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Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.

Active Transport, Cell Nucleus↗
PubMed2001

Murine and human SDF2L1 is an endoplasmic reticulum stress-inducible gene and encodes a new member of the Pmt/rt protein family.

We isolated murine and human cDNAs for SDF2L1 (stromal cell-derived factor 2-like1) and characterized the genomic structures. Northern blot analysis of the gene expression in various tissues revealed that both murine Sdf2l1 and human SDF2L1 genes are expressed ubiquitously, with particularly high expression in the testis. The SDF2L1 protein has an endoplasmic reticulum (ER)-retention-like motif, HDEL, at the carboxy (C)-terminus. Interestingly, SDF2L1 protein also shows significant similarity to the central hydrophilic part of protein O-mannosyltransferase (Pmt) proteins of Saccharomyces cerevisiae, the human homologues of Pmt (POMT1 and POMT2) and Drosophila melanogaster rotated abdomen (rt) protein. In a murine hepatocellular carcinoma cell line, Sdf2l1 was strongly induced by tunicamycin and a calcium ionophore, A23187, and weakly induced by heat stress but was not induced by cycloheximide. In conclusion, SDF2L1 protein is a new member of Pmt/rt protein family and Sdf2l1 is a new ER stress-inducible gene.

Amino Acid Sequence↗
PubMed2001

Focal eosinophilic myositis.

Idiopathic hypereosinophilic syndrome (HES) is a heterogeneous group of disorders with the common features of prolonged eosinophilia of underdetermined cause and multiple organ system dysfunction. Focal eosinophilic myositis is an uncommon manifestation of HES. We report a case of focal eosinophilic myositis with tender muscle swelling followed by proximal weakness, but without non-systemic symptoms and muscle trophism in the lower limbs. Muscle biopsy specimen showed acute myositis with eosinophil infiltration. Electromyographic features were typical of myositis. The clinical and biochemical response to corticosteroids was excellent, and a relapse that occurred because the steroid dose was not lowered, responded well.

Adult↗
PubMed2001

Lymphocyte proliferation in response to acute heavy resistance exercise in women: influence of muscle strength and total work.

Little is understood about the immune responses to heavy resistance exercise. The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on lymphocyte proliferation after an acute bout of heavy resistance exercise. A group of 50 healthy but nonstrength trained women were recruited for the study and tested for their one repetition maximum (i.e. 1 RM or maximal mass lifted once). From the normal distribution of strength the top and bottom 8 women [mean age 22.5 (SD 3.1) years] were asked to volunteer to define our two groups (i.e. high strength and low strength). The two groups were significantly different (P < 0.05) in 1 RM squat strength [low strength 39.9 (SD 4.6) kg, 0.65 (SD 0.08) kg.kg body mass-1 and high strength 72.2 (SD 10.7) kg, 1.1 (SD 0.12) kg.kg body mass-1] but were not significantly different in body mass, age, activity levels, and menstrual status (all in same phase). Each performed a resistance exercise protocol consisting of six sets of 10 RM squats with 2 min rest between the sets. The 10 RM loads and total work were significantly greater in the high strength group than in the low strength group. Blood samples were obtained pre-exercise and immediately post-exercise for test for lactate (significant increase with exercise) and cortisol (no changes) concentrations with no differences noted between groups. Immunological assays on the blood samples determined the incorporation of tritiated thymidine by lymphocytes in responses to concanavalin A (ConA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Following the squat exercise, there was a significant decrease in lymphocyte responsiveness to PWM in the high strength but not in the low strength group for both total proliferation and proliferation adjusted per B or T cell. On the other hand, lymphocytes from the low strength group proliferated to a significantly greater extent (adjusted per T cell) in response to ConA and PHA. These data indicate that the heavy resistance exercise protocol reduced the lymphocyte proliferative responses only in the stronger group of subjects. This effect may have been due to the high absolute total work and the greater exercise stress created by the resistance exercise protocol in the high strength group. Therefore, individuals performing at the same relative exercise intensity (i.e. 10 RM) in a resistance exercise protocol may have different immune responses stemming from differences in absolute total work performance.

Adult↗
PubMed2001

Brome mosaic virus replicase proteins localize with the movement protein at infection-specific cytoplasmic inclusions in infected barley leaf cells.

