Noninvasive detection of coronary artery bypass graft patency by intravenous electron beam computed tomographic angiography

This study evaluates the usefullness of intravenous electron beam computed tomographic angiography (EBA) for the detection of coronary artery bypass graft patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary artery bypass graft surgery. EBA was performed a few days before selective bypass graft angiography (SGA). Forty axial cross-sections of angiographic images of the heart were acquired consecutively by an electrocardiographic trigger signal at 40% of the RR interval, which corresponds to the end-systolic phase. EBA data were reconstructed as a three-dimensional shaded surface display of the heart and bypass grafts. Detectability of the patency of bypass gratis was evaluated, taking selective angiographic images of the bypass grafts as a gold standard. One hundred and nine grafts (96%) out of 114 grafts were subjected to evaluation: 37 grafts were left internal mammary artery grafts (LIMA), 7 were right internal mammary artery grafts (RIMA), 6 were gastroepiploic artery grafts (GEA), 7 were free gastroepiploic artery grafts with venous drainage (free-GEA), 7 were radial artery grafts (RAG), and 45 were saphenous vein gratis (SVG). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBA were 98%, 100%, 100%, 91%, and 98%, respectively. EBA sampled at the end-systolic period was determined to be useful for the detection of coronary artery bypass graft patency and occlusion.     

Follow-up studies of Hokkaido residents with Kawasaki disease

OBJECTIVES: Sixteen national surveys of Kawasaki disease in Japan from 1970 to 2000 have identified a total of 169,117 patients with Kawasaki disease. Based on that figure, 8,460 residents of Hokkaido probably have a history of Kawasaki disease. It is also estimated that almost 270 Hokkaido residents would have Kawasaki disease-related coronary artery disease. We underwent follow-up studies of Hokkaido residents > or = 15 years with Kawasaki disease. METHODS: We mailed a questionnaire to the departments of internal medicine, cardiology or cardiovascular surgery inquiring about the health status of patients with Kawasaki disease at 451 hospitals with 20 or more beds in Hokkaido. RESULTS: We obtained replies from 185 hospitals (41.0%). Only 11 hospitals(5.9%) reported experience of patients with Kawasaki disease(with or without coronary artery disease) at hospital follow-up. Detailed patient histories for 60 patients from 7 hospitals were obtained: Twenty patients had Kawasaki disease complicated with coronary artery disease, whereas 40 patients had a history of Kawasaki disease and no present coronary artery disease. Thirty-seven patients without coronary artery disease were followed up at one hospital. The 60 patients were aged from 15 to 36 years. Thirty-nine patients(65%) were in the 15 to 20 year age bracket. Coronary aneurysms were recognized in 25 patients(24 males and 1 female) with Kawasaki disease(41.7%) at the onset of the disease. Twenty patients had an aneurysm(s) in the left main trunk and/or the left anterior descending artery, and 13 patients in the right coronary artery. There was a history of myocardial infarction in four patients (6.7%) and nine patients(15.0%) still suffered from angina pectoris. Aortocoronary bypass surgery was performed in one patient, whereas two patients required percutaneous coronary intervention. CONCLUSIONS: Our study suggests that the majority of Hokkaido residents with Kawasaki disease(with or without coronary artery disease) are not being followed up at area hospitals. The characteristics of patients who were followed up included age < or = 20 years, male sex and the presence of severe coronary artery disease other than circumflex involvement.     

A novel role for interleukin-18 in human natural killer cell death: high serum levels and low natural killer cell numbers in patients with systemic autoimmune diseases

