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Biomedical subjects

K Higashino

Publications and source records attributed to K Higashino.

At least 217 records · Page 12Linked to original sources

Serum pseudouridine as a biochemical marker in patients with hepatocellular carcinoma.

The concentration of serum pseudouridine, a degradation product of transfer ribonucleic acid, was determined by high-performance liquid chromatography in patients with hepatocellular carcinoma, liver cirrhosis, other benign hepatobiliary diseases, and healthy controls. The serum pseudouridine concentration in patients with hepatocellular carcinoma was significantly higher than that in patients with cirrhosis or the controls. Twenty-seven (51.9%) of 52 patients with hepatocellular carcinoma had serum pseudouridine concentrations higher than the mean value for healthy controls plus 2 SD. Fourteen of the 36 patients who had serum alpha-fetoprotein levels below 400 ng/ml, had elevated serum pseudouridine concentration. In total, 36 of the 52 patients (69.2%) could be detected by combination of these two markers. Two patients who had developed hepatocellular carcinoma during the course of cirrhosis and were continuously negative for alpha-fetoprotein, had higher levels of the pseudouridine concentration when hepatocellular carcinoma occurred. Furthermore, 4 of the 7 patients who had a very small cancer and were negative for alpha-fetoprotein, had elevated serum pseudouridine concentration. These results indicate that serum pseudouridine is a useful biochemical marker and that serum pseudouridine and alpha-fetoprotein in combination are considered to serve as complementary markers, for the diagnosis of hepatocellular carcinoma.

Aged↗

Direct determination of urinary pseudouridine by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method was developed for the determination of pseudouridine in urine. This method does not need pretreatment by boronate affinity gel. Therefore, it can be used in screening patients with malignant disease and for monitoring clinical response to chemotherapy with other tumor markers.

Biomarkers, Tumor↗

Both B151-T cell replacing factor 1 and IL-5 regulate Ig secretion and IL-2 receptor expression on a cloned B lymphoma line.

In the present study, we have demonstrated that both B151-T cell-replacing factor 1 and rIL-5 are responsible for the activity to partially induce CL-3 cells into IgM-synthesizing cells and also to synergize with IL-2 to augment IL-2R expression on and IgM synthesis in CL-3 cells. These actions of rIL-5 on a homogeneous cloned line (BCL1-CL-3 cells) allow us to identify and characterize the two alternated B cell developmental pathways. One is an IL-2-independent, IL-5-driven differentiation pathway without preceding up-regulated IL-2R expression, and the other is an IL-5 plus IL-2-dependent augmented differentiation pathway with preceding up-regulated IL-2R expression. We have also demonstrated the functional difference of two distinct B cell growth-promoting factors, B cell-stimulating factor 1 (rIL-4) and rIL-5. CL-3 cells are equally stimulated to grow by rIL-4 and rIL-5, whereas only rIL-5 can render CL-3 cells responsive to rIL-2, indicating that these two lymphokines affect B cells in a strikingly different manner.

Animals↗

Tumor markers in pleural effusion diagnosis.

In order to discriminate between malignant and benign effusions, the values of carcinoembryonic antigen (CEA), ferritin, beta2-microglobulin (BMG), acid-soluble glycoprotein (ASP), tissue polypeptide antigen (TPA), adenosine deaminase (ADA), and immunosuppressive acidic protein (IAP) were measured in the pleural fluid of 54 patients with lung cancer, 20 with malignancies other than lung cancer, 18 with tuberculous pleurisy, and 22 with benign diseases other than tuberculosis. CEA levels in malignant effusions were significantly higher than those in benign effusions. At a cutoff level of 5 ng/ml, 68% of the patients with lung cancer and 44% of the patients with other malignancies showed elevated pleural fluid CEA levels. In 13 lung cancer cases with negative pleural fluid cytology, nine cases had elevated pleural fluid CEA levels. The mean pleural fluid BMG level of patients with benign diseases was significantly higher than that of patients with malignant diseases, but there was a marked overlap between those with malignant and benign diseases. No significant differences were found in the pleural fluid ferritin, ASP, TPA, and IAP levels between malignant and benign conditions. ASP and IAP pleural fluid levels showed significant correlations with the pleural fluid C-reactive protein (CRP) concentrations suggesting that they also reflect inflammatory activity. The mean ADA activity in tuberculous effusion was significantly higher than that resulting from other causes of pleural effusion.

