Accelerated dynamic MR imaging with a parallel imaging technique for hypervascular hepatocellular carcinomas: usefulness of a test bolus in examination and subtraction imaging

PURPOSE: To assess the impact of the accelerated dynamic MR imaging (ADMRI) approach using parallel imaging for detecting hypervascular hepatocellular carcinomas (HCCs) and to evaluate the usefulness of a test bolus in examination and subtraction imaging in this setting. MATERIALS AND METHODS: Thirty patients with 135 HCCs underwent ADMRI using a two-dimensional gradient-recalled echo sequence with parallel imaging. Seventeen patients were evaluated without a test bolus and 13 patients with a test bolus. The detectability of HCCs was calculated between the groups with and without a test bolus. ADMRI was evaluated regarding the signal-to-noise ratio (SNR) of the lesion and the liver, the contrast-to-noise ratio (CNR) of the lesion vs. the liver, and the feasibility of subtraction images. RESULTS: ADMRI with and without a test bolus had almost equal sensitivity (92.5% and 92.6%). No significant difference was seen in the SNR of lesions and the CNR of lesions vs. livers between both groups. With a test bolus, ADMRI could depict the peak enhancement of nodules on the 2nd or 3rd dynamic phases and optimized the timing of peak lesion enhancement. Subtraction images could be obtained regarding minimal slice misregistration. CONCLUSION: ADMRI had high detectability of HCCs with and without a test bolus.     

ASC/TMS1, a caspase-1 activating adaptor,is downregulated by aberrant methylation in human melanoma

ASC/TMS1 is an adaptor protein activating caspase-1 that stimulates processing of proIL-1beta and proIL-18. ASC was reported to be aberrantly methylated and silenced in human breast cancers. In our present study, ASC expression was examined in 12 melanoma cell lines by Western blot analysis and in 18 benign melanocytic nevi and 32 melanoma tissues by immunohistochemical staining. ASC expression was absent or reduced in 7 of 12 (58.3%) cell lines and in 20 of 32 (62.5%) melanoma tissues, whereas all 18 benign melanocytic nevi showed intensive ASC expression. To investigate whether ASC silencing in melanoma is involved in aberrant methylation, methylation specific PCR was carried out. Five of ten (50%) melanoma tissues exhibited methylation in CpG island of ASC companied with reduced ASC expression. Six of twelve (50%) melanoma cell lines showed aberrant methylation in the ASC gene, and 4 of the 6 (66.7%) methylation positive cell lines exhibited reduced ASC expression. We characterized methylation patterns in melanoma cell lines by using bisulfite genomic sequencing, and found that the degree of aberrant methylation correlated with the level of reductive ASC expression. Treatment with demethylating agent 5-aza-2'-deoxycytidine resulted in both demethylation of the ASC gene and the upregulation of ASC expression in the methylation positive melanoma cell lines. Our study shows that ASC is downregulated in melanoma, and that its suppression is partially mediated by aberrant methylation.     

Cysteine conjugate of methazolamide is metabolized by beta-lyase

Bovine kidney and liver homogenates degraded a cysteine conjugate of methazolamide, S-(5-acetylimino-4-methyl-Delta2-1,3,4-thiadiazolin-2-yl)cysteine. We isolated the degradation product following incubation with kidney homogenate by high-performance liquid chromatography on reversed-phase columns. The chemical structure was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR, respectively), and elemental analysis by high-resolution mass spectrometry to be N-(3-methyl-5-mercapto-Delta4-1,3,4-thiadiazol-2-yl)acetamide, a thiol compound. The reaction is thought to be catalyzed by a pyridoxal-dependent enzyme(s) as indicated by an inhibition study using aminooxyacetic acid. Possible involvement of the thiol compound in the development of an adverse effect is discussed.     

Placento-thyroidal relationship in normal pregnancy.

Estimations of serum HCT, HTSH, T4, T3, PBI, ETR, Triosorb, TBG-binding capacity, BMR and urinary total estrogen were made simultaneously in 160 women in normal pregnancy. TRH stimulation tests were made in 20 cases in each trimester of pregnancy. HCT was detectable even in early pregnancy, tending to increase gradually toward the terminal stage of pregnancy as serum thyrotrophin bioactivity showed. On the other hand, serum TSH level measured by radio-immunoassay remained essentially the same throughout the course of pregnancy as in the nonpregnant state, moreover, it was suggested by the TRH stimulation test that pituitary TSH secreting function of pregnant women was similar to that of the non-pregnant. These findings suggest that thyroid hyperfunction during pregnancy which is shown by progressively increased T3, T4, and PBI may not be due to high estrogen-high TBG binding capacity-low free thyroxinenegative feed back-high TSH secretion but to HCT originating from placenta. In spite of thyroid hormone increase, it is true that the clinical picture of hyperthyroidism is not manifest among normal pregnant women, and ETR remained within the non-pregnant range throughout the course of pregnancy. We have also demonstrated that Triosorb decreased progressively. This may be interpreted to be due to the increase of TBG binding capacity which is increased progressively and binds more of free thyroxine during pregnancy. Such a change in TBG binding capacity is well known to be caused by the effect of estrogen which is progressively increased during pregnancy. In a word, it is possible to say that there is a placento-thyroidal system in pregnancy; HCT elevates thyroid function and TBG increased by estrogen carries thyroid hormone to target organ.     

