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Biomedical subjects

S Homma

Publications and source records attributed to S Homma.

At least 55 records · Page 3Linked to original sources

Carotid plaque and intima-media thickness assessed by b-mode ultrasonography in subjects ranging from young adults to centenarians.

UNLABELLED: BACKGROUND AND PURPOSE-To investigate relationships among plaque formation, increasing intima-media thickness, and age, we examined ultrasonographically carotid arteries of subjects who had no major atherosclerotic risk factors and who ranged in age from young adults to centenarians. METHODS: We studied 319 healthy subjects (154 men, 165 women; age range, 21 to 105 years) with no history of hypertension, diabetes mellitus, or atherosclerotic disease. Mean intima-media wall thickness (IMT) of common carotid arteries at plaque-free sites and prevalence of plaques were evaluated by B-mode ultrasound. RESULTS: Mean common carotid IMT increased in a linear manner with age for all decades of life, including centenarians [IMT=(0.009xAge)+0.116] (r=0.83). In centenarians (n=30), intima-media complexes were diffusely thickened (mean IMT, 1.01 mm). Plaque prevalence increased up to the tenth decade of life (83.3%, n=30) but decreased in centenarians (60.0%). IMT and plaque prevalence were closely associated in the seventh and eighth decades of life but not at older ages. CONCLUSIONS: The present study indicates that increased IMT is a physiological effect of aging that corresponds to diffuse intimal thickening, especially in very elderly persons, and that IMT is distinct from pathological plaque formation.

Adult↗

Assessment of left ventricular systolic function using contrast two-dimensional echocardiography with a high-frequency transducer in the awake murine model of myocardial infarction.

The estimation of global left ventricular function using M-mode echocardiography has technical limitations in the murine model of myocardial infarction (MI), but the recent improvements in 2-dimensional (2-D) echocardiography using a high-frequency transducer provide more accessible images. Furthermore, intravenous injection of contrast agent has the additional benefit of enhancing the endocardial border in the murine heart. The present study was designed to evaluate the value of 2-D echocardiography with intravenous injection of contrast agent in the assessment of global systolic function of the murine heart with MI. Two-dimensional and M-mode echocardiography without and with intravenous injection of contrast agent (Optison, 0.1-0.15 ml) were performed in 76 awake mice 2 days before and 2 days after left coronary artery ligation. Fractional shortening (FS) was calculated from the end-diastolic and end-systolic diameters on M-mode echocardiography, and fractional area change (FAC) from the end-diastolic and end-systolic areas on 2-D echocardiography. Both FS and FAC were compared with the areas of hypoperfusion observed in the pathological samples. The use of contrast agent improved the number of hearts that could be evaluated by both the M-mode and 2-D method (M-mode: non-contrast 87% vs contrast 99%, p<0.01; 2-D: non-contrast 26% vs contrast 89%, p<0.001). FAC from the 2-D method correlated better with the region of hypoperfusion in the pathological samples than did FS from the M-mode method (FAC: r=0.84 vs FS: r=0.51). In conclusion, FAC obtained from 2-D contrast echocardiography is useful for noninvasive assessment of global systolic function in infarcted murine hearts and can be used to serially assess systolic function in various models of the murine heart.

Albumins↗

Relationship between the enzymatic browning and phenylalanine ammonia-lyase activity of cut lettuce, and the prevention of browning by inhibitors of polyphenol biosynthesis.

Cut lettuce stored at 4 degrees C gradually turned brown on the cut section after several days of storage. Three factors for enzymatic browning, the polyphenol content, polyphenol oxidase activity, and phenylalanine ammonia-lyase (PAL) activity, were examined during the cold storage of cut lettuce. A relationship between the browning and PAL activity was apparent. We tried to prevent this browning by using the two enzyme inhibitors, 2-aminoindane-2-phosphonic acid (AIP), an inhibitor of the phenylpropanoid pathway, and glyphosate, an inhibitor of the shikimate pathway. AIP and glyphosate significantly inhibited the browning of cut lettuce. The polyphenol content and PAL activity were both reduced by the treatment with AIP. These results show that regulating the biosynthesis of polyphenols is essential to prevent the browning of cut lettuce.

