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Biomedical subjects

K Okajima

Publications and source records attributed to K Okajima.

At least 199 records · Page 11Linked to original sources

Dynamic aspects of thrombus formation in mutant analbuminemic rats.

To elucidate the mechanism for thrombus formation in hypoalbuminemic and hyperlipidemic subjects, the experimental thrombus formation was analyzed in Nagase analbuminemic rats (NAR). The mutant rat reveals similar biochemical findings to those of NS, such as hyperlipidemia. When thrombus was induced in a small branch of the mesenteric artery by inserting a glass micropipette, thrombus formation was observed within 4 min in NAR and Sprague-Dawley rat (SDR). In SDR, the thrombus gradually grew up in size and detached from the inserted glass micropipette within 4 min after its formation. In contrast, the thrombus formed in NAR did not dissociate from the micropipette until 10-13 min after its formation. The maximum size of the thrombus formed in NAR was about 4 times larger than that in SDR. In the presence of fibrin, the plasma samples from NAR inhibited the activity of tissue-plasminogen activator (t-PA) 1.7 times more potently than did SDR plasma. Plasma gamma 2-plasmin inhibitor activity was significantly higher than that in SDR. Albumin significantly enhanced the t-PA-catalyzed activation of plasminogen, suggesting that the serum albumin might contribute, at least in part, to the plasma fibrinolytic activity. Thus, the higher thrombogenic potential in NAR than in SDR might be due to the reduced thrombolytic activity in NAR.

Animals↗

Antithrombin III Kumamoto: identification of a point mutation and genotype analysis of the family.

We previously reported a variant antithrombin III (AT III Kumamoto) associated with a 31-year-old female who suffered from recurrent thrombotic episodes. To define the molecular basis for the variant AT III, we used a combination of genomic amplification followed by cloning, sequencing, and hybridization with allele-specific oligonucleotide probes. We obtained evidence for a cytosine to thymine transition in exon 2 (codon 47) of the AT III gene in the proband. This mutation converts arginine 47 to cysteine. Oligonucleotide hybridization procedures were used for confirmation of the mutation and for genotype analysis of the family members.

Adult↗

[Prognostic significance of nuclear DNA content in breast cancer].

The relationship between nuclear DNA content determined by cytofluorometry in the primary focus of breast cancer and the survival rate was analyzed to clarify the prognostic significance of nuclear DNA content in breast cancer. The relationships of the ploidy pattern and the frequency of polyploid cells (4c or above) with the survival rate were studied in patients who underwent extended radical mastectomy and were comparable in the clinical stage and other prognostic factors. The survival rate was significantly lower in those of the non-diploid type showing no prominent peak at 2c or those in whom the frequency of polyploid cells was more than 30% than in those of the diploid type with a prominent peak at 2c or those showing few polyploid cells, even when the disease stage (Stage II by TNM classification and stage III by Tnm classification), histological lymph node metastasis (n (+), n1 beta), and histological type (papillotubular carcinoma, scirrhous carcinoma) were identical. From these findings, nuclear DNA content is considered to be a parameter of the malignancy of breast cancer and to have clinical significance as an important prognostic factor.

Breast Neoplasms↗

Sensitive enzyme immunoassay for human aldolase A.

A sensitive sandwich-type enzyme immunoassay for the aldolase isozyme, A4, was developed using purified antibodies specific to the A subunit of aldolase. The antibodies were raised in sheep being immunized with purified aldolase A4 and then purified by immunoaffinity chromatography on a column of aldolase A4-coupled Sepharose. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody F(ab')2 fragments labeled with beta-D-galactosidase from Escherichia coli. The assay was sensitive enough to detect 10 pg/tube of aldolase A4. The assay was specific to the A subunit of aldolase (aldolase A). It cross-reacted about 40% to aldolase A3C, 7% to A2C2 and 0.3% to AC3, but not cross-reacted with C4 nor B4. Coefficients of variation in intra- and inter-assay were less than 16%. Serum aldolase A levels were determined in healthy adults, which were about 200 ng/ml. The distribution and concentrations of immunoreactive aldolase A in various human tissues were also determined. High concentrations of aldolase A were found in skeletal muscle, heart muscle, cerebrum and lymphatic tissue.

