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Objective Among different PET tracers, 18F-fludeoxyglucose (FDG) and 11C-choline are known to have a high tumor uptake correlated with a high mitotic index of tumor cells. Thus, the uptake of 18F-FDG and 11C-choline may be dependent on the cell cycle. In the present study, we examined the uptake of 18F-FDG and 11C-choline in cancer cell lines by cell cycle synchronization to clarify the biological properties of cancer cells with respect to each tracer. Methods HeLa S3 Cells were synchronized by the double thymidine (TdR) block methods. 18F-FDG and 11C-choline were administered to synchronized cells, and the radioactivity per cell was measured to compare the cellular uptake of the tracers during S, G2/M, and G1 phases. Flow cytometry (FCM) was performed to measure the proportion of cells in G1, S, and G2/M phases. Furthermore, the levels of glucose transporter 1 (GLUT1) and choline transporter-like protein 1 (CTL1) in the cell were evaluated by FCM. Results The uptake of 18F-FDG was the highest in S to G2/M phases, and markedly decreased in G1 phase. The uptake of 11C-choline reached its peak in G2/M, and decreased in G1 phase. The level of GLUT1 expression was similar to that of 18F-FDG uptake during the cell cycle, and the level of CTL1 expression was similar to that of 11C-choline uptake throughout the cell cycle. Conclusions In this in vitro study, we demonstrated that 18F-FDG and 11C-choline had the highest uptake in S to G2/M phases and in G2/M phase, respectively, with a rapid decrease in G1 phase. These findings suggest that 18F-FDG and 11C-choline have a high accumulation in tumor cells with a high mitotic index. Furthermore, our study suggests that the expression of GLUT1 and CTL1 has cell cycle dependence, and the changes of 18F-FDG and 11C-choline accumulation seem to be caused by the above properties of these transporters.

Background: Magnetocardiography (MCG) has the potential for collecting three-dimensional (3D) intracardiac electric information, because the magnetic field is unaffected by the shape of the lungs and torso. In the present study, we report on the generation of a 3D heart outline and conduction pathway by means of a current density map using a 64-channel SQUID system, and an evaluation of its significance in patients with atrial flutter (AFL) and atrial fibrillation (AFIB) Methods: The subjects consisted of 20 healthy volunteers, and 3 patients with AFL and 4 patients with AFIB. A 64-channel MCG was recorded after digitization at 500 Hz, and a 3D current density was reconstructed from the magnetic fields using a space filter in conjunction with the minimum normalization method of Tikhonov. A 3D heart outline was generated from the integrated current density by the space filter. The conduction pathway was superimposed on a heart outline generated by a magnetic field. The heart outline was verified by the silhouette on the magnetic resonance (MR) images. An MCG was recorded pre- and post interventional therapy, and therapeutic efficacy was evaluated. Results: The 3D heart outline of the atrium and ventricle corresponded to the silhouette of the right atrium and left ventricle, respectively, on an MR image. The serial conduction pathway of the QRS segment superimposed on the 3D heart outline map demonstrated the conduction pattern generated within the heart. The MCG revealed a counter-clockwise rotation in patients with AFL, and random micro-reentry in the case of AFIB. After interventional therapy, restoration of the sinus rhythm was verified in patients with both AFL and AFIB. Conclusions: A 64-channel MCG was used to evaluate the 3D heart outline and conduction pathway in patients with AFL and AFIB without the need for MR images. Condensed Abstract A 64-channel MCG was used to evaluate the 3D heart out line and conduction pathway in patients with AFL and AFIB.

Objectives It is known that, in fluorine-18 fluorodeoxyglucose Positron Emission Tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake.

Objective: Research on FDG-uptake by blood cells has revealed that FDG is incorporated by macrophages and granulocytes, as well as activated lymphocytes. These characteristics of FDG suggest the possibility of visualizing the distribution of immunocytes in target organs. The aim of this study was to investigate if mouse spleen-derived lymphocytes, activated by macrophages presenting sheep red blood cell (sRBC) antigens, could be traced by FDG.Methods: One percent of a sRBC suspension was injected into the peritoneal cavity of mice thereby creating immunity to the sRBC antigen. The splenocytes, consisting mostly of lymphocytes, were isolated, and serum containing the anti-sRBC antibody was mixed with sRBC to prepare sRBC-antibody complexes (sRBC-AbCs). Then five percent of a thioglycolate medium was injected into the peritoneal cavity of the same mice, and macrophages of ascitic cell origin were obtained. These macrophages were added to the sRBC-AbCs to induce sRBC antigen presenting macrophages. These were incubated with splenocytes obtained from sRBC immunized mouse (sRBC immunized splenocytes) or nonimmunized splenocytes to induce a T cell immune response. [3H]deoxyglucose ([3H]DG) and FDG were incorporated in splenocytes, and the quantity of their uptake was measured.Results: [3H]DG uptake by sRBC-immunized splenocytes was about eleven times as high as that of non-immunized splenocytes. In contrast, [3H]DG uptake by sRBC-immunized splenocytes, co-cultured with macrophages phagocytizing sRBC-AbCs, was about 40 times higher compared with non-immunized splenocytes. Splenocytes in non-immunized mice picked up very little [3H]DG, despite co-culture with macrophages phagocytizing sRBC-AbCs. Similar tendencies were observed with FDG.Conclusions: These results suggest that the SUV calculated in PET reflects not only the number of lymphocytes, but also the activation state of the lymphocytes themselves. In addition, the biodistribution of antigen specific lymphocytes, that have been taken up FDGin vitro and returned to the body, can be observed through PET.

