PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease

The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.     

Genetic alterations at 5p15: a potential marker for progression of precancerous lesions of the uterine cervix

BACKGROUND: Development of uterine cervical cancer is preceded by preneoplastic proliferative changes in the cervical epithelium called "intra-epithelial neoplasia" or "dysplasia." The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. PURPOSE: To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5p14-ter in precancerous and cancerous lesions. METHODS: Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS); the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic microsatellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. RESULTS: LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Among the loci tested, D5S406 (5p15.1-15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5p14-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. CONCLUSION: These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. IMPLICATIONS: The future molecular cloning of the candidate tumor suppressor gene at 5p15.1-15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers.     

A clinical, MRI and neurophysiological study of acute transverse myelitis

There is paucity of studies correlating the MRI and evoked potential changes in acute transverse myelitis (ATM). We studied ten patients with ATM (age range 14-57 years; 8 men, 2 women) who were subjected to clinical, MRI and neurophysiological evaluation. The latter included median and tibial somatosensory evoked potentials (SEP), motor evoked potentials (MEP) to upper and lower limbs and concentric needle EMG. The outcome was defined on the basis of three month Barthel Index score. All the patients had pronounced lower limb and three had upper limb weakness. Magnetic resonance imaging scans revealed diffuse to hypointense lesions in T1, which became hyperintense in T2 in all except one patient, who had patchy hyperintense lesions in both T1 and T2 sequences suggesting haemorrhage. The signal changes extended at least three segments above the sensory level. Tibial SEP and central motor conduction time to tibialis anterior (CMCT-TA) were abnormal in nine patients each. Median SEP was normal in all, but CMCT to abductor digiti minimi (CMCT-ADM) was abnormal in four patients. The extent of MRI signal alterations and CMCT-TA correlated with the outcome. Seven patients had a poor outcome, in them MRI changes extended 10 spinal segments or more. In these patients, MEP on lumbar stimulation was either unrecordable or of low amplitude and extensive fibrillations were present in the lower limb muscles. From this study, we conclude that in ATM, extensive MRI changes, unrecordable MEP to lower limbs especially on lumbar stimulation and evidence of denervation in leg muscles seem to predict a poor outcome.     

D优化的实验设计在IC工艺和器件优化中的应用

论述了实验设计技术与ＴＣＡＤ相结合用于半导体工艺和器件性能优化的新途径，它可以极大地减少开发和研制新工艺、新器件的时间和成本。     

Isomeric Structures of Furoxan-Fused [2,2]paracyclophane—A DFT Study

The present study theoretically deals with furoxan-fused [2,2]paracyclophane systems and some structures possibly involved in their isomerization processes. These intermediate structures are certain di- and tetra-nitroso derivatives and systems having dioxadiazatidine ring(s). Computationally, B3LYP/6–31G(d,p) level of density functional theory has been employed. Certain properties of the systems, such as geometries, energies, and aromaticity of the benzenoid rings, are harvested and discussed.