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Biomedical subjects

N Ueki

Publications and source records attributed to N Ueki.

36 records · Page 2Linked to original sources

Elevated serum hepatocyte growth factor/scatter factor levels in inflammatory lung disease.

Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in tissue repair in liver and renal damage. The clinical significance of this growth factor in these diseases has also been reported. The lung is one of the major sources of HGF/SF; because of this, we investigated serum HGF/SF levels in 26 patients with inflammatory lung disease (15 with interstitial pneumonitis [IP], 11 with bacterial pneumonia [BP]) by enzyme-linked immunosorbent assay. As controls, we measured HGF/SF in the serum of 13 stable outpatients with chronic respiratory failure. All patients had no significant liver or renal dysfunction. Serum HGF/SF levels were significantly elevated in patients with IP (1.16 +/- 0.22 ng/ml) or BP (0.96 +/- 0.27 ng/ml) compared with those in the control subjects (0.29 +/- 0.03 ng/ml, both p < 0.01). Serum HGF/SF levels in 14 healthy subjects were also studied, and the results (0.30 +/- 0.02 ng/ml) were not remarkably different from those of the control subjects. There were no significant correlations between serum HGF/SF levels and C-reactive protein and lactate dehydrogenase. Serum HGF/SF levels in the surviving patients rapidly decreased with treatment, but they did not change in the patients who ultimately died. Our results demonstrate the clinical significance of serum HGF/SF level as a useful indicator of prognosis in inflammatory lung disease.

Adolescent↗

Aspartate aminotransferase-linked immunoglobulin complexes in serum of a patient with primary biliary cirrhosis.

A 51-year-old woman who had been treated for primary biliary cirrhosis (PBC) was admitted to our hospital for evaluation of unexplained, isolated, persistently increased aspartate aminotransferase (AST) activity. Results of laboratory tests on admission showed: AST 171 KU, alanine aminotransferase 28 KU, and anti-mitochondrial titer 1/1280. Results of hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab; C100-3) assays were negative. Histology of a liver biopsy specimen was compatible with a diagnosis of PBC (stage III of Scheuer's classification). The molecular size of serum AST was estimated to be more than 500,000 by high-performance size-exclusion liquid chromatography. Electrophoretic analysis showed an abnormal band of AST between supernatant AST (sAST) and mitochondrial AST (mAST), which band was characteristic of AST-immunoglobulin complexes (AST-Ig). Ouchterlony double-diffusion and immunoprecipitation tests identified the immunoglobulin component as IgM. The presence of AST-Ig appeared to be responsible for the elevated serum AST.

Aspartate Aminotransferases↗

Transforming growth factor-beta 1 (TGF-beta 1)- and beta 2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer.

We investigated the levels of TGF-beta in malignant pleural effusions (MPE) caused by malignant mesothelioma (MESO) or primary lung cancer. TGF-beta levels in MPE caused by MESO were 283.9 +/- 219.2 pm (mean +/- s.d.) and were three to six times higher than those due to primary lung cancers (P < 0.01 or P < 0.05). We also evaluated TGF-beta 1- and beta 2-like activities in MPE using specific polyclonal antibodies. Although TGF-beta 1-like activity could be detected in all cases, TGF-beta 2-like activities were detected in five of seven in MESO and in a few cases with primary lung cancer. These results demonstrate that the levels of total TGF-beta and TGF-beta 2-like activity may be clinically useful to differentiate MESO from primary lung cancer. Our data also suggest that TGF-beta may help further characterize the clinical features of MESO.

Carcinoma, Small Cell↗

Distribution of bent DNA structures in the fission yeast centromere.

To gain a clue as to the functional significance of DNA curvature, we experimentally characterized the distribution of bent DNA structures throughout the 35-kb cen1 sequence, one of the isolated functional centromeric DNA of the fission yeast, Schizosaccharomyces pombe. It was revealed that a relatively large central portion of cen1, covering a 2.2-kb DNA sequence, displays a remarkable DNA curvature.

Centromere↗

Potentiation of metastatic capacity by transforming growth factor-beta 1 gene transfection.