OBJECTIVE: Patients with systemic autoimmune diseases have been reported to have reduced numbers of peripheral blood natural killer (NK) cells compared with healthy subjects. The ability of selected cytokines to trigger NK cell death prompted us to compare the levels of peripheral blood cytokines with the numbers of NK cells in patients with various systemic autoimmune diseases. METHODS: We used enzyme-linked immunosorbent assays to measure the concentration of selected cytokines (interleukin-18 [IL-18], IL-15, IL-12, IL-2, interferon-gamma [IFNgamma], and tumor necrosis factor alpha [TNFalpha]) in sera from 58 patients with systemic autoimmune diseases and 33 healthy controls. The absolute number of T cells and NK cells in the peripheral blood was measured in parallel using flow cytometry. The ability of selected cytokines to induce NK cell death was then measured using 3,3'-dihexyloxacarbocyanine iodide dye, propidium iodide staining, and caspase 3 activity. RESULTS: Levels of IL-18, IL-15, IFNgamma, and TNFalpha were elevated in sera from patients with systemic autoimmune diseases compared with normal controls. The percentage of NK cells and natural killer T cells were significantly decreased in the peripheral blood of patients with systemic autoimmune diseases compared with normal controls. Serum concentrations of IL-18, IL-15, and TNFalpha were inversely related to the number of NK cells in both patients and healthy controls. The combination of IL-18 and IL-15 or IL-18 and IL-12 induced NK cell death in vitro. The combination of IL-18 and IL-15 or IL-18 and IL-12 enhanced IFNgamma and TNFalpha production by NK cells in vitro. Cytokine-induced NK cell death is caspase-dependent and is partially blocked by neutralizing antibodies against TNFalpha. CONCLUSION: High levels of IL-18 and IL-15 are associated with the decreased number of NK cells that is observed in patients with systemic autoimmune diseases.     

Long-Term Outcomes of Japanese Type 2 Diabetic Patients With Biopsy-Proven Diabetic Nephropathy

OBJECTIVE

We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy.

RESEARCH DESIGN AND METHODS

Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy (n = 260) were enrolled. Patients were stratified by albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the time of renal biopsy. The outcomes were the first occurrence of renal events (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, coronary interventions, or nonfatal stroke), and all-cause mortality.

RESULTS

The factors associated with albuminuria (proteinuria) regardless of eGFR were hematuria, diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors associated with low eGFR regardless of albuminuria (proteinuria) were age and diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular, tubulointerstitial, and vascular lesions in patients with normoalbuminuria (normal proteinuria) and low eGFR were more advanced compared to those in patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In addition, compared to patients with micro-/macroalbuminuria (mild/severe proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were similar or more advanced in contrast to glomerular lesions. The mean follow-up period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and 45 deaths. The pathological determinants were glomerular lesions, interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events, arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The major clinical determinant for renal events and all-cause mortality was macroalbuminuria (severe proteinuria).

CONCLUSIONS

Our study suggests that the characteristic pathological lesions as well as macroalbuminuria (severe proteinuria) were closely related to the long-term outcomes of biopsy-proven diabetic nephropathy in type 2 diabetes.Diabetic nephropathy occurs in 20–40% of patients with diabetes (1). The prevalence of diabetic nephropathy is increasing in proportion to the increase in prevalence of diabetes, and it has been predicted to continue to increase in future (2). Diabetes is a risk factor of cardiovascular disease and death, and diabetic nephropathy further increases these risks (3). In addition, diabetic nephropathy is the leading cause of end-stage renal disease requiring dialysis or transplantation in developed countries (4–6).In recent years, many clinical studies have suggested strict glycemic control and blood pressure management by use of appropriate medication to suppress the onset and progression of diabetic nephropathy. Thus, it is important to identify patients at risk in the early stages to improve prognosis in patients with diabetic nephropathy (1). Albuminuria and glomerular filtration rate (GFR) are recommended for use as clinical markers of diabetic nephropathy (1,7–9). On the other hand, selection of pathological markers is complicated because a variety of renal lesions can be found in diabetic nephropathy in addition to factors such as obesity, hypertension, dyslipidemia, and aging, which are frequently complicated in type 2 diabetes, causing a wide variety of pathological changes (10).We previously reported on the clinical factors related to the development and progression of renal lesions in diabetic nephropathy by the evaluation of serial renal biopsies or autopsy (11). In this report, we demonstrated a significant relationship between the progression of diabetic glomerulosclerosis and clinical factors such as the control of blood glucose, type of diabetes, age at onset, type of treatment, and degree of obesity.After this study, we conducted a long-term retrospective study to evaluate the structural-functional relationships and the predictive impacts of clinicopathological parameters for renal events, cardiovascular events, and all-cause mortality among Japanese patients with biopsy-proven diabetic nephropathy in type 2 diabetes.     

