[A catecholamine-secreting glomus jugular tumor].
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Catecholamines↗
Biomedical subjects
Hitoshi Yokoyama
Publications and source records attributed to Hitoshi Yokoyama.
Anteroposterior axis formation in Xenopus limb bud recombinants: a model of pattern formation during limb regeneration.
We previously showed that recombinant limb buds with dissociated and reaggregated mesenchyme develop more than 30 digits in Xenopus laevis, which exhibits different capacities for limb regeneration at different developmental stages (Yokoyama et al. [1998] Dev Biol 196:1-10). Cell-cell contact among anterior- and posterior-derived mesenchymal cells is required for anteroposterior (AP) axis formation of recombinant limbs in an intercalary manner. However, whether one-way induction from posterior cells to anterior cells as proposed by the polarizing zone model or interactions between anterior and posterior cells evoke the AP axis formation in recombinant limbs remains unclear. In this study, we found, by a combination of X-ray irradiation and a recombinant limb technique, that not one-way induction but interactions between anterior and posterior cells accompanied by cell contribution are indispensable for AP axis formation in recombinant limbs. Shh was expressed in posterior-derived not anterior-derived cells. We propose that the recombinant limb is an excellent model for examining the axis formation mechanism in regenerating limbs because, as in recombinant limbs, cell-cell contact among cells derived from different positions of an amputation plane occurs in the blastema of regenerating limbs.
Animals↗
Electron-dense deposition patterns and the outcomes of idiopathic membranous nephropathy in Japanese.
A considerable diversity in prognosis is seen with membranous nephropathy (MN). In terms of pathological findings, the presence of tubulointerstitial lesions was emphasized as a poor prognostic factor. However, the glomerular factors affecting the long-term outcome of idiopathic human MN have remained unclear. We reviewed the initial clinicopathological factors affecting the primary and secondary outcomes in 105 patients with primary MN, as well as reviewing previous reports. Based on electron microscopic (EM) findings, we could divide patients into two subtypes and one subgroup; i.e., homogeneous type with a synchronous phase of electron-dense deposits, with large dense deposits (deep subgroup) and heterogeneous type with various phases of dense deposits. The homogeneous type showed no endstage renal failure, and had earlier remission as compared with the heterogeneous type. For the secondary outcome, heterogeneous type and deep subgroup were also independent risk factors. However, there was no significant difference in the final primary or secondary outcome for any treatment subgroups. These results indicated that our category of EM findings was a beneficial marker of the primary and secondary outcomes in MN; the homogeneous type of MN with synchronous phase of electron-dense deposits (except for the "deep" subgroup) had a good outcome.
Female↗
The beneficial effects of lymphocytapheresis for treatment of nephrotic syndrome.
A considerable permeability factor (or factors) derived from circulating T cells has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was followed with corticosteroid therapy with or without cyclosporine A in 5 patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a dramatic decrease of proteinuria (-30% and -94%) in their urine protein/creatinine ratio. Three out of 4 patients had a complete or partial remission (proteinuria <1g/day) within 8 weeks following immunosuppressive therapy. During the LCAP, T cells, especially activated T cells, decreased significantly in the response group. The other 2 patients, 1 with FSGS and 1 with MN, however, had no response to LCAP and following immunosuppressive therapy or low-density lipoprotein apheresis and suffered from end-stage renal failure or death by pneumonia. These results suggested that LCAP might have a beneficial effect on the treatment of NS, especially MCNS and in some patients with FSGS, despite varying responses to LCAP and concomitant immunosuppressive therapy.
Adolescent↗
Focal glomerulosclerosis expanding from the glomerular vascular pole in a Japanese male with mitochondrial-DNA mutation.
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Adolescent↗
Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice.
