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Biomedical subjects

K Okabe

Publications and source records attributed to K Okabe.

At least 127 records · Page 7Linked to original sources

Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases.

Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Experimental study on veno-venous extracorporeal membrane oxygenation for respiratory failure after lung transplantation.

Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.

Animals↗

[Hepatic fibrosis and its serum markers].

As serum markers for hepatitis fibrosis, prolyl hydroxylase (PH), type III procollagen peptide (PIIIP), type IV collagen, mesenchymal metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and laminin are reliable for clinical application. PH, PIIIP, MMP, TIMP and LM are regarded as the marker of ongoing hepatic fibrosis. Type IV collagen and LM are indicative for the extent of hepatic fibrosis.

Biomarkers↗

[Immunohistochemical study on keratin of squamous cell carcinoma of the uterine cervix].

An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18), squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed. In the cases of squamous metaplasia, there were two types of staining of which one type had 56KD positive and 68KD negative and another type had both positive. In the cases of dysplasia, there were two types of staining the same as in squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there were three types of staining of which the first type had both 56KD and 68KD negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15), and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma (n = 23), there were two types of staining the same as in dysplasia of which one type had 56KD positive and 68KD negative (n = 17) and another type had both positive (n = 6). The keratin negative cases in CIS showed morphologically atypical reserve cell hyperplasia composed of atypical small cells with round nuclei and had a small lesion compared with other types. This result suggested that keratin negative CIS was an early form of CIS which was keratin positive. The results indicating that all dysplasia had 56KD keratin positive and CIS had not always 56KD keratin positive suggested that dysplasia was not always a precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[A case of right pulmonary hypoplasia with congenital diaphragmatic hernia and dextrocardia].

Chest X-ray of a 28-year-old woman revealed an abnormal shadow in the right lower lung field and dextrocardia, for which detailed investigation was performed. Since the CT number of the tumor shadow corresponded to that of the liver on chest CT, diaphragmatic hernia of the liver was suspected, and was confirmed by MRI and angiography of the abdomen. In addition, the pulmonary artery and vein were hypoplastic, and angiography of the pulmonary artery demonstrated pulmonary hypoplasia. This case was considered to have primary pulmonary hypoplasia, because the dextrocardia was considered to have occurred secondary to pulmonary hypoplasia and the diaphragmatic hernia of the liver was not sufficiently large to cause pulmonary hypoplasia. Pulmonary hypoplasia first diagnosed in adulthood is rare, with a clinical course and roentgenographic appearance differing from those of pulmonary hypoplasia in children.

Adult↗

[Study on cases of resected primary lung cancer in young persons].

A clinical study was conducted of 17 patients aged less than 40 years who received resection for lung cancer in our department. The 17 cases made up 1.8% of the total series of 924 resected lung cancer cases, with the number of cases increasing as the age of 40 years was approached. The male-female ratio was 1.1:1, with proportion of women higher than in the total series of lung cancer cases. The histological type of included a high proportion of adenocarcinomas (47.0%), while squamous cell carcinomas were few. In addition, the proportion of tumors of low-grade malignancy such as carcinoid tumors and mucoepidermoid carcinomas was high. The majority (58.8%) of cases were detected by mass screening. As a result, the number of stage I cases was high (10 cases, 58.8%), and curative resection could be performed in 70.8%. The prognosis of these young patients did not differ significantly from that of the total resected group, with a 5-year survival rate of 62.4% achieved. It was considered that the prognosis of lung cancer in young persons can also be improved with early detection by mass screening and active surgical intervention.

Adenocarcinoma↗

[A giant bladder stone with a small urethral stone].

A 71-year-old man had pollakisuria, macrohematuria and sense of urinary retention. His urethrogram showed a giant bladder stone with a small urethral stone. He received cystolithotomy. The giant bladder stone was removed. It weighed 310 g and is the 32nd reported in Japan.

Aged↗

[Congenital lobar emphysema successfully treated by right upper lobectomy at five hours after delivery: a case report].

Lobar emphysema is a rare disease and one of the causes of respiratory disturbance in the newborn and infancy. A case report is presented and compared with related data in the literature in Japan. Maternal echographic findings indicated the cystic lung disease of the fetus. The cystic space was punctured and aspirated three times. The baby was delivered by caesarean section after having taken sufficient precaution to prevent respiratory failure. Since the baby developed dyspnea gradually, at five hours following the delivery, right upper lobectomy was performed and the major symptoms were eliminated. The pathological diagnosis was congenital lobar emphysema and the etiology was concluded to be bronchiectasis.

Cystic Adenomatoid Malformation of Lung, Congenita↗

Absorption, plasma concentration, and excretion after single administration of 14C-(+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride in rats and dogs.

The absorption, plasma concentrations, and excretion of a newly synthesized calcium antagonist, TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) were studied following a single oral or intravenous administration of 14C-labelled compound. After oral administration, 14C-TC-81 was rapidly and well absorbed from the gastrointestinal tract. The peak plasma concentrations of radioactivity were observed at 0.5-1 h (rats) and 1-2 h (dogs) h after dosing. The elimination of the radioactivity in plasma was biphasic with a half-life of 3.8-5.2 h (a phase) and 42.9-56.2 h (beta phase) in the rats or 3.2 h (a phase) and 61.5 h (beta phase) in dogs. Maximum plasma concentrations of unchanged drug after oral administration of TC-81 to male rats at the doses of 0.5, 1.0, and 3.0 mg/kg were 1.7, 7.3 and 15.6 ng/ml, respectively. They were attained at 0.5 h after dosing in every dose examined. Plasma levels of unchanged drug declined with a half-life of 0.39-1.15 h. When TC-81 was orally administered to male dogs at the doses of 0.1, 0.2 and 0.5 mg/kg, plasma concentrations of unchanged drug reached the maximum level at 0.5 h after dosing and the values were 0.8, 3.3 and 9.6 ng/ml, respectively. They were eliminated with a half-life of 2.4-2.8 h. The absolute bioavailability of unchanged drug was estimated to be 2.6-7.0% (rats) and 5.3-15.5% (dogs) of the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Distribution to and elimination from tissues following a single or repeated administration of 14C-(+-)-3-(benzyl-methylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedica rbo xylate hydrochloride in rats.