Clinical analysis of HLA-DR-negative non-M3 AML

The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.     

CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions

L-type Ca(2+) channels have a wide tissue distribution and play essential roles in physiological responses. Recent studies have indicated that regulation of L-type Ca(2+) channels involves the assembly of macromolecular signaling complexes such as the beta(2)-adrenergic receptor signaling complex, the small G-protein kir/Gem and the BK channel. Here, we report the previously unidentified role of another protein in binding to the II-III linker of the alpha(1C) subunit of the L-type Ca(2+) channel. This protein is COP9 signalosome subunit 5 (CSN5)/Jun activation domain-binding protein 1 (Jab1). We have demonstrated that CSN5 interacts specifically with the II-III linker of the alpha(1C) subunit in a yeast two-hybrid system. The alpha(1C) subunit and CSN5 were coimmunoprecipitated in rat heart and both proteins were colocalized in sarcolemmal membranes and transverse tubules of cardiac myocytes. Silencing of CSN5 mRNA using siRNA decreased the endogenous protein level of CSN5 and activated L-type Ca(2+) channels expressed in COS7 cells. These data indicate that CSN5 is a protein that plays a newly defined functional role in association with the cardiac L-type Ca(2+) channel.     

Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria): Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis

BACKGROUND: The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined. OBJECTIVE: We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria). METHODS: We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria. RESULTS: The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05). CONCLUSION: Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.     

A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome

Deletions or translocations of chromosome band 13q14, the locus of the retinoblastoma gene (RB1), have been observed in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We describe here a novel unbalanced translocation der(13)t(7;13)(p13;q14) involving 13q14 in a patient with MDS. A 66-year-old woman was diagnosed as having MDS, refractory anemia with excess of blasts (RAEB-1) because of 7.4% blasts and trilineage dysplasia in the bone marrow cells. G-banding and spectral karyotyping analyses showed complex karyotypes as follows: 46,XX,der(6)t(6;7)(q11;?),der(7)del(7)(?p13)t(6;7)(q?;q11)t(6;13)(q?;q?),der(13)t(7;13)(p13;q14). Fluorescence in situ hybridization (FISH) analyses demonstrated that one allele of the RB1 gene and the microsatellite locus D13S319, located at 13q14 and telomeric to the RB1 gene, was deleted. Considering other reported cases, our results indicate that submicroscopic deletions accompanying 13q14 translocations are recurrent cytogenetic aberrations in MDS. The RB1 gene or another tumor suppressor gene in the vicinity of D13S319, or both, may be involved in the pathogenesis of MDS with 13q14 translocations by monoallelic deletion.     

Final report of the working group for the future planning of the Japanese Association of Anatomists

The working group for the future planning of the Japanese Association of Anatomists (JAA) has been working to address the issues that were consulted from the president of JAA since October 2009. After making the interim report in March 2010, a public hearing for general members of the JAA was held and a final report was submitted to the President in January 2011. The report contains the analysis of the current situation, the directions in which we should proceed, and recommendations of concrete actions that JAA should take for each issue. The issues discussed were as follows: 1. Future prospects of anatomy and morphological sciences. How can we maintain the specialties of morphological and anatomical sciences in the rapidly advancing field of life sciences and develop collaborations with other fields? 2. Improvement of the JAA academic meetings. How can we increase JAA members and young participants in the academic meetings of the JAA? 3. Fostering the next generation of young researchers. How can we increase young researchers graduated from the schools of Medicine or Dentistry? 4. Future prospects of education of gross anatomy. Prospects of education in gross anatomy and the body donation registration system in relation with some new cadaver-related movements.