Catechol Oxidase↗

A transgenic apple callus showing reduced polyphenol oxidase activity and lower browning potential.

Polyphenol oxidase (PPO) is responsible for enzymatic browning of apples. Apples lacking PPO activity might be useful not only for the food industry but also for studies of the metabolism of polyphenols and the function of PPO. Transgenic apple calli were prepared by using Agrobacterium tumefaciens carrying the kanamycin (KM) resistant gene and antisense PPO gene. Four KM-resistant callus lines were obtained from 356 leaf explants. Among these transgenic calli, three calli grew on the medium containing KM at the same rate as non-transgenic callus on the medium without KM. One callus line had an antisense PPO gene, in which the amount and activity of PPO were reduced to half the amount and activity in non-transgenic callus. The browning potential of this line, which was estimated by adding chlorogenic acid, was also half the browning potential of non-transgenic callus.

Agrobacterium tumefaciens↗

Nephron distribution of total low Km cyclic AMP phosphodiesterase in mouse, rat and rabbit kidney.

The activity of cAMP degradation enzyme, cAMP phosphodiesterase (cAMP PDE), in renal tubules is a critically important factor in determining cellular cAMP levels, particularly in response to hormones. In this study we examine the nephron distribution of cAMP PDE activity in the mouse, rat and rabbit kidney and important cellular regulators of cAMP PDE, namely calmodulin and adenosine triphosphate (ATP). We assayed total low Km cAMP PDE in microdissected tubule segments, using 10(-6) M (3H) cAMP as a substrate. Activities were expressed in fentomol cAMP hydrolyzed per minute per mm tubular length or per one glomerulus. The content of ATP was measured in outer medullary collecting duct and medullary thick ascending limb of Henle's loop with microbioluminescence assay using firefly luciferase. In mouse kidney, cAMP PDE was significantly higher in all tubular segments compared to glomerulus. Proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb of Henle's loop (mTAL), and outer medullary collecting duct (OMCD) had intermediated activity. Greater cAMP PDE activity was detected in cortical ascending limb of Henle's loop (cTAL), cortical collecting duct and in distal convoluted tubule (DCT). The highest activity was found in connecting tubules. In rat, nephron distribution of cAMP PDE activities was similar to mouse, except that activity in glomeruli was higher than in mouse glomeruli. In rabbit, nephron distribution of cAMP PDE activities was different from those of mouse and rat. There was no single prominent segment with high cAMP PDE activity. DCT and cTAL showed low enzyme activity. Overall, the highest cAMP PDE activities were measured in the mouse and the lowest were measured in the rabbit nephrons, with those of rat nephron showing an intermediate activity. The maximum effective dose of the calmodulin antagonist, trifluoperazine (200 microM), inhibited cAMP PDE in all nephron segments from the rat kidney. However, there is no statistical significance of its inhibition among nephron segments. In OMCD and mTAL of the rat kidney, cAMP PDE activity was inhibited by ATP (5 mM to approximately 10 mM) which is far beyond the physiological concentartion of ATP in normal epithelial cell. Actual determinations of ATP in mTAL and OMCD were 0.1 mM and 0.17 mM, respectively. These observations show that distal segments of tubules have more active catabolism of cAMP than proximal segments. cAMP PDE in each nephron segment appear to be almost equally dependent on trifluoperazine-sensitive pathway that may reflect the Ca2+-calmodulin system. Cellular concentration of ATP might not be involved in the regulation of the total low Km cAMP PDE activity in rat mTAL and OMCD.

3',5'-Cyclic-AMP Phosphodiesterases↗

Roles of caspases in the programmed cell death of motoneurons in vivo.

