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Biomedical subjects

K Sugimura

Publications and source records attributed to K Sugimura.

At least 109 records · Page 6Linked to original sources

Identification of proteolipid from an extremely halophilic archaeon Halobacterium salinarum as an N,N'-dicyclohexyl-carbodiimide binding subunit of ATP synthase.

ATP synthesis in an extremely halophilic archaeon, Halobacterium salinarum, was inhibited by N-cyclohexyl-N'-[4-(dimethylamino)-alpha-naphthyl]carbodiimide (NCD-4), a fluorescent analog of N,N'-dicyclohexylcarbodiimide (DCCD). By tracing the fluorescent signal, a hydrophobic 8-kDa protein (proteolipid) was purified from the halobacterial membrane as one of the most DCCD-reactive proteins and its N-terminal amino acid sequence was determined. The gene encoding the proteolipid was found in the region upstream of the genes encoding the two major subunits of halobacterial A-type ATPase [K. Ihara and Y.Mukohata (1991) Arch. Biochem. Biophys. 286, 111-116]. Halobacterial proteolipid was more similar in size to the proteolipid of F-type ATPase than that of V-type ATPase. However, multiple amino acid sequence alignment of proteolipids showed a higher degree of relatedness between V-type and A-type ATPase proteolipids. Together with the recent finding of a triplicate proteolipid encoding gene from the methanogenic archaeon Methanococcus jannaschii [C. J. Bult et al. (1996) Science 273, 1058-1073], proteolipids from archaea seem to have diverse characteristics in comparison with those from eubacteria or from eukaryotes.

Adenosine Triphosphatases↗

Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation.

The Goosecoid (gsc) gene is a homeobox-containing gene expressed first in the gastrula, and later during organogenesis in development. The gsc gene transcript is found in the first and second branchial arches, frontonasal mass in its late phase of expression. We have previously shown that targeted mutation of the mouse gsc gene leads to neonatal death and craniofacial defects. In this study, we performed histological studies on craniofacial phenotypes in order to elucidate the processes underlying the neonatal death of gsc mutant mice. We found that gsc mutant mice have aplastic nasal cavities and lack the Sinus Paranasalis. We also showed that secretory olfactory glands in the basal layers are aplastic. This is suggested to be essential defects for olfaction. gsc mutant mice also show several pharyngeal phenotypes, including defects in the pharyngeal muscles and the pharyngeal mucosa. It is therefore suggested that mutant mice develop lethal gastro-intestinal phenotypes caused by defects in breathing and sucking of milk as a consequence of these craniofacial disorders. These results should help elucidating the molecular genetic programs essential to the neonatal development of mammals.

Animals↗

Trace element composition and histological analysis of rat bones from the space shuttle.

The physiological and pharmacobiological changes associated with space flight are of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ functions. Alterations include decreases in muscle and liver mass, changes in bone structure and integrity, and changes in cardiovascular functions. Zero-gravity in particular has been reported to inhibit several physiological processes of bone formation, retard bone growth and impair the mechanical properties of bones. This report examines the effect of 14 days of spaceflight on the bone trace element compositions of rapidly growing rats. Marked changes of bone trace element contents were found in either weight-bearing bones or non-weight-bearing bones, depending on the metal species. Histological examination revealed an irregular thickening of the endosteal surface of the cortical bone (thoracic vertebrae) of the in-flight rat, whereas it was uniform in the ground control. We suggest that the microgravity environment causes several bone alternations, such as abnormal trace element compositions and defects in vertebral maturation.

Animals↗

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats.

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.

Animals↗

Production of hepatocyte growth factor is increased in chronic renal failure.

Hepatocyte growth factor (HGF) facilitates recovery from tissue injuries. We previously reported that serum HGF levels were elevated in chronic renal failure (CRF) patients. In the present study Western blot analysis of CRF patients' sera showed the majority of their serum HGF was a single-chain precursor molecule. In CRF rats developed by 5/6 nephrectomy or high adenine diet, both HGF mRNA expression levels and tissue HGF concentrations were increased in liver and spleen. The results suggest that HGF production increases in CRF, which may be a response to chronic progressive renal injuries in an endocrine manner.

Adult↗

Hepatocyte growth factor in glycerol-induced acute renal failure.

Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). Here we investigated the HGF production in glycerol-induced ARF rats. HGF mRNA expression levels were elevated in liver, spleen, and lung 6-24 h after glycerol injection. Tissue HGF protein levels determined by an enzyme-linked immunosorbent assay also increased in liver and spleen, whereas they decreased in the injured kidney 24 h after injection. Immunohistochemical studies showed that the number of HGF-producing cells did not increase in the liver. HGF receptor/c-Met mRNA levels were elevated only in the kidney. These results indicate that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF.

Acute Kidney Injury↗

Carcinosarcoma of the uterus: magnetic resonance imaging.