This study was designed to assess whether the excessive secretion of transforming growth factor-beta 1 (TGF-beta 1) by Chinese hamster ovary (CHO) cells transfected with TGF-beta 1 gene may be linked to the development of a metastatic phenotype. We observed large numbers of metastatic colonies in the lungs of nude mice inoculated with the transfected CHO cells. The tumors derived from these transfected cells demonstrated marked angiogenesis. We postulate that the overproduction of TGF-beta 1 by these tumors may participate in the metastatic progression following establishment of angiogenesis at the primary tumor site.

Animals↗

Local production and localization of transforming growth factor-beta in tuberculous pleurisy.

Transforming growth factor-beta (TGF-beta) is one of the cytokines which play an immunosuppressive role in an inflammatory process. To investigate the local production of TGF-beta, we evaluated the levels of TGF-beta in tuberculous pleural effusions (TBPE) and non-tuberculous benign pleural effusions (non-TBPE) by the growth inhibition assay with Mv1Lu mink lung epithelial cells. The mean level of TGF-beta in TBPE (46.1 +/- 31.5 pM; mean +/- s.d.) was higher than in non-TBPE (21.7 +/- 12.3 pM) (P < 0.05). Although the level of interferon-gamma (IFN-gamma) in TBPE measured by ELISA was significantly higher than in non-TBPE, there was no significant difference in the levels of tumour necrosis factor-alpha (TNF-alpha) measured by ELISA between these two groups. Moreover, to elucidate localization of TGF-beta in tuberculous pleurisy, immunohistochemical studies of pleura, using the rabbit polyclonal antibody Ab39 against latent TGF-beta 1 binding protein (LTBP) were performed. Results revealed that LTBP was localized in immature fibrotic areas where infiltrations of T lymphocytes and macrophages were absent. Importantly, the major sources of LTBP in these areas were thought to be mesothelial cells and fibroblasts. LTBP was not found in granulomas and mature fibrotic areas. Our data suggest that TGF-beta in tuberculous pleurisy may play important roles for regression of granulomatous inflammation and pleural fibrosis for tissue repair.

Animals↗

Excessive production of transforming growth-factor beta 1 can play an important role in the development of tumorigenesis by its action for angiogenesis: validity of neutralizing antibodies to block tumor growth.

Angiogenesis is an important part of tumor growth in vivo. We used the transfected Chinese hamster ovary (CHO) cells that overproduced recombinant transforming growth-factor beta 1 (TGF-beta 1) to examine the possible role of this factor in tumor growth and angiogenesis in a nude mouse model. The in-vitro proliferation of TGF-beta 1-transfected CHO cells was unaffected by the treatment of either recombinant TGF-beta 1 or an anti-TGF-beta 1 antibody. The TGF-beta 1-transfected cells grew more rapidly than the parental CHO cells when injected subcutaneously into nude mice. The tumors derived from the TGF-beta 1-transfected cells showed prominent tumor-associated angiogenesis, whereas the parental cells produced tumors without such angiogenesis. In addition, an anti-TGF-beta 1 neutralizing antibody was able to inhibit both growth and angiogenesis in the tumors derived from TGF-beta 1-transfected cells. These findings suggest that the overproduction of TGF-beta 1 by tumor cells can contribute to neovascularization and may help promote tumor development in vivo.

Animals↗

Primary characterization of curved DNA segments cloned from Streptomyces DNA with extremely high G/C-contents.

Until recently, it was assumed that any short DNA segment could be regarded as a straight rod. Many instances, however, have been reported in which the helical axis was curved. In this study, to gain a general insight into the structural features of sequence-directed DNA curvatures, we constructed a set of plasmids carrying curved DNA segments, which were randomly cloned from Streptomyces total DNA with extremely high G/C-contents. The results of primary characterization of these curved DNA segments are presented. Although the cloned DNA segments had high G/C-contents, in all cases, several homopolymeric [dA] and [dT] stretches were found to be clustered around the centres of the determined nucleotide sequences. Furthermore, the clustered [dA] and [dT] stretches were located nearly in phase with the DNA helical screw. One of the DNA segments characterized in this study appeared to be derived from the giant linear plasmid, SCP1, and another from the circular fertility plasmid, SCP2.

Base Composition↗

[A case of diphenylhydantoin-induced pneumonitis].

