Dehydroepiandrosterone sulfate and estradiol in men with diabetic nephropathy.
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Aged↗
Biomedical subjects
K Dohi
Publications and source records attributed to K Dohi.
Role of monocyte chemotactic peptide 1 in diabetic nephropathy.
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Adult↗
Serum levels of advanced glycosylation end products in diabetic nephropathy.
BACKGROUND/AIMS: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. METHODS: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. RESULTS: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 +/- 0.73 mU/ml; 15-24%, 4.01 +/- 0.71 mU/ml; 25% or more, 5.12 +/- 0.64 mU/ml). CONCLUSIONS: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.
Adult↗
FcgammaRIIa polymorphism in Japanese patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an immune complex-mediated disease and organ damage is caused by the deposition of immune complex. Receptors which recognize the Fc portion of immunoglobulin G (FcgammaR) play a key role in the phagocytosis of immune complexes. As the gene encoding for FcgammaR of class IIa (FcgammaRIIa) has two allelic forms, H131 and R131, which differ in their affinity to IgG2, this polymorphism might have implications in handling immune complex. We studied the distribution of the FcgammaRIIa polymorphism in 90 Japanese patients with SLE. We also examined the association between FcgammaRIIa polymorphism and the disease activity of SLE and the histopathological findings of lupus nephritis. FcgammaRIIa polymorphism was determined by PCR and dot blot analysis. The allelic frequency of H131 in patients with SLE was significantly lower (H131/R131 = 0.44/0.56) than that of normal controls (H131/R131 = 0.62/0.38; P < 0.05). No significant association was observed between FcgammaRIIa polymorphism and the clinical parameters for the activity of SLE. There was no association between FcgammaRIIa polymorphism and the histological findings in lupus nephritis. The difference in the distribution of FcgammaRIIa alleles between patients with SLE and normal subjects indicates that this polymorphism is a candidate of susceptibility gene for SLE in Japanese.
Adolescent↗
Functional role of endogenous endothelin-1 in congestive heart failure treated with angiotensin II receptor antagonist.
Interactions between angiotensin (ANG) II and endothelin (ET)-1 receptor transduction pathways have been unclear in congestive heart failure (CHF). Therefore the objects of this study are, in CHF, whether production of ET-1 is modulated by ANG II and/or whether hemodynamic effects of endogenous ET-1 are modulated by ANG II. Twelve dogs were randomly assigned to two groups: untreated (n = 6) and treated with ANG II type 1 (AT1) receptor antagonist (TCV116, 1.5 mg/kg/d) (n = 6). After rapid ventricular pacing (240 bpm) for 4 weeks, plasma and cardiac ET-1 levels were compared between the two groups. Acute hemodynamic effects of a nonspecific ET(A&B) receptor antagonist, TAK044 (3 mg/kg plus 3 mg/kg/h i.v.) were examined in both groups by a conductance catheter and a micromanometer. After 4 weeks of pacing, plasma and cardiac tissue ET-1 levels were elevated in both groups to a similar degree. In the group treated with TCV116, TAK044 produced an increase in stroke volume and a decrease in total systemic resistance; heart rate was unchanged. The time constant of left ventricular (LV) relaxation was significantly decreased. The slope of LV end-systolic pressure-volume relation (E(ES)) was increased (p < 0.05), indicating an increased LV contractility. Thus endogenous ET-1 produces an arterial vasoconstriction and impairs LV contractility and relaxation in CHF with AT1 receptor antagonism. These hemodynamic responses to TAK044 in CHF treated with TCV116 were similar in untreated CHF. These results suggest that the production of ET-1 and the cardiac effects of endogenous ET-1 in CHF may be unaffected by ANG II acting through AT1 receptors.
Angiotensin Receptor Antagonists↗
Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations.
Liddle's syndrome is a rare form of hereditary hypertension caused by mutations of the epithelial sodium (Na(+)) channel (ENaC). Analysis of the diseased pedigrees indicates an autosomal dominant inheritance, and the identified mutations are heterozygotes of gain-of-function mutations. However, sporadic cases of Liddle's syndrome have been reported in the literature, including one recently reported case caused by a de novo mutation of ENaC. We identified two patients with Liddle's syndrome who did not have family histories of hypertension. Sequence analysis showed a mutation in each case (P616L in betaENaC and W576X in gammaENaC), both confirmed to be de novo mutations. These data indicate that Liddle's syndrome should be considered even in patients without a family history of hypertension.
Adult↗
[A case of polyarteritis nodosa presenting as a mass in scrotum].
A 16-year-old boy with a painful tumor in the left scrotum was referred to our department. CT scans showed a low density area in the left testis, so we diagnosed a left testicular tumor and performed left inguinal orchiectomy. Histological examination revealed polyarteritis nodosa (PN) of the testis and epididymis. Systemic examination revealed no other evidence of PN. Although induration developed in the right epididymis after the operation, it resolved with steroid therapy. The patient is currently asymptomatic and is being followed at our clinic. The pathogenesis and management of this rare condition are discussed.
