Simultaneous multi-section perfusion CT and CT angiography for the assessment of acute ischemic stroke

Summary Background. Introduction of helical computed tomography (CT) scanning has enabled rapid imaging of the vascular status by means of CT angiography and perfusion CT. By virtue of recent multi-detector technology, helical CT has the ability to perform both CT angiography and multi-section perfusion CT simultaneously. This study investigated the clinical feasibility of simultaneous assessment of perfusion CT and CT angiography in patients with acute ischemic stroke.Method. Perfusion CT and CT angiography were performed simultaneously in a series of consecutive 31 acute ischemic stroke patients. The time required for the entire processing was about 15 minutes. Contrast agent was used in a total dose of 100ml (35ml for perfusion CT and 65ml for CT angiography).Findings. Simultaneous perfusion CT scans and CT angiographies were of diagnostic quality for 29 patients (94%). In large territorial infarct patients, perfusion CT could predict all perfusion deficits of the final lesions (10 out of 10 lesions) and CT angiography could detect 9 of 10 occlusions of major cerebral arteries (90%). In patients with small lacunar or subcortical infarcts, perfusion CT could predict 9 out of 19 lesions (47.4%), and false-negative were encountered in small lesions (three patients) or in inadequate coverage of data acquisition (seven patients). Acute stage thrombolytic intervention could be carried out based on the findings, and the success of thrombolytic therapy could be demonstrated by follow-up study.Conclusions. Simultaneous perfusion CT and CT angiography is the very useful tool for the rapid and adequate diagnosis of almost all of the large territorial infarcts and some of non-territorial lacunar infarcts. It is an easy-to-perform and safe imaging technique to assess acute ischemic stroke.     

Induction of hepatocellular carcinoma in rat liver by initial treatment with benzo(a)pyrene after partial hepatectomy and promotion by phenobarbital

The hepatocarcinogenicity of benzo(a)pyrene(BP) in the rat was examined. Rats were treated with BP after partial hepatectomy and then kept on a diet containing phenobarbital (PB) as a promoter. Tumors including a hepatocellular carcinoma developed in the rat liver by week 52.     

Anti-angiogenic therapy and chemotherapy affect 99mTc sestamibi and 99mTc-HL91 accumulation differently in tumour xenografts

BACKGROUND: Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments. METHODS: Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions. RESULTS: 99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro. CONCLUSION: These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.     

Pedicled Ileal Flap to Repair Large Duodenal Defect After Right Hemicolectomy for Right Colon Cancer Invading the Duodenum

Although right-sided colon cancer occasionally invades the second part of the duodenum, there is no standard procedure for reconstructing a large duodenal defect after resection. This report describes a new approach we recently devised. After resecting the right hemicolon and the involved duodenum, a segment of terminal ileum was isolated on the vascular pedicle, sacrificing the adjacent ileum. We created a flap by opening the segment along the antimesenteric border, and used this flap to cover the defect. This method does not create a nonanatomical bypass and fewer intestinal anastomoses are required than for Roux-en-Y reconstruction.     

Gradually glycosylated protein C mutants (Arg178Gln and Cys331Arg) are degraded by proteasome after mannose trimming

Proteins that fail to attain their correct three-dimensional structure are retained in the endoplasmic reticulum (ER) and eventually degraded within the cells. We investigated the degradation of mutant proteins, using naturally occurring protein C (PC) mutants (Arg178Gln and Cys331Arg) which lead to congenital deficiencies. Chinese hamster ovary (CHO) cells were transfected with normal or mutant expression vectors. The introduction of mutation at Asn329 of an unusual sequence Asn-X-Cys for N-linked glycosylation revealed that the mutation at Cys331, which may preclude a formation of disulfide bond with Cys345, resulted in no addition of N-linked oligosaccharides at Asn329. PC mutants with 4 glycosylation sites were gradually glycosylated in the ER, and the fourth glycosylation site is less accessible for glycosylation as reported for PC in plasma. The half lives of PC178 and PC331 mutants were about 5 and 4 h, respectively. PC mutants were degraded, but the degradation was inhibited by inhibitors for proteasome. Mannose trimming of N-linked oligosaccharides after glucose removal targeted PC mutants for degradation by proteasomes. And also the inhibition of glucose trimming immediately led to mannose trimming, resulting in the accelerated degradation of PC mutants. These degradations were inhibited by mannosidase I inhibitor, kifunensine. These results indicate that the initiation of mannose trimming by mannosidase I leads to the proteasomemediated degradation of glucose-trimmed or untrimmed PC mutants.     

