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Biomedical subjects

Y Maruyama

Publications and source records attributed to Y Maruyama.

At least 91 records · Page 5Linked to original sources

Association of Graves' disease with Evans' syndrome in a patient with IgA nephropathy.

A 20-year-old woman with IgA nephropathy was admitted to Jikei University Hospital for the treatment of rapid deterioration of renal function after receiving 131I-therapy against hyperthyroidism on October 23,1999, and hemodialysis was started. On admission, she was diagnosed as having Evans' syndrome in addition to known Graves' disease. Renal biopsy revealed end-stage renal damage, then, hemodialysis was maintained. Treatment for Evans' syndrome was also started and her general condition gradually improved. The present case implied that "Graves' disease" and "Evans' syndrome" could represent some of the manifestations of an underlying immunological disorder in the patient.

Adult↗

High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT.

OBJECTIVE: The purpose of this study was to determine the correlation between high-resolution CT morphologic features of small peripheral lung adenocarcinomas and tumor growth patterns. MATERIALS AND METHODS: We examined high-resolution CT morphologic features of 59 small, surgically resected peripheral lung adenocarcinomas (diameter, 6-20 mm) that were detected on screening for lung cancer using low-dose helical CT. Among these adenocarcinomas, 14 (24%) were visible and 45 (76%) were invisible on conventional chest radiography. The correlation between high-resolution CT morphologic features and tumor growth patterns was analyzed. RESULTS: Sixteen (94%) of 17 type A (Noguchi's classification) adenocarcinomas appeared as nodules of pure ground-glass attenuation (high-resolution CT type I). Ten (71%) of 14 type B tumors appeared as heterogeneous, low-attenuation nodules (type II). Seven (29%) of 24 type C tumors appeared as nodules with ground-glass attenuation in the periphery and a high-density central zone (type III), and 12 (50%) of 24 type C tumors appeared as homogeneous nodules with soft-tissue density (type IV). Among tumors with a replacement growth pattern, the size and CT values of type C tumors were larger than those of type A or type B tumors (p < 0.05), whereas the percentage of ground-glass attenuation and retained air space in type C tumors was smaller than those in type A or type B tumors (p < 0.01). All (100%) four type D tumors appeared to be homogeneous nodules with soft-tissue density (type IV). CONCLUSION: Small peripheral lung adenocarcinomas shown on CT exhibit four high-resolution CT patterns that corresponded to the histopathologic findings of different tumor growth patterns.

Adenocarcinoma↗

Immune thrombocytopenia in an elderly patient treated successfully by pulse therapy with cyclophosphamide.

Thrombocytopenia due to immune mechanisms is rare and difficult to manage in elderly patients. We describe a case of an 89-year-old female with severe immune thrombocytopenia (ITP) who rapidly improved by pulse therapy with cyclophosphamide. She was admitted to our hospital because she had arthralgia in both sides of her femoral region since January 1999, aphthous stomatitis and ecchymosis of the leg since April 1999, and bloody phlegm in July 1999. On admission, her peripheral blood count revealed severe thrombocytopenia (0.1 x 10(4)/microl). Her megakaryocyte count from bone marrow was increased to 512/microl without abnormal cells. Systemic lupus erythematosus was suspected because of strong positive protein in the urine in addition to the clinical and hematological findings described above, but she was negative for all the autoantibodies examined. Finally, she was diagnosed as having ITP on the basis of high platelet associated immunoglobulin G in addition to hematological and physical findings and she was treated with prednisolone. It was difficult to maintain her platelet count with only prednisolone, but 600 mg of cyclophosphamide rapidly increased her platelet count in spite of tapering the prednisolone. In September 2000, her platelet count was kept within normal limits by administration of 15 mg/day of prednisolon. It is suggested that immunosuppressive therapy for ITP using high-dose cyclophosphamide is useful in elderly patients as well as in juvenile adult patients.

