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Biomedical subjects

N Kubo

Publications and source records attributed to N Kubo.

At least 55 records · Page 3Linked to original sources
PubMed2000

Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma.

We investigated whether the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was consistent with the proposed roles of these proteins in promoting metastasis in colorectal cancer. The expression of MT1-MMP was significantly more frequent in deeply invasive carcinomas (P = 0.007) and in cases of vascular invasion (P = 0.02). The frequency of detection of MMP-2 in the stroma was much greater in vascular invasion-positive cases (42%) than in negative cases (20%; P = 0.02). The rate of detection of TIMP-2 in tumour cell cytoplasm increased with the depth of invasion (P = 0.03). TIMP-2 in the stroma was found more frequently in tumours with lymphatic invasion and lymph node metastasis (P < 0.05). Significant correlations were found between detection of MT1-MMP and MMP-2 in tumour cell cytoplasm (P < 0.05), of MT1-MMP and TIMP-2 in tumour cell cytoplasm (P < 0.01), and of MMP-2 and TIMP-2 in tumour cell cytoplasm (P < 0.01). Immunohistochemical detection of MT1-MMP and TIMP-2 might be useful for monitoring infiltration in colorectal carcinoma but is not correlated with distant metastases.

Adenocarcinoma↗
PubMed2000

Selective thermocoagulation of unresectable pancreatic cancers by using radiofrequency capacitive heating.

Recent investigations indicated that hyperthermia has antitumor effects. Several interstitial hyperthermic techniques were developed, and their clinical usefulness and safety were evaluated. However, few authors have attempted to study the use of interstitial hyperthermia for the treatment of pancreatic carcinomas. Therefore the efficacy of local selective thermocoagulation by radiofrequency was evaluated in 20 patients with unresectable carcinomas of the pancreas. A laparotomy and radiofrequency heating were performed in 20 patients with unresectable pancreatic carcinomas after informed consent. Local heat coagulation was induced by a 13.56-MHz radiofrequency pulse, produced by the heating apparatus. Four 2-cm needle electrodes were placed in the tumor, in a square array, at intervals of 2 cm. The heat was then administered for 15 min at a controlled temperature of 50 degrees C in the radiofrequency field (2x2x2 cc). All the patients were evaluated by computed tomographic scanning. Tumor markers in the blood also were assayed before and after the heating. Follow-up computed tomographic scans demonstrated that the tumor mass was enhanced heterogeneously, and after selective thermocoagulation, images revealed a change to a homogeneous low-density area. The blood levels of tumor markers decreased to below pretreatment values in 15 patients. Of the 20 cases treated with thermocoagulation, two had critical complications. One patient had septic shock, and another had gastrointestinal bleeding. The other 18 patients had no significant complications. These observations suggest that the selective thermocoagulation of tumor tissues using this equipment was relatively safe. These results justify further clinical trials for the treatment of patients with unresectable tumors without metastasis, or patients with benign pancreatic tumors such as insulinomas.

Adenocarcinoma↗
PubMed2000

Induction of ubiquitin-conjugating enzyme by aggregated low density lipoprotein in human macrophages and its implications for atherosclerosis.

Recently, we have found that aggregated low density lipoprotein (agLDL) inhibits apoptosis of lipid-bearing macrophages, thereby facilitating foam cell formation and atherosclerosis. To clarify the mechanisms by which agLDL inhibits apoptosis of macrophages, we isolated the genes specifically induced by agLDL by using a subtraction-based cloning strategy. One of the cloned genes, termed low density lipoprotein (LDL)-inducible gene (LIG), encodes a human homologue of bovine ubiquitin-conjugating enzyme E2-25K. Although LIG mRNA was ubiquitously expressed among human tissues, including hematopoietic cells, the abundance of transcripts was markedly increased by agLDL treatment in activated monocytes. LIG mRNA expression was not enhanced by nonatherogenic lipoproteins such as native LDL and high density lipoprotein, suggesting a role in atherosclerosis. Polyubiquitination of intracellular proteins was observed in monocytes cultured with agLDL, which coincided with upregulation of LIG. Furthermore, ubiquitin-dependent degradation of p53, an inducer of apoptosis, was accompanied by LIG induction in agLDL-treated monocytes. The antiapoptotic effect of agLDL was abrogated by a specific proteasome inhibitor, which also increased the half-life of p53 in monocytes. These results suggest that LIG contributes to foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequent degradation of p53.