Subcellular localization of the Brome mosaic virus replicase-related 1a and 2a proteins, and the 3a movement protein in infected barley leaves was examined by immunogold electron microscopy. The 1a and 2a proteins colocalized at infection-specific electron-dense cytoplasmic inclusions. The 3a protein was also detected in these inclusions. The inclusions were oval or amorphous, and contained electron-lucent regions. Electron microscopic autoradiography showed that the inclusions were sites of [3H]uridine incorporation, suggesting that they are sites of viral RNA synthesis.

Bromovirus↗
PubMed2001

Primary Sjögren's syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest.

We report a case of hypokalaemic, flaccid quadriparesis with sudden respiratory arrest in a 27-year-old Japanese woman in whom the discovery of distal renal tubular acidosis led to the diagnosis of primary Sjögren's syndrome (SS). Hypokalaemic periodic paralysis as the initial manifestation of primary SS is rare, but when it occurs it may precede symptoms of xerostomia and xerophthalmia. The diagnosis of primary SS should be considered in premenopausal women who present with rapidly progressive weakness and hypokalaemia. with or without the sicca complex.

Adult↗
PubMed2001

Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro.

OBJECTIVE: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM concentration is increased in patients with various heart diseases, and both myocytes (MCs) and non-myocytes (NMCs) secrete AM and express its receptors. These facts suggest that cardiac cells possess an autocrine/paracrine capability mediated by AM. METHODS: MCs and NMCs were prepared from cardiac ventricles of neonatal rats. AM and endothelin-1 concentrations were measured by radioimmunoassays, and interleukin-6 level by a specific bioassay. Total nitrite/nitrate contents were measured with a fluorescence assay kit. RESULTS: A basal secretion rate of AM from NMCs was 2.8-fold higher than that from MCs. Interleukin-1beta, tumor necrosis factor-alpha and lipopolysaccharide stimulated AM secretion from NMCs but not from MCs. AM stimulated interleukin-6 production in the presence of these cytokines or lipopolysaccharide, which was more prominent in NMCs. In the presence of interleukin-1beta, AM augmented nitric oxide synthesis 2.7-fold in NMCs, but slightly in MCs. NMCs secreted endothelin-1 at a rate nine times higher than MCs, and AM inhibited endothelin-1 secretion from NMCs. CONCLUSION: This in vitro study suggests that AM in the heart is mainly produced in NMCs and exerts its effects through NMCs, especially under inflammatory conditions.

Adrenomedullin↗
PubMed2001

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Aged↗
PubMed2001

C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and peritoneal macrophages.

OBJECTIVE: C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Cultured endothelial cells secrete CNP, and its secretion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha, which participate in the pathophysiology of inflammation. In this study, we investigated the regulation of CNP secretion from monocytes and macrophages to estimate its contribution to the progression of inflammation. MATERIALS AND METHODS: CNP secretion rates from two human leukemia cell lines (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, monocytes, monocyte-derived macrophages, and mouse peritoneal macrophages were measured under conditions with or without stimulation. Immunoreactive CNP levels in the culture media of these cells were measured by a specific radioimmunoassay. RESULTS: The secretion rates of CNP from THP-1 and HL-60 cells were augmented according to the degree of their differentiation into macrophage-like cells under the stimulation with phorbol ester. Peripheral blood monocytes also increased the CNP secretion rate after their differentiation into macrophages. Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gamma, interleukin-1beta, tumor necrosis factor-alpha, or phorbol ester. In contrast, the phorbol ester-stimulated CNP secretion rate from THP-1 cells was suppressed with dexamethasone, which inhibits monocyte differentiation into macrophage. CONCLUSIONS: The secretion rate of CNP from monocytes was shown to be regulated based on the degree of their differentiation. This study provides evidence that the monocyte/macrophage system is one of the sources of CNP, especially under inflammatory conditions.

Animals↗
PubMed2001

Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis.

In this study, we measured the mRNA levels of adrenomedullin (AM), C-type natriuretic peptide, vascular endothelial growth factor, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive) and 30 healthy volunteers. mRNA levels were measured using a real-time quantitative PCR METHOD: Compared with healthy volunteers, IL-6 mRNA levels were elevated in LN patients (P < 0.005), while AM mRNA levels were decreased (P < 0.05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in active LN patients compared with inactive LN patients. In addition, IL-6 mRNA levels positively correlated and AM mRNA levels negatively correlated with SLE disease activity index and laboratory findings, such as blood urea nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary excretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negatively correlated with AM mRNA levels within the same LN patients. With regard to pathological findings, our results showed that IL-6 mRNA levels were higher, and AM mRNA levels significantly lower in patients with a high activity index compared to those with a low activity index. Following treatment with prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRNA levels increased to levels comparable to those in inactive LN and healthy volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA levels in active LN patient PBMC were suppressed by the addition of adrenomedullin. Our results suggest that an imbalance between IL-6 and AM levels may play an important role in the progression of SLE, and that the mRNA levels of these genes in PBMC may be used as a disease activity index for SLE.