Aged↗

Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis.

Recent developments in our understanding of the atherosclerotic process and factors that trigger ischemic cardiovascular disease have led to the consideration of antioxidative responses or exogenous antioxidants, which are proposed to inhibit multiple proatherogenic and prothrombotic events in arterial wall. Heme oxygenases (HO), an enzyme essential for heme degradation, have been shown to have such antioxidative properties via the production of bile pigments, carbon monoxide and ferritin induction. We have demonstrated that mildly oxidized LDL markedly induces HO-1, an inducible form of HO, in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis induced by mildly oxidized LDL. We also confirmed abundant expression of HO-1 in human, murine and rabbit atherosclerotic lesions. By modulating HO activities in LDL-receptor knockout mice and Watanabe heritable hyperlipidemic rabbits during their atherosclerotic lesion developments, anti-atherogenic properties of HO have demonstrated as judged by the quantitative analyses of atherosclerotic lesion formation. HO expression was inversely correlated with the levels of plasma and tissue lipid peroxides. HO also influenced on nitric oxide pathway. These observations may suggest that HO, induced during atherosclerotic process, functions as an intrinsic protective pathway in vascular wall.

Animals↗

Involvement of Sp1 elements in the promoter activity of genes affected in keratoconus.

PURPOSE: Keratoconus is a progressive disease that thins and scars the corneal stroma. In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of the inhibitors alpha1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) are reduced, especially in the epithelial layer. An increased expression of the transcription factor Sp1 was also demonstrated. The role of Sp1 in regulation of the genes affected in keratoconus was examined in this study. METHODS: DNA segments, containing 5'-flanking promoter sequences of the alpha 1-PI, LAP, cathepsin B, and alpha 2-M genes were ligated into the secreted alkaline phosphatase (SEAP) reporter gene vector. These constructs, along with the pSV beta-galactosidase control vector, were transfected into cultured human corneal epithelial and stromal cells and skin fibroblasts. Cotransfection with the Sp1 expression vector was performed in parallel. SEAP and beta-galactosidase enzyme activities were assayed. RESULTS: In corneal epithelial cells, as in stromal cells, alpha 1-PI promoter activity was suppressed by cotransfection of pPacSp1. The LAP, cathepsin B, and alpha 2-M promoters were functional in corneal cells, whereas activities of these promoters were much lower in skin fibroblasts. Cotransfection experiments indicated that the up- or downregulation of LAP, cathepsin B, and alpha 2-M observed in keratoconus-affected corneas was not mediated by Sp1. CONCLUSIONS: These results support the theory that the corneal epithelium, along with the stroma, is involved in keratoconus. An upstream role of Sp1 is indicated and the Sp1-mediated downregulation of the alpha 1-PI gene may be a key event in the disease development.

Acid Phosphatase↗

[A case of enucleation for multiple renal cell carcinomas in unilateral kidney with microwave tissue coagulator].

A 67-year-old man, who had undergone left nephroureterectomy for ureteral tumor (transitional cell carcinoma, G1) eight years previously, was found to have two renal tumors in the residual right kidney by the follow-up computed tomography (CT). We performed non-ischemic enucleation for multiple tumors at the upper and lower pole in the unilateral kidney using a microwave tissue coagulator (MTC). We confirmed by means of ultrasonography during operation the absence of any other satellite tumors. The operation time was 154 minutes and bleeding during operation was 267 ml. There was no difference between creatinine before (0.73 mg/dl) and after (0.79 mg/dl) operation. On the follow-up CT, there was a low density area after enucleation. This area gradually decreased and disappeared on enhanced CT 18 months after operation. We enucleated multiple renal cell carcinomas using MTC without reduction of renal function or remarkable side effects. These results suggested that non-ischemic enucleation using MTC would be useful for multiple renal cell carcinoma in the unilateral kidney.

Aged↗

Association between circulating leptin and soluble receptors for tumor necrosis factor-alpha in hemodialysis patients.