A 60-year-old man had been administered diphenylhydantoin (DPH) for prevention of convulsive seizures following clipping of an aneurysm of the middle cerebral artery. About one month after the commencement of DPH administration, he developed cough and low grade fever. He was treated with various antibiotics, but his condition increasingly worsened. Chest X-ray film revealed bilateral interstitial processes throughout the entire lung fields. Transbronchial lung biopsy was performed and the obtained specimen showed histological findings compatible with drug-induced pneumonitis. Administration of DPH was stopped immediately and 50 mg/day of prednisolone was started. The patient's condition rapidly improved, and the abnormal shadows on chest X-ray film gradually diminished. The lymphocyte stimulation test by DPH was positive with a stimulation index of 282%.

Humans↗

Caldesmon: a common actin-linked regulatory protein in the smooth muscle and nonmuscle contractile system.

Caldesmon was originally purified from gizzard smooth muscle as a major calmodulin-binding protein which also interacts with actin filaments. It has an alternative binding ability to either calmodulin or actin filaments depending upon the concentration of Ca2+ ("flip-flop binding"). Two forms of caldesmon (Mr's in the range of 120-150 kDa and 70-80 kDa) have been demonstrated in a wide variety of smooth muscles and nonmuscle cells. Immunohistochemical studies suggest that caldesmon is colocalized with actin filaments in vivo. Considering its abundance, the Ca2+-dependent flip-flop binding ability to either calmodulin or actin filaments, and its intracellular localization, caldesmon is expected to be involved in contractile events. Recent results from our laboratory have led to the conclusion that caldesmon regulates the smooth muscle and nonmuscle actin-myosin interaction and the smooth muscle actin-high Mr actin-binding protein (ABP or filamin) interactin in a flip-flop manner. It might function in cell motility by regulating the contractile system.

Animals↗

Expression of high and low molecular weight caldesmons during phenotypic modulation of smooth muscle cells.

We investigated the expression of two molecular weight forms of caldesmon in a wide range of tissues and cells. The distribution of high molecular weight caldesmon (h-caldesmon, Mr 120,000-150,000) was restricted to smooth muscles where it was found in large quantity. The low molecular weight protein (l-caldesmon, Mr 70,000-80,000) was widely distributed in nonmuscle tissues and cells. Therefore, the expression of h-caldesmon might be much more specific to smooth muscles. We then examined the expressional changes of two caldesmons during phenotypic modulation of smooth muscle cells (SMCs). In developing gizzards, the expression of caldesmons switched from the l- to the h-form. Contrarily, the expression turned from h- to l-caldesmon in association with dedifferentiation of aortic SMCs in primary culture. In agreement with these observations, the levels of those mRNAs that direct the synthesis of both caldesmons were apparently in proportion to the quantities of protein, as determined by use of an in vitro translation system. In addition, h-caldesmon in smooth muscle-like BC3H1 cells increased in its amount with a concomitant reduction of l-caldesmon following serum-depleted and contact-inhibited cytodifferentiation. These results suggest that the expressional changes of two caldesmons are closely correlated with the phenotypic modulation of SMCs.

Animals↗

Preovulatory secretion of progesterone, luteinizing hormone, and prolactin in 4-day and 5-day cycling rats.

Timing of ovulation and changes in plasma progesterone, luteinizing hormone (LH), and prolactin (PRL) during periovulatory stages were determined in Holtzman rats exhibiting regular 4- or 5-day cycles under a daily artificial illumination from 0500 to 1900 h. The 5-day cycling rats ovulated between 0130 and 0930 h on estrus, whereas some of the 4-day cycling animals ovulated as early as about 0130 h and others as late as 1130 h on estrus. Onset time of preovulatory LH and progesterone surges was about 1500 h on proestrus in both the 4- and the 5-day cycling rats. Peak levels of plasma LH and progesterone were measured at 1700 to 1900 h on proestrus, while the first rises and peak values of plasma PRL were evident a few hours earlier than those of plasma LH in the rats with two cycle lengths. Plasma LH levels at 1900 h on proestrus as well as plasma progesterone levels at 1600 and 2300 h on proestrus and at 0130 and 0330 h on estrus were significantly lower in the 5-day cycling rats than in the 4-day cycling animals (p less than 0.05). In contrast, PRL levels from 1500 through 2300 h on proestrus remained consistently higher in 5-day cycling rats than in 4-day cycling rats, and significant differences in PRL levels between these rats were apparent at 1500, 1600, and 2100 h (p less than 0.05-0.01). Thus, these results demonstrate that the 5-day cycling rats exhibit the attenuated magnitude of LH surge accompanied by the augmented preovulatory PRL release, and that plasma progesterone levels reflect the magnitude of LH surge. A tentative working hypothesis concerning the etiology of the 5-day cycle has been proposed.