A newly synthesized calcium antagonist, TC-81((+-)-3-benzylmethylamino)-2,2-dimethylpropyl methyl-4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) was administered to adult male rats, pregnant and lactating rats with a single oral dose or with repeated doses of 0.3 mg/kg for 2 weeks. The distribution to tissues, placental transfer and secretion of the radioactive drug into milk was studied using whole body autoradiography methods and quantitative determination of total radioactivity after autopsy. 14C-TC-81 was distributed rapidly but disproportionately to the tissues after single administration. The highest concentration of radioactivity was observed in the liver. The radioactivity in the various tissues declined slowly comparing to the plasma but at 96 h after dosing the radioactivity was detected only in the liver. The radioactivity penetrated the blood-placental barrier to a low extent after oral administration of 14C-TC-81 to pregnant rats. When 14C-TC-81 was administered to lactating rats, the radioactivity was secreted into the milk with the maximum concentration of radioactivity, 86% of the corresponding plasma concentration. Following 14-day oral treatments of male rats the equivalent concentration in the plasma was increased 1.5 fold as compared to the single treatment. In all tissues, the AUC0-24 h after 1, 7, and 14 days treatment were gradually increased, but these increases were almost the same as or even less than the rise observed in the plasma. After the last dosing, the radioactivity declined slowly with time in most of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Control of K+ channels by G proteins.

Heterotrimeric G3 proteins are though to couple receptors to ionic channels via cytoplasmic mediators such as cGMP in the case of retinal rods, cAMP in the case of olfactory cells, and the cAMP cascade in the case of cardiac myocytes. G protein-mediated second messenger effects on K+ channels are dealt with elsewhere in this series. Recently, membrane-delimited pathways have been uncovered and an hypothesis proposed in which the alpha subunits of G proteins directly couple receptors to ionic channels, particularly K+ channels. While direct coupling has not been proven, the membrane-delimited nature has been established for specific G proteins and their specific K+ channel effectors.

Animals↗

ELISA for F-TCF (human hepatocyte growth factor/hHGF)/fibroblast-derived tumor cytotoxic factor antigen employing monoclonal antibodies and its application to patients with liver diseases.

For determination of fibroblast-derived tumor cytotoxic factor, F-TCF (human hepatocyte growth factor/hHGF), sensitive two-step sandwich enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was developed. Microplates were coated with monoclonal antibody (P1C8) and bound F-TCF was quantitated with the second monoclonal antibody (P2D6) linked to peroxidase. The standard curve for F-TCF was found to be linear in the range of 0.16 to 10 ng of F-TCF per ml. The assay was specific for F-TCF but not for plasminogen. The assay can be used for determination of F-TCF antigen in both human plasma and serum. The variation of absorbance was little in duplicate samples. Recoveries of exogenous F-TCF added to serum or plasma samples showed theoretical values. F-TCF antigen levels in 21 healthy volunteers was found to be 0.56 +/- 0.43 ng/ml. In contrast, mean F-TCF levels in patients with liver diseases were all higher than those of healthy subjects. This ELISA system has the advantage of using a sensitive and reproducible set of monoclonal antibodies, and is a useful method for monitoring F-TCF levels in patients with liver diseases.

Animals↗

Preventing denervation atrophy of a grafted muscle.

Electrodes were implanted in the grafted muscles of rabbits to generate continuous stimulation for the purpose of preventing denervation atrophy. Denervation atrophy could be prevented, to some extent, in dissected muscles with vascular pedicles not occluded during the experiment. Denervation atrophy was found to be promoted, rather than prevented, in grafted muscles with occluded vascular pedicles. The crucial conditions are varying stimulation and the long duration of occlusion (90 min). Overly strong stimulation of muscle contraction appears to result in "fatigue" of grafted muscles in which blood circulation has been blocked for more than the 90 min used in the reported experiment. Further investigations are necessary of the conditions of stimulation and the point in time at which stimulation should commence after grafting.

Animals↗

The nature and origin of spontaneous noise in G protein-gated ion channels.

Arrival of agonist is generally thought to initiate the signal transduction process in G protein-receptor coupled systems. However, the muscarinic atrial K+ (K+[ACh]) channel opens spontaneously in the absence of applied agonist, giving a noisy appearance to the current records. We investigated the nature and origin of the noise by measuring single channel currents in cell-attached or excised, inside-out membrane patches. Guanosine triphosphate (GTP) produced identical single channel currents in a concentration- and Mg(2+)-dependent manner in the presence or absence of carbachol, but the requirements for GTP were greater in the absence of agonist. Hence the agonist-independent currents appeared to be produced by an endogenous G protein, Gk. This prediction was confirmed when an affinity-purified, sequence-specific Gi-3 alpha antibody or pertussis toxin (PTX) blocked the agonist-independent currents. Candidate endogenous agonists were ruled out by the lack of effect of their corresponding antagonists. Thus agonist-independent currents had the same nature as agonist-dependent K+[ACh] currents and seemed to originate in the same way. We have developed a hypothesis in which agonist-free, empty receptors prime Gk with GTP and Gk activates atrial K+ [ACh] channels producing basal currents or noise. Agonist-independent activation by G proteins of effectors including ion channels appears to be a common occurrence.

Adrenocorticotropic Hormone↗

Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.

Alkaloids↗