Transport mechanism of 11C-labeled L- and D-methionine in human-derived tumor cells

IntroductionS-methyl-¹¹C-labeled l- and d-methionine (¹¹C-l- and d-MET) are useful as radiotracers for tumor imaging. However, it is not known whether the transport mechanism of ¹¹C-d-MET is the same as that for ¹¹C-l-MET, which is transported by the amino acid transport system L. In this study, we investigated the transport mechanism of ¹¹C-l- and d-MET by analyzing the expression of transport system genes in human-derived tumor cells.MethodsThe expression of transport system genes in human-derived tumor cells was quantitatively analyzed. The mechanism of MET transport in these cells was investigated by incubating the cells with [S-methyl-³H]-l-MET (³H-l-MET) or [S-methyl-³H]-d-MET (³H-d-MET) and the effect of 2-amino-2- norbornane-carboxylic acid, a system L transport inhibitor, or α-(methylamino)isobutyric acid, a system A transport inhibitor, on their transport was measured. The transport and metabolic stability of [S-methyl-¹⁴C]-l-MET (¹⁴C-l-MET) and ³H-d-MET was also analyzed using bearing mice with H441 or PC14 tumor cells.Results³H-d-MET was mainly transported by both systems L and alanine–serine–cysteine (ASC), while system L was involved in ³H-l-MET transport. There was a high correlation between both ³H-l-MET and ³H-d-MET uptake and the expression of amino acid transport system genes. In the in vivo study, H441-cell accumulation of ³H-d-MET was higher than that of ¹⁴C-l-MET. Hepatic and renal accumulation of ³H-d-MET was lower than that of ¹⁴C-l-MET.ConclusionThe transport mechanism of ³H-d-MET was different from that of ³H-l-MET. Since ³H-d-MET has high metabolic stability, its accumulation reflects the transporter function of system L and ASC.     

Ultrasonogram of hepatocellular carcinoma is associated with outcome after radiofrequency ablation

AIM:To investigate the association between B-mode ultrasound classification of small hepatocellular carcinoma(HCC) and outcome after radiofrequency ablation(RFA).METHODS:Ninety-seven cases of HCC treated using RFA between April 2001 and March 2006 were reviewed.Ultrasound images were classified as follows:type 1,with halo(n=29);and type 2,without halo(n=68).Type 2 was further categorized into three subgroups:type 2a,homogenous hyperechoic(n=9);type 2b,hypoechoic with smooth margins(n=43);and type 2c(n=16),hypoechoic with irregular or unclear margins.Patients with type 2a HCC were excluded from analysis due to the small number of cases.RESULTS:Two year recurrence rates for type 2b,type 1 and type 2c were 26%,42% and 69%,respectively,with significant differences between type 2b and type 2c(P<0.01),and between type 1 and type 2c(P<0.05).Five year survival rates were 89%,43% and 65%,respectively.Survival was significantly longer for type 2b than for other types(type 1 vs type 2b,P<0.01;type 2b vs type 2c,P<0.05).On univariate analysis,factors contributing to recurrence were number of tumors,tumor stage,serum level of lens culinaris agglutinin-reactive alpha-fetoprotein and ultrasound classification(P<0.05).Factors contributing to survival were tumor stage and ultrasound classification(P<0.05).Multivariate analysis identified ultrasound classification as the only factor independently associated with both recurrence and survival(P<0.05).CONCLUSION:B-mode ultrasound classification of small HCC is a predictive factor for outcome after RFA.     

Occurrence of tumor-associated ganglioside antigens with Hanganutziu-Deicher antigenic activity on human melanomas

The specificity of antibody to NeuGc alpha 2-3Gal beta 1-4Glc-cer (GM3(NeuGc] was carefully reexamined by the method of enzyme-immunostaining on a thin layer plate. The affinity-purified antibody was found to react with NeuGc alpha 2-8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuGc] and NeuGc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuAc], but not with NeuAc alpha 2-8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuGc)) or NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuAc]. From this result together with the previous results, it (GD3(NeuAc-NeuAc], From this result together with the previous results, it could be concluded that the antibody recognizes the outer portion of molecular species of sialic acids in the gangliosides. By using this antibody, the expression of Hanganutziu-Deicher (HD) gangliosides could be demonstrated in human malignant melanoma. The molecular species were different among individuals examined. Among HD-antigenic gangliosides, GM3(NeuGc) was commonly found in melanoma tissues. One of the patients examined expressed GD3(NeuGc-NeuGc) and GD 3(NeuGc-NeuAc), which may be characteristic gangliosides in human melanomas, since these gangliosides could not be detected in human colon cancer or human fetal tissues.     