Animals↗

[Reversible asynergy in acute transmural myocardial infarction: evaluations of patients with inferior infarction].

To evaluate the significance of chronological changes in wall motion abnormalities, echocardiography was performed for 46 patients with acute transmural inferior myocardial infarction without previous infarction or complications. Asynergy was analyzed by two-dimensional echocardiography (2-D Echo) on the third day (acute stage) and the 28th day (convalescent stage) after the onset of infarction. Asynergy was quantitatively estimated by dividing the left ventricle into 17 segments. The degree of asynergy was graded on a four-point scale as dyskinesis = 3, akinesis = 2, hypokinesis = 1, and normokinesis = 0. The total wall motion score (TWMS) was calculated on the both days. Improvement of asynergy was observed in 39 cases (84.8%). Among them, both the extent and degree of asynergy were improved in 17 cases (37.0%). In 10 cases (21.7%) the extent of asynergy was reduced. In the remaining 12 cases (26.1%), only the degree of asynergy was decreased. Concerning the relationship between the degree of asynergy on the 3rd day and the subsequent alteration of asynergy on the 28th day, two of four dyskinetic segments still had dyskinesis, and the other two reverted to akinesis. Among 156 akinetic segments, 80 did not change, but 58 reverted to hypokinesis and 18, to normokinesis. Among 82 hypokinetic segments, 48 did not change, but 34 became normal. The relationship between severity of asynergy on the third day indicated by the total wall motion score (TWMS 3rd) and the improvement in the score on the 28th day (TWMS 28th) was investigated in three patient groups: group-A (n = 19) showed TWMS 3rd greater than 9; group-B (n = 22), 9 greater than or equal to TWMS 3rd greater than or equal to 3; group-C (n = 5), TWMS 3rd less than 3. The frequency of "no improvement" was slightly higher in the group-C (62.5%) than in the group-A (52.1%) and in the group-B (56.4%). On comparison, improvement of asynergy was observed in the group-A in 47.9% and in the group-B in 43.6%, but the rate of resolution of asynergy was higher in group-B (53.6%) than in the group-A (40.3%). In the group-C, there was no case of significant coronary artery stenosis greater than 75% in diameter and sigma CPK was smaller than in the other two groups (p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Immediate prognosis in acute myocardial infarction: serial changes in immediate mortality rate and cause of death.

In order to evaluate the effect of coronary care on the immediate mortality rate of acute myocardial infarction and to clarify the problems in coronary care, we attempted to investigate the immediate mortality rate and causes of deaths in 492 patients with acute myocardial infarction who had admitted to the hospital within 24 hours after the onset of infarct from January, 1972 to December, 1981. Three hundred and seventy-nine were men and 113 were women, and their mean age was 61.8 years ranging from 28 to 91 years. One hundred and twenty-seven patients had a previous history of myocardial infarction and 365 patients had none. One hundred and ninety patients of these 365 patients without a previous infarction had anterior infarction, 152 patients inferior infarction and 23 patients subendocardial infarction. All patients were subdivided into four stages according to the time of the onset of infarct: Stage 1 (29 patients); 1972-1975, Stage 2 (101 patients); 1976-1977, Stage 3 (148 patients); 1978-1979 and Stage 4 (214 patients); 1980-1981. No significant differences in age, sex and infarct site among the four periods were found. Time interval between the onset of infarct and admission shortened serially and the ratio of reinfarction to initial infarction increased. Immediate mortality rate (within four weeks after the onset of infarct) was 20.5% in all patients. Immediate mortality rate in Stage 1 was 24.1%, 26.7% in Stage 2, 23.0% in Stage 3 and 15.4% in Stage 4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