BACKGROUND: Various types of chemokines/cytokines play important roles in ischaemia/reperfusion injury in kidneys. However, the roles of p38 mitogen-activated protein kinase (MAPK) in the inflammatory processes of renal ischaemia/reperfusion injury remain to be investigated. We explored the effect of FR167653, a specific inhibitor of p38 MAPK, on renal ischaemia/reperfusion injury in mice. METHODS: The renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. FR167653 was injected 2 h before or 24 h after renal vessel clamp. Renal tissues were removed for pathological examination 4, 24 or 48 h after reperfusion. RESULTS: We observed a large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischaemia/reperfusion injury in mice. FR167653 significantly decreased cell infiltration into outer medulla, and the extent of acute tubular necrosis 24 and 48 h after reperfusion. FR167653 markedly decreased the transcription of interleukin-1beta, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and regulated upon activation, normal T cell expression and secreted in diseased kidneys. Moreover, FR167653 decreased the number of phosphorylated p38 MAPK-positive cells 4 h after reperfusion. CONCLUSION: These results suggest that FR167653 markedly ameliorated renal ischaemia/reperfusion injury, possibly by inhibiting cytokine/chemokine expression and consequent phosphorylation of p38 MAPK in renal tissue.
Animals↗
p38 MAPK phosphorylation and NF-kappa B activation in human crescentic glomerulonephritis.
BACKGROUND: p38 mitogen-activated protein kinase (p38 MAPK) followed by the activation of NF-kappa B participates in the intracellular signal transduction and production of cytokines and chemokines. The pathophysiological roles of p38 MAPK and NF-kappa B in human glomerulonephritis, however, remain to be investigated. METHODS: We investigated the phosphorylated p38 MAPK (p-p38 MAPK) and activated NF-kappa B immunohistochemically in the kidneys of 34 patients with crescentic glomerulonephritis and 26 control patients with thin basement membrane disease and minimal change nephrotic syndrome. We also explored the co-localization of p-p38 MAPK with CCR5, the signal of which leads to p38 MAPK activation. Furthermore, urinary levels of MIP-1 alpha, the cognate ligand for CCR5, were determined by enzyme-linked immunosorbent assay. RESULTS: p-p38 MAPK-positive cells and activated NF-kappa B-positive cells were mainly detected in crescentic lesions, tubular epithelial cells, and interstitial mononuclear infiltrates. The number of p-p38 MAPK-positive cells in patients with crescentic glomerulonephritis was higher than that in control patients. The number of p-p38 MAPK-positive cells in glomeruli was well correlated with the percentage of cellular crescents, the number of CD68-positive cells, and urinary MIP-1 alpha levels. In addition, the number of activated NF-kappa B-positive cells was well correlated with the number of p-p38 MAPK-positive cells in glomeruli. Dual staining revealed that most of CCR5-positive cells were positive for p-p38 MAPK. Finally, p-p38 MAPK-positive cells and activated NF-kappa B-positive cells decreased during glucocorticoid therapy-induced convalescence. CONCLUSIONS: We conclude that the phosphorylation of p38 MAPK associated with the activation of NF-kappa B may be involved in the upregulation of intrarenal MIP-1 alpha and the utilization of CCR5 signalling, which may result in human crescentic glomerulonephritis.
Female↗
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 null mutant mice develop renal lesions mimicking obstructive nephropathy.
BACKGROUND: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 is distinguished from other a disintegrin and metalloproteinase molecules by the presence of thrombospondin type 1 motifs at its C-terminus and anchors to the extracellular matrix. We studied the biological role of ADAMTS-1 in the kidney. METHODS: We developed ADAMTS-1 null mice by replacing exons 2-4, which encode most of the metalloproteinase domain, with the neomycin resistance gene. RESULTS: In normal mice, ADAMTS-1 was detected in the epithelial cells of collecting ducts, and more intensely in the urinary epithelium at the ureteropelvic junction in kidney. We found that targeted disruption of the mouse ADAMTS-1 gene resulted in enlarged renal calices accompanied by bilateral hydronephrosis and papillary atrophy approximately 4 weeks after birth. Electron microscopic examination revealed the fibrotic changes and hypervascularity of capillaries between the urinary epithelial cell layer and smooth muscle cell layer at the ureteropelvic junction. CONCLUSION: ADAMTS-1 appears necessary for normal kidney morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.