Adolescent↗
[Significance of retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy in patients with vasospastic angina].
OBJECTIVES: This study investigated retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) scintigraphy in patients with vasospastic angina. METHODS: Twenty-three patients with vasospastic angina showed abnormal uptake of BMIPP before medical treatment and had coronary vasospasm induced by acetylcholine. The patients were divided into two groups according to uptake of BMIPP after medical treatment: retardation of abnormal uptake of BMIPP(Group R, n = 4) and normal uptake of BMIPP(Group N, n = 19). Frequency of chest pain, medical treatment and autonomic nervous activity were compared between the two groups. Furthermore, the frequency of chest pain and uptake of BMIPP in group R were obtained after intensive medical treatment. Autonomic nervous activity was evaluated by heart rate variability on Holter electrocardiography. Heart rate variability contained high-frequency elements(HF; 0.15-0.4 Hz) and low-frequency elements(LF; 0.04-0.15 Hz). LF/HF was estimated for sympathetic nervous activity and HF was estimated for parasympathetic nervous activity. Daytime and nighttime autonomic nervous activity were compared between the two groups. RESULTS: The frequency of chest pain was higher in Group R than in Group N(p < 0.05). Medical treatment was not different between the two groups. Circadian variation of sympathetic and parasympathetic nervous activity were absent in Group R. During the nighttime, Group R showed higher sympathetic nervous activity(p < 0.05) and lower parasympathetic nervous activity(p < 0.01) than Group N. The frequency of chest pain was significantly lower after intensive medical treatment(p < 0.05), and uptake of BMIPP returned to normal in Group R. We suspected that the disorder in autonomic nervous activity was more severe in Group R, and thus induced coronary vasospasm. CONCLUSIONS: Retardation of abnormal uptake of BMIPP in patients with vasospastic angina indicates poor control of coronary vasospasm. Uptake of BMIPP is useful in the evaluation of coronary vasospasm control in such patients.
Adult↗
[Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia].
Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.
Acute Kidney Injury↗
Usefulness of long axis M-mode echocardiographic measurements for optimum dialysis in patients on maintenance hemodialysis: comparison with changes in plasma levels of atrial natriuretic peptide and brain natriuretic peptide.
UNLABELLED: It has been suggested that analyzing the left ventricular long axis motion can result in the sensitive detection of cardiac functional disorders. AIM: To evaluate the usefulness of left ventricular long axis indices in managing patients on maintenance hemodialysis. METHODS: Eighteen hemodialysis patients (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9 years) were examined. Echocardiograms were recorded, and the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured before and after a session of hemodialysis. The following parameters were measured: the left atrial diameter (LAD) and end-diastolic left ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A ratio from transmitral Doppler, the atrial systolic excursion of long axis motion of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode echocardiograms. RESULTS: LAD, LVDd, LVEDV, and ALAM showed a positive correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and plasma levels of ANP during hemodialysis were larger in the subgroup of ALAM < or = 0.55 cm before hemodialysis than in the subgroup of ALAM < 0.55 cm before hemodialysis. CONCLUSION: These results indicate that the left ventricular long axis index can detect a disorder of left ventricular diastolic function, and that a hemodialysis patient whose ALAM before hemodialysis is < 0.55 cm is dialyzed with good volume control conditions.
Adult↗
Elongation factor-1 alpha is a novel substrate of rho-associated kinase.
Rho-associated kinase (Rho-kinase), which is activated by the Rho small GTPase, phosphorylates the myosin-binding subunit (MBS) of myosin phosphatase, myosin light chain (MLC), the ERM family proteins, and adducin, thereby regulating the formation of stress fibers, focal adhesions, microvillus formation, and cell motility. Here, to further understand the role of Rho-kinase in the regulation of the numerous cellular processes by Rho, we purified a novel substrate of Rho-kinase having a molecular mass of 48 kDa (p48) from a rat liver cytosol extract. Mass spectral analysis revealed p48 to be elongation factor-1 alpha (EF-1 alpha), which is known as an actin-binding protein besides a cofactor of polypeptide elongation. Rho-kinase directly phosphorylated recombinant EF-1alpha in vitro. A high- speed cosedimentation assay revealed that phosphorylation of EF-1 alpha by Rho-kinase decreased the binding activity of EF-1 alpha to filamentous actin (F-actin). A low-speed sedimentation assay revealed that phosphorylation of EF-1 alpha by Rho-kinase decreased the F-actin-bundling activity. In addition, EF-1 alpha bound to MBS of myosin phosphatase, suggesting that both Rho-kinase and myosin phosphatase regulate the phosphorylation state of EF-1 alpha downstream of Rho as other substrates of Rho-kinase, i.e., MLC, adducin, and the ERM family. These results suggest that the Rho/Rho-kinase pathway regulates the organization of actin cytoskeleton via the phosphorylation of EF-1 alpha.
Actins↗
Affinity selection of cDNA libraries by lambda phage surface display.
