Significant associations of metabolic syndrome and its components with silent lacunar infarction in middle aged subjects.

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of ischaemic stroke, including silent brain infarction. No study has examined its association with the lacunar subtype. The present cross sectional study examined the relationship between MetS, its components and silent lacunar infarction (SLI) in middle aged subjects. METHODS: We studied 2076 subjects aged 40-59 years with no history of stroke or clinical symptoms, who visited a health care facility for a routine health checkup and underwent brain MRI. MetS was defined according to the National Cholesterol Education Programme Adult Treatment Panel III report. A multiple logistic regression model was used to examine the associations between MetS and SLI while adjusting for age, gender, a past history of ischaemic heart disease and current smoking. RESULTS: MetS was strongly associated with the presence of SLI (adjusted OR 6.52; 95% CI 4.30 to 9.90). Regarding MetS components, elevated blood pressure, impaired fasting glucose, hypertriglyceridaemia and large waist circumference were significantly associated with SLI, independent of an interrelationship between the components, while low high density lipoprotein cholesterol was not significantly associated. CONCLUSIONS: MetS was significantly associated with the prevalence of SLI in middle aged persons. Independent risk factors for SLI not only included elevated blood pressure and impaired fasting glucose, which are well known risk factors, but also hypertriglyceridaemia and large waist circumference.

Significant association between leukoaraiosis and metabolic syndrome in healthy subjects.

OBJECTIVE: To investigate the relationship between leukoaraiosis (LA), which has been considered as an intermediate substitute of ischemic brain damages, and metabolic syndrome (MetS), which attracts attention as a risk factor for cerebrovascular diseases, in healthy subjects derived from various age groups. METHODS: We studied 1,030 healthy persons at ages between 28 and 78 years (mean, 52.7 years) with no history of stroke who visited a health care facility for routine health checkups. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III. LA was assessed using the rating scale of the Atherosclerosis Risk in Communities study on MRI. Logistic regression analysis was performed to examine associations between LA and MetS. RESULTS: A total of 296 (28.8%) subjects had LA on MRI. MetS was significantly associated with the presence of LA (adjusted OR, 3.33; 95% CI, 2.30, 4.84). The association was constant across grades of LA; the adjusted OR was 3.41 (95% CI, 2.30, 5.06) for minimal LA and 3.07 (95% CI, 1.75, 5.38) for LA combining mild, moderate, and severe grades. As for MetS components, elevated blood pressure (adjusted OR, 2.16; 95% CI, 1.57, 2.99), impaired fasting glucose (adjusted OR, 1.64; 95% CI, 1.13, 2.39), and hypertriglyceridemia (adjusted OR, 1.56; 95% CI, 1.08, 2.28) were independently associated with all grades of LA. CONCLUSIONS: Metabolic syndrome (MetS) was significantly associated with every grade of leukoaraiosis (LA), including the minimal LA. Impaired fasting glucose and hypertriglyceridemia were associated with LA independently of elevated blood pressure. MetS can play an important role in identifying healthy subjects who have an increased risk of LA.

Prognostic significance of CDC25B expression in gliomas.

BACKGROUND: CDC25B is a cell-cycle regulatory protein, which is considered to be related to tumorigenesis and progression of tumours. AIMS: To elucidate the role of CDC25B in glioma, the expression of CDC25B and the association of the CDC25B expression with the clinicopathological parameters were investigated. METHODS: Fifty seven gliomas, which included 21 low-grade astrocytomas, 17 anaplastic astrocytomas and 19 glioblastomas, were studied. Protein expressions of CDC25B were evaluated by immunohistochemical methods. Semiquantitative and real-time RT-PCR analyses for the expression of CDC25B mRNA were also carried out. Disease-free survival (DFS) data were analysed by using the Kaplan-Meier method. RESULTS: High expression of CDC25B was identified in 18 of the 19 glioblastomas, in 10 of the 17 anaplastic astrocytomas, but not in any of the 21 low-grade astrocytomas. The CDC25B mRNA expression increased with the rise in histological grade. Increased CDC25B expression was correlated significantly with a shorter period of DFS, as shown by multivariate analysis. CONCLUSIONS: Patients with an unfavourable clinical outcome are characterised by the increased expression of CDC25B in their glioma samples. Useful clinical information, especially on its relevance as a prognostic indicator, is provided by the evaluation of CDC25B expression in gliomas.

Oculopharyngodistal myopathy is genetically heterogeneous and most cases are distinct from oculopharyngeal muscular dystrophy.

The question whether oculopharyngodistal myopathy (MIM 164310) is a distinct disease entity or a variant of oculopharyngeal muscular dystrophy (MIM 164300) persists. To answer this question, we examined five patients with the clinical characteristics of oculopharyngodistal myopathy for GCG expansion in poly(A)-binding protein nuclear 1 gene (previously called poly(A)-binding protein 2), the causative gene defect for oculopharyngeal muscular dystrophy. Only one of our five patients had the significant GCG expansion. Thus, oculopharyngodistal myopathy is a genetically heterogeneous disorder, which includes patients with oculopharyngeal muscular dystrophy but, for the most part, is different genetically from oculopharyngeal muscular dystrophy.

Glucocorticoid stimulates primate but inhibits rodent alpha-fetoprotein gene promoter.

