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T Kokubu

Publications and source records attributed to T Kokubu.

280 records · Page 16Linked to original sources

Serum apolipoprotein A-I, A-II and B levels and their discriminative values in relatives of patients with coronary artery disease.

Serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I, A-II and B concentrations were measured in 109 first-degree relatives of patients with angiographically defined coronary artery disease (CAD). Age- and sex-matched healthy factory employees were chosen as a control group. Male relatives of the CAD patients had significantly higher serum triglyceride and apoB levels, and significantly lower serum HDL-C and apoA-I levels than the controls. Female relatives of the CAD patients also showed similar differences in serum HDL-C, apoA-I and apoB levels. Discriminant analysis indicated that apolipoproteins were better discriminators than lipids in both patients with CAD and their relatives. In univariate analysis, the best discriminator was apoB between male relatives and the controls, and apoA-I between female relatives and the controls. The percentage of exact classification achieved using three variables (serum cholesterol, triglyceride and HDL-C) was 74% in male relatives and 70% in female relatives. By adding variables of apoA-I and apoB, the percentage of correctly classified subjects was increased to 82% and 80%, respectively. These results indicate that serum apolipoprotein abnormalities are prevalent in relatives of the CAD patients. These abnormalities may explain the familial aggregation of CAD.

Adult↗

Production of angiotensin-converting enzyme in rat epididymis.

Unilateral ductuli efferentia testis of immature rat were severed in order to interrupt the continuity between testis and epididymis and angiotensin-converting enzyme (ACE) activities were measured 5 weeks after the operation. The epididymal ACE on the operated side increased to nearly the same level as that on the contralateral side, but the testicular ACE activity on the operated side was markedly lower than that on the contralateral side. On immunofluorescent study using antiserum against purified rat lung ACE, ACE could be found in the tubular epithelial cells of the operated epididymis. These results suggest that epididymis itself synthesize ACE without connection to testis.

Animals↗

Role of glandular kallikrein in the activation process of human plasma inactive renin.

Completely inactive renin was isolated from normal human plasma by DEAE-Sepharose column chromatography and Blue-Sepharose column chromatography. This inactive renin had a molecular weight of 54,000 daltons as determined by gel filtration on Ultrogel AcA 44. When the inactive renin was activated by trypsin, its molecular weight decreased to 48,000 daltons. The trypsin-activated renin differed from a native form of active renin in plasma with respect to molecular weight (active renin, 43,000), pI value (active renin, 5.20; trypsin-activated renin, 5.06), km value (active renin, 60 nmoles/liter; trypsin-activated renin, 89 nmoles/liter), Ki value for pepstatin A (active renin, 2.6 mumoles/liter; trypsin-activated renin 5.0 mumoles/liter) and pH profile for angiotensin formation. Glandular kallikrein (human urinary or pig pancreatic) did not activate the inactive renin. When the trypsin-activated renin was treated with glandular kallikrein, its activity was unchanged, but its molecular and kinetic properties except pI value (trypsin-activated kallikrein-treated renin, 4.82) coincided with those of a native form of active renin in plasma. These results indicate that glandular kallikrein does not directly activate inactive renin but participates in the activation process of inactive renin. The results also suggest that inactive renin in human plasma is a renin precursor.

Chromatography↗

Existence of prokallikrein in the kidney. Its biochemical properties compared to three active glandular kallikreins from the kidney, serum, and urine of the rat.

Prokallikrein in the kidney was partially purified with immunoaffinity and DEAE Sephadex A-50 column chromatographies, and its biochemical properties were studied in comparison to three active glandular kallikreins purified from kidney, serum, and urine of the rat. The properties of the enzyme obtained by trypsin activation of prokallikrein were identical with those of active glandular kallikreins from the kidney, serum, and urine of the rat. Apparent molecular weights of prokallikrein, trypsin-activated kallikrein, active renal kallikrein, and glandular kallikrein in rat serum were 38,000 and of active urinary kallikrein, 37,000. Prokallikrein fraction was activated only by trypsin, but not by acidification, pepsin, and rat urinary esterase A treatments. Renal kallikrein, purified in the presence of soybean trypsin inhibitor (SBTI), contained 85% prokallikrein, but the enzymic fraction, purified in the absence of SBTI, contained 23% prokallikrein. Prokallikrein contents of urinary kallikrein and glandular kallikrein in rat serum were 16% and 20% respectively. These results suggest that prokallikrein is produced in the kidney and activated easily by a trypsin-like enzyme. Since rat serum contains active glandular kallikrein, kallikrein in the kidney may be secreted not only into the urine, but also into the blood.

Animals↗

Highly potent and specific inhibitors of human renin.

Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.

Angiotensin I↗

Discrimination of tuberculous from carcinomatous pleural effusion by biochemical markers: adenosine deaminase, lysozyme, fibronectin and carcinoembryonic antigen.