Amino Acid Sequence↗
PubMed2000

Participation of innate and acquired immunity in atherosclerosis.

Coronary artery disease, the major manifestation of atherosclerosis, is the leading cause of death in the Western world. However, the pathogenesis of atherosclerosis is still poorly understood. Controversy exists regarding the participation of innate immunity involving macrophages and natural killer (NK) cells vs antigen-specific acquired immunity involving lymphocytes. Macrophages predominate in atherosclerotic lesions. NK cells, although smaller in number, are present as well. Furthermore, T lymphocytes that participate in acquired immunity are frequently observed in lesions and can modulate lesion progression. By using mouse models of hyperlipidemia, our laboratory is addressing in vivo the participation of both innate inflammatory responses and acquired immune responses in atherosclerosis.

Animals↗
PubMed2000

Leukocyte CD11b expression is not essential for the development of atherosclerosis in mice.

CD11b is an alpha chain of the leukocyte beta(2)-integrin, Mac-1, which mediates binding and extravasation of leukocytes. Because this event is critical in atherosclerosis, we examined the role of CD11b in lesion formation. Atherosclerosis-susceptible, low density lipoprotein receptor-deficient (LDL-R(-/)-) mice were irradiated and repopulated with bone marrow cells from CD11b-deficient (CD11b(-/)-) mice. After 4 weeks, <2% of the peripheral blood leukocytes of the CD11b(-/)- bone marrow-transplanted LDL-R(-/)- mice expressed CD11b, whereas approximately 25% of the CD11b(+/)+ bone marrow-transplanted LDL-R(-/)- mice expressed CD11b. After consuming a high-fat diet for 16 weeks the mean lesion aortic valve area, cholesterol accumulation in the aorta, and the degree of intimal macrophage infiltration were similar in mice reconstituted with either CD11b(+)(/+) or CD11b(-/)- bone marrow cells. The studies confirm that CD11b expression of bone marrow-derived cells does not influence the development of atherosclerosis in hypercholesterolemic LDL-R(-/)- mice.

Animals↗
PubMed1999

A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins.

The rice mitochondrial genome has a sequence homologous to the gene for ribosomal protein S14 (rps14), but the coding sequence is interrupted by internal stop codons. A functional rps14 gene was isolated from the rice nuclear genome, suggesting a gene-transfer event from the mitochondrion to the nucleus. The nuclear rps14 gene encodes a long N-terminal extension showing significant similarity to a part of mitochondrial succinate dehydrogenase subunit B (SDHB) protein from human and a malarial parasite (Plasmodium falciparum). Isolation of a functional rice sdhB cDNA and subsequent sequence comparison to the nuclear rps14 indicate that the 5' portions of the two cDNAs are identical. The sdhB genomic sequence shows that the SDHB-coding region is divided into two exons. Surprisingly, the RPS14-coding region is located between the two exons. DNA gel blot analysis indicates that both sdhB and rps14 are present at a single locus in the rice nucleus. These findings strongly suggest that the two gene transcripts result from a single mRNA precursor by alternative splicing. Protein blot analysis shows that the size of the mature RPS14 is 16.5 kDa, suggesting removal of the N-terminal 22.6-kDa peptide region. Considering that the rice mitochondrial genome lacks the sdhB gene but contains the rps14-related sequence, transfer of the sdhB gene seems to have occurred before the transfer of the rps14 gene. The migration of the mitochondrial rps14 sequence into the already existing sdhB gene could bestow the capacity for nuclear expression and mitochondrial targeting.

Alternative Splicing↗
PubMed1999

Occurrence of heavy chain of 7S IgM half-molecule whose NH2-terminal sequence is identical with that of kappa light chain sequence in patients with Waldenstrom macroglobulinemia.