ADAM Proteins↗
Dietary sodium restriction restores nocturnal reduction of blood pressure in patients with primary aldosteronism.
The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.
Adrenal Cortex Neoplasms↗
Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury.
Cytokines and chemokines produced by renal tubular epithelial cells and infiltrated cells are critical factors in inflammatory processes of renal ischemia-reperfusion injury. In vitro studies reveal that renal tubular epithelial cells have the potential to produce diverse cytokines, chemokines and other mediators, such as tumor necrosis factor-alpha, interleukin-1 (IL-1), monocyte chemoattractant protein-1, IL-8, platelet-derived growth factor, regulated upon activation, normal T cell expressed and secreted, endothelin-1 and vascular endothelial growth factor (VEGF). Huge numbers of in vivo studies show that cytokines, chemokines and adhesion molecules in diseased kidney together govern critical aspects of ischemia-reperfusion injury. Leukocyteendothelial cell interactions are critical processes of leukocytic infiltration, which are pathologically key factors in inflammatory processes of renal ischemia-reperfusion injury. Leukocyteendothelial interactions are regulated by a cascade of molecular steps of cytokines, chemokines and adhesion molecules. In contrast, the intracellular cascades of cytokine and chemokine expression in the renal ischemia-reperfusion injury remain to be investigated. p38 mitogen-activated protein kinase is one of the essential mediators in cytokine and chemokine expression through the activation of nuclear factor-kappaB and activating protein-1. Moreover, hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by reductions in oxygen concentration. HIF-1related gene expression, such as erythropoietin or VEGF, results in protection of ischemia reperfusion injury. This review focuses on the contribution of cytokines, chemokines and their related molecules to the inflammatory cascade in renal ischemia-reperfusion injury. (c) 2002 Prous Science. All rights reserved.
Journal Article↗
Aortic arch aneurysm complicated with coronary artery disease: still a surgical challenge?
Recent surgical strategies and outcomes for the simultaneous operation of aortic arch repair (AAR) and coronary artery bypass grafting (CABG) were reviewed. The surgical treatment of aortic arch aneurysm complicated with coronary artery arteriosclerosis has been a challenge. In spite of recent improvements in cerebral protection during AAR such as deep hypothermia and circulatory arrest with/without retrograde cerebral perfusion, or antegrade selective cerebral perfusion (SCP), additional CABG poses a considerable surgical risk resulting in extremely higher mortality rates when compared with solo AAR. To minimize the cardiac ischemic time, several techniques such as distal coronary artery anastomosis on the perfused fibrillating heart, and coronary artery perfusion through a cardioplegic line during AAR have been employed. Recently, open stent grafting instead of aortic distal anastomosis has been attempted to minimize the cardiopulmonary time and operative complexity. Our recent experience suggested off-pump coronary artery bypass and AAR with the aid of SCP decreased cardiac ischemic time and cardiopulmonary time followed by improved operative morbidity and mortality. Further less-invasive surgical modalities that enhance the adequate myocardial protection and minimize the adverse effect of cardiopulmonary bypass can improve the outcome of this demanding operation for these elderly patients with aortic arch aneurysm and coronary artery occlusive disease.
Aorta, Thoracic↗
[Guidelines for the management of refractory nephrotic syndrome--from investigations between 1997 and 2001--research project team for progressive renal lesions in the Ministry of Health, Labor and Welfare, Japan].
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Blood Component Removal↗
A new anti-inflammatory compound, FR167653, ameliorates crescentic glomerulonephritis in Wistar-Kyoto rats.