Glucocorticoids inhibit rodent alpha-fetoprotein (AFP) gene activity but stimulate expression of the human homologue. Like human, activity of the AFP promoter from other primates was stimulated by the synthetic glucocorticoid dexamethasone (Dex) in various cell lines. A glucocorticoid responsive element (GRE) is located within 180 bp upstream of the transcription initiation site of all AFP genes examined. Comparative analysis of the GRE in the two different groups of promoters revealed a common 3' hexamer, 5'-TGTCCT-3', but the 5' hexamers were different. This difference converts the rodent GRE to a DR-1 motif. DR-1 is a binding site for members of the nuclear receptor superfamily including the orphan receptor hepatocyte nuclear factor-4 (HNF-4). The presence of DR-1 in the rodent but not human may underlie the opposite actions of Dex on the AFP promoter. We tested this hypothesis using a transient transfection assay. In hepatoma cells that expressed GR and HNF-4, reporter-activity was inhibited by Dex. The same construct in nonhepatoma cells was strongly induced by over expression of HNF-4 and the induced activity was inhibited by Dex. The findings show that Dex induction of human AFP is mediated by a GRE. But Dex repression of the rodent promoter requires a DR-1 motif that interacts with GR and HNF-4.

Immunohistochemical analyses of cell cycle-related proteins, apoptosis, and proliferation in pituitary adenomas.

To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:1193-1194, 2001)

Novel gastroinsular axis involving a gastric transmural glucose flux and vagal mediation.

To determine whether the appearance of nutrients into the gastric lumen per se provokes insulin secretion, glucose solution was instilled into the pylorus-cannulated stomach via an orogastric tube in anesthetized dogs. When 200 ml of 0, 5, 10, and 20% glucose solution were sequentially instilled, transgastric gradients (TGG) of plasma glucose concentration across the fundus [short gastric vein (SGV) - femoral artery, TGG(SGV)] and insulin levels in the superior pancreaticoduodenal vein (SPDV) increased stepwise. Upon instillation of 300 ml of 10% glucose, but not 1.8% saline, for 12 min followed by 48-min spontaneous drainage via the cannula (n = 5 each), TGG(SGV) and insulin levels in the SPDV increased concomitantly and significantly by 0.95 mM and 1,334 pM (mean), respectively, regardless of unaltered arterial glucose levels. The amount of secreted insulin (area under the curve) significantly correlated with the maximum TGG(SGV) (r = 0.693). In selectively gastric-vagotomized dogs (n = 5), insulin levels in the SPDV did not increase upon instillation despite a TGG(SGV) rise comparable to that in normal dogs. These results indicate that intragastric glucose appearance provokes vagus-mediated insulin secretion probably related to the transfundic glucose flux, suggesting the presence of a novel neurogenic gastroinsular axis.

[A case of familial cerebral cavernous angioma and review of Japanese cases].

We present one pedigree of familial cerebral cavernous angioma (FCCA). Case 1 was a 52-year-old male with right hemiplegia. When he was 37 years old, a left occipital lesion was excised and histologically diagnosed as cavernous angioma. MR image showed many cavernous angiomas in the right temporal lobe, the right paraventriclar white matter, the right frontal lobe, the left basal ganglia, and the left parietal lobe. Stereotactic radiosurgery was undertaken for all the lesions. Although the size of each lesion was unchanged, neither hemorrhage nor neurological deterioration were recognized after radiosurgery. Case 2 was a 24-year-old male, a son of the patient in case 1. He has manifested tonic-clonic type epilepsy since the age of 2. MR image showed cavernous angiomas in the pons, the right frontal, and the left intra-Sylvian regions, and many paraventricular cysts with rims indication of previous hemorrhages. Two de novo lesions were observed on subsequent annual MR screening. Surgical excision for the left intra-Sylvian lesion and stereotactic radiosurgery for all lesions were undertaken. Histological diagnosis was cavernous angioma. In the literature, there were 17 pedigrees and 37 cases of FCCA in Japan. The incidence of both multiple lesions and hemorrhage were less than in found in Spanish or French cases. Stereotactic radiosurgery is considered an useful treatment for FCCA, because lesions are multiple and de novo lesions occur.

Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1.

Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, HNF1 (hepatocyte nuclear factor 1) and a repressive transcription factor, ATBF1 (AT motif binding factor 1). RNase protection assays revealed that the production of AFP in gastric cancer cells did not directly associate with HNF1 expression. An inverse relation between the expressions of ATBF1 and AFP was clearly observed in gastric cancer cells. CAT assays showed the direct inhibition of AFP gene expression by ATBF1. Methylation analysis of the AFP promoter region in gastric cancer cells suggested that methylation itself could not explain the silencing of the AFP gene. Immunohistochemistry of resected clinical samples revealed that AFP producing cells lacked ATBF1 immunoreactivity. Our data suggests that the absence of ATBF1 is responsible for AFP gene expression in gastric cancer, and the absence of ATBF1 is a distinct characteristic of AFP-GC and might be important for its highly malignant nature.

Complete nucleotide sequence of Tulip virus X (TVX-J): the border between species and strains within the genus Potexvirus.

The complete nucleotide sequence of the genomic RNA of Tulip virus X Japanese isolate (TVX-J) has been determined. The sequence is 6056 nucleotides in length, excluding the poly(A) tail at the 3' terminus, and contains five open reading frames (ORFs) coding for proteins of Mr 153, 25, 12, 10, and 22 kDa (ORFs 1 through 5, respectively). The genome organization of TVX-J is similar to that of potexviruses, and the encoded proteins share a high degree of homology to the corresponding proteins of other potexviruses. Phylogenetic analyses based on the RNA-dependent RNA polymerase (RdRp) protein (the methyltransferase, helicase, and polymerase domains) encoded by ORF1 and the capsid protein (CP) encoded by ORF5, revealed a close relationship of TVX-J to Plantago asiatica mosaic virus (PlAMV). Pairwise comparison analyses revealed that the relationship between TVX and PlAMV is intermediate between that of strains and species, though previously they have not been considered related. Due to the relatively distant relationships of their replication apparatus and triple gene blocks, we conclude that TVX and PlAMV should be classified as distinct viruses. In addition, the borderline between species and strains of potexviruses is discussed.