BACKGROUND: The expression of leptin, an adipocyte-derived protein, is regulated by tumor necrosis factor-alpha (TNF-alpha). Since circulating leptin levels adjusted for body fat mass are reported to be increased in dialysis patients, we examined if the TNF-alpha system may influence blood leptin levels in hemodialysis (HD) patients. PATIENTS AND METHODS: Sixty-three stable HD patients who had no signs of infection, collagen disease or malignancy were enrolled in the study (age: 63 +/- 1 years, duration of HD: 14 +/- 1 years, male/female = 34/29). We measured serum leptin, TNF-alpha, soluble receptors for TNF-alpha (sTNFR p55, p80) and interleukin-6 (IL-6) concentrations with ELISA kits. Body fat mass was determined using DEXA. To evaluate the potential association between serum leptin and the TNF-alpha system, we compared serum leptin and sTNFR levels, which has been validated as a sensitive marker of activation of the TNF-alpha system. RESULTS: Serum leptin levels were significantly higher in female patients compared to male patients (14.07 +/- 3.60 vs. 4.26 +/- 0.85 ng/ml, p < 0.005). A strong correlation was found between serum leptin levels and estimated body fat mass both in males (r = 0.742, p < 0.0001) and females (r = 0.769, p < 0.001), respectively. Serum TNF-alpha, sTNFR p55, p80 and IL-6 levels were significantly increased in HD patients compared to normal subjects. However, no association was found between serum leptin and serum TNF-alpha, sTNFR p55, p80 and IL-6 levels. Serum leptin levels were significantly correlated with the atherosclerotic index both in men (r = 0.382, p = 0.027) and women (r = 0.281, p = 0.041). In contrast, there was no relationship between circulating leptin values and serum albumin, transferrin, creatinine levels, or normalized protein catabolic rate in each sex. CONCLUSION: These findings suggested that serum leptin is independent of the TNF-alpha system, and is mainly correlated with body fat volume in HD patients. Elevation of circulating leptin may be associated with the disturbance of the serum lipid profile rather than malnutrition in patients receiving long-term HD.

Adipose Tissue↗

G alpha(i) and G alpha(o) are target proteins of reactive oxygen species.

Reactive oxygen species (ROS) have been identified as central mediators in certain signalling events. In the heart, ROS have important functions in ischaemia/reperfusion-induced cardiac injury and in cytokine-stimulated hypertrophy. Extracellular signal-regulated kinase (ERK) is one of the ROS-responsive serine/threonine kinases. Previous studies showed that tyrosine kinases and small G proteins are involved in the activation of ERK by ROS; however, the initial target protein of ROS that leads to ERK activation remains unknown. Here we show that inhibition of the betagamma-subunit of G protein (G betagamma) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The G betagamma-responsive ERK activation induced by H2O2 is independent of ligands binding to Gi-coupled receptors, but requires phosphatidylinositol-3-kinase and Src activation. In in vitro studies, however, treatment with H2O2 increases [35S]GTP-gammaS binding to cardiac membranes and directly activates purified heterotrimeric Gi and Go but not Gs. Analysis using heterotrimeric Go and its individual subunits indicates that H2O2 modifies G alpha(o) but not G betagamma, which leads to subunit dissociation. We conclude that G alpha(i) and G alpha(o) are critical targets of oxidative stress for activation of ERK.

Animals↗

Differential distribution of ionic channels and muscarinic receptors at the cat tracheal neuromuscular junction.

