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Biomedical subjects

M Nonaka

Publications and source records attributed to M Nonaka.

At least 37 records · Page 2Linked to original sources

[Acute pulmonary thromboembolism complicating lung lobectomy; report of a case].

Acute pulmonary thromboembolism is fatal if the diagnosis and treatments are delayed. Here we present a case of acute thromboembolism to the right and left pulmonary arteries after right lung lobar resection. A 52-year-old woman who admitted to our hospital with lung cancer was performed right upper lobectomy with mediastinal lymph node dissection (pT1N0M0, well differentiated adenocarcinoma). Two days after surgery, she complained sudden chest discomfort and dyspnea. The blood pressure and oxygen saturation were rapidly decreased. Because there was no lung edema or atelectasis in the chest portable roentgenogram and no ischemic change in the electrocardiogram, pulmonary thromboembolism was suspected and emergency chest computed tomography (CT) was performed. The CT showed left and right pulmonary arterial thromboembolism and immediate anti-coagulator therapy was started. Her condition was improved and chest CT, which was performed three days after the onset of the thromboembolism, showed decreased but still remained thrombus. The anti-coagulator therapy was continued and one month after the onset of the thromboembolism, thrombus was disappeared on chest CT. She is doing well 17 months after surgery. Early diagnosis and treatments are critical for the pulmonary thromboembolism.

Adenocarcinoma↗

Contribution of central amiloride-sensitive transport systems to the development of hypertension in spontaneously hypertensive rats.

This study was conducted to examine if central amiloride-sensitive transport systems are involved in the development and/or maintenance of hypertension in spontaneously hypertensive rats (SHR). Either amiloride (75 microg/60 microl/day) or artificial cerebrospinal fluid (aCSF, 60 microl/day) was infused centrally (i.c.v.) for 4 weeks to development (4-5-weeks-old) and maintenance (10-12-weeks-old) phases of hypertension in SHR. In development phase, amiloride i.c.v. (n=14) blunted the elevation of blood pressure (BP) compared to aCSF i.c.v. (n=9) (amiloride vs. aCSF; after 3 weeks of i.c.v., 146+/-3 vs. 166+/-5 mmHg, P<0.001). The difference of BP at 3 weeks of i.c.v. was canceled after ganglionic block with hexamethonium (115+/-4 vs. 117+/-5 mmHg). Further, pressor responsiveness to norepinephrine was augmented in amiloride i.c.v. rats (amiloride, n=11 vs. aCSF, n=6; %Delta BP at 800 ng/kg/min.: 16.9+/-1.3 vs. 10.8+/-1.4 mmHg, P<0.05) and this augmentation disappeared after ganglionic block. Pressor responsiveness to angiotensin II and cumulative sodium balance did not differ in the two groups. Intravenous administration of amiloride at the same dose did not attenuate the development of hypertension. On the other hand, in maintenance phase, amiloride i.c.v. by the same protocol as in development phase had no effect on BP in SHR. Also, amiloride i.c.v. did not affect BP in normotensive Wistar-Kyoto rats. These results suggest that central amiloride-sensitive transport systems are involved in the development, but not in the maintenance, of hypertension in SHR through the modulation of autonomic neural mechanisms.

Amiloride↗

Far-reaching effects of the Hawaiian Islands on the Pacific Ocean-atmosphere system.

Using satellite data, we detected a wind wake trailing westward behind the Hawaiian Islands for 3000 kilometers, a length many times greater than observed anywhere else on Earth. This wind wake drives an eastward ocean current that draws warm water from the Asian coast 8000 kilometers away, leaving marked changes in surface and subsurface ocean temperature. Standing in the path of the steady trade winds, Hawaii triggers an air-sea interaction that provides the feedback to sustain the influence of these small islands over a long stretch of the Pacific Ocean.

Journal Article↗

Novel androgen-dependent promoters direct expression of the C4b-binding protein alpha-chain gene in epididymis.

C4b-binding protein (C4BP) is a large plasma protein composed of seven alpha-chains and one beta-chain and is involved in the fluid phase regulation of the classical pathway of the complement system. Complement inhibitory activity is located in the alpha-chain, and its mRNA has been detected only in liver to date. Here, we have isolated cDNA clones encoding the alpha-chain of guinea pig C4BP (C4BP alpha) and have demonstrated significant C4BP alpha mRNA expression in epididymis as well as liver. The level of C4BP alpha transcripts increased in the epididymis after birth, while it remained constant in the liver. C4BP alpha mRNA was also detected in the normal murine epididymis at a significant level, but it decreased drastically after castration, suggesting that epididymal expression of the C4BP alpha gene is regulated by androgen. Gene analysis of guinea pig C4BP alpha indicated that liver and epididymis C4BP alpha mRNA share the coding region and 3'-untranslated region, but are transcribed from independent promoters on a single-copy gene. Two novel epididymis-specific promoters were identified in the region corresponding to the first intron of liver transcripts. The binding motif for hepatocyte NF-1 occurs in the promoter used for transcription of liver C4BP alpha, whereas androgen-responsive elements occur in both promoters used in the epididymis. These findings present a novel link between complement regulators and reproduction. Furthermore, variation in the 5'-untranslated regions, arising from alternative splicing of the newly identified exons, is demonstrable in the guinea pig C4BP alpha transcripts.