We measured adenosine deaminase (ADA), lysozyme, fibronectin and carcinoembryonic antigen (CEA) in the pleural fluid of tuberculous and carcinomatous pleural effusion in order to discriminate these two groups. Tuberculous pleural effusion had significantly higher levels of ADA and lysozyme than did carcinomatous effusion. When ADA activity of more than 33 IU/l is considered, diagnostic tests of tuberculous effusions showed a sensitivity of 100%, specificity of 95% and accuracy of 96%. A pleural fluid/serum ADA ratio (pl-ADA/s-ADA) above 1.1 was found in 100% of tuberculous and in 53% of carcinomatous effusions (sensitivity 100%, specificity 47%, diagnostic accuracy 70%). A lysozyme level above 12 micrograms/ml, selected as the discriminating limit, was found in 100% of tuberculous and in 17% of carcinomatous effusions (sensitivity 100%, specificity 83%, diagnostic accuracy 88%). Pleural fluid/serum lysozyme ratio (PL/SL) was also valuable in the discrimination of these two groups. When the cut-off level of 1.2 was considered, diagnostic tests of tuberculous effusions showed a sensitivity of 100%, specificity of 88% and accuracy of 93%, respectively. The mean fibronectin concentration in pleural fluid with tuberculous effusion was significantly higher than that in carcinomatous effusion, but there was a marked overlap between these two groups. On the other hand, CEA was significantly higher in carcinomatous effusions than in tuberculous effusions. At a cut-off level of 5 ng/ml, 53% of patients with carcinomatous effusion showed elevated pleural fluid CEA levels, while none of the tuberculous effusion did (sensitivity 53%, specificity 100%, diagnostic accuracy 65%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗

Total lipodystrophy with heart failure and renal failure: report of a case.

A 38-year-old female was admitted to our hospital because of dyspnea. The diagnosis of total lipodystrophy was made by following findings: (1) gaunt appearance; (2) insulin-resistant diabetes mellitus; (3) hyperlipidemia; (4) fatty liver. Chest X-ray demonstrated cardiomegaly, pulmonary edema and pleural effusion. Echocardiogram was characterized by left ventricular hypertrophy with asymmetrical septal hypertrophy and left ventricular dysfunction. Renal biopsy revealed focal glomerulosclerosis. We reported a patient with total lipodystrophy combined with heart failure and renal failure, which have been rarely associated with the disease.

Adult↗

A case of isolated thyrotropin deficiency with Cushing's syndrome.

The first case of isolated thyrotropin (TSH) deficiency with Cushing's syndrome was reported. A 46-year-old female was admitted to our hospital because of fatigability, puffy eye-lids, leg edema and petechia. She was treated with thyroid hormone. A low free triiodothyronine continued. Serum TSH was undetectable and serum thyrotropin releasing hormone (TRH) was elevated. No response of serum TSH and normal response of serum prolactin after administration of exogenous TRH suggested the abnormalities of anterior pituitary gland. The secretion of growth hormone and gonadotropin were intact, but the secretion of adrenocorticotropic hormone (ACTH) was impaired. A high level of serum cortisol, no response of serum ACTH by metyrapone test and a tumor mass of abdomen detected by computed tomography led to the diagnosis of Cushing's syndrome. Histological examination of the tumor revealed adrenal adenoma. Twenty two months after the surgery, serum ACTH level was normalized, but the secretion of serum TSH to exogenous TRH was still absent. The results indicated that hypothyroidism in our patient was due to isolated TSH deficiency.

Adenoma↗

Soluble interleukin-2 receptors in pulmonary tuberculosis.

Serum levels of soluble interleukin-2 receptor (IL-2R) were measured in patients with pulmonary tuberculosis, nontuberculous pulmonary diseases (bacterial pneumonia, lower respiratory tract infection, lung cancer), and in normal volunteers. Patients with tuberculosis had increased levels of soluble IL-2R compared to normal controls. Abnormally elevated levels were also shown in patients with nontuberculous pulmonary diseases, suggesting that elevations of soluble IL-2R are not specific for tuberculosis. In patients with tuberculosis, elevated levels of soluble IL-2R were steadily decreased to normal levels during successful treatment. Additionally, soluble IL-2R levels in tuberculosis were closely correlated with adenosine deaminase levels. Thus, it seems possible that measurements of soluble IL-2R may be beneficial in the diagnosis and the management of patients with tuberculosis. Furthermore, we demonstrated that elevated levels of soluble IL-2R in tuberculosis appear to be a consequence of cellular activation of mononuclear cells and not to be the result of cell death with subsequent IL-2R release.

Adenosine Deaminase↗

[Malignant fibrous histiocytoma of the chest wall in a nonagenarian].

We report a case of malignant fibrous histiocytoma of the chest wall observed in a 94-year-old woman. She noticed appetite loss and general edema a week before admission. The patient was diagnosed as having congestive heart failure due to valvular heart disease on the basis of echocardiographic findings and became symptom-free by treatment with vasodilators and diuretics. However, chest roentgenogram disclosed a extrapleural mass in the left mid-lateral chest. About 2 months after admission, she experienced left lateral chest pain for the first time. The chest CT scan revealed a 5 x 5 x 2 cm mass, adjacent to the lateral-posterior chest wall and projecting into the thoracic cavity and rib osteolysis. Gallium-67 citrate scintigram showed abnormal isotope accumulation in the left middle chest. Biopsy was not done. The therapeutic approach was mainly pain relief, and no tumor resection, chemotherapy, or radiotherapy was performed. The mass increased in size, and increasingly extended into the thoracic cavity on follow-up CT scans. Furthermore, marked invasion of the tumor to subcutis and subscapula was found. She died of cachexia and respiratory failure 34 weeks after admission. Histologic examination revealed malignant fibrous histiocytoma.

Aged↗