The pathophysiologic effects of FR167653 were investigated in a model of crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in Wistar-Kyoto rats. The rats developed crescentic glomerulonephritis by 6 d after the administration of serum. The subcutaneous administration of FR167653 (32 mg/kg) markedly decreased the severity of the renal damage. In a group of rats treated with FR167653 daily from day 0 to day 6, glomerular damage, including crescent formation and proteinuria, was virtually absent. FR167653 markedly decreased urinary levels of monocyte chemoattractant protein-1 (MCP-1). In addition, FR167653 reduced production of MCP-1 protein and transcripts in the diseased kidneys. In a group of rats for which treatment was initiated on day 3, shortly after the appearance of glomerular abnormalities, the progression of renal disease was appreciably retarded, with partial inhibition of MCP-1. In contrast, when rats were treated only on the first day, no beneficial effects were observed and severe proliferative and necrotizing glomerulonephritis, with crescent formation, was induced by day 6, with the upregulation of MCP-1. These results suggest that FR167653 may be effective against crescentic glomerulonephritis, possibly via the inhibition of MCP-1. In addition, there was marked reduction in renal injury even when FR167653 treatment was initiated after glomerular inflammation was established, suggesting that the therapeutic application of FR167653 may be clinically useful for human renal diseases.
Animals↗
High endothelial venule-like vessels in the interstitial lesions of human glomerulonephritis.
To clarify the characteristics of high endothelial venule (HEV) -like vessels in the interstitium of human glomerulonephritis, we investigated the expression of HEVs related molecules such as P-selectin and L-selectin ligands; MECA-79 epitope and variant sulfated forms of sialyl Lewis X (variant sLe(X), clones 2H5, 2F3, GS-13 and GS-36) in kidney specimens by means of immunohistochemical studies, and P-selectin and hevin mRNA signals by using in situ hybridization analyses. In lymphoid organs, HEVs strongly expressed P-selectin, MECA-79, variant sLe(X) and hevin mRNA signals. In normal kidneys (n = 4), only P-selectin was faintly positive in the vessels of interstitium, but other molecules could not be detected. Interstitial P-selectin expression was upregulated in patients with tubulointerstitial diseases (n = 4) and proliferative glomerulonephritis (n = 51) such as IgA-related nephropathy (n = 39), membranoproliferative glomerulonephritis (n = 4) and crescentic glomerulonephritis (n = 2), but not in nonproliferative glomerular diseases (n = 39) such as minimal change nephrotic syndrome (n = 18) (1.00 +/- 0.41, 0.64 +/- 0.11, 0.21 +/- 0.05, respectively). Interstitial P-selectin expression also correlated with interstitial local cellular infiltration (r = 0.60, p < 0.0001). In addition, P-selectin mRNA signals were detected on the peritubular capillaries and HEV-like vascular endothelial cells. MECA-79 and variant sLe(X) (2H5 and 2F3) were weakly expressed on the HEV-like vessels located at the corticomedullary regions in three cases (7%) and in nine cases (27%) with interstitial cellular infiltration, respectively. However, we could not detect GS-13, GS-36 or hevin mRNA signals in the diseased kidney specimens. In conclusion, HEV-like vessels in renal interstitium expressed molecules somewhat different from HEVs in lymphoid organs and were associated with interstitial leukocyte accumulation in human proliferative glomerulonephritis possibly through the de novo expression of P-selectin and partly L-selectin ligands (MECA-79 epitope and variant sLe(X)) in the interstitial lesions.
Endothelium, Vascular↗
Unilateral stent implantation for renal function in bilateral atherosclerotic renovascular hypertension--a case report.
Renal artery stenting improves or preserves renal function in patients with bilateral renovascular disease and chronic renal insufficiency. An 80-year-old male was admitted to the hospital for elevated blood pressure accompanied by congestive heart failure. He had renal insufficiency and severe hypertension secondary to bilateral atherosclerotic renal artery stenosis. Unilateral renal artery stenting in the left kidney resulted in the recovery of renal function, whereas renal artery stenting in the right kidney was technically difficult due to a tortuous aorta. After the left unilateral stent implantation, the serum creatinine concentration decreased from 2.0 to 1.3 mg/dL, and control of his blood pressure required fewer antihypertensive drugs, namely a calcium antagonist, an angiotensin-converting enzyme inhibitor, and diuretics. Fifteen months after stenting, renal scintigraphy demonstrated improved function of the right kidney, despite severe renal artery stenosis, as well as improved function of the left kidney. Renal angioplasty or stenting should be attempted in bilateral atherosclerotic renovascular hypertension with renal insufficiency, even though it may only be successful unilaterally.
Aged↗