We report a rare case of a half molecule 7S IgM (HM 7SIgM) consisting of a unique mu heavy chain and kappa light chain found in blood and urine samples from a patient with primary Waldenstrom macroglobulinemia. A 64kDa abnormal immunoglobulin was detected in serum and urine by immunoblot method, and purified by a two-dimensional SDS-PAGE after separation from IgG and albumin fractions on gel filtration. NH2-terminal amino acid sequence analysis of the heavy chain revealed that residues 1-20 were identical to those of the NH2-terminal region of kappa light chain derived from the same patient. This sequence was then followed by a sequence that could not be identified by a computer homology search on the protein database. Using polypeptide segments obtained from the unique mu chain by digestion with endopeptidase, we identified a sequence spanning from residue 127 in the variable region of the known mu chain to residue 19 in the known CH1 domain and a sequence spanning from residues 67-82 in the heavy chain variable region class II. From these results, we concluded that the 64 kDa protein was an abnormal half molecule 7S IgM consisting of a kappa light chain and a unique mu heavy chain of 35 kDa polypeptide in which the NH2-terminal 20 amino acids were replaced by 20 amino acids derived from the sequence of kappa light chain in the NH2-terminal region.

Amino Acid Sequence↗
PubMed1999

A new Lp(a) assay that is unaffected by apo(a) size polymorphism.

We developed sandwich ELISA methods in which anti-apo(a) kringle 4 type 5 through protease (K4 x 5-Pro) domain monoclonal antibody (clone: 203E2) is employed in each instance as the capture antibody and one of the three species of monoclonal antibody [Mab] (clones: 108B8, 202A9, 2B3) is used as the labeled antibody. Using serum containing apo(a) with 34 repeats of kringle 4 as the calibrator, a commercial kit using anti-Lp(a) polyclonal antibody (Pab) or anti-apo(a) Mab overestimated the Lp(a) concentration in samples containing apo(a) with more than 34 repeats of kringle 4 and underestimated the Lp(a) concentration in samples containing apo(a) with fewer than 34 repeats of kringle 4. Moreover, it was demonstrated that the ratios of commercial kit values to anti-apo(a) K4 x 5-Pro Mab-based method values increased as the size of apo(a) increased. The ratios of apo(a) K5 x Pro Mab-based method values to anti-apo(a) K4 x 5-Pro Mab-based method values, however, remained almost constant regardless of the size polymorphism. Thus, we suggest that apo(a) size heterogeneity can significantly affect Lp(a) measurement in the Lp(a) assay using anti-Lp(a) Pab. The novel Lp(a) assay method, using only anti-apo(a) K4 x 5-Pro Mab, is not subject to this phenomenon.

Antibodies, Monoclonal↗
PubMed1999

Selective ablation of porcine and rabbit liver tissue using radiofrequency: preclinical study.

Temperature changes and their distribution induced by 13.56-MHz radiofrequency (RF) heating of agar phantom and porcine and rabbit liver were investigated. It was possible to produce selective local heating of approximately 50 degrees C in the RF field of 2 x 2 x 2 cm(3) of the pig or rabbit liver. Coagulation necrosis after heating became pronounced and the margin between the coagulated lesion and normal tissue became clearer with time. Within 1 week after RF heating at 50 degrees C for 20 min, the coagulated area was replaced selectively and totally by necrotic tissue.

Animals↗
PubMed1999

[Assessment of left ventricular function by electrocardiogram-gated myocardial single photon emission computed tomography using quantitative gated single photon emission computed tomography software].

Electrocardiogram (ECG)-gated myocardial single photon emission computed tomography (SPECT) can assess left ventricular (LV) perfusion and function easily using quantitative gated SPECT (QGS) software. ECG-gated SPECT was performed in 44 patients with coronary artery disease under post-stress and resting conditions to assess the values of LV functional parameters, by comparison to LV ejection fraction derived from gated blood pool scan and myocardial characteristics. A good correlation was obtained between ejection fraction using QGS and that using cardiac blood pool scan (r = 0.812). Some patients with myocardial ischemia had lower ejection fraction under post-stress compared to resting conditions, indicating post-stress LV dysfunction. LV wall motion and wall thickening were significantly impaired in ischemic and infarcted myocardium, and the degree of abnormality in the infarcted areas was greater than in the ischemic area. LV functional parameters derived using QGS were useful to assess post-stress LV dysfunction and myocardial viability. In conclusion, ECG-gated myocardial SPECT permits simultaneous quantitative assessment of myocardial perfusion and function.

