Exercise-induced changes of functional mitral regurgitation in asymptomatic or mildly symptomatic patients with idiopathic dilated cardiomyopathy

It has remained unclear why functional mitral regurgitation (MR), even if it is of a mild degree, has prognostic importance in patients with idiopathic dilated cardiomyopathy (IDC). Exercise-induced changes in functional MR, which might be a clue to this question, have not been fully clarified. Thus, in this study, semisupine exercise echocardiography was performed on 32 asymptomatic or mildly symptomatic patients with IDC (29 men, mean age 45 +/- 14 years). The mean ejection fraction was 28 +/- 10% (range 13% to 45%). The effective regurgitant orifice (ERO) area of MR was measured, as well as echocardiographic parameters including mitral valve geometry. ERO at rest was associated best with systolic mitral tenting area (r(S) = 0.85, p <0.001). Functional MR did not newly appear during exercise in 9 subjects without MR at rest. In the remaining 23 subjects with functional MR at rest, all showed exacerbations of MR, with a median ERO of 10.5 mm(2) (interquartile range 6.3 to 16.5) to 18.7 mm(2) (interquartile range 9.5 to 29.3) (p <0.001). An increase in ERO was correlated best with the enlargement of tenting area (r(S) = 0.90, p <0.001) and was the strongest independent determinant of exercise duration (beta = -0.55, p = 0.002, multiple R(2) = 0.46). In conclusion, functional MR complicated with IDC was significantly exacerbated during exercise, with mitral valve deformation, which was strongly related to exercise intolerance; thus, the clinical impact of functional MR in patients with IDC could be more serious than can be expected by its degree at rest.     

New analytical method for pancreas and liver regeneration: normalization of streptozotocin-induced hyperglycemia by retrograde injection of insulin producing cells

We established a new analytical system in which functioning cells were transplanted directly into the pancreas and liver. The retrograde transplantation of beta cell line, Min6 cells, into the streptozotocin-diabetic mice normalized plasma glucose and insulin levels. The injected cells were protected from pancreatic enzymes with enzyme inhibitor. Blood glucose decreased gradually over 10 days and the diabetic mice recovered weight at the same time. Intraperitoneal glucose tolerance test showed that the peak of plasma glucose of the transplanted mice was less than half that of the control. The insulin secretion of the transplanted mice was recovered and stimulated 4.6 times from the basal secretion. Histological analyses showed that the pancreas and liver were characterized by Min6 cell clusters dispersed throughout the organs. Min6 cells were detected near the pancreatic or bile ducts. It is suggested that the injected cells obstructed the peripheral ducts where they settled. The weight of pancreas and liver did not differ significantly in either Min6 transplanted or the control mice. The metabolic effects on the weights of these organs appeared the same in both groups. This is the first report that cells transplanted via ducts into the pancreas and liver performed their biological function. Our transplantation model makes possible the in vivo analysis of the regeneration machinery of the pancreas and liver.     

Role of protein kinase C isozymes in cellular functions and pathological conditions

Protein kinase C (PKC) is a superfamily of lipid-dependent protein Ser/Thr kinases consisting of at least 10 isozymes. The present article summarizes the papers presented at the congress symposium of the 74th Annual Meeting of the Japanese Pharmacological Society, in which six special topics regarding PKC isozyme-dependent cellular functions and pathological disorders were discussed. Using a GFP-tagged PKC expression technique, each PKC subtype was suggested to vary its targeting-site in each cell in response to each stimulus and that the targeting to the specific compartment is necessary for the specific cellular responses (NS). A cardioprotective agent, JTV519, was shown to attenuate post-ischemic myocardial injury by mimicking ischemic preconditioning through specific activation of PKC delta (YK). Using an antisense technique, PKC alpha and delta/epsilon were shown to be necessary for gene expression of inducible NO synthase by interleukin-1, one of the proinflammatory cytokines, by a stimulated transactivation of NF-kappa B (TH). In canine cerebral artery, PKC delta and PKC alpha play important roles in the development and the maintenance of vasospasm induced by subarachnoid hemorrhage, respectively (SN); and stretch-induced MLC20 phosphorylation involves MLCK and PKC alpha but not PKC delta activities facilitated by inactivation of myosin phosphatase through Rho activity (KO & KN). To clarify the role of PKC isozymes in insulin resistance, the effects of insulin on glucose uptake, PKC isozyme activation and PI3K activation in rat adipocytes were shown and then platelet PKC beta activation in diabetic patients with various diabetic complications, including diabetic retinopathy, was reported (TI). These studies will promisingly open the way to a new era for the development of novel drugs controlling an isozyme-specific activity of the protein kinase C superfamily and improvement in the knowledge about the role of the protein kinase in health and disease.     