We report the magnetic resonance imaging (MRI) findings with a paramagnetic enhancement agent (gadopentetate dimeglumine (Gd-DTPA)) in a 70-year-old woman with carcinosarcoma of the uterus. In the present patient, the polypoid portion histologically most abundant in the sarcomatous component was strongly enhanced by Gd-DTPA and was clearly demonstrated with high signal intensities on contrast-enhanced T1-weighted images. We suggest that MRI with Gd-DTPA may be clinically useful for detection of carcinosarcoma, and that any patient having endometrial carcinoma with the polypoid portion, which is more strongly enhanced by Gd-DTPA within the tumor, may be suspected of carcinosarcoma.

Aged↗

Evaluation of biological responses to polymeric biomaterials by RT-PCR analysis. II: Study of HSP 70 mRNA expression.

In order to investigate how cells recognize biomaterials, mRNA that was expressed in attached HeLa S3 cells on various substrates was evaluated. As culture substrates, cellulose, ethylene-vinyl alcohol copolymer (EVAL), nylon, tissue culture polystyrene (TCPS), high-density polyethylene (PE), silicone rubber, and tetrafluoroethylene-hexafluoropropylene copolymer (6F) were used. HeLa S3 cells were cultured on these substrates for 24 h. The expressed HSP 70s mRNA was then isolated and detected using the RT-PCR method. As a result, the expression of HSP 70B mRNA was largely induced in cells that adhered to hydrophilic surfaces. On the other hand, on hydrophobic surfaces, the HSP 70B mRNA expression was low. It is concluded that HSP 70B mRNA expression is sensitive to differences in the hydrophilicity-hydrophobicity of the substrates.

Biocompatible Materials↗

[Myocardial wall motion analysis with phase shift imaging: cine phase contrast technique].

MR imaging can be used to measure proton velocity directly as a phase shift with the bipolar gradient method. This method is applied in MR angiography as a phase contrast(PC) technique. We attempted to evaluate myocardial motion utilizing the PC technique. With the cine PC technique, 16-cardiac phased 3D velocity images of the myocardium were obtained. In normal subjects, the myocardial velocity throughout the cardiac cycle were changes regular in space as well as in time, and there was no inconsistency between the motion directions. Whereas, in cases with myocardial infarction, 3D velocity images revealed some regions with zero velocity and/or some regions which showed reverse direction motions compared with the surrounding normal myocardium.

Heart↗

[In vivo gene transfer methods into bladder without viral vectors].

For the application of gene therapy to bladder cancer, we examined four in vivo gene transfer methods without viral vectors. For lipofection cationic liposomes (Lipofectin) were instilled into murine bladders. The hemagglutinating virus of Japan (HVJ)-liposomes possessing membrane fusion activity were also injected intraluminally. Using a particle gun, rabbit bladder mucosa was bombarded with DNA-coated gold microcarriers. Electrotransfection was examined in rabbit bladder by pulse direct currents (0.15-0.2 A, 50 msec, repeated 8 times) generated between needle electrodes after submucous injection of DNA solution. beta-galactosidase gene and chloramphenicol acetyltransferase (CAT) gene were used as marker genes. Although lipofection was inefficient in normal urothelium, cancerous urothelium was transfected slightly. HVJ-liposomes more efficiently transfected superficial layers of urothelium with a peak of expression on day 5. The particle gun produced non-uniform but efficient transfection in deeper layers of the urothelium. By electrotransfection, submucous interstitial cells were transfected as well as urothelium. No major complications were observed after these four procedures. HVJ-liposomes are potentially useful for the treatment of carcinoma in situ and the latter two methods may be suitable for the adjuvant therapy of localized bladder tumors.

Animals↗

Hepatocyte growth factor is a paracrine regulator of rat prostate epithelial growth.

Hepatocyte growth factor (HGF) is a mesenchymal-derived growth factor which predominantly targets various epithelial and endothelial cells. We here investigated the biological function of HGF in rat dorsolateral prostatic tissue. HGF stimulated proliferation and DNA synthesis of prostatic epithelial cells in primary culture. c-Met/HGF receptor mRNA was specifically expressed in isolated epithelial cells. An immunohistochemical study revealed that HGF is located in prostatic stromal cells. When stromal cells were isolated and cultured, they produced significant amounts of HGF, which was further stimulated by prostaglandin E2, 12-O-tetradecanoylphorbol-13-acetate, and dibutyryl cyclic AMP, but not by testosterone. These results indicate that HGF is a stromal-derived potent mitogen for dorsolateral prostatic epithelial cells which may function as a paracrine regulator for growth of the prostatic glands.

Animals↗

Magnetic resonance imaging and serum CA-125 in evaluating patients with endometriomas prior to medical therapy.

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) and serum levels of CA-125 can be used to evaluate patients with endometriomas before initiating medical treatment. DESIGN: Comparative study before and after medical treatment. SETTING: Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Eleven consecutive patients with at least one endometrioma > 10 mm in maximal diameter that was diagnosed by laparoscopy and treated with 900 micrograms/d buserelin acetate for 6 months. INTERVENTIONS: Magnetic resonance imaging and blood sampling was performed < 2 weeks before laparoscopy. MAIN OUTCOME MEASURES: Signal intensity of edometrioma/signal intensity of gluteus maximum muscle on T2-weighted image (T2SI:MSI); volume of endometrioma and serum CA-125. RESULTS: There was a positive linear correlation (r = 0.787) between T2SI:MSI before treatment and the extent of decrease in the volume of endometrioma. There was a negative linear relationship between serum CA-125 before treatment and the mean extent of decrease in the cyst volume (r = 0.678). The reduction in volume of endometrioma and T2SI:MSI before treatment related to the outcome of patients. CONCLUSION: The T2SI:MSI on MRI and serum CA-125 may be useful for estimating the outcome of patients with endometriomas before initiating medical treatment.