The ionic and pharmacological properties of atropine-sensitive excitatory junction potentials (EJPs) were investigated by the double sucrose gap and microelectrode membrane potential recording methods, and compared with those of inward currents evoked by carbachol (I(CCh)), in cat tracheal smooth muscle. A single and repetitive field stimulation (10-30 V, 50 micros, 20 Hz) evoked atropine-inhibitable EJPs and associated twitch-like contractions. Reduction in external Na+ concentration strongly, but in the external Cl- concentration, decreased the EJP amplitude after 5 min superfusion, although prolonged exposure to low Cl- solutions attenuated the EJPs modestly. Chloride channel blockers such as 9-AC and niflumic acid (each 100 microM), at concentrations high enough to inhibit I(CCh) almost completely, failed to abolish the EJPs. Pirenzepine, AF-DX116 and 4-DAMP all effectively inhibited the EJPs at their concentrations to block respective muscarinic receptor subtypes relatively specifically, while depletion of internal stores by 10 mM caffeine and/or 3 microM ryanodine caused only a partial decrease in the EJP amplitude. These properties are considerably different from those of I(CCh) which is activated exclusively through activation of the M3 receptor/IP3-mediated Ca2+ release pathway and reflects mostly a Ca2+-dependent Cl- current, and suggests the differential distribution of muscarinic receptors and ionic channels inside and outside of the cholinergic neuromuscular junction of this muscle.

Acetylcholine↗

Effect of 2-deoxy-D-glucose on acetylcholine and histamine levels in gastric juice of pylorus-ligated rats anesthetized with urethane.

Acetylcholine (ACh) in gastric juice was detected and measured by pretreatment of acetylcholinesterase inhibitor, 1 mM eserine (1 ml/rat, p.o.), in pylorus-ligated rats, by liquid chromatography with electrochemical detection. In order to elucidate whether or not the ACh level in gastric juice reflects the activity of cholinergic neurons, the effect of 2-deoxy-D-glucose (2-DG), a vagus stimulant, on the levels of ACh, histamine and gastric acid in gastric juice was investigated in pylorus-ligated rats anesthetized with urethane (1.25 g/kg, i.p.). Under the non-anesthetic condition, ACh, histamine and gastric acid levels were 100+/-25 pmol/h, 120+/-10 ng/h, and 240+/-32 microequiv./h, respectively. These levels were completely inhibited by urethane anesthesia. Under the anesthetized condition, 2-DG (50-200 mg/kg, i.v.) significantly increased ACh and histamine levels in gastric juice, as well as acid secretion. The 2-DG (200 mg/kg, i.v.)-induced increases in these levels were completely inhibited by vagotomy. These results suggest that ACh level measured in gastric juice reflects the activity of cholinergic transmission. Furthermore, these results also support the conclusion that vagus stimulation facilitates not only cholinergic transmission but also histaminergic transmission related to gastric acid secretion.

Acetylcholine↗

Highly concentrated vascular endothelial growth factor in platelets in Crow-Fukase syndrome.

We report a marked difference in concentration of vascular endothelial growth factor (VEGF) between serum and plasma in patients with Crow-Fukase syndrome (CFS). The serum/plasma VEGF levels in 4 CFS patients were 8,634/152, 5,203/176, 3,724/127, and 868/13 pg/ml, respectively. We also showed that platelets were a major source of this VEGF and that VEGF was released during platelet aggregation by physiological stimulation. It is suggested that in CFS, local VEGF concentration is markedly elevated by aggregation of platelets containing excessive VEGF and their adhesion to vascular walls, resulting in excessive physiological activities of VEGF. Our findings provide important information for developing more effective therapeutic trials.

Adenosine Diphosphate↗

Correlation between high-resolution computed tomographic, magnetic resonance and pathological findings in cases with non-cancerous but suspicious lung nodules.

Computed tomography scans, including thin-section high-resolution computed tomography (HRCT), occasionally fail to differentiate between small non-cancerous nodules from lung cancers. We describe nine such lesions ( < 20 mm in diameter) initially identified through our screening program for lung cancer using CT scanning. Pathological diagnoses included nodular fibrosis (n = 4), granuloma (n = 1), cryptococcoma (n = 1), localised organising pneumonia (n = 1), inflammatory pseudo-tumour (n = 1) and sclerosing haemangioma (n = 1). High-resolution CT findings, together with MRI findings with contrast-enhanced dynamic studies, were retrospectively evaluated. Additional cases should be identified and radiologically characterised in order to reduce the number of non-cancerous tumours that are treated by unnecessary surgery.

