Possible roles of angiotensin II-forming enzymes, angiotensin converting enzyme and chymase-like enzyme, in the human aneurysmal aorta.

Aortic aneurysm is a chronic degenerative condition associated with atherosclerosis. Recent studies have revealed that angiotensin (Ang) II plays important roles in atherosclerosis. In this study, to investigate the relationship between aortic aneurysm and Ang II, we measured the activities of the angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase-like enzyme, in human aneurysmal and control aortae. Aneurysmal aortic specimens were obtained from 16 aneurysm patients and control aortic specimens were obtained from 16 patients who underwent coronary artery bypass surgery (8 patients in each group were administered ACE inhibitors). The ACE and chymase-like enzyme activities were determined using extracts from vascular tissues. Both the ACE and chymase-like enzyme activities in the aneurysmal aortae were significantly higher than those in the control aortae (p < 0.01). In the patients treated with ACE inhibitors, the ACE activity in the aneurysmal aortae tended to be low, but the chymase-like enzyme activity tended to be high. In the aneurysmal aortae, the chymase-like enzyme activity in the adventitia was significantly higher than that in the intimal or medial layers (p < 0.01), while differences in ACE activity were not observed. Our results suggest that increases in local Ang II formation induced by chymase-like enzymes may play important roles in the pathogenesis of aneurysmal formation.     

Ventricular Fibrillation Associated With J-Wave Manifestation Following Pericarditis After Catheter Ablation for Paroxysmal Atrial Fibrillation

We present a patient with ventricular fibrillation (VF) associated with J-wave manifestation following pericarditis after catheter ablation of paroxysmal atrial fibrillation (AF). The premature ventricular contraction induced VF with J-waves in the inferior leads 2 days after the procedure. The patient's juvenile onset of AF and a family history of sudden cardiac death strongly suggested an underlying hereditable channelopathy. The late gadolinium enhancement in the posterior wall, viewed by cardiac magnetic resonance imaging, matched the leads of the J-waves. VF might develop in juvenile onset of AF especially in individuals with a family history of sudden cardiac death.     

Health-related quality of life in Japanese patients with multiple sclerosis

Journal of Neurology - Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related...     

Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia

The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking between subcellular compartments and is triggered by the ARF family of small GTPases. We previously identified SMAP1 as an ARF6 GTPase-activating protein that functions in clathrin-dependent endocytosis. Because abnormalities in clathrin-dependent trafficking are often associated with oncogenesis, we targeted Smap1 in mice to examine its physiological and pathological significance. Smap1-deficent mice exhibited healthy growth, but their erythroblasts showed enhanced transferrin endocytosis. In mast cells cultured in SCF, Smap1 deficiency did not affect the internalization of c-KIT but impaired the sorting of internalized c-KIT from multivesicular bodies to lysosomes, resulting in intracellular accumulation of undegraded c-KIT that was accompanied by enhanced activation of ERK and increased cell growth. Interestingly, approximately 50% of aged Smap1-deficient mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities similar to myelodysplastic syndrome (MDS) in humans. Furthermore, some Smap1-deficient mice developed acute myeloid leukemia (AML) of various subtypes. Collectively, to our knowledge these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking may be involved in the development of MDS and subsequent AML.     

Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m²) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie–Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response.Renal impairment (RI) is a major cause of morbidity and mortality in patients with multiple myeloma (MM) and approximately 50 and 20% of patients have RI and acute renal failure depending of its definition.^{1, 2, 3, 4} The presence of RI limits the use of antimyeloma agents and eligibility for stem cell transplantation, and, therefore, places these patients at higher risk for disease progression and myeloma-related complications. RI is also associated with an increased risk of early death,^5,6 although the recent introduction of effective novel agents, such as thalidomide, bortezomib and lenalidomide, has led to the improved survival even in patients with RI.^7,8The most common cause of RI in MM is cast nephropathy, which may be seen in up to 30% of patients;⁹ other causes of RI include monoclonal immunoglobulin (Ig) deposition disease and amyloidosis. It should be noted that non-paraprotein-associated renal lesions are also seen in 25% of patients. As most patients with MM are elderly, age-related comorbidities such as hypertension and diabetes may also be associated with the decline of renal function.As the reversibility of renal function may be dependent on the pathogenesis of renal disease,¹⁰ correct renal pathology is necessary for successful treatment. Use of bortezomib-based regimens in combination with or without plasma exchange has been reported to yield high rates of renal recovery in patients with cast nephropathy.^{11, 12, 13, 14} However, reversibility of renal function in cases other than cast nephropathy is largely unknown. Kidney biopsy cannot be performed in all patients with MM and RI because of its various limitations and possible complications. Recently, Nasr et al.⁹ reported the clinicopathologic correlations in MM patients with kidney biopsy; they reported the highest levels of albuminuria in patients with amyloidosis and lowest levels in those with cast nephropathy.Despite the heterogeneity of renal pathology, urine albuminuria is thought to reflect glomerular injury, and patients with cast nephropathy usually show tubulointerstitial injury and lack heavy albuminuria. Therefore, we postulated that renal response may be different according to urinary albumin excretion. In this study, we retrospectively analyzed the clinical variables that may affect renal response in 116 MM patients with RI at our hospital. We also examined the predictive capacity of urinary albumin and serum-free light-chain (FLC) reduction on renal recovery of RI patients with MM.     

Usefulness of ultrasonography for rapidly diagnosing cutaneous sinus tracts of dental origin

Background

Cutaneous sinus tracts of dental origin are frequently misdiagnosed and incorrectly treated. Intraoral roentgenograms are valuable for diagnosing such tracts. Since these lesions are usually not accompanied by dental symptoms, patients tend initially to consult dermatologists or general physicians, who are not familiar with oral diseases or intraoral X-rays.

Objectives

We sought to determine the usefulness of ultrasonography for detecting cutaneous sinus tracts of dental origin.

Materials and methods

Three patients who had skin lesions that were suspected of being cutaneous sinus tracts based on the findings of clinical and histological examinations were enrolled in this study. B mode and color Doppler ultrasonography were used to image the skin lesions in their entirety and to assess the associations between the subcutaneous lesions and any alveolar bone defects.

Results

In each case, ultrasonography depicted a hypoechoic band that originated from the cutaneous lesion and extended through the subcutaneous tissue to the alveolar bone. Bone loss was also observed, and color Doppler ultrasonography detected increased blood flow in the peripheral regions of the tracts.

Conclusions

In the present study, the patients’ sinus tracts were rapidly detected using ultrasonography, which enabled appropriate treatment. Thus, ultrasonography is a convenient tool for diagnosing cutaneous sinus tracts of dental origin.

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