3' Untranslated Regions↗

Cloning and characterization of integrin alpha subunits from the solitary ascidian, Halocynthia roretzi.

Recent molecular and biochemical analysis has revealed the presence of an opsonic complement system in the solitary ascidian, Halocynthia roretzi, composed of at least C3, two mannan binding protein-associated serine proteases, and factor B. To elucidate further the structure and function of this apparently primitive complement system in the urochordates, we looked for the ascidian complement receptor type 3 (CR3), or type 4 (CR4), which are members of the leukocyte integrin family in mammals. Using degenerate primers, we isolated two integrin alpha subunits (alpha(Hr1) and alpha(Hr2)) from the hemocyte mRNA of H. roretzi, by RT-PCR, and the entire coding sequence of alpha(Hr1) was determined from cDNA clones. alpha(Hr1) contains an I domain, the inserted domain characteristic of a subset of mammalian alpha subunits, including the leukocyte integrin family. A phylogenetic tree constructed for the alpha subunits also supports the ancestral position of alpha(Hr1) in the monophyletic cluster of I domain-containing alpha integrins. The alpha(Hr1) gene shows hemocyte-specific expression on Northern blot analysis. Western blot analysis and immunocytochemical staining of the hemocytes of H. roretzi using anti-alpha(Hr1) Ab showed that alpha(Hr1) subunits exist on the surface of a subpopulation of phagocytic hemocytes. Furthermore, anti-alpha(Hr1) Ab inhibited C3-dependent phagocytosis, but not basic phagocytosis, of yeast cells by ascidian hemocytes. These observations strongly suggest that alpha(Hr1) constitutes an integrin molecule on the hemocytes of H. roretzi that functions as an ancestral form of CR3 and CR4 and mediates phagocytosis in the primitive complement system of the ascidian.

Amino Acid Sequence↗

Autoantibody to gravin is expressed more strongly in younger and nonthymomatous patients with myasthenia gravis.

Gravin is expressed in several cell and tissue types as either 300 kDa doublet or 250 kDa proteolytic products. It is a cytoplasmic antigen that reacts with the serum of patients with myasthenia gravis (MG). Autoantibodies to gravin residues 1477-1781 are highly specific for MG. In the present study, we examined residues 1477-1781 in detail and found that residues 1542-1547 of gravin protein, which had sequence homology with the binding sequences of two protein A-kinase anchoring proteins, were highly reactive to MG serum. Antigravin antibody activities were stronger in younger and nonthymomatous patients. These findings suggest that antigravin antibody activities could be a useful prognostic factor and that the gravin antibody of MG may have a function which prevents the protein A-kinase binding pathway.

A Kinase Anchor Proteins↗

Expression of the prothymosin-a gene as a prognostic factor in lung cancer.

Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis.

Aged↗

Comparative genomics of medaka: the major histocompatibility complex (MHC).

The major histocompatibility complex (MHC) is one of the best characterized regions of the vertebrate genome. The human MHC has three subregions, classes I, II, and III. The MHC of chicken and Xenopus contain all three subregions. In contrast, in all teleost species so far analyzed, the class I and II genes are not linked to each other, suggesting that there was extensive genomic reorganization of the MHC region during an early stage of vertebrate evolution. To elucidate the details of this reorganization, we carried out genetic and physical analyses of the medaka MHC genes. We isolated the medaka counterparts of human MHC genes, class I A, class II B, LMP2, LMP7, TAP2, complement Bf and C4, and subjected them to linkage analysis. Except for the linkage of class IA, LMP2, LMP7, and TAP2 on linkage group (LG)11, all other genes were assigned to separate linkage groups. Thus, the class IA gene and the genes involved in class I antigen presentation seem to form the evolutionary stable core of the MHC. A physical analysis of medaka MHC class I region is in progress.

Journal Article↗

Evolution of the complement system.

The origin of the complement system is much more ancient than that of adaptive immunity, which is only found in jawed vertebrates. Recently, complement components of the alternative and lectin pathways have been identified in jawless fishes, and even in some deuterostome invertebrates. The primitive complement system of these animals is one of the most highly organized innate immune systems.