Prevalence of hepatitis C virus and HIV infection among injection drug users in two Mexican cities bordering the U.S

OBJECTIVE: To estimate the prevalence of the hepatitis C virus (HCV) and HIV infection and associated risk behaviors among injection drug users (IDUs) in two northern Mexican cities. MATERIAL AND METHODS: Between February and April 2005, IDUs were recruited in Tijuana (N=222) and Ciudad Juarez (N=206) using respondent-driven sampling (RDS), a chain referral sampling approach. Interviewer-administered questionnaires assessed drug-using behaviors during the prior six months. Venous blood was collected for immunoassays to detect HIV and HCV antibodies. For HIV, Western blot or immunofluorescence assay was used for confirmatory testing. Final HCV antibody prevalence was estimated using RDS adjustments. RESULTS: Overall, HCV and HIV prevalence was 96.0% and 2.8%, respectively, and was similar in both cities. Most IDUs (87.5%) reported passing on their used injection equipment to others, and 85.9% had received used equipment from others. CONCLUSIONS: HIV prevalence was relatively high given the prevalence of HIV in the general population, and HCV prevalence was extremely high among IDUs in Tijuana and Ciudad Juarez. Frequent sharing practices indicate a high potential for continued transmission for both infections. HCV counseling and testing for IDUs in Mexico and interventions to reduce sharing of injection equipment are needed.     

Usefulness of monoclonal antibody HIK1083 specific for gastric O-glycan in differentiating cutaneous metastasis of gastric cancer from primary sweat gland carcinoma

Distinguishing cutaneous metastasis of gastric cancer from primary sweat gland carcinoma can be problematic in some cases, especially with a single lesion. Previously we showed that a monoclonal antibody HIK1083 directed to alpha1,4-GlcNAc-capped O-glycans expressed in gastric gland mucin reacts to gastric cancer cells. By contrast, it was reported that immunohistochemistry for cytokeratin 20 (CK20) may be helpful in the differential diagnosis between cutaneous metastasis of gastric cancer and primary sweat gland carcinoma. Here, we immunohistochemically examined the expression of alpha1,4-GlcNAc-capped O-glycans and CK20 in 7 primary sweat gland carcinomas, 7 cutaneous metastases of gastric cancer, and 21 cutaneous metastases of other origin including breast, lung, colorectum, prostate, thyroid and pancreas using HIK1083 and CK20-specific Ks 20.8 antibodies and then assessed the usefulness of these antibodies in distinguishing cutaneous metastases of gastric cancer from primary sweat gland carcinoma and other cutaneous metastatic tumors. Both alpha1,4-GlcNAc-capped O-glycans and CK20 were positive in 5 of 7 cases of cutaneous metastases of gastric cancer, while neither alpha1,4-GlcNAc-capped O-glycans nor CK20 were detected in any of the primary sweat gland carcinomas. By contrast, alpha1,4-GlcNAc-capped O-glycans was not detected in any of the cutaneous metastases other than that of gastric cancer, whereas CK20 was detected in cutaneous metastases of colorectal cancer (2/2), breast cancer (2/13), and lung adenocarcinoma (1/3). These findings indicate that immunohistochemistry using HIK1083 antibody is superior to immunohistochemistry for CK20 in distinguishing cutaneous metastasis of gastric cancer from primary sweat gland carcinomas and other cutaneous metastases.     

Clinical and analytical evaluation of an enzyme immunoassay for myelin basic protein in cerebrospinal fluid

BACKGROUND: RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a biochemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. METHODS: The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody. The bound antibody complex was quantified with streptavidin-horseradish peroxidase. MBP was determined in CSF from 84 MS patients and 55 patients with other neurological diseases. RESULTS: The respective within- and between-assay CVs were 4.7% and 7.2% at 200 ng/L, and 6. 3% and 8.8% at 2000 ng/L. The detection limit was 30 ng/L. Most of the MS patients with acute exacerbations had markedly increased MBP in the CSF. Longitudinal studies of six MS patients with recurrent exacerbation confirmed this observation. MBP concentrations from 78 MS patients, as tested with our ELISA, correlated well with those obtained by RIA (r = 0.9; P: <0.01), but the detection limit of the ELISA was much lower than that of the RIA. CONCLUSIONS: This convenient ELISA with higher sensitivity than the existing assays is a suitable routine assay that provides a diagnostic indicator of myelin breakdown in the central nervous system; moreover, it is an excellent indicator of MS disease activity.     

Karl-Axel Ekbom (1907–1977)

Journal of Neurology -