Denoising parameter dependence of coronary artery depictability in compressed sensing magnetic resonance angiography.

Using numerical indices and visual evaluation, we evaluated the dependence of coronary-artery depictability on the denoising parameter in compressed sensing magnetic resonance angiography (CS-MRA). This study was conducted to clarify the acceleration factor (AF) and denoising factor (DF) dependence of CS-MRA image quality. Vascular phantoms and clinical images were acquired using three-dimensional CS-MRA on a clinical 1.5 T system. For the phantom measurements, we compared the full width at half maximum (FWHM), sharpness, and contrast ratio of the vascular profile curves for various AFs and DFs. In the clinical cases, the FWHM, sharpness, contrast ratio, signal-to-noise ratio, noise level values, and visual evaluation results were compared for various DFs. Phantom image analyses demonstrated that the respective measurements of the FWHM, sharpness, and contrast ratios did not significantly change with an increase in AF. The FWHM and sharpness measurements slightly changed with the DF level. However, the contrast ratio tended to increase with an increase in the DF level. In the clinical cases, the FWHM and sharpness showed no significant differences, even when the DF level was changed. However, the contrast ratio tended to decrease as the DF level increased. When the DF levels of the clinical cases increased, the background signals of the myocardium, fat, and noise levels decreased. We investigated the dependence of the coronary-artery depictability on AF and DF using CS-MRA. Analysis of the coronary-artery profile curves indicated that a better image quality was achieved with a stronger DF on coronary CS-MRA.

Detection of intracranial aneurysms using deep learning-based CAD system: usefulness of the scores of CNN's final layer for distinguishing between aneurysm and infundibular dilatation.

PURPOSE: We evaluated the diagnostic performance of a clinically available deep learning-based computer-assisted diagnosis software for detecting unruptured aneurysms (UANs) using magnetic resonance angiography and assessed the functionality of the convolutional neural network (CNN) final layer score for distinguishing between UAN and infundibular dilatation (ID). MATERIALS AND METHODS: EIRL brain aneurysm (EIRL_BA) was used in this study. The subjects were 117 UAN and/or ID cases including 100 UAN lesions (average sizes of 2.56 ± 1.45 mm) and 40 ID lesions (average sizes of 1.75 ± 0.41 mm) in any of internal carotid artery, middle cerebral artery, and anterior communicating artery, and 123 normal controls. The sensitivity, specificity, and accuracy of EIRL_BA were determined for UAN and ID or UAN only. Furthermore, the relationship between the lesion category and score was examined using a linear regression analysis model, and the receiver operating characteristic (ROC) analysis was used to assess whether the scores represent UAN-like characteristics. RESULTS: EIRL_BA showed a total of 203 candidates (an average of 1.73/case) in UAN and/or ID cases and 98 candidates (an average of 0.80/case) in normal controls. For diagnosing either UAN/ID, EIRL_BA showed an overall sensitivity of 80%, specificity of 84.2%, and accuracy of 83.7%, resulting in the positive likelihood ratio of 5.0. For diagnosing UAN only, the overall sensitivity of 89.0, specificity of 82.6%, and accuracy of 83.2% resulting in the positive likelihood ratio of 5.1. In a linear regression analysis, the scores significantly increased in the candidates' first and second ranks in UAN (p < 0.05) but not in ID. An ROC analysis using the score for diagnosing UAN showed an area under the curve of 0.836. CONCLUSION: EIRL_BA is applicable for detecting small UAN, and the CNN's final layer scores may be an effective index for discriminating UAN and ID and representing the likelihood of UAN.

Noise power spectrum in compressed sensing magnetic resonance imaging.

Compressed sensing magnetic resonance imaging (CS-MRI) uses random undersampling and nonlinear iterative reconstruction. This study was conducted to clarify the noise power spectrum (NPS) characteristics of CS-MRI. We measured two-dimensional (2D) NPS of CS-MRI with various acceleration factors (AF) and denoising factors (DF) and compared their appearance to those of conventional parallel MR images. Results showed that the 2D NPS of CS-MRI exhibited the following characteristics: (1) local decrease in the low-frequency region, (2) gradual decrease in the high-frequency region, and (3) a stripe pattern aligned at unequal intervals in the phase-encoding direction. Specifically, the 2D NPS of CS-MRI reflects the random undersampling pattern of k-space data. Additionally, 2D NPS allowed visualization of AF-dependent noise characteristics of CS-MRI. Furthermore, 1D NPS graph shapes clarified the CS-MRI noise characteristic dependence on AF and DF.

