High-voltage electron microscopy of E-PTA-stained synaptic junctions in the rat frontal cortex

The E-PTA-stained synaptic junctions in the adult rat frontal cortex were examined with high-voltage electron microscopy (HVEM). Perforated whole synaptic junctions were clearly shown in the stereo image. The E-PTA staining procedure provides a useful marker for studies of the 3-dimensional structure of synaptic junctions by means of HVEM.     

Regional cerebral blood flow during an attack of vertebrobasilar insufficiency

Using technetium-99m-labeled hexamethylpropyleneamineoxime [( 99mTc]HM-PAO) and single-photon emission computed tomography, we measured changes in regional cerebral blood flow in a 58-year-old man during an attack of vertebrobasilar insufficiency. Angiography demonstrated compression of the left vertebral artery by the osteophytes of cervical spondylosis when the patient turned his head to the left. Measured in the orthostatic position while turning his head to the left during a typical attack of vertebrobasilar insufficiency, regional cerebral blood flow was significantly reduced in the left cerebellum and the right occipital region. Our study illustrates the capability of [99mTc]HM-PAO single-photon emission computed tomography to measure transient reductions in regional cerebral blood flow and to relate these changes to the pathophysiology of vertebrobasilar insufficiency.     

A Case of Gilles de la Tourette's Syndrome Accompanied with Alcoholism

A case of Gilles de la Tourette's syndrome with alcoholism and migraine is described. Multiple motor tics and coprolalia were suppressed by the treatment with haloperidol. The concentrations of HVA and 5–HIAA in the cerebrospinal fluid were measured and increment of HVA concentrations was outstanding while his symptoms were aggravated. This might be evidence for hyperactivity of dopaminergic neurons involved in manifest symptomatology of this syndrome.     

Significance of gastric secretory changes in the pathogenesis of stress ulcers

Analyses of gastric juice withdrawn 3 hours after the pylorus was ligated and of plasma corticosterone and blood glucose after animals were exposed to rotational stress revealed that gastric secretion was highest in controls, intermediate in stressed rats that developed ulcers, and lowest in stressed rats that did not develop ulcers. Neither high nor low gastric secretion correlated with stress-ulcer formation. When initial mucosal ischemia and secretory inhibition, which occurred in all stressed rats, were considered, those that developed ulcers manifested gastric hypersecretion when compared with those that did not develop ulcers. The pathogenetic significance of gastric hypersecretion in stress-ulcer formation is discussed and correlated with mucosal microvascular changes during stress. Mean plasma corticosterone was highest in stressed rats that developed ulcers, next highest in stressed rats that did not develop ulcers, and lowest in control rats. Compared with normal rats, mean blood glucose was lowest in stressed rats and highest in controls. Hypoglycemic changes were more marked in stressed rats that developed ulcers than in stressed rats that did not develop ulcers.     

The lung cancer database project at the National Cancer Center, Japan: study design, corresponding rate and profiles of cohort

BACKGROUND: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. METHODS: Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. RESULTS: Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. CONCLUSIONS: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.     

Successful chemotherapy with carboplatin and docetaxel for an elderly patient with advanced non-small cell lung cancer

A 79-year-old man was admitted to our hospital with right hypochondrium pain. His chest X-ray and CT scan showed a mass lesion on the left upper lobe, and multiple metastases in the liver. The diagnosis was non-small cell carcinoma of the lung. He received 4 courses of combined chemotherapy of carboplatin and docetaxel every 4 weeks. At the end of 4 courses, a partial response was achieved. Two courses of a in similar regimen were added at the time of a later recurrence, and the effect was a partial response. Carboplatin+docetaxel combined chemotherapy, which can be conducted relatively safely on an outpatient basis, may be an effective treatment for non-small cell lung cancer in the elderly.     

Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe

Pactimibe sulfate, [7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate, a novel Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, was investigated in vitro and in vivo to characterize its potential. Pactimibe exhibited dual inhibition for ACAT1 and ACAT2 (concentrations inhibiting 50% [IC₅₀s] at micromolar levels) more potently than avasimibe. Kinetic analysis revealed pactimibe is a noncompetitive inhibitor of oleoyl-CoA (K_i value: 5.6 μM). Furthermore, pactimibe markedly inhibited cholesteryl ester formation (IC₅₀: 6.7 μM) in human monocyte-derived macrophages, and inhibited copper-induced oxidation of low density lipoprotein more potently than probucol. Pactimibe exerted potent lipid-lowering and anti-atherosclerotic effects in atherogenic diet-fed hamsters. At doses of 3 and 10 mg/kg for 90 days, pactimibe decreased serum total cholesterol by 70% and 72%, and aortic fatty streak area by 79% and 95%, respectively. Despite similar cholesterol lowering, fatty streak area reduction was greater by 10 mg/kg. These results suggest that ACAT1/2 dual inhibitor pactimibe has anti-atherosclerotic potential beyond its plasma cholesterol-lowering activity.