Fructose-Bisphosphate Aldolase↗

Effect of protein C and activated protein C on coagulation and fibrinolysis in normal human subjects.

Although protein C (PC) and activated protein C (APC) have been postulated to be useful for treating patients with thrombosis, their critical effect remains to be studied in human subjects. To examine whether purified PC or APC are useful for treating patients with thrombosis without showing any adverse effect, we studied effects on coagulation and fibrinolysis in normal human subjects. When highly purified human PC was administered intravenously to healthy subjects, plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously administered APC decreased with a half-life of 23 min as measured by prolongation of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the plasma half-life of APC when it was measured immunologically. These findings suggested that a significant fraction of the administered APC was rapidly inhibited by plasma inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting factor VIII (F-VIII) decreased transiently as measured by clotting assay. However, when determined by a chromogenic assay method in which 120-fold diluted plasma samples were used, plasma levels of F-VIII remained unchanged. Plasma levels of F-V did not decrease after APC administration. These findings suggested that prolongation of APTT and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator inhibitor in normal subject was not affected by administration of APC. Thus, PC or APC seems to function selectively at the site of thrombin-formation without lowering plasma levels of coagulation factors.

Adult↗

Sensitive enzyme immunoassay for human Cu/Zn superoxide dismutase.

A highly sensitive enzyme immunoassay method for measurement of human Cu/Zn superoxide dismutase (SOD) was established. Antisera were raised in rabbits by injecting SOD purified from human erythrocytes, and antibodies to SOD were purified by the use of Cu/Zn SOD-coupled Sepharose 4B. The assay system consisted of polystyrene balls with immobilized monospecific antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive, and the minimum detection limit was 3 pg or 0.1 fmol/assay tube. Serum Cu/Zn SOD levels of normal healthy subjects (36.3 +/- 15.6, n = 120, 16-64 years old) were not related to age and sex. It was confirmed that Cu/Zn SOD levels in erythrocytes and blood plasma were significantly enhanced in patients with Down syndrome. Immunoreactive Cu/Zn SOD was detectable in all the tissues examined and was present at high concentrations in brain, adrenal gland, liver, heart and kidney.

Adult↗

Treatment of patients with disseminated intravascular coagulation by protein C.

The therapeutic effect of highly purified protein C (PC) or activated protein C (APC) on three patients with disseminated intravascular coagulation (DIC) was tested. In two out of three cases, although therapeutic dose of heparin was not effective, PC or APC administration significantly improved the hypercoagulable state. In one case with acute leukemia who developed DIC with the severe gastrointestinal bleeding, APC corrected the hypercoagulable state without aggravating bleeding. These findings suggested that PC and/or APC might be effective in correcting hypercoagulable state without any adverse effect.

Anticoagulants↗

Endoscopic laser coagulation through an optical laser balloon.

An endoscope was equipped with a saline-filled latex rubber balloon at its tip to displace contaminating blood, bile, or gastric contents during operative portoscopy, biliary endoscopy, or upper gastrointestinal endoscopy. A fiber with its tip inside the balloon transmitted energy from an Nd:YAG laser for coagulation of tumors in one bile duct cancer, in six portal vein growths from primary liver cancers, and in a superficially growing stomach cancer. The balloon increased the precision of irradiation by making lesions easier to identify through displacement of bile or blood and by keeping the fiber tip at a fixed position relative to the lesion. The technique, basic experimental studies, and clinical experiences are reported.

Animals↗

Perifocal brain oedema in experimental brain abscess in rats.

An experimental cerebral abscess model in which staphylococcus aureus was inoculated into the brain parenchyma of rats was evaluated for perifocal brain oedema. Blood-brain barrier permeability was studied using various kinds of tracers; sodium fluorescein as a small molecule and Evans blue and HRP as macromolecular tracers. Brain abscess with clear delineation of fibrous capsule formation were found in all animals. Extravasation of tracers was demonstrated in the capsule (Evans blue), extracellular space (HRP) and white matter (sodium fluorescein). There were two types of oedema formation, so called vasogenic oedema and cytotoxic brain oedema.