Bacteriophage lambda surface display was used to isolate cDNA clones encoding autoantigens recognized by sera from patients with Sjögren's syndrome (SS). We made cDNA libraries from human HeLa and HepG2 cells, using the expression vector lambdafoo. By repeating affinity selection of the libraries with the sera immobilized in microtiter wells, we isolated three clones that encode previously unknown antigens as well as four clones previously known as SS autoantigens. The newly identified autoantigens include TRK-fused gene product (TFG), survival motor neuron gene product (SMN) and pM5, which has a similarity to the metal-binding domain of human fibroblast collagenase. Thus, the bacteriophage lambda surface display is powerful for isolating cDNA clones by affinity screening.
Antibody Affinity↗
[Physiopathology and treatment of focal segmental glomerulosclerosis].
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Adult↗
L-histidine but not D-histidine attenuates brain edema following cryogenic injury in rats.
Oxygen free radicals have been implicated in the genesis of traumatic brain injury and brain edema (BE). Recent studies have suggested that hydroxyl radical can initiate lipid peroxidation, thus producing lipid-free radicals that may become important sources of singlet oxygen. L-histidine, a singlet oxygen scavenger, potentially can be used to treat BE. In this study we investigated the effects of L-histidine and D-histidine on BE following cryogenic injury in rats. Male Wistar rats were anaesthetized with chloral hydrate. Vasogenic BE was produced by a cortical freezing lesion. Generation of singlet oxygen from photoactivation of rose bengal was studied by electron spin resonance (ESR). Animals were separated into four groups: sham rats (n = 5), saline-treated rats (n = 10), L-histidine treated rats (n = 6) and D-histidine treated rats (n = 7). Each agent (100 mg/kg) was administered intravenously at 30 minutes before lesion production. Animals were sacrificed at 24 hours after lesion production and the brain water content was determined by the dry-wet weight method. L-histidine had no effect on rectal and brain temperature. Election Spin Resonance studies demonstrated that L-histidine is a singlet oxygen scavenger. L-histidine but not D-histidine significantly attenuated BE following cryogenic injury (p < 0.05). In conclusion, L-histidine is useful in the treatment of traumatic BE.
Animals↗
Protective effect of a novel vitamin E derivative on experimental traumatic brain edema in rats--preliminary study.
Oxygen free radicals have been proposed to be one of the major mechanisms of secondary brain damage in traumatic brain injury. Protective effect by vitamin E against oxidative damage has attracted much attention. Recent studies have demonstrated a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), has excellent water-solubility and antioxidant activity. The purpose of this study was to investigate protective effects of TMG on experimental traumatic brain edema (BE). Male Wistar rats were anaesthetized with chloral hydrate. Traumatic BE was produced by a cortical freezing lesion. Animals were separated into three groups: saline-treated rats (n = 4), TMG-treated (4 mg/kg) rats (n = 7) and TMG-treated (40 mg/kg) rats (n = 8). Saline or TMG was administered intravenously before lesion production. Animals were sacrificed at 6 hours after lesion production and the brain water content was determined by the dry-wet weight method. Half-life of TMG after intravenous administration of TMG was also investigated. The half life of TMG was approximately 5 minutes. TMG (40 mg/kg) significantly attenuated BE following cryogenic brain injury (p < 0.01). In conclusion, this preliminary study has demonstrated that a novel vitamin E derivative might be promising in the treatment of traumatic BE.
Animals↗
Secreted protein acidic and rich in cysteine (SPARC) in patients with diabetic nephropathy and tubulointerstitial injury.
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Aged↗
Nondestructive and real-time evaluation of liver viability in brain dead donor for liver transplantation using near-infrared spectroscopy.
A reliable and less-invasive method is currently desired to assess the hemodynamic and functional alteration associated with brain death in the organs of donor candidates. Near-infrared spectroscopy (NIRs) was applied to rat liver in brain-dead donors for assessing tissue oxygenation and intracellular energy metabolism as a means of monitoring the liver viability in the brain-dead donor. Brain-dead rats were divided into 4 according to doses of epinephrine and vasopressin administered. Arterial ketone bodies ratio (AKBR), hyaluronic acid (HA), and NIRs monitoring of a liver graft were performed in the brain-dead phase before the grafts were transplanted into syngeneic rats. NIRs monitoring of oxygenated hemoglobin (Hb) and cytochrome aa3 oxidase (Cytaa3) redox state reflected changes in the hepatic microcirculation and intracellular oxygenation. The administration of high-dose epinephrine proved to be contraindicated due to catecholamine-induced hypoxic stress, while combined administration of adrenaline and vasopressin at an optimal dose rate was beneficial for preservation of the liver viability. The data obtained by NIRs were significantly correlated with the 7-day survival of recipients after liver transplantation. Thus, we conclude that NIRs is a sensitive and nondestructive method for monitoring alterations in the viability of brain-dead liver and can predict liver graft outcome.
Animals↗
Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.
It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.
Administration, Oral↗