Adult↗

Renal excretion of purine bases. Effects of probenecid, benzbromarone and pyrazinamide.

Experiments were conducted which revealed the renal transport mechanism(s) of oxypurines by employing uricosuric agents and pyrazinamide. All specimens being drawn from healthy, normal subjects, the data showed that probenecid increased fractional uric acid, fractional hypoxanthine and fractional xanthine clearance, 3.97-, 1.52- and 2.31-fold, respectively, while benzbromarone increased fractional uric acid clearance 2.11-fold, decreased fractional xanthine clearance 0.48-fold and had no effect on fractional hypoxanthine clearance. In addition, pyrazinamide decreased both fractional uric acid clearance 0.35-fold and fractional xanthine clearance 0.44-fold but increased fractional hypoxanthine clearance 1.49-fold. These results suggest the possibility of differing renal transport mechanisms among the purine bases, uric acid, hypoxanthine and xanthine.

Adult↗

Urinary pseudouridine as a biochemical marker in the diagnosis and monitoring of primary hepatocellular carcinoma.

The urinary level of pseudouridine, primarily a degradation product of transfer ribonucleic acid (tRNA), was determined in 38 patients with primary hepatocellular carcinoma, 18 with liver cirrhosis, 12 with chronic hepatitis, nine with acute hepatitis, and 28 healthy subjects. The mean urinary pseudouridine concentration was significantly higher in the patients with hepatoma [38.2 +/- 12.8 (SD) nmol/mumol creatinine] than in those with liver cirrhosis (20.3 +/- 6.8), chronic hepatitis (24.4 +/- 8.2), and acute hepatitis (21.7 +/- 8.2), and in healthy subjects (23.8 +/- 4.9). Urinary pseudouridine level was elevated above the mean value plus 2 SD for the healthy subjects (33.6 nmol/mumol creatinine) in 71% of our hepatoma cases. Serum alpha-fetoprotein levels correlated poorly with urinary pseudouridine levels, thus, the combination assay for urinary pseudouridine and serum alpha-fetoprotein could detect 79% of the patients with hepatoma. Moreover, urinary pseudouridine level was reduced after effective transcatheter arterial embolization therapy.

Adult↗

[Treatment methods for scirrhous carcinoma of the stomach--with special reference to total gastrectomy and chemotherapy in early postoperative period].

The problems existing in surgical treatment methods for scirrhous carcinoma of the stomach include the following: (1) highly advanced cases are frequent, (2) remnants of carcinoma in the proximal line of resection is frequent, and (3) peritoneal dissemination is frequent. Investigations were made on 76 cases of scirrhous carcinoma of the stomach in the care of our department, and the treatment methods in these cases were as follows: 1) Lymph node dissection: Lymphadenectomy of over R2 is performed. 2) Operative methods: When the cancer lesion is in A, AM, M, or MA, and when the proximal line of resection can be made in the excess of 5 cm from the tumor margin, than a sub-total gastrectomy is performed. For cancer lesions in areas other than the above, and for cancer lesions in the above but when the OW cannot be made to measure over 5 cm, a total gastrectomy is performed. In cases in which the cancer invasion extends beyond EGJ and when non-curative resection factors are absent, then an abdomino-thoracic approach is adopted. 3) Chemotherapy: There was some efficacy among the curative resected cases. Since most of the cases result in peritoneal dissemination, chemotherapy is applied during operation and during the early postoperative period.

Adenocarcinoma, Scirrhous↗

A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies.

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.

Antibodies, Monoclonal↗

A newly discovered apolipoprotein B-containing high-density lipoprotein produced by human hepatoma cells.