Animals↗

Enhancement of S-100 beta protein in blood of patients with Down's syndrome.

The human gene encoding the beta subunit of S-100 protein (S-100 beta) was mapped on chromosome 21. In order to confirm the expression of gene-dosage effect of S-100 beta in patients with Down's syndrome (DS), concentrations of immunoreactive S-100 alpha and S-100 beta proteins were determined in the blood plasma and lymphocytes fraction of the patients and control subjects. Cu/Zn-superoxide dismutase (SOD), a protein that is known to show the gene-dosage effect on the trisomy of chromosome 21, also was immunoassayed in the same blood samples as control proteins. In blood plasma, S-100 beta protein as well as Cu/Zn SOD was enhanced (P less than 0.001) in the patients (160 +/- 70 pg S-100 beta/ml and 87 +/- 83 ng SOD/ml, N = 44) as compared with control individuals (76 +/- 25 pg/ml, and 18 +/- 11 ng/ml, respectively, N = 28). However, concentrations of S-100 alpha in blood plasma of DS patients were similar to those of normal subjects. Concentrations of S-100 beta in lymphocyte fractions of DS patients (24.7 +/- 10.9 ng/mg protein) were also higher (P less than 0.001) than those of control subjects (10.1 +/- 5.8 ng/mg protein). These results indicate that gene-dosage effect of S-100 beta levels are expressed in DS patients.

Adolescent↗

CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 2. Clinical application.

We have performed radiotherapy treatment planning (RTP) with a new system called CT simulator in 72 patients. With the system, RTP is performed with the patient lying on the CT couch within a short period of time. All the CT images scanned were immediately transported to the multi-image monitors and to the treatment planning device. Radiotherapy treatment planning could be performed not only at the beam center but also at any CT slice. Using a laser-beam field projector, field outlines were drawn over the patient's skin. In clinical use, the system was useful for cases in which a target lies adjacent to dose limiting organs, cases with a complicated target shape, cases with complicated dose distribution curves, and cases treated with tangential fields. This system enables us to make optimum use of CT information and to make accurate 3-dimensional treatment planning programs.

Computer Simulation↗

Review of pancreatic cancer.

In 83 cases of pancreatic cancer (25 resected and 58 non-resected cases) which underwent laparotomy in the Department of General and Gastroenterological Surgery, Osaka Medical College Hospital over the past 11 years, we analyzed symptoms at diagnosis, duration of illness, tumor markers, surgical procedures, and long-term results. In many cases, jaundice was the premonitory symptom of pancreatic cancer. There was no relationship between duration of illness and tumor resectability. In analysis of tumor markers, abnormal CA19-9 levels were noted in 71% of resected cases and 89% of non-resected cases, and abnormal CEA, elastase and amylase levels were found in 38, 46 and 47% of resected cases and 76, 58 and 27% of non-resected cases, respectively. Operative mortality was higher for non-resected cases (22%) than that for resected cases (8%). Long-term results were significantly better in resected cases than non-resected cases. However, 1-, 2- and 3-year survival rates after macroscopic curative resection were 45, 19 and 9%, respectively. Prognosis of patients after absolute non-curative resection was poor, indicating no efficacy of the resection. To improve these very poor surgical results for pancreatic cancer, the early cancer detection and multi-disciplinary therapy seem to be necessary.

Antigens, Tumor-Associated, Carbohydrate↗

[Studies on the role of leukocytes in the activation of intravascular coagulation in septicemia].

