Background and Purpose-The purpose of the present study was to assess the incidence and clinical significance of the intraparenchymal hyperdense areas on the posttherapeutic CT scan just after intra-arterial reperfusion therapy. Methods-Seventy-seven patients with acute middle cerebral artery occlusion were studied prospectively with posttherapeutic CT. Hyperdense areas were classified into three groups: those in the lentiform nucleus, insular cortex and cerebral cortex. We investigated the incidence of hyperdense areas and hemorrhagic transformations and assessed whether location of hyperdense areas may play a role in the incidence of hemorrhagic transformations. We also evaluated correlation between early CT signs and hyperdense areas. Results-Forty-five hyperdense areas were seen in 37 of the 77 patients (48.1%): 19 of the 45 (42.2%) were confirmed to be hematomas themselves, 6 (13.4%) showed later conversion to petechial hemorrhages, and 20 (44.4%) showed rapid disappearance without hemorrhagic transformations. Eleven of the 37 patients (29.7%) had neurological worsening due to massive hematoma (symptomatic hemorrhage), whereas none of the 40 patients without hyperdense areas had symptomatic hemorrhage. The incidence of hemorrhage among hyperdense areas was significantly lower in the insular cortex than in the other 2 regions (PϽ0.01). On the other hand, hyperdense areas in the lentiform nucleus had a significantly higher incidence of neurological worsening (PϽ0.05). There was a significant correlation between early CT signs and hyperdense areas (PϽ0.0001). Conclusions-The presence of hyperdense areas was a significant risk factor for severe hemorrhagic transformations, although only 29.7% of patients with hyperdense areas had symptomatic hemorrhage. On the contrary, the absence of hyperdense areas was a reliable negative predictor for symptomatic hemorrhage.
This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.
Background and Purpose-The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion. Methods-Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days. Results-There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (PϽ0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (Pϭ0.03).Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group; Pϭ0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%; Pϭ0.04). Conclusions-Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.
This epidemiologic study was undertaken to determine whether working overtime is associated with anthropometric indices and serum lipids, risk factors for obesity, in white-collar workers. Non-management white-collar male workers were eligible. Body weight and height, waist circumference, skinfold thickness, serum total cholesterol and triglycerides were measured. Weight, height and waist circumference data obtained 3 years previously were also used. Lifestyle information was obtained by means of a self-administered questionnaire. Overtime hours correlated significantly with the 3-year change in body mass index (r = 0.206, p < 0.0017) and waist circumference (r = 0.218, p = 0.0091), but not with either the most recent anthropometric indices or serum lipids. Overtime hours were also intercorrelated (r = 0.436, p < 0.0001) with dinner time. The present study suggested that working overtime is associated with the increases in BMI and waist circumference over a 3-year period although the associations were weak. Additionally, eating habits of those with working overtime might reflect an intervening effect on the anthropometric changes.
Glioblastoma multiforme (GBM) is a malignant brain tumor characterized by rapid growth and extensive invasiveness. Overexpression of insulin-like growth factor-binding protein-2 (IGFBP-2) has been reported in GBM. However, it remains to be determined how IGFBP-2 is involved in the progression of GBM. We utilized short hairpin-RNA (shRNA) expression retroviral vectors to inactivate the IGFBP-2 gene permanently in two human GBM cell lines, U251 and YKG-1. The stable knockdown of IGFBP-2 resulted in decreased invasiveness, decreased saturation density of the cells in vitro, and decreased tumorigenicity in nude mice. Transcriptional profiling of both lines revealed several genes that were significantly down-regulated by inactivation of IGFBP-2. One such gene was CD24, which has been implicated in progression of various cancers. Indeed, CD24 was expressed in most GBM cases and the inactivation of CD24 in GBM cells suppressed cellular invasiveness, as was the case for IGFBP-2. Forced overexpression of CD24 led to increased invasiveness of both IGFBP-2-inactivated GBM cell lines and also A172, a human GBM cell line with low endogenous CD24. Further supporting the inter-relationship between IGFBP-2 and CD24, knockdown of IGFBP-2 suppressed the CD24 promoter activity. Moreover, both CD24 promoter activity and in vitro invasiveness were restored in knockdown cells by transfection with an IGFBP-2 expression plasmid. These results indicate that CD24 is modulated by IGFBP-2 and contributes to IGFBP-2-enhanced invasiveness of GBM cells.
The substrate specificity of squalene-hopene cyclase was investigated using the C10-C25 analogs including naturally occurring substances, e.g. geraniol (C10), farnesol (C15) and geranylgeraniol (C20). No cyclization occurred for geraniol, but a significantly high conversion ratio (64%) was observed for farnesol, yielding the cyclic sesquiterpenes consisting of 6/6-fused bicyclic ring systems. Among them, an attractive compound having C30 was produced, in the structure of which acyclic the farnesol unit is linked to the bicyclic skeleton through ether linkage. Conversion of geranylgeraniol was low (ca. 12%). The squalene analogs having C20 and C25 also were cyclized in yields of ca. 33-36%, but the analogs having the methyl group at C7 and/or at C11 underwent no cyclization; the large steric bulk size of C7-Me and/or C11-Me, which is arranged in [small alpha]-disposition for all the pre-chair conformation, would have interacted repulsively with the cyclase recognition site near to the C7 and/or C11, resulting in no construction of the all-chair conformation inside the reaction cavity. A relatively low yield of geranylgeraniol indicated that a less bulky hydrogen atom must be located at C14 for the efficient polycyclization reaction. The squalene cyclase shows remarkably broad substrate specificity to accept the truncated analogs having carbon-chain lengths of C(15)-C25 in addition to C30.
Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SMI, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9±3.4%[mean±SD]), and were modulated to the embryonic phenotype (SMemb-positive and SM2-negative). They migrated into I ntravascular stents have been extensively investigated as tools of angioplasty and proved useful in elastic recoil, restenosis, and dissection after balloon angioplasty.1 They have also been applied to various sites of stenotic lesions, including coronary arteries.1 -4 Several clinical trials have demonstrated that intracoronary stenting may be more effective than percutaneous transluminal coronary angioplasty (PTCA) in maintaining long-term vessel patency and may reduce the incidence of restenosis after angioplasty. "9 Such reduction in the restenosis rate is considered to be due to a larger acute gain obtained by stent implantation, although late loss of diameter is greater after stenting than that after PTCA. 7 9 Thus, restenosis after stenting still remains an unsolved problem.Pathological specimens of restenotic lesions after stenting show intimal hyperplasia, composed of abundant smooth muscle cells (SMCs) mixed with various degrees of connective tissue matrix. This study was presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.Reprint requests to Hikaru Matsuda, MD, First Department of Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.© 1994 American Heart Association, Inc.the intima and proliferated most frequently on day 7 (PCNA index in the intima: 20.3±5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implantation model demonstrates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of SMCs and their phenotypic modulations.
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