Apolipoprotein B-containing high-density lipoprotein was detected in the high-density lipoprotein fraction of the concentrated conditioned medium of human hepatoma HuH-7 cells (Apo-B-containing HDLHuH-7). Electrophoretically, the Apo-B-containing HDLHuH-7 migrated more slowly and broadly than beta-lipoprotein on agarose gel. The Apo-B-containing HDLHuH-7 was not precipitated by heparin-Mn2+ treatment. High-performance gel filtration chromatography indicated that the peak of Apo-B-containing HDLHuH-7 was eluted faster than that of plasma LDL and electron microscopic analysis demonstrated that the particles of Apo-B-containing HDLHuH-7 ranged from 140 A to about 450 A, indicating the heterogeneity of Apo-B-containing HDLHuH-7. The protein/lipid ratio of HDLHuH-7 (1.35) is higher than that of plasma HDL3 (1.2). The lipids of HDLHuH-7 are composed of phospholipids (170 micrograms/mg protein), free cholesterol (410 micrograms/mg protein), cholesterol ester (20 micrograms/mg protein) and triacylglycerols (140 micrograms/mg protein). The results described above indicated that Apo-B-containing HDLHuH-7 was a novel lipoprotein discovered for the first time.

Apolipoproteins B↗

Serum pseudouridine as a biochemical marker in small cell lung cancer.

The serum level of pseudouridine, primarily a degradation product of tRNA, was determined by high-performance liquid chromatography in 24 patients with small cell lung cancer (SCLC), 13 patients with non-SCLC with advanced stages, 15 patients with pulmonary infectious diseases, and 18 healthy controls. The mean serum pseudouridine concentration was significantly higher in the patients with SCLC [4.75 +/- 1.76 (SD) nmol/ml] than that in the patients with pulmonary infectious diseases (3.39 +/- 1.38 nmol/ml) or in healthy controls (2.21 +/- 0.78 nmol/ml). The mean serum pseudouridine concentration in the patients with non-SCLC (4.07 +/- 0.95 nmol/ml) was significantly higher than that in healthy controls but not statistically different from that in the patients with pulmonary infectious diseases. The serum pseudouridine level was elevated above the mean value plus 2 SD for the healthy subjects (3.77 nmol/ml) in 66.7% of all patients with SCLC including 3 of 8 (37.5%) with limited disease and 13 of 16 (81.3%) with extensive disease, and 53.8% of the patients with non-SCLC. Serum carcinoembryonic antigen was elevated (greater than 5 ng/ml) in 29.2% and serum neuron-specific enolase (greater than 10 ng/ml) in 58.3% of the cases with SCLC. In the patients with SCLC followed up during chemotherapy, serum pseudouridine levels changed considerably parallel with the changes in the clinical response. These findings indicate that serum pseudouridine may be a useful biochemical marker in the patients with SCLC.

Adult↗

Demonstration of up-regulated IL 2 receptor expression on an in vitro cloned BCL1 subline.

We have established BCL1 CL-3 cells capable of responding to B15-TRF and interleukin 2 (IL 2). This clone has both high affinity and low affinity receptors for IL 2 (IL 2R), but IL 2 by itself did not stimulate either proliferation or immunoglobulin (Ig) secretion. B15-TRF, which possesses both growth and differentiation activity, causes an increase in size of CL-3 cells and renders CL-3 cells responsive to IL 2, including an increased expression of IL 2R (eight-fold to 10-fold) and the differentiation of CL-3 cells into Ig secretion (60 to 80% of cultured cells). CL-3 cells pretreated with B15-TRF for 12 hr become competent to respond to IL 2 by up-regulation of IL 2R within 12 hr. In contrast CL-3 cells pretreated with IL 2 for 12 hr required 24 hr B15-TRF stimulation to result in IL 2R up-regulation. Thus the ordered action of B15-TRF and IL 2 is the most effective operational pathway for the up-regulation of IL 2R. This IL 2-mediated IL 2R up-regulation and induction of Ig synthesis depends upon the concentration of IL 2 in the culture. Both responses seem to be caused by IL 2 molecules bound to high affinity IL 2R. However, the possibility of involvement of low affinity IL 2R can not be vigorously excluded. In fact the level of IL 2 required for a response is far higher than that needed for activated T cell proliferation. This cloned BCL1 subline promises to be a useful tool for studying the regulation and mechanisms of B cell responses.

Animals↗