Animals↗

Mechanisms of phytosterolemia in stroke-prone spontaneously hypertensive and WKY rats.

Analysis of sterol composition in serum, liver, adipose tissue, adrenals, and abdominal aorta demonstrated that the contents of plant sterols, campesterol and sitosterol, were evidently higher in WKY and stroke-prone spontaneously hypertensive (SHRSP) rats than in Wistar and WKA rats fed a diet containing a 0.5% plant sterol mixture. Lymphatic 24-hour recovery of 3H-sitosterol was about 2-fold higher in the WKY and SHRSP rats than in the WKA rats. Lymphatic absorption of 14C-cholesterol was also higher in WKY and SHRSP rats compared with WKA rats, but the difference was smaller than in the case of sitosterol. The remarkable increase of sitosterol absorption in WKY and SHRSP rats was observed between 9 and 24 hours after the administration. In SHRSP rats, lymphatic absorption of sitosterol between 0 and 3 hours was also higher than those in the other rat strains. Markedly less esterified 3H-sitosterol was detected in lymph than 14C-cholesterol in all strains, and in WKY and SHRSP rats, only a small increase in the esterified forms of sitosterol and cholesterol was observed. Although the incorporation of micellar 3H-sitosterol and 14C-cholesterol into intestinal brush border membranes was higher in SHRSP rats than in WKA rats, no difference was observed between WKY and WKA rats. These observations suggest that the incorporation into the brush border membranes and the esterification of sterols are not the major determinants for the hyperabsorption of sitosterol and cholesterol in SHRSP and WKY rats. Secretion of sitosterol and cholesterol in the bile of rats fed a plant sterol mixture was lower in SHRSP than in WKA rats. These results suggest that WKY and SHRSP strains deposit plant sterols in the body by enhancing the absorption and lowering the excretion of plant sterols. These strains of rats may be suitable models for studying mechanisms of differential absorption of various sterols.

Adipose Tissue↗

Serum hepatocyte growth factor levels are increased in patients with congestive heart failure.

BACKGROUND: Hepatocyte growth factor (HGF) is a potent endothelial cell-specific mitogen. We investigated the clinical importance of HGF in congestive heart failure (CHF). METHODS AND RESULTS: Thirty-five patients with acute exacerbation of CHF and 7 control subjects were examined. Serum and peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood on days 1, 7, and 14 after admission. PBMCs were cultured at a density of 1 x 10(7) cells/mL for 24 hours. HGF levels in serum and the PBMC culture medium and serum interleukin 6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Serum HGF levels in patients with CHF were markedly increased at admission compared with those in control subjects and gradually returned to control levels during hospitalization. HGF levels in the PBMC culture medium were also significantly increased in CHF patients compared with control subjects. There was a positive correlation between HGF levels in serum or those in the PBMC culture medium and serum IL-6 levels. HGF levels in serum and the culture medium were not notably different between CHF patients regularly treated with and without angiotensin-converting enzyme inhibitors. CONCLUSIONS: HGF levels in serum are increased in patients with acute exacerbation of CHF.

Adult↗

Dietary gamma-linolenic acid dose-dependently modifies fatty acid composition and immune parameters in rats.

gamma-linolenic acid (GLA) has been reported to improve several inflammatory disorders through regulation of eicosanoid production. However, since GLA is a precursor of arachidonic acid, it may bring about increasing tissue arachidonic acid levels with subsequent pro-inflammatory events. To explore this possibility, we examined the effect of high-dose GLA acid on the fatty acid profile of immune cells, leukotriene B4 production by peritoneal exudate cells and immunoglobulin productivity of mesenteric lymph node lymphocytes of Sprague-Dawley rats. Male rats were fed 10% fat diets containing graded levels, 0, 20, 40 and 60% of GLA for 3 weeks. The results showed the distinction in activity of metabolizing GLA between immune cells and liver. Thus, in immune cells such as mesenteric lymph node and spleen lymphocytes and peritoneal exudate cells, more dihomo-gamma-linolenic acid was found than in the liver. Leukotriene B4 production by peritoneal exudate cells was significantly suppressed when fed the highest level of GLA suggesting a lower risk of allergic reaction. Moreover, immunoglobulin productivity in mesenteric lymph node lymphocytes was promoted by dietary GLA. The present study indicates that a high dose of GLA may exert anti-inflammatory effects through suppression of leukotriene B4 release and strengthening of gut immune system, thus ameliorating allergic reaction.

Animals↗

Dietary manipulations of body fat-reducing potential of conjugated linoleic acid in rats.