Adult↗

Magnetic resonance relaxation time in evaluating the cyst fluid characteristics of endometrioma.

To determine whether the cyst fluid characteristics of endometrioma can be evaluated by magnetic resonance imaging (MRI), 36 endometriomas obtained from 24 patients (age range 21-43 years; mean 34 years) were studied. MRI was performed < 2 weeks before laparoscopy or laparotomy. Comparative studies of the density and concentration of iron in the endometrioma and the signal intensity (SI) of MRI [calculated relaxation time T1 value, calculated relaxation time T2 value, signal intensity on a T1-weighted image (T1SI) and on a T2-weighted image (T2SI) of the cyst; T1SI/signal intensity of the gluteus maximus muscle (MSI), and T2SI/MSI of the cyst] were performed. The density of the cyst fluid and its iron concentration were found to be directly proportional. There was a significant relationship between the concentration of iron and the T2SI, T2SI/MI and calculated T2 values. In particular, the concentration of iron and the ration of T2SI/ MSI were inversely proportional. Therefore, T2SI/MSI reflected the concentration of iron in endometriomas without recourse to measurement of the calculated T2 value, which suggests that the MRI and T2 signal intensity may be useful for evaluating the cyst fluid characteristics of endometriomas.

Adult↗

Prognostic application of magnetic resonance imaging in patients with endometriomas treated with gonadotrophin-releasing hormone analogue.

We evaluated the usefulness of magnetic resonance imaging (MRI) for assessing the response of patients with endometriomas to medical therapy. MRI was performed before and after treatment in 20 consecutive patients with at least one endometrioma with a maximal diameter >10 mm diagnosed by laparoscopy who received 900 microg of buserelin acetate daily for 6 months. Patients were categorized as good responders (group I, n = 13) and poor responders (group II, n = 7) depending on the results of a third-look laparoscopy performed 6 months after treatment. We determined the ratio of the signal intensity (SI) of the endometrioma to the SI of the gluteus maximus muscle on T2-weighted images [T2SI/M (muscle) SI] and the volume of the endometrium. The volume decreased by >50% in 61.5% of the good-response group and 57.1% of the poor-response group. There was no significant difference between the two groups. The T2SI/MSI decreased in 12 of 13 patients in group I but in only one of seven patients in group II, a significant difference (P < 0.05) between the two groups. In the good-response group, there was a positive linear correlation between the decrease in the volume of the endometrioma and the decrease in the T2SI/MSI after treatment (r = 0. 561, P < 0.05). Therefore, the T2SI/MSI determined from MR images may be useful in assessing the therapeutic response of patients with endometriomas.

Adult↗

Th1/Th2 response profiles to the major allergens Cry j 1 and Cry j 2 of Japanese cedar pollen.

Cry j 1 and Cry j 2 are known to be the major allergens of Japanese cedar pollen. A comparative study was carried out on the immune responses to stimulation with Cry j 1 and Cry j 2 in 24 symptomatic patients and six nonallergic subjects. In T-cell proliferation assays, mean stimulation indexes (SI) were 10.6 for Cry j 1 and 11.7 for Cry j 2 stimulation, respectively, in the allergic patients. Two of the nonallergic subjects showed strong T-cell proliferation to both allergens, while the remainder did not. All the allergic subjects (17/17) showed high titers of anti-Cry j 1 IgE antibody at a mean value of 165 U/ml, whereas only 64% responded to Cry j 2 with low titers at a mean value of 26 U/ml. Nonallergic subjects did not respond with IgE production. Allergic subjects were further examined for their cytokine production profiles. All allergic subjects tested (16/16) produced high levels of interferon-gamma (IFN-gamma) in response to Cry j 1 with a mean value of 918 pg/ml, while only five subjects showed significant elevation of IFN-gamma production in response to Cry j 2 with a mean value of 679 pg/ml. The remainder produced small amounts of IFN-gamma. Cry j 1 induced higher levels of interleukin (IL)-10 gene expression than did Cry j 2 stimulation, while both allergens induced IL-4 expression at a similar level. The IL-12 p35 gene was constitutively expressed, whereas the IL-12 p40 gene expression in Cry j 1-stimulated cells was elevated eightfold over that of nonstimulated cells. Increased expression of the IL-12 p40 gene was negligible in Cry j 2-stimulated cells. Thus, Cry j 1 stimulated mixed features of Th1 and Th2-like responses, while Cry j 2 played a minor role in inducing IgE production and cytokine (IFN-gamma, IL-10, and IL-12) production, except for IL-2 production and strong T-cell proliferative activity. Therefore, it was concluded that Cry j 1 is the more important allergen, and that T-cell proliferation assays do not necessarily reflect the level of allergenicity.

Allergens↗