To elucidate the role of leukocytes in intravascular clotting in patients with septicemia, plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty out of 33 patients revealed a marked leukopenia (leukocyte count was less than 1,000/microliters) due to suppression of hematopoiesis by the administration of chemotherapeutic agents for the treatment of hematological malignancies. Thirteen out of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients with leukopenia were significantly lower than those in patients whose leukocyte counts were higher than 1,000/microliters. Plasma fibrinogen levels were significantly lower in patients whose leukocyte counts were higher than 1,000/microliters than those in patients with leukopenia. Plasma TAT levels were found to correlate well with the number of leukocytes in these patients with the correlation coefficient (R) of 0.67 (p less than 0.001). Significantly high positive correlation was observed between plasma TAT levels and the number of monocytes (R = 0.92, p less than 0.001). Significant correlation was also observed between plasma SFMC levels and the number of monocytes (R = 0.72, p less than 0.001). No significant correlation was found between the number of platelets and TAT levels. These findings suggest that leukocytes (especially monocytes) play a critical role in activating intravascular coagulation in septicemic patients.

Antithrombin III↗

[Plasma concentration of polymorphonuclear leukocyte elastase-alpha 1-proteinase inhibitor complex in patients with gastric ulcer].

To test the possible participation of activated leukocytes in the pathogenesis of gastric ulcer, plasma levels of polymorphonuclear leukocyte-elastase-alpha 1-proteinase inhibitor complex (PMN-EC), a discerning indicator for the activation of leukocytes, were determined in patients with gastric ulcer. Plasma levels of PMN-EC in patients with gastric ulcer (185.2 +/- 21.6 micrograms/l, mean +/- S.E.M.) were significantly higher than those in normal healthy subjects (67.6 +/- 4.4 micrograms/l, p less than 0.01). On the other hand, plasma levels of C-reactive protein and sialic acid increased in only 17.8% and 7.1% of patients with gastric ulcer, respectively. No significant correlation was observed between PMN-EC and the plasma levels of CRP or sialic acid. Plasma levels of PMN-EC decreased with the healing of the ulcerative lesion as judged by gastro-endoscopic observation. These findings suggested that activation of leukocytes might deeply be correlated with the pathologic mechanism of gastric ulceration and the measurement of PMN-EC might be useful for monitoring the patients with gastric ulcer.

Humans↗

[A case of giant osteoma in the occipital bone].

A 51-year-old female patient, admitted with a chief complaint of dizziness, had bulging of the occipital area, which had started insidiously. On admission, a bony hard swelling with a smooth surface was noted in the left occipital region, extending over the midline of the skull. Plain X ray films revealed a uniform shadow of an osteoid mass inside the occipital bone. A tomogram indicated that the mass originated in the diploë or outer table of the skull, although there was no evidence of destruction of the inner table. CT scan revealed mixed density mass with high density of bone and an irregularly shaped low density area. In the T1-weighted images of MRI, the entire mass showed a low intensity, while in the T2-weighted image the mass showed 3 areas with different intensities. Bone scintigraphy was performed with 99mTc-MDP and revealed an image of accumulation in the mass. Carotid and vertebral angiograms were negative for evidence of feeding arteries to the mass, for tumor stain, and for occlusion of either sigmoid sinus or transverse sinus. The mass was diagnosed as a giant osteoma, and was totally removed. The excised tumor measured 10 x 9 x 5 cm, and inspection at operation revealed it to be composed of a fragile osteoid portion and a comparatively soft connective tissue portion. The histological diagnosis of the mass was that it was a spongy osteoma including a comparatively large amount of connective tissue. The postoperative recovery of the patient was satisfactory and her dizziness disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Homozygous variant of antithrombin III that lacks affinity for heparin, AT III Kumamoto.

Abnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F.Xa), while both progressive antithrombin and antifactor Xa activities were normal. The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelectrophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose revealed that the propositus' AT III did not bind to heparin. When heparin cofactor II (HC II) was removed from propositus' plasma, heparin cofactor activity of AT III was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity found in the presence of thrombin. The patient's parents and three of her brothers demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50% of normal levels in the presence of both thrombin and F.Xa. These findings indicate that the propositus' AT III lacks affinity for heparin and the mode of its inheritance seems to be autosomal dominant and, hence, the propositus would be a homozygote. For this variant, the name of AT III Kumamoto is proposed.

Adult↗