Aged↗

Effect of overexpression of very low density lipoprotein receptor on cell growth.

The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor gene family and binds only apoE-containing lipoproteins. Although the VLDL receptor has been shown to play an important role in the proliferation of vascular smooth muscle cells and the formation of foam cells as primary responses of atherogenesis, its actual functions are still unclear. To understand the biological roles of the VLDL receptor in foam cell formation and cell growth, we tried to overexpress VLDL receptors in various cells. When COS-7 cells were transfected with an expression plasmid containing VLDL receptor cDNA, cell growth was inhibited by overexpression of the receptor and this growth inhibition was ligand-independent. The O-linked glycosylation region, but not the cytoplasmic domain, of the receptor appeared to be responsible for this growth inhibition. On the other hand, VLDL receptor expression induced enhanced incorporation of lipids and cytoplasmic enlargement. These changes were dependent on the exogenous ligand and the cytoplasmic domain of the receptor. These results suggest that the VLDL receptor functions as a regulator of cell growth and differentiation, which may be distinct from its lipid-incorporating function.

Animals↗

Apoptosis in relevant clinical situations: contribution of apoptosis in myocardial infarction.

Myocardial infarction is associated with increased TUNEL-positivity in cardiac resident and infiltrated cells. Apoptosis of proliferated interstitial myofibroblasts and infiltrated inflammatory cells may have a role in terminating tissue repair processes after infarction. Lateral and endocardial border zones of infarction within the risk area have frequent appearance of TUNEL-positive cardiomyocytes. Although the typical ultrastructural morphology of apoptosis has rarely been detected in ischaemic cardiomyocytes, there are many reports in which the TUNEL method was used for assessment of cardiomyocyte apoptosis. It has become evident that TUNEL-positivity reflects a wide range of cellular conditions; viable cells undergoing DNA repair, apoptosis, and necrosis. Therefore, it is controversial whether TUNEL-positive cardiomyocytes in infarcted myocardium are all apoptotic. Methods which will be more specific for identifying apoptosis are required for future study. TUNEL-positivity can be attenuated by anti-apoptotic interventions such as inhibition of caspases, mitochondrial protection, free radical scavenging, and some conventional pharmacotherapies. However, it remains to be determined whether anti-apoptotic interventions result in satisfactory reduction of infarct size. The injurious impact of myocardial ischaemia comes from a mixture of pro-apoptotic and necrosis-promoting signals, and the target of both signals is mitochondria. Through a common pathway they may cause permeability transition. Interventions which act only at the post-mitochondrial stage of apoptosis may fail to reduce infarct size, whereas those acting at pre-mitochondrial and mitochondrial stages may reduce infarct size. Progress in investigating the basic mechanisms of apoptosis and recognition of the modes of cardiomyocytes death will contribute to advances in cardioprotective therapy in myocardial infarction.

Adenosine↗

Posterolateral dislocation of the ankle without fracture.

We report an unusual case of open posterolateral dislocation of the ankle without fracture following a motor vehicle accident. Most of previously reported cases are posteromedial dislocation. The anterolateral, posterolateral, and purely superior dislocations of the talus make up smaller percentage. The mechanism of this injury appears to be forced eversion of the foot when it is maximally plantar flexed and axially loaded. Our case was treated by manual reduction and percutaneous fixation and anatomical repair of the disrupted deltoid ligament at the time of initial débridement, also achieved good long-term functional and radiographic results.

Accidents, Traffic↗

Effects of drugs acting as histamine releasers or histamine receptor blockers on an experimental anxiety model in mice.