To study whether the body fat-reducing potential of conjugated linoleic acid (CLA) could be increased through dietary manipulations, the effects of the combination of CLA with different proteins, fats, and sesamin were examined in rats. Male rats were fed diets containing 1% CLA or linoleic acid (LA) in combination with different proteins (20% of casein or soybean protein), fats (7% perilla oil or soybean oil) and 0.2% sesamin (SES) for 3 or 4 weeks. When the dietary fat source was soybean oil, CLA, as compared with LA, significantly reduced weights of epididymal and perirenal adipose tissues, irrespective of the dietary protein sources. However, the highest reducing effect was shown when soybean protein was given as a protein source. SES stimulated the reduction of epididymal and perirenal adipose tissue weights in both protein diets. In contrast, CLA increased the weight of brown adipose tissue, and SES further increased it in combination with soybean oil but not with perilla oil. No effect of dietary manipulation was observed on serum leptin and TNF-alpha levels. Thus, the body fat-reducing potential of CLA can be increased by an appropriate combination with food factors that may stimulate fatty acid beta-oxidation.

Adipose Tissue↗

Implantation of xenografts into the parkinsonian rat brain after portal venous administration of xenogeneic donor spleen cells.

OBJECT: The purpose of the present study was to examine the effect of pretransplantation portal venous immunization with ultraviolet B (UVB)-treated donor spleen cells on neural xenograft transplantation. METHODS: Cells from a murine catecholaminergic cell line derived from the B6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian rats were divided into three different treatment groups. Group 1 received saline in the dopamine-denervated striatum; Group 2 received xenograft cells; and Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function was determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantation by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Groups 2 and 3); however, the animals in Group 3 displayed a significantly reduced rotational behavior compared with Group 2. In Group 2, many inflammatory cells and a few THase-positive cells were found at the graft sites 4 weeks after transplantation. In Group 3, however, a large number of THase-positive cells were found with few inflammatory cells. The THase-positive cells disappeared in the Group 2 rats at 12 weeks, but remained in Group 3 animals. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte reaction was suppressed in a donor-specific fashion. CONCLUSIONS: This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiated xenogeneic donor splenocytes. On the basis of these findings, the authors suggest the possibility of creating donor-specific immunological tolerance in the brain by administration of xenogeneic donor lymphocytes via the portal vein.

Animals↗

[Leiomyoma of the esophagus shown as a cervical tumor].

A 44-year-old female was admitted to our hospital because of the left cervical tumor. Radiologic examination showed that the tumor was 5 cm in diameter and was inhomogeneous. The tumor was spread to the upper mediastinum. Esophagoscopy showed that the tumor was covered by the normal mucosa. Percutaneous fine needle biopsy did not appear the histopathological diagnosis. The patient underwent surgical resection through the cervical approach and the tumor was located between the mucosal and muscular layers of the esophagus. The tumor was enucleated without any complication. Histopathological diagnosis was leiomyoma. Postoperative course was uneventful. Expecting diagnosis and positive complete resection is recommended for leiomyoma of the esophagus.

Adult↗

Interactions of dietary fats and proteins on fatty acid composition of immune cells and LTB4 production by peritoneal exudate cells of rats.

The interaction of dietary fats and proteins on lipid parameters of rats was studied using safflower oil (linoleic acid-rich), borage oil (gamma-linolenic acid-rich) or perilla oil (alpha-linolenic acid-rich) in combination with casein or soybean protein. The experiment was focused on the fatty acid composition of immune cells and the leukotriene B4 production by peritoneal exudate cells. Serum total cholesterol, triglyceride, and phospholipid levels were low in perilla oil-fed or soybean protein-fed rats. Fatty acid compositions of serum and liver phospholipids reflected those of dietary fats. However, feeding borage oil resulted in a marked increase in the proportion of dihomo-gamma-linolenic acid in phospholipids of peritoneal exudate cells, spleen lymphocytes, and mesenteric lymph node lymphocytes in relation to those of liver and serum. It is suggested that activities of metabolic n-6 polyunsaturated fatty acids are different between immune and other tissues. In addition, the magnitude of the reduction of the proportion of linoleic acid of perilla oil in immune cells was considerably more moderate than serum and liver, indicating a different degree of interference of alpha-linolenic acid with linoleic acid metabolism. Leukotriene release from peritoneal exudate cells was in the order of safflower oil > borage oil > perilla oil groups as reflecting the proportion of arachidonic acid, and tended to be lower in soybean protein-fed groups. These suggest an anti-inflammatory property of gamma-linolenic acid as well as alpha-linolenic acid tended to be strengthened when they were combined with soybean protein than with casein.

Animals↗