Bronchial Artery Embolization for Hemoptysis Due to Benign Diseases: Immediate and Long-Term Results

Purpose: To clarify the immediate effect and long-term results of bronchial artery embolization (BAE) for hemoptysis due to benign diseases and the factors influencing the outcomes. Methods: One hundred and one patients (aged 34–89 years) received bronchial artery embolization with polyvinyl alcohol particles and gelatin sponge for massive or continuing moderate hemoptysis caused by benign pulmonary diseases and resistant to medical treatment. Results: After BAE, bleeding stopped in 94 patients (94%). The immediate effect was unfavorable in cases where feeder vessels were overlooked or the embolization of the intercostal arteries was insufficient. Long-term cumulative hemoptysis nonrecurrence rates after the initial embolization were 77.7% for 1 year and 62.5% for 5 years. In bronchitis (n = 9) and active tuberculosis (n = 4) groups, an excellent (100%) 5-year cumulative nonrecurrence rate was obtained. The rate was lower in groups with pneumonia/abscess/pyothorax (n = 8) or with pulmonary aspergillosis (n = 9) (53.3%, 1-year cumulative nonrecurrence). There were higher incidences of early recurrence among patients with massive hemorrhage or more marked vascularity and systemic artery–pulmonary artery shunt in angiography: however, these trends were not statistically significant Conclusions: BAE can yield long-term benefit in patients with hemoptysis due to benign diseases. Technical problems in the procedure had an impact on the short-term effect. The degree of hemorrhage or the severity of angiographical findings were not significant factors affecting the outcome. The most significant factor affecting long-term results was whether the inflammation caused by the underlying disease was medically well controlled.     

Angiotensin converting enzyme genotype influences the response to the angiotensin II receptor antagonist losartan in patients with hypertension.

To examine whether the response to the angiotensin II receptor antagonist losartan varies depending on the angiotensin converting enzyme (ACE) genotype, we prospectively studied the effect of losartan in 42 hypertensive patients (20 men, 22 women; mean age: 60.4 years). After a 4-week observation period, losartan was administered at 50 mg/day and blood pressure was measured every 2 to 4 weeks for 12 weeks. Among the 42 patients, 19, 11, and 12, respectively, had the II, ID, and DD ACE genotypes. The baseline plasma ACE activity in patients with the ID or DD genotype was significantly higher than that in patients with the II genotype (13.8 +/- 4.2 vs. 9.6 +/- 2.3 IU/l; p = 0.0002). However, age, gender, baseline systolic and diastolic blood pressure (SBP/DBP), and body mass index (BMI) were not different among the groups. After 12 weeks of treatment with losartan alone, DBP in the ID+DD group was significantly higher than that in the II group (85.0 +/- 9.0 vs. 77.8 +/- 9.6 mmHg, p = 0.018), while the percent reduction in DBP in the ID+DD group was significantly smaller than that in the II group (7.9 +/- 8.8 vs. 14.3 +/- 10.1%, p = 0.035). Multiple regression analysis showed that the significant predictors of the DBP at 12 weeks were age (p = 0.030), ACE genotype (p = 0.029) and baseline DBP (p = 0.0001). The ACE genotype may be a determinant of the response to losartan in hypertensive patients.     

A case of amyotrophic lateral sclerosis and breast cancer

We report a case of breast cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old Japanese woman diagnosed with ALS 6 years previously noticed a mass in the left breast. We performed a modified radical mastectomy for the mass lesion. Invasive ductal carcinoma without lymph node metastasis was diagnosed. During the operation, she had no worsening of her neurological symptoms. The patient has been cancer-free for 11 months since her operation and no improvement has been seen in her neurological condition. To the best of our knowledge, this is the first case of breast cancer occurring in a patient with ALS in Japan.     

Multiple aneurysms arising from the posterior inferior cerebellar artery with unknown etiology--case report--

A 67-year-old man presented with multiple aneurysms arising from the caudal loop of the posterior inferior cerebellar artery (PICA), possibly as a result of blunt trauma. Computed tomography of the head revealed subarachnoid hemorrhage in the posterior fossa and sylvian fissure. Repeated angiography demonstrated an aneurysmal dilatation and an irregular wall on the caudal loop of the PICA. Under the operating microscope, two lesions were observed 10 mm distal to the apex of the caudal loop, both consisting of a tiny hole on the vessel wall with a fragile fringe of connective tissue and covered with a firm clot. The height of the lesions corresponded to the C-l lamina, so the lesions were probably traumatic rather than saccular.