Experimental anxiety in mice was evaluated using a light/dark test at 60 min after injection of various histaminergics. Thioperamide, a histamine H(3) receptor inhibitor (5-20 mg/kg, intraperitoneal [IP]), Compound 48/80, a mast cell degranulator (0.1-10 microg/2 microl, intracerebroventricularly [ICV]), mepyramine, a histamine H(1) receptor antagonist (0.1-10 microg/2 microl, ICV) or cimetidine, a histamine H(2) receptor antagonist (0.1-10 microg/2 microl, ICV) alone did not affect the locomotive activity, the time spent in the light zone, and number of shuttle crossings in the light/dark test. However, the time spent in the light zone and the number of shuttle crossings significantly decreased only when cimetidine (0.1-10 microg/2 microl, ICV) was co-treated with either thioperamide (10 mg/10 ml/kg, IP) or Compound 48/80 (1.0 microg/2 microl, ICV). The decrease in these behavioral parameters suggests induced experimental anxiety in mice. The experimental anxiety was antagonized by mepyramine (10 microg/2 microl, ICV). These results suggest that not only neuronal histamine release induced by thioperamide but also non-neuronal (mast cells) histamine release induced by Compound 48/80 play an important role in inducing experimental anxiety via post-synaptic H(1) and H(2) receptors. In addition, it is likely that the anxiety may be mediated by the stimulation of H(1) receptors, while H(2) receptors may inhibit the anxiety produced by the activation of H(1) receptors.

Animals↗

Anxiolytic-like effect of saiboku-to, an oriental herbal medicine, on histaminergics-induced anxiety in mice.

Effect of saiboku-to, an oriental herbal medicine, on anxiety in mice was investigated using a light/dark test. Anxiogenic- and anxiolytic-like effects were evaluated on the basis of shortened and prolonged time spent in the light zone of the test. Subacute administration (once a day for 7 days) of saiboku-to (0.5-2.0 g/kg, p.o.) induced anxiolytic-like effect. To assess the effect of saiboku-to on brain histaminergic system in a state of anxiety, Compound 48/80 (1.0 microg/2 microl, i.c.v.), a non-neuronal mast cell histamine releaser, or thioperamide (10.0 mg/kg, i.p.), a neuronal histamine releaser possessing the inhibitory effect of histamine H(3) autoreceptors, induced decrease in the time spent in the light zone by co-injection with cimetidine (10.0 microg/2 microl, i.c.v.), a H(2) inhibitor, suggesting anxiety-like effect. These histaminergics-induced experimental anxieties were inhibited by pre-treatment with subacute administration of saiboku-to, as well as single treatment with diazepam. The results suggest that saiboku-to exhibits anxiolytic-like effect closely related to histaminergic system in the brain.

Animals↗

Comparative assessment of the anxiolytic-like activities of honokiol and derivatives.

Honokiol has previously been shown to be an effective anxiolytic-like agent in mice when administered for 7 days at 0.2 mg/kg/day prior to evaluation in an elevated plus-maze, while 20 mg/kg is required for efficacy as a single oral dose. The aim of this study was to find analogs of honokiol that are more effective for acute administration. Among the eight analogs evaluated, one partially reduced derivative of honokiol [3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol] exhibited significant anxiolytic-like activity at 0.04 mg/kg. Following oral administration of 1 mg/kg of this analog, anxiolytic-like activity was clearly evident at 1 h, peaked at 3 h, and remained significant for longer than 4 h after treatment. Combined administration of the derivative with diazepam led to enhanced anxiolytic-like efficacy. Moreover, as with diazepam, the anxiolytic-like effect of the analog was reduced by flumazenil. In contrast, bicuculline, a GABA(A) antagonist, had no effect on the activity of the derivative. Taken together, these results suggest that this analog of honokiol acts at the benzodiazepine recognition site of the GABA(A)-benzodiazepine receptor complex.

Animals↗