Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening.

Cutaneous arteritis (CA) is a single-organ vasculitis that exclusively affects the small to medium-sized arteries of the skin. Diagnosis depends on a histological investigation with skin biopsy, which could be burdensome for both patients and clinicians. Moreover, the pathogenesis of CA remains unstudied, and treatment has not yet been established. Herein, we applied our proteome-wide autoantibody screening method to explore autoantibodies in the serum of CA patients. As a result, anti-transcobalamin receptor (TCblR) antibodies (Abs) were specifically detected in 24% of CA patients. Patients with positive anti-TCblR Abs were spared from peripheral neuropathy compared to those with negative anti-TCblR Abs, showing characteristics as CA confined to the skin. In addition, we revealed that anti-TCblR Abs trigger the autocrine loop of interleukin-6 mediated by tripartite motif-containing protein 21 in human endothelial cells and induce periarterial inflammation in murine skin. Furthermore, we demonstrated that methylcobalamin, a ligand of TCblR, ameliorates inflammation caused by anti-TCblR Abs both in vitro and in vivo. Collectively, our investigation unveils the pathologic significance of anti-TCblR Abs in CA and their potential as a diagnostic marker and a pathophysiology-oriented therapeutic target.

Anti-Ku antibody-positive myositis presenting as a wide range of axial myopathies and myocarditis: A case report and review of the literature.

Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases predominantly affecting proximal muscles; paraspinal muscle involvement is relatively rare. Because paraspinal myopathies do not always cause clinically evident symptoms, the diagnosis of IIMs with axial myopathies can be challenging. Anti-Ku autoantibodies, initially reported in polymyositis/systemic sclerosis overlap syndrome, are myositis-associated antibodies observed in patients with a wide variety of connective tissue diseases. Few reports have been published demonstrating predominant axial myopathy in IIM patients with anti-Ku antibodies. Herein, we investigated a previously healthy Japanese woman in her early 70s who presented with Raynaud's phenomenon, back pain, and exertional dyspnoea. The creatine kinase was elevated and antinuclear antibody staining was positive, but myositis-specific antibodies were negative. Magnetic resonance imaging revealed myocarditis and a wide range of axial muscle inflammation, including bilateral thoracolumbar paraspinal, infraspinatus, and trapezius muscles. The muscle biopsy was consistent with IIM. In addition, anti-Ku antibody was positive. The administration of prednisolone and tacrolimus quickly alleviated the symptoms, and the creatine kinase level returned to normal. The diagnosis of IIM was arduous in this case because she did not present with camptocormia, muscle weakness involving the proximal limbs was not apparent, and myositis-specific antibodies were negative. Whether axial myopathy and myocarditis are more prevalent in IIM patients with than without anti-Ku antibodies is uncertain. Clinicians should suspect axial myopathy and myositis-associated antibodies, such as anti-Ku antibodies, especially in patients in whom muscle weakness of the proximal limbs is not noticeable.

The Use of External-beam Radiotherapy for Muscle-invasive Bladder Cancer in Elderly or Medically-fragile Patients.

AIM: To evaluate the clinical results of external-beam radiotherapy (EBRT) for muscle-invasive bladder cancer (MIBC) in elderly or medically-fragile patients. PATIENTS AND METHODS: Twenty-five consecutive patients with MIBC (cT2-4N0-1M0) receiving EBRT were retrospectively analyzed. Their median age was 82 years. Radiotherapy median dose was 60 Gy administered in 30 fractions. RESULTS: Median follow-up period was 14.7 months. Median overall survival (OS) and progression-free survival (PFS) were 14.7 months and 7.8 months, respectively. The OS, cause-specific survival (CSS), and PFS rates at 1-year were 56.0%, 68.5%, and 40.0%, respectively. The local progression-free rates (LPFR) at 6 months and 1 year were 89.3% and 59.5%, respectively. Performance status 3 was a significantly unfavorable factor for OS, CSS, and progression-free survival; clinical N stage was a significantly unfavorable factor for progression-free survival; and lower irradiation dose (≤50.4 Gy) was a significantly unfavorable factor for LPFR. CONCLUSION: EBRT for elderly or medically-fragile patients is feasible, and achieves acceptable local progression-free status.

Fatal Unusual Miliary Tuberculosis in which a Patient Developed Acute Respiratory Distress Syndrome Induced by Infliximab: An Autopsy Case Report.

Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB. It is important, particularly for patients receiving anti-TNFα agents, to constantly consider the possibility of TB and to prepare for appropriate management.

[Localized amyloidosis of the seminal vesicle: a case report].

Primary amyloidosis of the seminal vesicle is a rare disease entity. We report here a case of localized seminal vesicle amyloidosis with hematospermia. A 66-year-old man visited our hospital with a chief complaint of hematospermia. T2 weighted magnetic resonance imaging (MRI) showed a hypointensity mass in the left seminal vesicle. Needle biopsy revealed amyloidosis of the seminal vesicle. Without any specific treatment, the mass lesion disappeared on MRI, and hematospermia was improved.

Ectopic ureter accompanied by giant ureteral stone and pyonephrosis.

We report a rare case of ectopic ureter accompanied by a giant ureteral stone and pyonephrosis. A 19-year-old Japanese woman consulted our hospital due to low-grade fever and pain in the left flank. The patient had seeping urinary incontinence since childhood. Ultrasonography demonstrated left dysplastic lumbar kidney with hydronephrosis and plain kidney-ureter-bladder film showed a left giant ureteral stone. The left kidney showed no excretion of contrast medium on drip infusion pyelography. After further examination, a diagnosis of left simple ectopic ureter emptying into the vagina was made. Percutaneous nephrostomy penetrating the major psoas muscle was carried out for intractable pyonephrosis, followed by left nephroureterectomy and lithectomy. These procedures resulted in improvement in the patient's symptoms.

Incarcerated intestinal hernia in a hernia sac of reversed ileal conduit wall protruding through the stoma.

The case is reported of incarcerated intestinal hernia in a hernia sac of reversed ileal conduit wall protruding through the stoma. An 82-year-old woman presented with suspected parastomal intestinal hernia. The patient had undergone total cystectomy with ileal conduit construction 3 years previously, followed by stomal reconstruction surgery for stomal stenosis 2 years later. She had been taking various kinds of purgatives for severe constipation. Initially, this case was diagnosed as parastomal hernia, but emergency surgery demonstrated that incarcerated intestinal hernia in a hernia sac of reversed ileal conduit wall was protruding through the stoma. This case was apparently caused by high abdominal pressure and thinning of the ileal conduit wall.

[Matrix stone: a case report].

Here, we report a case of matrix stone in a 32-year-old man with diabetes, gout, and chronic renal failure. The patient complained of pain in the left flank. He had undergone an operation for bilateral vesicoureteral reflex at the age of 17 and matrix stone discharge was repeated. Computed tomography revealed a soft tissue mass in the right hydroureter. Percutaneous ureteral lithotripsy was performed successfully. Analysis of the stone components revealed the stone to be composed entirely of protein. Radiological imaging of matrix stones may be difficult to separate from urothelial cancers.

Central muscarinic receptor subtypes regulating voiding in rats.

PURPOSE: Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. RESULTS: In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. CONCLUSIONS: Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.