A pooled-analysis of age and sex based coronary artery calcium scores percentiles.

BACKGROUND: Age and sex based coronary artery calcium score (CAC) percentiles have been used to improve coronary artery disease (CAD) risk prediction. However, the main limitation of the CACs percentiles currently in use is that they are often based on single studies. We performed a pooled analysis of all available studies that reported on CAC percentiles, in order to develop more generalizable age and sex nomograms. METHODS: PubMed/Medline and Embase were searched for studies that reported nomograms of age and sex-based CACs percentiles. Studies were included if they reported data collected among asymptomatic individuals without a history of cardiovascular disease. Absolute CACs for each specific percentile stratum were pooled and new percentiles were generated taking into account the sample size of the study. RESULTS: We found 831 studies, of which 12 met the inclusion criteria. Data on CACs percentiles of 134,336 Western and 33,488 Asians were pooled separately, rendering a weighted CACs percentile nomogram available at https://www.calciumscorecalculator.com. Our weighted percentiles differed by up to 24% from the nomograms in use today. CONCLUSIONS: Our pooled age and sex based CACs percentiles based on over 155,000 individuals should provide a measure of risk that is more applicable to a wider population than the ones currently in use and hopefully will lead to better risk assessment and treatment decisions.

Comparison of axial and coronal acquisitions by non-contrast-enhanced renal 3D MR angiography using flow-in time-spatial labeling inversion pulse.

OBJECTIVE: We evaluated image quality differences between axial and coronal non-contrast-enhanced renal three-dimensional (3D) magnetic resonance angiography (MRA) acquisitions, using time-spatial labeling inversion pulse (Time-SLIP) with flow-in balanced steady-state free precession (bSSFP). MATERIALS AND METHODS: Axial and coronal images were acquired in 128 subjects using non-contrast-enhanced 3D-MRA with Time-SLIP flow-in bSSFP on a clinical 1.5-T MRI system. Visualization of source and maximum intensity projection (MIP) images of renal arteries were compared between the axial and coronal acquisitions using a four-point scale. For quantitative analysis, vessel-to-background contrast ratios of aorta and renal arteries were calculated. RESULTS: Both acquisitions yielded similarly excellent quality. In source image evaluation, coronal acquisitions showed significantly more motion degradation (p < 0.01) than did axial acquisitions. In MIP image evaluation, coronal acquisitions yielded superior image quality, less motion degradation, and better visualization of the number of renal branches than did axial acquisition. The renal artery to background signal contrast was greater in coronal than in axial acquisitions (p < 0.01). CONCLUSION: Coronal acquisition provides superior contrast between the renal arteries and background and allows more persistent visualization than axial acquisitions in non-contrast-enhanced MRA using flow-in bSSFP with Time-SLIP. First-line screening of renal non-contrast-enhanced MRA should involve coronal acquisition.

Hepatic Sclerosing Hemangioma with Predominance of the Sclerosed Area Mimicking a Biliary Cystadenocarcinoma.

We report here an extremely rare case of hepatic sclerosing hemangioma mimicking a biliary cystadenocarcinoma. A previously healthy 39-year-old woman was referred to our hospital because of a large tumor in the liver. Abdominal computed tomography revealed early peripheral ring enhancement in the arterial phase and slight internal heterogeneous enhancement in the delayed phase. Magnetic resonance imaging revealed a tumor with low intensity in the T1-weighted image and very high intensity in the fat-saturated T2-weighted image. The patient underwent hepatectomy for a possible malignant liver tumor. Grossly, the tumor appeared as a white, solid, and cystic mass (weighted 1.1 kg and measured 170×100×80 mm) that was elastic, soft, and homogeneous with a yellowish area. Histological examination showed that the tumor mostly consisted of fibrotic areas with hyalinization. The typical histology of cavernous hemangioma was confirmed in part, and the tumor was diagnosed as a sclerosing hemangioma with predominancy of the sclerosed area. A review of 20 cases reported previously revealed that only 2 (10%) patients were diagnosed as having sclerosing hemangioma preoperatively.