DNA repair and cancer: lessons from mutant mouse models

DNA damage, if the repair process, especially nucleotide excision repair (NER), is compromised or the lesion is repaired by some other error-prone mechanism, causes mutation and ultimately contributes to neoplastic transformation. Impairment of components of the DNA damage response pathway (e.g., p53 ) is also implicated in carcinogenesis. We currently have considerable knowledge of the role of DNA repair genes as tumor suppressors, both clinically and experimentally. The deleterious clinical consequences of inherited defects in DNA repair system are apparent from several human cancer predisposition syndromes (e.g., NER-compromised xeroderma pigmentosum [XP] and p53 -deficient Li-Fraumeni syndrome). However, experimental studies to support the clinical evidence are hampered by the lack of powerful animal models. Here, we review in vivo experimental data suggesting the protective function of DNA repair machinery in chemical carcinogenesis. We specifically focus on the three DNA repair genes, O ⁶-methylguanine-DNA methyltransferase gene ( MGMT ), XP group A gene ( XPA ) and p53 . First, mice overexpressing MGMT display substantial resistance to nitrosamine-induced hepatocarcinogenesis. In addition, a reduction of spontaneous liver tumors and longer survival times were evident. However, there are no known mutations in the human MGMT and therefore no associated cancer syndrome. Secondly, XPA mutant mice are indeed prone to spontaneous and carcinogen-induced tumorigenesis in internal organs (which are not exposed to sunlight). The concomitant loss of p53 resulted in accelerated onset of carcinogenesis. Finally, p53 null mice are predisposed to brain tumors upon transplacental exposure to a carcinogen. Accumulated evidence in these three mutant mouse models firmly supports the notion that the DNA repair system is vital for protection against cancer.     

Co-expression of parathyroid hormone and chromogranin A in secondary hyperparathyroidism: a functional marker for secretory activity of hyperplastic nodules

The relationship between secretion of parathyroid hormone (PTH) and biologic characteristics, including cell proliferation or monoclonality, is not yet fully understood. To evaluate secretory activity of glands or nodules histopathologically, we focused on the co-expression of chromogranin A (CgA) and parathyroid hormone (PTH) in each gland or nodule. A total of 55 glands from 38 patients with normal parathyroid glands, hyperplastic glands (diffuse and nodular) and primary adenomas were compared. Co-expression of PTH and CgA was decreased to 44.4% in diffuse hyperplastic glands, and to 39.6% in 91 hyperplastic nodules, in contrast to normal glands and primary adenomas that showed constant co-expression of PTH and CgA. Immunohistochemical study of PTH showed a coarse granular pattern predominantly in PTH-positive/CgA-positive nodules, and a dot-like pattern mainly in PTH-positive/CgA-negative nodules. Laser scanning microscopy and immunoelectron microscopy confirmed that a dot-like pattern is based on a positive reaction of PTH at the Golgi apparatus. MIB-1 LI was 12.6 +/- 11.6 in PTH-positive/CgA-positive, and 19.3 +/- 27.3 in PTH-positive/CgA-negative nodules. In conclusion, a combination of PTH and CgA could provide more information about the physiologic state of secretory activity of each nodule than does the simple observation of PTH immunoreactivity.