Electrocardiography↗
PubMed1999

Reproducibility of the oxygen uptake efficiency slope in normal healthy subjects.

BACKGROUND: To elucidate the intertest agreement of the oxygen uptake efficiency slope (OUES) in comparison with those of the maximal oxygen uptake (VO2max) and the ventilatory anaerobic threshold (VAT). METHODS EXPERIMENTAL DESIGN: A comparative study. SETTING: Institutional practice. A total of 19 healthy volunteers underwent two sessions of maximal exercise testing with an interval of no more than 7 days. The testing was conducted on a cycle ergometer with the work rate increased by either 20, 30, or 40 Watts (W)/min so that the subject would reach exhaustion within 9 to 12 min of exercise. VAT was defined as the level of oxygen uptake (VO2) at which either an increase in the ventilatory equivalent for oxygen without a concomitant increase in the ventilatory equivalent for carbon dioxide or a change in the slope of the linear relationship between carbon-dioxide production (VCO2) and VO2 occurred. OUES was determined by the following equation: VO2 = a log VE + b, where VE was minute ventilation and "a" was the OUES. Intertest reproducibility was assessed by coefficient of repeatability (COR). RESULTS: The intertest reproducibility of VO2max and OUES were excellent (COR = 570 ml/min [16%] and 740 [20%], respectively). VAT showed poor agreement between the two tests (COR = 650 ml/min [31%]). CONCLUSIONS: Results show that OUES is reproducible and reliable, supporting the clinical usefulness of this index.

Adult↗
PubMed1998

Development of a dissecting aneurysm on the vertebral artery immediately after occlusion of the contralateral vertebral artery: a case report.

A 49 year old female presented with subarachnoid hemorrhage due to a ruptured dissecting aneurysm on the left vertebral artery (VA). Following an occlusion test, we performed proximal occlusion of the left VA with detachable balloons. However, a dissecting aneurysm on the right VA developed three weeks later. After an occlusion test had showed no change in cerebral blood flow, auditory brain stem response, or neurological status, proximal occlusion of the right VA was performed. The patient has returned to normal life without neurological deficits. Bilateral dissecting aneurysms of the VA are quite common, but de novo VA dissecting aneurysms or enlargement of such aneurysms after occlusion of contralateral VA are rare. This case suggests that hemodynamics stress may be a causal factor in the development of VA dissecting aneurysms. Careful pre- and post-operative neuroradiological examination of the contralateral VA are required in patients undergoing VA occlusion for dissecting aneurysms.

Aortic Dissection↗
PubMed1998

Genes for the ribosomal S4 protein encoded in higher plant mitochondria are transcribed, edited, and translated.

Here we describe the structure and expression of the mitochondrial gene that encodes the S4 subunit of the mitochondrial ribosome (rps4) in two higher plants, rapeseed and rice. The ORFs of rapeseed and rice rps4 genes are 362 and 352 codons long, respectively, and their corresponding transcripts are edited (C-to-U conversions) in 19 and 15 positions, respectively. The amino acid sequences deduced from the sequences of the two rps4 genes are 78.1% identical to each other and show about 50% identity to the liverwort (Marchantia polymorpha) mitochondrial RPS4 polypeptide. Both higher plant mitochondrial genes have an inserted sequence (of 137 and 141 codons for rapeseed and rice, respectively) relative to the liverwort rps4 gene. In rice rps4, the 3' portion of the inserted sequence can potentially form two stem-loop structures that resemble two domains characteristic of group II introns, i.e., domains V and VI. However, RT-PCR analysis showed that these sequences were not spliced out during maturation of the rps4 transcripts. Antibodies specific for the plant RPS4 proteins were prepared. Protein blot analysis revealed that RPS4 polypeptides are present in both rapeseed and rice mitochondria, whose sizes are in agreement with the molecular weights calculated from the non-spliced sequences. The rps4 genes and RPS4 polypeptides have been also identified in the mitochondria of wheat, maize, soybean, and turnip by Southern and Western analyses, respectively.

Amino Acid Sequence↗