Treatment of nonocclusive mesenteric ischemia with type B aortic dissection using intra-arterial catheterization after trauma surgery: case report.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is a mesenteric arterial spasm and intestinal ischemia. This disease is a highly lethal disease because diagnosis and decision of appropriate treatments are often difficult. Operations cannot resolve the spasms and may worsen the situation. However, the safety and effectiveness of catheterization for NOMI with aortic dissection (AD) have not yet been elucidated. Here, we report a successful case of early diagnosis and treatment of NOMI with type B AD involving the superior mesenteric artery (SMA) using the intra-arterial infusion of a vasodilator via the SMA. CASE PRESENTATION: An 83-year-old man was admitted to our hospital because of abdominal pain after a motor accident. We performed intestinal resection and splenectomy for intestinal perforation and splenic hemorrhage and treated conservatively for acute AD, liver injury, renal hematoma, and pneumothorax. On postoperative day (POD) 2, the patient had localized abdominal pain. Follow-up computed tomography suggested a smaller superior mesenteric vein sign and segmental lack of enhancement in the intestinal wall and ascites without SMA occlusion. Thus, the patient was diagnosed with NOMI. Although the patient had type B AD including the SMA, we performed selective mesenteric arteriography and transcatheter papaverine infusion via the SMA and prostaglandin via the peripheral vein. Seven days post treatment, mesenteric blood flow improved and intestinal wall enhancement was restored. CONCLUSION: The intra-arterial infusion of a vasodilator is highly efficient and safety treatment option for NOMI with type B AD. Prompt and accurate management can prevent massive small bowel resection, and this procedure is essential in resolving a spasm independent of whether a necrotic bowel has been resected.

Effect of Tea Catechins on Folate Analysis in Green Tea by Microbiological Assay.

Green tea is thought to be a primary source of folate in the Japanese diet, based on folate content analyzed by a microbiological assay. Green tea also contains high amount of catechins, in particular, epigallocatechin gallate (EGCg), which was demonstrated to be able to inhibit the digestive enzyme activities and microbial growth in the folate assay. In the present study, we examined whether tea catechins interfered with components of the folate assay for green tea. A marked inhibitory effect of EGCg on microbial growth was observed at an inhibitory concentration of higher than 10 µg/mL. Tea catechins without the galloyl moiety did not show an inhibitory effect. EGCg inhibited the activity of the three enzymes used for assay sample preparation at an inhibitory concentration of higher than 750 µg/mL for α-amylase, 1,000 µg/mL for protease, and 50 µg/mL for conjugase. However, with each step of the assay, the actual concentration of EGCg was decreased to below the inhibitory concentration of each analytical step. Lack of influence of EGCg on green tea folate assay was confirmed by an addition of folate standard in tea infusion. These results suggested that tea catechins have no practical impact on folate analysis in green tea, using the general microbiological assay.

Prevalence and distribution of coronary calcium in asymptomatic Japanese subjects in lung cancer screening computed tomography.

BACKGROUND: Coronary artery calcium (CAC) is associated with a risk of coronary heart disease. The prevalence and distribution of the CAC score have been examined in Western countries, but few studies have been performed in Asia, and especially in Japan. The goal of this study was to investigate CAC scores in an asymptomatic Japanese population. METHODS: CAC score and risk factors were analyzed in 1834 asymptomatic subjects who underwent lung cancer screening computed tomography. RESULTS: CAC was present in 26.9% of all the subjects, 29.8% of the males, and 17.1% of the females. In all age groups, the CAC score was higher in males. In multivariate analysis, male gender [odds ratio (OR) 2.461, 95% confidence interval (CI) 1.361-4.452, p=0.002], aging (OR 1.102, 95% CI 1.081-1.123, p<0.001), dyslipidemia (OR 1.740, 95% CI 1.216-2.490, p=0.002), and fasting glucose (OR 1.008, 95% CI 1.002-1.015, p=0.012) were significantly associated with a CAC score >100. CONCLUSION: The results of this study provide a pattern of CAC distribution based on age and gender in asymptomatic Japanese subjects. This pattern was similar to that in Western countries, although the absolute CAC scores were lower. High CAC scores were associated with male gender, aging, dyslipidemia, and fasting glucose.

