Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library

Two new 6,6-spiroacetal polyketides, spirotoamides A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces griseochromogenes JC82-1223 by screening of structurally unique compounds based on a search of spectral database. The fraction library was constructed using a systematic separation method to efficiently discover new metabolites from microbial sources such as actinomycetes and fungi. The structures of 1 and 2 were elucidated by 2D-NMR and mass spectrometric measurements. They belong to a class of polyketides, and contain a 6,6-spiroacetal core structure and a carboxamide group. The biosynthetic pathway of 1 and 2 is discussed in the text.     

Glucose and methionine uptake and proliferative activity in meningiomas

Abstract

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of2-[18F]fluoro-2-deoxyglucose ([18F]FDC) and L-fmethyl-11 CJmethionine ([71C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of I11C]MET', an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDC uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11 C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas. [Neurol Res 1999; 21: 640-644]     

Effects of sublingual nitroglycerin in patients receiving transdermal nitroglycerin for coronary artery disease: Prevention of cross-tolerance

The systemic hemodynamic and coronary dilative responses to sublingual nitroglycerin were studied in patients receiving transdermal nitroglycerin. A total of 48 patients with coronary artery disease were divided into 4 groups: 12 patients receiving 1 tablet of sublingual nitroglycerin without transdermal nitroglycerin (Group 1), 12 patients receiving 1 tablet of sublingual nitroglycerin with 12-hour-daily intermittent therapy of transdermal nitroglycerin (Group 2), 12 patients receiving 1 tablet of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 3), and 12 patients receiving 2 tablets of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 4). Before and during administration of sublingual nitroglycerin, aortic pressure, left ventricular pressure, and coronary artery diameter were examined at diagnostic cardiac catheterization in all patients. During sublingual nitroglycerin, the decreases of aortic systolic pressure and left ventricular end-diastolic pressure were greater in Group 1, 2, and 4 than in Group 3. Dilation of coronary arteries by sublingual nitroglyerin tended to be greater in Group 1, 2, and 4 than in Group 3. Thus, the effects of sublingual nitroglycerin for the relief of ischemia might be more prominent in patients with intermittent therapy of transdermal nitroglycerin than in those with continuous therapy. The increased dose of sublingual nitroglycerin for the relief of ischemia might be more effective in patients with continuous therapy of transdermal nitroglycerin.     

A food poisoning outbreak caused by purple Washington clam contaminated with norovirus (Norwalk-like virus) and hepatitis A virus

A party of 57 people dined together in a restaurant in Hamamatsu City on December 11, 2001. The next day, 22 of them developed symptoms of acute gastroenteritis, such as diarrhea, vomiting, and fever. Examination of 4 fecal specimens from these patients by ELISA for Norovirus (Norwalk-like virus, NV) detected both genogroup I (GI) and genogroup II (GII) NV in all the 4 specimens. In addition, RT-PCR and real-time PCR methods for NV detected the NV gene. Approximately one month after the outbreak of the food poisoning (acute gastroenteritis) by NV, 4 individuals in the same party developed type A hepatitis. Both RT-PCR and real-time PCR methods for hepatitis A virus (HAV) detected the HAV gene in their fecal specimens. The party of these patients ate purple Washington clam (Saxidomus purpuratus, imported from China) steamed with red pepper. Since this food appeared to have caused the viral infections, the one with the same lot number was subjected to viral examinations, which successfully detected the NV GI, NV GII, and HAV genes. These results led to the conclusion that the clam contaminated with NV and HAV had caused the food poisoning. The DNA sequences of the NV detected in the patients and the clam had 74 to 99% homology, indicating strains of various genotypes. All the strains of HAV that were derived from the patients and the clam were genotype 1A, and these sequences had over 95% homology, but were not completely identical. This outbreak led to the demonstration of imported fishery products as a cause of type A hepatitis, and indicated the need for guiding and enlightening people on the importance of adequate cooking of bivalves.     

Clinical significance of lipoprotein(a) in carotid plaque types and ischemic stroke in the elderly

Background:   The relationship between lipoprotein(a) (Lp(a)) and ischemic stroke is still controversial in the elderly. The purpose of the present paper was to evaluate the significance of Lp(a) in the development of extracranial carotid lesions and ischemic stroke.
Methods:   A total of 371 elderly subjects, studied with carotid ultrasonography (US) and brain computed tomography (CT), was stratified into two groups according to serum Lp(a) levels: the normal Lp(a) and high Lp(a) (>40 mg/dL) groups. Carotid plaques were divided into three types based on the US echogenicity: hypoechoic, hyperechoic, and heterogeneous plaques. Low-density areas (LDA) on brain CT images were classified into three groups depending on their distribution: basal ganglionic, cortical and only leuko-araiosis types.
Results:   The incidence of bilateral carotid lesions and the ratios of hypoechoic and heterogeneous plaques were significantly higher in the high Lp(a) group than in the normal Lp(a) group. Both the mean height and length of plaque were also greater in the high Lp(a) group. Mean Lp(a) levels were significantly elevated in cases with hypoechoic and heterogeneous types, compared to the cases without lesions. Higher mean Lp(a) levels were seen in cases with any kind of LDA than in normal subjects on CT, but there was no significant difference in the incidence of each LDA between the two groups.
Conclusions   These findings indicate that serum Lp(a) is strongly related to carotid lesions, especially hypoechoic and heterogeneous plaque types, in Japanese elderly patients. This suggests that Lp(a) could promote the formation of lipid-rich atheromatous plaque with intraplaque hemorrhage or superimposed thrombi. Serum Lp(a) also seemed to be a risk for all types of LDA.