Cysteine proteases comprising the caspase family have been considered one of the major executioners of programmed cell death. However, detailed analyses of the programmed cell death of developing motoneurons in mice following the genetic deletion of two key caspases, casp-3 and casp-9, and in the chick embryo following treatment with caspase inhibitors, indicate that normal amounts of cell loss occur although the death process is delayed. Motoneurons undergoing programmed cell death without caspase activities exhibit a nonapoptotic morphology in which nuclear changes such as chromatin condensation are absent or reduced and which exhibit extensive cytoplasmic vacuolization such as is rarely observed in degenerating control neurons. These results suggest that caspases are involved in, but are not indispensable for, the developmental death of motoneurons, and that one function of caspases may be to facilitate the removal of cells that are destined to die. Possible alternative caspase-independent pathways for the programmed death of motoneurons are discussed.

Animals↗

Hypoglycemia induced by secretion of high molecular weight insulin-like growth factor-II from a malignant solitary fibrous tumor of the pleura.

A 49-year-old woman with a malignant solitary fibrous tumor of the pleura presented with hypoglycemia. Most of the serum insulin-like growth factor II (IGF-II) existed as high molecular weight IGF-II. Furthermore, there were larger amounts of high molecular weight IGF-II found in the tumor cystic fluid than in the serum. After surgical resection of the tumor, high molecular weight IGF-II was not detected in the serum and the hypoglycemia resolved. Immunohistochemically, IGF-II was localized in the so-called Golgi area of the tumor cell. These findings suggest that hypoglycemia in this patient was caused by the high molecular weight IGF-II produced by the tumor.

Female↗

[Suggestions from a centenarian study--aging and inflammation].

With the numbers of elderly increasing rapidly, it is important for both individuals and society that the oldest old maintains autonomy. To know how to attain successful aging, we investigate the status of centenarians. The characteristics of centenarians in Tokyo is 1) low level of nutritional parameters, 2) low level of cholesterol and HDL-cholesterol, 3) low level of red blood cells and hemoglobin, 4) high level of CRP, 5) high level of homocysteine, 6) high level of von Willbrand factor. The incidence of dementia is 59.3%. Are these characteristics due to aging itself or other factors? We examined the effect of nutritional status, inflammation and level of homocysteine on the characteristics. The level of albumin is associated with serum level of lipid, RBC, ADL and cognitive function. The level of CRP is related to the level of albumin, suggesting that inflammation is related to nutritional status. The level of homocysteine is associated with the level of von Willbrand factor, suggesting that homocysteine is related to endothelial injury. From these data, we propose the hypothesis that proinflammatory status is associated with aging, resulting in a part of characteristics of centenarians. Homocysteine is partly responsible for endothelial injury. Intervention to suppress proinflammatory status and homocysteine level may promote QOL in the oldest old.

Aged↗

cAMP pulse during preservation inhibits the late development of cardiac isograft and allograft vasculopathy.

The causes of transplant-associated coronary artery disease remain obscure, and there is no known treatment. Preservation injury of murine heterotopic vascularized cardiac isografts caused a small, albeit significant, increase in neointimal formation; preservation injury of allografts markedly increased both the incidence and severity of transplant-associated coronary artery disease. As cAMP is an important vascular homeostatic mediator the levels of which decline during organ preservation, buttressing cAMP levels solely during initial preservation both improved acute allograft function and reduced the severity of transplant-associated coronary artery disease in grafts examined 2 months later. Inhibiting the cAMP-dependent protein kinase abrogated these beneficial effects. cAMP treatment was associated with an early reduction in leukocyte infiltration and a reciprocal decrease in superoxide and increase in NO levels. These data indicate that alloantigen-independent injury to the graft, which occurs at the time of cardiac preservation, can set in motion pathological vascular events that are manifest months later. Furthermore, a cAMP pulse during cardiac preservation reduces the incidence and severity of transplant-associated coronary artery disease.

Animals↗

Expression pattern of GDNF, c-ret, and GFRalphas suggests novel roles for GDNF ligands during early organogenesis in the chick embryo.