Relationship between Alcohol Intake and Risk Factors for Metabolic Syndrome in Men.

OBJECTIVE: The precise relationship between alcohol intake and metabolic syndrome (MetS) is still unclear, and the results from previous studies have been inconclusive. Thus, we examined the effect of alcohol intake on the risk of MetS in men in order to gain more information on a potential relationship. METHODS: This study included 22,349 men who were divided into four groups according to their average alcohol intake [non-, light (less than 20 g ethanol/day), heavy (equal or more than 20 g and less than 60 g ethanol/day) and very heavy (equal and greater than 60 g ethanol/day) drinkers]. We measured each subject's body mass index (BMI), waist circumference and blood pressure (BP) and conducted a blood test to obtain a complete blood count and biochemical panel. These results were used to obtain the MetS prevalence. Additionally, fatty liver was diagnosed using abdominal ultrasonography. RESULTS: Light drinkers had smaller waist circumferences. Heavy and very heavy drinkers had larger waist circumferences, a higher BMI, a higher BP, higher fasting plasma glucose levels, higher triglycerides (TG) levels and higher high-density lipoprotein (HDL) cholesterol levels while they had lower low-density lipoprotein cholesterol levels than nondrinkers. The prevalence of high BP, hyperglycemia and high TG was significantly higher in heavy and very heavy drinkers than in nondrinkers. The prevalence of low HDL cholesterol levels decreased with an increase in alcohol consumption. The prevalence of MetS was significantly lower in light drinkers and higher in very heavy drinkers compared with nondrinkers. CONCLUSION: Alcohol intake significantly influences the risk of MetS in men. A significant association was seen between an alcohol intake of 60 g/day or higher and the prevalence of MetS.

Potential impact of joint association of alanine aminotransferase and gamma-glutamyltransferase on insulin resistance in Japan: The Toranomon Hospital Health Management Center Study 19 (TOPICS 19).

AIM: To investigate the potential impact of joint association of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) on insulin resistance and ß-cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes. METHODS: This study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion. RESULTS: Mean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes. CONCLUSION: Combining the two liver function markers would be effective for identifying individuals with insulin resistance.

Prognostic factors for regression from impaired glucose tolerance to normal glucose regulation in Japanese patients with nonalcoholic fatty liver disease.

OBJECTIVE: The aim of this retrospective cohort study was to assess the predictive factors for the regression from impaired glucose tolerance (IGT) to normal glucose regulation (NGR) in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 164 NAFLD patients who had IGT in the first 75-g oral glucose tolerance test (OGTT) and underwent a repeated OGTT five years later were enrolled. A multivariate logistic regression analysis was carried out to identify factors predicting the regression from IGT to NGR. RESULTS: Out of the 164 patients, 29 regressed from IGT to NGR within five years after the first OGTT. The multivariate analysis by logistic regression showed that regression from IGT to NGR occurred when the patient was young (risk ratio for ten years: 0.38; 95% confidence interval [CI] 0.20-0.72; p=0.003), had a fasting plasma glucose (FPG) level of <100 mg/dL (risk ratio: 6.53; 95%CI 1.88-21.73; p=0.003), had a 2-hr post-load plasma glucose (PG) level of <160 mg/dL (risk ratio: 4.86; 95%CI 1.08-22.72; p=0.040), a body mass index (BMI) decrease of ≥1.5 (risk ratio: 5.20; 95% CI 1.41-19.24; p=0.014), physical activity of ≥2 Metabolic Equivalent of Task (MET) h/day (risk ratio: 5.57; 95%CI 1.68-18.44; p=0.005), and showed disappearance of the fatty liver by ultrasonography at five years (risk ratio: 9.92; 95%CI 2.87-34.34; p<0.001). CONCLUSION: Our results suggest that six factors: young age, FPG <100 mg/dL, 2-hr post-load PG of <160 mg/dL, BMI decrease of ≥1.5, physical activity of ≥2 MET h/day, and the disappearance of fatty liver predict the regression from IGT to NGR in NAFLD patients.

