a newly developed hollow fiber oxygenator with an ultra-thin layer of silicone is reported. A comparative study of biocompatibility between the new oxygenator and a heparin coated oxygenator is also described. The CPB was performed with a silicone coated oxygenator, Mera Excelung Binding Prim HPO 15 H-C (Group I, n = 6) or Binding Prim HPO 25 H-C (Group II, n = 10) (Senko Medical Instrument Mfg., Tokyo, Japan). Air could be vented through the silicone coated hollow fibers, and it was easy to prime the circuits. The CPB duration was 101 +/- 37 min and 170 +/- 64 min for Groups I and II, respectively. There were no deaths and no complications from CPB. Partial arterial pressure of O2 levels 60 minutes after the start of CPB were 529 +/- 28 mm Hg and 529 +/- 28 mmHg for Group I and II, respectively. Partial arterial pressure of CO2 levels 60 min after the start of CPB were 36.4 +/- 4.6 mmHg and 39.4 +/- 4.4 mmHg, respectively. Plasma free hemoglobin at 60 min was 33.5 +/- 17.2 mg/ dL and 46.7 +/- 26.1 mg/dL for Groups I and II, respectively. As an evaluation of biocompatibility, the effects of the new oxygenator on platelet activation (GP Ib, IIb/IIIa), coagulation (TAT), fibrinolysis (PIC), and inflammatory response (C3a, granulocyte elastase) were investigated during CPB and comparing to those of the heparin coated oxygenator. There were no significant differences in GP Ib, GP IIb/IIa, TAT, PIC, and granulocyte elastase between the two oxygenators. However, 60 min after the start of CPB, the C3a was significantly lower for the new oxygenator group than for the heparin coated oxygenator group (p < 0.03). The new oxygenator showed good gas transfer, low hemolysis, and good biocompatibility. Because of its durability and good biocompatibility, the new oxygenator was determined to be suitable for prolonged extra corporeal circulation.

Adult↗

Superiority of interleukin-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice.

Interleukin-12 (IL-12) is a heterodimeric cytokine that consists of p40 and p35 subunits. IL-12 has been regarded as a potent inducer of host antitumor immunity through interferon-gamma (IFN-gamma) production and development of Th1 helper T cells from Th0 cells. Here, we demonstrate the immunomodulatory actions of an IL-12-transduced murine lung cancer cell line, Lewis lung carcinoma (LLC) (LLC/IL12) cells, in syngeneic C57BL/6 mice. We also report on their therapeutic potency. Three LLC/IL12 cells producing different levels of IL-12 were cloned and found to have diminished tumorigenicity in C57BL/6 mice depending on their level of IL-12 production. In vivo depletion assay demonstrated that the loss of tumorigenicity of LLC/IL12 depended on both CD4+ and CD8+ T cells, and that natural killer (NK) cells were involved, especially in the early phase of immunity. The strong systemic antitumor immunity against challenge with wild type LLC (LLC/wt) cells was also induced by LLC/IL12 cells. The systemic antitumor memory was found to be dependent mainly on the CD4+ T-cell subset. 51Cr-release assay revealed that the killer activity consisted of a specific killer activity directed at the parental LLC/wt cells and a nonspecific killer activity directed at both LLC/wt and syngeneic EL-4 thymoma cells. In addition, LLC/IL12 apparently had a much stronger antitumor effect against the established LLC/wt tumor than LLC transduced with B7-1 or GM-CSF cDNA. IL-12 can be considered an efficient candidate molecule for immunogene therapy for lung cancer in this experimental system.

Animals↗