Genetic polymorphism of human factor H (HF,β1H globulin) in Chinese han population in northeast China

Summary The distribution of human factor H of serum phenotypes were studied using ultrathin polyacrylamide gel isoelectric focusing (PA-GIEF) and subsequent immunoblotting techniques in 203 Chinese of Han population in Liaoning Province of northeast China. The gene frequencies of HF^*A and HF^*B were 0.4828 and 0.5172, respectively. All the observed numbers of the phenotypes were in agreement with the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies among Chinese, Japanese, and Caucasian populations were compared.This paper is a part of results in a joint research project between two university departments in Japan and China.     

In vitro proton magnetic resonance spectroscopic lactate and choline measurements, 18F-FDG uptake, and prognosis in patients with lung adenocarcinoma.

It has been reported that (18)F-FDG uptake, lactate concentration, and choline concentration are good indicators of malignant grade in several different kinds of tumors. In this study, we investigated the correlation between (18)F-FDG uptake in (18)F-FDG PET imaging, lactate concentration and choline concentration measured by in vitro (1)H magnetic resonance spectroscopy (MRS), and survival probabilities in human lung adenocarcinoma. METHODS: Nineteen patients with lung adenocarcinoma underwent (18)F-FDG PET before surgery. The (1)H MRS spectra were obtained in vitro from methanol-chloroform-water extracts of lung adenocarcinomas and normal lungs. The ratios of the lactate (R(lac)) or choline (R(cho)) concentration of lung adenocarcinoma to normal lung from the same patient were correlated with the mean standardized uptake value (SUV). The Kaplan-Meier life table method was used to analyze the relationship between (18)F-FDG uptake, R(lac), R(cho), and patient survival probabilities. RESULTS: There was no significant correlation between mean SUV and R(lac) or R(cho) in patients with lung adenocarcinoma. An SUV > 5 means poorer survival probabilities in patients with lung adenocarcinoma (P = 0.004). A higher R(lac) probably indicates a trend for patients with lung adenocarcinoma to have poorer survival probabilities; however, R(cho) is not an indicator of survival probability. (18)F-FDG uptake significantly correlated with cell differentiation (P = 0.007), whereas R(lac) and R(cho) had no correlation with it. CONCLUSION: No significant correlation was found between SUV and R(lac) or R(cho) in patients with lung adenocarcinoma. Compared with R(lac) and R(cho) measured by in vitro MRS, (18)F-FDG uptake is a better indicator of prognosis in patients with lung adenocarcinoma.     

Fine structure of cartilage elastic system fibers, in particular those of the mandibular condyle

Light microscopy of the mandibular joint tissues from fetal mice show a distribution of fibrillar structures in the articular fibrous capsule covering the condylar head. Further SEM and TEM studies were conducted on autoclaved xiphoid and mandibular condylar processes of the fetuses for observation of the elastic system fibers in these cartilaginous tissues. SEM showed that non-collaginous fibers branched and united to form a complicated network in the cartilage. A fine structure study on diameter distribution of the fibers indicated elastogenesis in the differentiating cell layer and fiber maturation in the articular surfaces and calcification layer, thus suggesting a sequential development, growth, and degeneration of the cellular and fibrillar components in the cartilage, as well as bidirectional cell differentiation in the growing mandibular joint. A further TEM study on these autoclaved connective tissues showed the elastic system fibers in the network to be composed of fine microfibrils and amorphous elastin. The elastic fibers in the condylar cartilage were a loose network having many tortuous main and oblique elastic fibers, and coiling oxytalan fibers.     

Psychosomatic tendency for suicide among the elderly in Mie Prefecture, Japan

Background: The aim of the present study is to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, Japan, and to discuss the prevention of the suicidal influences in elderly patients. Methods: We investigated all inquest records during the 14‐year period 1989–2002 in cooperation with the First Department of Criminal Investigation of Mie Prefectural Police Headquarters. From all cases classified as suicides, we extracted data on age, sex and background, and we focused on suicide in the elderly group. Results: During the test period, there were 5048 suicides (3276 male and 1772 female suicides) of which 1513 (691 male and 822 female) were in the elderly group. The rate of suicide in the elderly group was approximately 30% of the total in all age groups. The rate of female suicides in the elderly group was approximately 46.3%. The major causative factors of suicide among the elderly were ‘suffering from physical illness’, and ‘psychiatric disorders’. ‘Physical diseases’ were not negligible backgrounds in middle and elderly groups. Among physical diseases, the number of malignant neoplasm was clearly less than the other diseases. Notably, ‘cardiovascular disease’ and ‘orthopedic disorders’ were most frequent causative factors of suicide other than malignant neoplasm. Conclusion: It is consequently concluded that improvements in the system of home nursing and health care should be involved in the suicidal prevention of the elderly who ‘suffer from physical illness’. The patients who ‘suffer from physical illness’ should be given physical and mental support. In order to prevent suicide, not only psychiatrists but also general practitioners as well as medical staff and general public should be provided with education regarding depression among ‘psychiatric disorders’.