Giant coronary artery aneurysms associated with Kawasaki disease detected on whole-heart magnetic resonance coronary angiographic screening.

Kawasaki disease (KD) is one of the most important causes of coronary artery aneurysms in children and young adults. However, the natural course of the disease and the patient prognosis remain obscure. A 72-year-old asymptomatic man with undiagnosed KD underwent whole-heart magnetic resonance coronary angiography during a health checkup. The imaging disclosed giant aneurysms in the proximal portion of the right coronary artery and the left anterior descending artery. The patient was successfully treated with coronary artery bypass grafting. The present case suggests that there may be a substantial number of patients who have attained middle to old age with undiagnosed KD.

Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease.

AIM: The aim of this case-control study was to assess the efficacy and safety of dipeptidyl peptidase-4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD). METHODS: Twenty NAFLD patients with T2DM treated by sitagliptin were retrospectively enrolled as the sitagliptin group. These patients were given sitagliptin between January 2010 and July 2011. Another 20 NAFLD patients with T2DM treated only with diet and exercise for 48 weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48 weeks after the initiation of treatment. RESULTS: In the sitagliptin group, average HbA1c levels decreased approximately 0.7% at 48 weeks after the initiation of sitagliptin. Next, average FPG levels decreased approximately 15 mg/dL at 48 weeks after the initiation of sitagliptin. The serum levels of HbA1c and FPG in the sitagliptin group decreased with statistical significance compared to those in the control group (P < 0.05). All the patients could take sitagliptin of 50 mg/day without reduction necessitated by sitagliptin-related side-effects. There were no significant changes of average AST and ALT levels during follow up of 48 weeks in both sitagliptin and control groups. CONCLUSION: Our results indicate sitagliptin is effective and safe for the treatment of T2DM complicated with NAFLD.

Novel therapeutic vaccine: granulysin and new DNA vaccine against Tuberculosis.

PURPOSE: Multi-drug resistant (MDR) Mycobacterium Tuberculosis (M.TB) is a big problem in the world. We have developed novel TB therapeutic vaccines. METHODS AND RESULTS: DNA vaccine expressing mycobacterial heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. M. TB, MDR-TB or extremenly drug resistant (XDR-TB) was injected i.v. into DBA/1 mice, and treated with the vaccine three times. This HVJ-E/Hsp65DNA+IL-12DNA vaccine provided strong therapeutic efficacy against MDR-TB and XDR-TB (prolongation of survival time and the decrease in the number of TB) in mice. Therapeutic effect of this vaccine on TB infection was also demonstrated in chronic TB infection murine model using aerosol infection intratracheally. On the other hand, granulysin protein produced from CTL has lethal activity against TB. Granulysin protein vaccine also exerted strong therapeutic effect. Furthermore, we extended our studies to monkey model, which is currently the best animal model of human TB. Hsp65DNA+IL-12 DNA vaccine exerted strong therapeutic efficacy (100% survival and augmentation of immune responses) in the TB-infected monkeys. In contrast, the survival of the saline control group was 60% at 16 week post-challenge. HVJ-Envelope/HSP65 DNA+IL-12 DNA vaccine increased the body weight of TB-infected monkeys, improved the erythrocyte sedimentation rate, and augmentated the immune responses (proliferation of PBL and IL-2 production). The enhancement of IL-2 production from monkeys treated with this vaccine was correlated with the therapeutic efficacy of the vaccine. CONCLUSION: These data indicate that novel vaccines might be useful against TB including XDR-TB and MDR-TB for human therapeutic clinical trials.

Novel prophylactic vaccine using a prime-boost method and hemagglutinating virus of Japan-envelope against tuberculosis.

OBJECTIVE: Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. METHOD: A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. RESULTS: Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-γ. CONCLUSION: This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted.

Development of therapeutic and prophylactic vaccine against Tuberculosis using monkey and transgenic mice models.