Adrenomedullin↗
PubMed2001

Predictors of diabetic renal lesions in type 2 diabetes associated with microalbuminuria.

Not all type 2 diabetic patients with microalbuminuria show the same pattern of renal tissue injury, and heterogeneity in renal lesions has been reported. We determine clinical and laboratory findings that predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria. Twenty-three type 2 diabetic patients with microalbuminuria who underwent renal biopsy were investigated. Two patterns of renal biopsy findings were defined as type D (typical diabetic glomerulosclerosis) and type A (atherosclerotic nephropathy without evidence of diabetic glomerulopathy). Thirteen patients (57%) were classified as type D, and 10 (43%) as type A. In stepwise multiple regression analysis, severity of diabetic retinopathy (P = 0.0006), relatively high urinary N-acetyl-beta-D-glucosaminidase activity (P = 0.0013), and relatively low serum creatinine concentration (P = 0.0303) significantly predicted type D findings as opposed to type A (R2 = 0.734, P < 0.001). Certain patient characteristics can predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria.

Aged↗
PubMed2001

Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using the spin trap method.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide-DMPO spin adduct was strongly inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Low-volume circuit versus high-volume periodized resistance training in women.

PURPOSE: The purpose of this investigation was to determine the long-term training adaptations associated with low-volume circuit-type versus periodized high-volume resistance training programs in women. METHODS: 34 healthy, untrained women were randomly placed into one of the following groups: low-volume, single-set circuit (SSC; N = 12); periodized high-volume multiple-set (MS; N = 12); or nonexercising control (CON) group (N = 10). The SSC group performed one set of 8-12 repetitions to muscular failure 3 d x wk(-1). The MS group performed two to four sets of 3-15 repetitions with periodized volume and intensity 4 d x wk(-1). Muscular strength, power, speed, endurance, anthropometry, and resting hormonal concentrations were determined pretraining (T1), after 12 wk (T2), and after 24 wk of training (T3). RESULTS: 1-RM bench press and leg press, and upper and lower body local muscular endurance increased significantly (P < or = 0.05) at T2 for both groups, but only MS showed a significant increase at T3. Muscular power and speed increased significantly at T2 and T3 only for MS. Increases in testosterone were observed for both groups at T2 but only MS showed a significant increase at T3. Cortisol decreased from T1 to T2 and from T2 to T3 in MS. Insulin-like growth factor-1 increased significantly at T3 for SSC and at T2 and T3 for MS. No changes were observed for growth hormone in any of the training groups. CONCLUSION: Significant improvements in muscular performance may be attained with either a low-volume single-set program or a high-volume, periodized multiple-set program during the first 12 wk of training in untrained women. However, dramatically different training adaptations are associated with specific domains of training program design which contrast in speed of movement, exercise choices and use of variation (periodization) in the intensity and volume of exercise.

Adaptation, Physiological↗
PubMed2001

Effect of resistance training on women's strength/power and occupational performances.

