Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity.

Klotho is a circulating protein, and Klotho deficiency disturbs endothelial integrity, but the molecular mechanism is not fully clarified. We report that vascular endothelium in Klotho-deficient mice showed hyperpermeability with increased apoptosis and down-regulation of vascular endothelial (VE)-cadherin because of an increase in VEGF-mediated internal calcium concentration ([Ca(2+)]i) influx and hyperactivation of Ca(2+)-dependent proteases. Immunohistochemical analysis, the pull-down assay using Klotho-fixed agarose, and FRET confocal imaging confirmed that Klotho protein binds directly to VEGF receptor 2 (VEGFR-2) and endothelial, transient-receptor potential canonical Ca(2+) channel 1 (TRPC-1) and strengthens the association to promote their cointernalization. An in vitro mutagenesis study revealed that the second hydrolase domain of Klotho interacts with sixth and seventh Ig domains of VEGFR-2 and the third extracellular loop of TRPC-1. In Klotho-deficient endothelial cells, VEGF-mediated internalization of the VEGFR-2/TRPC-1 complex was impaired, and surface TRPC-1 expression increased 2.2-fold; these effects were reversed by supplementation of Klotho protein. VEGF-mediated elevation of [Ca(2+)]i was sustained at higher levels in an extracellular Ca(2+)-dependent manner, and normalization of TRCP-1 expression restored the abnormal [Ca(2+)]i handling. These findings provide evidence that Klotho protein is associated with VEGFR-2/TRPC-1 in causing cointernalization, thus regulating TRPC-1-mediated Ca(2+) entry to maintain endothelial integrity.

Fatal gastrointestinal bleeding due to IgA vasculitis complicated with tuberculous lymphadenitis: A case report and literature review.

We report a case of IgA vasculitis that developed during the treatment of tuberculosis. Patients with tuberculosis who are on antituberculosis treatment can be administered steroids for severe disease or complications.

A case report of Mycobacterium abscessus peritonitis in a peritoneal dialysis patient.

Peritonitis due to nontuberculous mycobacterium in peritoneal dialysis (PD) patients is rare. However, when it occurs, PD catheter removal is required in most cases because of resistance to antibiotic therapy. We report a case of Mycobacterium abscessus peritonitis subsequent to tunnel infection after PD catheter-replacement surgery. The patient underwent this surgery as her tunnel infection had not resolved following the usual 3 month course of antibiotic therapy. After surgery, tunnel infection of the second catheter and peritonitis occurred. Nontuberculous mycobacteria were detected on acid-fast stain from both the old and new exit-site drainage and the peritoneal effluent. The mycobacteria were identified as M. abscessus. Removal of the new catheter and surgical excision of the previous catheter tunnel were performed and multiple antibiotics were started. After 3 months the postsurgical wounds had healed completely. This case demonstrates the importance of further evaluation of unidentified PD catheter-related infections, including an examination for nontuberculous mycobacterium.

[Case of non-Hodgkin lymphoma with acute renal failure successfully treated with chemotherapy].

We report a case of non-Hodgkin lymphoma (NHL) with acute renal failure. A 62-year-old man was admitted to our hospital on March 8, 2002 with leg edema and dyspnea on effort. About 3 weeks before admission, he was found to have slightly high serum creatinine (Cr) and high lactate dehydrogenase (LDH) levels by another home doctor. Physical examination revealed anemic conjunctivae and leg edema, but the urinary volume was preserved. Blood examination showed high BUN (64 mg/dl) and Cr levels (3.91 mg/dl). Urinary analysis showed proteinuria (1.05 g/day) and high BMG (14,434/microg/day) and NAG (4.55 U/day) levels, suggesting severe tubulointerstitial injury. On ultrasonography of the kidney, the bilateral kidneys showed marked swelling without hydronephrosis. To investigate the genesis of renal failure, we performed a renal biopsy. The specimen showed normal glomeruli, but a large number of cells infiltrated in the tubulointerstitial area with normal tubulointerstitial structure. The cells stained positively with anti-leukocyte antigen and L26 (B cell marker), and negatively with cytokeratin and UCHL-1 (T cell marker). These findings indicate that the interstitial cells were non-Hodgkin lymphoma with B cell diffuse large cells. Chemotherapy was performed with VAD (vincristine sulfate, doxorubicin hydrochloride, dexamethasone) considering his renal dysfunction. To avoid tumor lysis syndrome after chemotherapy, hemodialysis was performed on days 1-4 after the initiation of chemotherapy. After a series of chemotherapy, the urinary volume increased and serum Cr levels decreased to 2 mg/dl. After additional therapy with 4 courses of CHOP, he improved and was discharged on day 180 after admission.

Neurovascular decompression of the rostral ventrolateral medulla decreases blood pressure and sympathetic nerve activity in patients with refractory hypertension.

Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and ß-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin-angiotensin system.