PURPOSE: BCG is not efficacious against M. tuberculosis (TB) in adult. Therefore, novel TB vaccines were established by using three kinds of animal models (cynomolgus monkey model which is the best animal model of human TB, IL-2R knock out SCID mice as a human immune model, and granulysin transgenic mouse). METHODS AND RESULTS: DNA vaccine expressing TB Hsp65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. The BCG prime followed by Hsp65+IL-12/HVJ vaccine boost showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). In contrast, 33% of monkeys were alive in BCG alone group. Furthermore, the prolongation of survival period of the monkey was observed by the combination of BCG and DNA vaccine even when the boost was performed after long-term period (4month) from prime. This combination also improved the erythrocyte sedimentation rate (ESR), increased the body weight, and augmented the proliferation of PBL and IL-12 production at higher levels than BCG alone or saline. Furthermore, this vaccine exerted therapeutic efficacy in IL-2R knock out SCID-PBL/hu mice, which were transplanted with human T cells. Granulysin is an important defensive molecule expressed by human T cells and NK cells and has a cytolytic activity against microbes including Mycobacterium tuberculosis (TB) and tumors. Expression of 15kD (15K) granulysin protein and mRNA in CD8 positive T cells in the patients infected with drug sensitive (TB) or multi-drug resistant (MDR-TB) M. tuberculosis were lower than that in the healthy volunteers, suggesting that granulysin treatment might improve the tuberculous disease in human. Therefore, we established two kinds of granulysin transgenic mice (15K granulysin transgenic mice and 9K granulysin transgenic mice). It was demonstrated that 15K granulysin transgenic mice as well as 9K granulysin transgenic mice exerted in vivo anti-TB effect, including the decrease of the number of TB and augmentation of the CTL activity. These are the first findings which demonstrate in vivo effects of 15K granulysin and 9K granulysin against TB infection. Moreover, DNA vaccine expressing 15K granulysin showed a therapeutic activity against TB in mice. CONCLUSION: These data indicate that monkey, IL-2R gene-knock out SCID-PBL/hu and granulysin transgenic mice models provide useful tools for the development of novel vaccines (HVJ-Envelope/Hsp65 DNA + IL-12 DNA vaccine and granulysin vaccine) against TB.

[A case of advanced gastric and rectal cancer (double cancer) successfully treated with mFOLFOX6 therapy].

A 75-year-old man was diagnosed with gastric cancer (UL post c0- II c (c T1N0) and M-less ctype II (cT2N0)) and rectal cancer (Rb ctype II (cT2N1) with multiple lung metastases (M1). The patient was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). Chest and abdominal CT scan revealed that multiple lung metastases and abdominal lymph node metastases were obviously reduced in size. The primary lesion of the rectum almost disappeared on endoscopic examination. As for the lesions of the stomach, the UL post c0- II c lesion completely disappeared, and the M-less ctype II lesion was reduced remarkably. Thus, a significant reduction of the tumors was observed. This case suggests that mFOLFOX6 regimen can be an option for gastric cancer.

A new therapeutic strategy for hypertrophic nonobstructive cardiomyopathy in humans. A randomized and prospective study with an Angiotensin II receptor blocker.

A randomized and prospective study was designed to prove the efficacy of angiotensin II receptor blockers (ARB) in the amelioration of myocardial impairment in hypertrophic nonobstructive cardiomyopathy (HNCM). Nineteen consecutive patients with HNCM were randomly assigned to two groups and then underwent cine magnetic resonance evaluation of left ventricular mass (LVM) twice just before and after one year of observation. In the ARB group, 50 mg of losartan potassium was administered once daily during the observation period. The ratio of LVM after the observation period over that before the period was blindly compared between the two groups to estimate morphologically the ameliorative effect of ARB. In the ARB group, LVM was 203 +/- 47 cm(3) before the treatment period and 190 +/- 55 cm(3) after the period and the ratio of the final LVM over the initial LVM was 0.93 +/- 0.10. In the non-ARB group the initial and final LVM values were 177 +/- 48 cm(3) and 179 +/- 45 cm(3), and the ratio of the final LVM over the initial LVM was 1.02 +/- 0.07. The ratio of the final LVM over the initial LVM in the ARB group was significantly smaller (P = 0.03) than that in the non-ARB group. The smaller ratio in the ARB group strongly indicates that ARB ameliorated the natural course of HNCM during the one year observation period. Thus, this is the first demonstration of the therapeutic efficacy of ARB in human HNCM.