We have cloned a partial cDNA of chicken glial cell line-derived neurotrophic factor (GDNF) and systematically examined its expression pattern as well as that of GDNF-binding components (GDNF family receptor alpha-1 and 2: GFRalpha-1 and 2) and a common signal transduction receptor (c-ret protooncogene: RET) during very early developmental stages. In addition, we also examined the expression pattern of an apparent avian-specific binding component, GFRalpha-4. The cloned chicken cDNA for GDNF had approximately 80% homology to mammalian counterparts. The expression of GDNF mRNA occurred in many spatially and temporally discrete regions such as the intermediate mesoderm, the floor plate of the spinal cord, pharyngeal endoderm contacting the epibranchial placodes, distal ganglia of cranial nerves, subpopulations of mesenchyme cells in the craniofacial region, and in the mesodermal wall of the digestive tract. Both a GDNF receptor signal transduction component (RET) and a binding component (GFRalpha-1 or GFRalpha-2) were independently expressed in nearby interacting tissues such as the somites, peripheral and central nervous system, and mesenchyme cells in the craniofacial region. These observations suggest that possible combinations of novel unidentified receptors acting with RET or with GFRalphas may mediate GDNF-derived signals and indicate that GDNF or other family members may have previously unidentified actions in early organogenesis in the chick embryo.

Amino Acid Sequence↗

Isopower mapping of electrogastrograms in short-bowel syndrome.

Methods for making topographic or isopower electrogastrographic (EGG) maps and for obtaining maximum power foci (MPFs) by means of 27-channel EGG recordings are briefly described. The methods are applied to short-bowel syndrome (SBS). The gastro-intestinal tract is traced by videofluorograms after X-ray-opaque barium has been ingested. The MPFs are generally located on the trace of the gastro-intestinal tract. The gastric area is occupied by 3 cycles x min(-1) (up to 28% of total MPFs) and 6 cycles x min(-1) MPFs (26%). The trace of the small intestine is occupied mainly by 8 cycles x min(-1) (39%) and 10 cycles x min(-1) (43%) MPFs. The trace of the colon is occupied almost evenly by all five spectral frequency groups, that is, by 1 (58%), 3 (53%), 6 (48%), 8 (57%) and 10 cycles x min(-1) (42%). Most interestingly, the numbers of 8-10 cycles x min(-1) power foci found on EGG maps (including MPFs and relatively higher power foci) are proportional to the remaining length at operation and to the length of the remaining small intestine in the long-term, over 6 years postoperatively. It is therefore possible to follow approximately the trace of the gastero-intestinal tract.

Adolescent↗

Key factors influencing bowel function after ileal W-pouch anal anastomosis: a spectral analysis of W-pouch motor activity.

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure-volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = -0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch.

Adult↗

Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure.

OBJECTIVES: To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure. BACKGROUND: Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown. METHODS: Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo. RESULTS: In response to oral administration of a single dose of study drug, the change in flow-mediated vasodilation after release of 1, 3 and 5 min of arterial occlusion was significantly greater in patients receiving sildenafil 25 mg (3.3 +/- 1.9, 3.8 +/- 1.8 and 4.0 +/- 1.8%, respectively, p < 0.05) and patients receiving sildenafil 50 mg (3.7 +/- 1.3, 4.1 +/- 1.1, 3.9 +/- 1.3%, respectively, p < 0.05) than that of patients receiving placebo (0.7 +/- 1.1, 0.2 +/- 1.2, 0.6 +/- 0.8%, respectively). CONCLUSIONS: Acute type 5 phosphodiesterase inhibition with sildenafil 25 and 50 mg increases endothelium-dependent, flow-mediated vasodilation in patients with chronic heart failure when compared with placebo.

Blood Circulation↗

Transgenic apple (Malus x domestica) shoot showing low browning potential.

Transgenic apple shoots were prepared from leaf disks by using Agrobacterium tumefaciens carrying the kanamycin (KM) resistance gene and antisense polyphenol oxidase (PPO) DNA. Four transgenic apple lines that grew on the medium containing 50 microgram/mL KM were obtained. They contained the KM resistance gene and grew stably on the medium for >3 years. Two transgenic shoot lines containing antisense PPO DNA in which PPO activity was repressed showed a lower browning potential than a control shoot.

Agrobacterium tumefaciens↗