PURPOSE: The effects of resistance training programs on strength, power, and military occupational task performances in women were examined. METHODS: Untrained women aged (mean +/- SD) 23 +/- 4 yr were matched and randomly placed in total- (TP, N = 17 and TH, N = 18) or upper-body resistance training (UP, N = 18 and UH, N = 15), field (FLD, N = 14), or aerobic training groups (AER, N = 11). Two periodized resistance training programs (with supplemental aerobic training) emphasized explosive exercise movements using 3- to 8-RM training loads (TP, UP), whereas the other two emphasized slower exercise movements using 8- to 12-RM loads (TH, UH). The FLD group performed plyometric and partner exercises. Subjects were tested for body composition, strength, power, endurance, maximal and repetitive box lift, 2-mile loaded run, and U.S. Army Physical Fitness Tests before (T0) and after 3 (T3) and 6 months of training (T6). For comparison, untrained men (N = 100) (MEN) were tested once. RESULTS: Specific training programs resulted in significant increases in body mass (TP), 1-RM squat (TP, TH, FLD), bench press (all except AER), high pull (TP), squat jump (TP, TH, FLD), bench throw (all except AER), squat endurance (all except AER), 1-RM box lift (all except aerobic), repetitive box lift (all), push-ups (all except AER), sit-ups (all except AER), and 2-mile run (all). CONCLUSIONS: Strength training improved physical performances of women over 6 months and adaptations in strength, power, and endurance were specific to the subtle differences (e.g., exercise choice and speeds of exercise movement) in the resistance training programs (strength/power vs strength/hypertrophy). Upper- and total-body resistance training resulted in similar improvements in occupational task performances, especially in tasks that involved upper-body musculature. Finally, gender differences in physical performance measures were reduced after resistance training in women, which underscores the importance of such training for physically demanding occupations.

Adolescent↗
PubMed2001

Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise.

This study evaluated the individual components of the insulin-like growth factor I (IGF-I) system [i.e., total and free IGF-I, insulin-like growth factor binding protein (IGFBP)-2 and -3, and the acid-labile subunit (ALS)] in 10 young, healthy men (age: 22 +/- 1 yr, height: 177 +/- 2 cm, weight: 79 +/- 3 kg, body fat: 11 +/- 1%) overnight for 13 h after two conditions: a resting control (Con) and an acute, heavy-resistance exercise protocol (Ex). The Ex was a high-volume, multiset exercise protocol that alternated between 10- and 5-repetition maximum sets with 90-s rest periods between sets. The Ex was performed from 1500 to 1700; blood was obtained immediately postexercise and sampled throughout the night (every 10 min for the first hour and every hour thereafter) until 0600 the next morning. For the first hour, significant differences (P < or = 0.05) were only observed for IGFBP-3 (Ex: 3,801 > Con: 3,531 ng/ml). For the overnight responses, no differences were observed for total or free IGF-I or IGFBP-3, whereas IGFBP-2 increased (Ex: 561 > Con: 500 ng/ml) and ALS decreased (Ex: 35 < Con: 39 microg/ml) after exercise. The results from this study suggest that the impact that resistance exercise exerts on the circulating IGF-I system is not in the alteration of the amount of IGF-I but rather of the manner in which IGF-I is partitioned among its family of binding proteins. Thus acute, heavy-resistance exercise can lead to alterations in the IGF-I system that can be detected in the systemic circulation.

Adult↗
PubMed2001

Enhanced expression of plasminogen activator inhibitor 1 in patients with nephrotic syndrome.

Hypercoagulability is present in patients with nephrotic syndrome. However, alterations in coagulation and fibrinolysis reflected in the glomeruli and urine are not fully understood. We examined plasma and urine concentrations of tissue-type plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) in 33 patients with nephrotic syndrome (nephrotic group). We compared these concentrations with the concentrations in 30 nonnephrotic patients with chronic glomerulonephritis (nonnephrotic group) and with the concentrations in 30 healthy volunteers (control group). We also examined fibrin/fibrinogen degradation products in serum and urine and plasma D-dimers. The expression of tPA and PAI-1 was examined in isolated glomeruli using RT-PCR methods. Deposition of fibrinogen/fibrin-related antigen was observed by direct immunofluorescence. The incidence of fibrinogen/fibrin-related antigen deposition in the nephrotic group was significantly higher than that in the nonnephrotic group. The concentrations of fibrin/fibrinogen degradation products in serum and urine and of plasma D-dimers were significantly elevated in the nephrotic group as compared with the nonnephrotic and control groups. The plasma concentrations of tPA in the nephrotic group were significantly higher than those in the control group. The urinary excretion of tPA in the nephrotic group was also significantly higher than in the nonnephrotic and control groups. The urinary excretion of PAI-1 in the nephrotic group was higher than that in the control group. The ratio of PAI-1 mRNA to tPA mRNA in glomeruli was increased in the nephrotic group as compared with the nonnephrotic group. These results indicate that the fibrinolytic activity is increased in patients with nephrotic syndrome despite urinary losses of tPA. However, a relatively enhanced expression of PAI-1 may be involved in the intraglomerular fibrinogen/fibrin-related antigen deposition seen in nephrotic syndrome.

Adolescent↗