A fluorescent x-ray tomography system is useful in performing fluorescent x-ray analysis for target atoms in biomedical objects utilizing a drug deliverly system. This tomography system is employed in order to measure iodine distribution in objects, and the system consists of a cerium x-ray generator, a 58-μm-thick stannum filter, a tungsten collimator, and a computed radiography system. Because K-series characteristic x-rays from the cerium target are absorbed effectively by iodine-based contrast media, iodine fluorescent x-rays from iodine atoms in the objects are produced. In the tomography system, when the objects are exposed by fan beams, the stannum filter easily transmits iodine Kα rays from a slice plane, and tomograms are obtained using the CR system and the collimator.

Madin-Darby canine kidney (MDCK) cells were originally anchorage-dependent epithelial cells. Here, we have isolated a novel MDCK-derived cell population, termed 6 M-4, by means of culturing MDCK cells in suspension for nearly 6 months in the presence of Streptomyces griseus metalloendopeptidase (MEP). The isolated cells showed unique proliferation characteristics, which differed from parental MDCK cells. They proliferated adherently on a polystyrene matrix, but proliferated non-adherently both in the presence of MEP and on a non-adhesive matrix coated with poly 2-methacryloyloxyethyl phosphorylcholine (MPC). The 6 M-4 cells consisted of at least two cell types. One type, termed 6 M-4-TR7, would not grow in soft agar and showed a novel phenotype in that the cells were susceptible to both TNF-alpha and verotoxin 1 (VT1). In addition, the isolated adhesion-independent cells sustained epithelial traits of parental MDCK cells. We further show that these MDCK-derivative cells are suitable for influenza virus cultivation. Hemagglutination (HA) titers of influenzaviruses A and B were increased in the suspension culture of 6 M-4-TR7 cells supplemented with the MEP in comparison to adherently growing cells in the presence of trypsin.

QT dispersion reveals heterogeneities in the repolarization time in the three-dimensional (3D) structure of the ventricular myocardium. In this study, we report on a 3D function map of recovery time (RT) dispersions as measured by 64-channel magnetocardiography (MCG). MCG were simultaneously recorded in 29 controls and 21 patients with previous myocardial infarction (MI). The 3D current density was calculated from 64-channel MCG data in the B z component using a space filter. The heart outline, reconstructed from the integrated the current density, revealed both the atrium and ventricle. The RT for the intervals between QRS onset and the time of the maximum dT/dt of T wave, and the peak to the end of the T wave (Tpeak-negative dT/dt) were automatically measured by means of a computer from 3D MCG data. The corrected RT (RTc) and corrected Tpeak-negative dT/dt were then calculated using Bazett’s formula. The 3D RTc and the corrected Tpeak-negative dT/dt dispersion map were superimposed on the heart outline generated by MCG. The RTc was significantly longer for the MI group than in the control group (67±25 ms1/2 vs. 16±6 ms1/2) (p

A 60-year-old woman presented with multicentric skin tumors of the head. The histologically proven hemangioendothelioma was bleeding as a result of disseminated coagulopathy. In addition to immunotherapy, 6 MeV electron beam radiotherapy was used for the purpose of hemostasis with a single portal, 20 x 20 cm in size, covering the whole scalp from the top of the head. The radiotherapy was discontinued after 39 Gy/13 fractions/20 days because of the progress in size of a peripheral tumor and the stability of coagulopathy. After another electron boost delivery by two portals focused to exophytic parietal and temporal tumors of 20 Gy/10 fractions, high dose rate brachytherapy with a surface mold technique was performed, 3 Gy/fraction, four fractions/week, for a total of 36 Gy. It induced partial regression of the tumor and complete recovery of platelet counts from 2.5 x 10(4) to 18.2 x 10(4). The tumor disappeared in 3 months. No late side effects occurred, except for permanent alopecia. The patient developed a cervical lymph node metastasis 1 year after and marginal recurrence 2 years after the initial treatment. Both recurrent tumors were successfully treated by 4 MV external photons of 60 Gy/20 fractions/46 days and electron beam irradiation of 60 Gy/20 fractions/29 days, respectively. She has remained disease free for 3 years after the initial presentation.

The abdominal ganglion of Aplysia includes neurons with a characteristic dopamine (DA) receptor, the activation of which induces a marked hyperpolarization with a specific increase in the permeability of the membrane to K+. The DA receptor of this type is called the "HK-type." A 2-min exposure to 1 microM serotonin (5-HT) had little effect on the resting membranes with the receptor of HK-type, but significantly depressed the responses to 10 microM DA. The depressing effect of 5-HT on this type of response was completely reversible after a 15-min washing with normal artificial Aplysia blood. Lineweaver-Burke type plotting of the DA-induced responses showed a systematic shift of the straight lines when the concentration of 5-HT was increased; the slope of the line became steeper but the intercept on the ordinate remained unchanged. The dose-inhibition curves, in which relative responses to a given [DA] were plotted against log [5-HT], showed a parallel shift toward the right when the concentration of DA increased. These findings suggest that 5-HT competes with DA for common binding sites at the DA receptor of HK-type, and that the blockade is not due to the interaction of 5-HT with K+-channels in the receptor membrane. The effect of other indole derivatives suggests that the DA receptor of HK-type includes anionic and cationic sites to which the NH2 group and 5-HO group of 5-HT could specifically bind, thus exhibiting competitive blockade.

Using the abdominal ganglion cells of Aplysia, we analyzed the effects of various enzymes and chemical modification reagents on the acetylcholine (ACh)-induced responses of the excitatory (Na+ -dependent) and inhibitory (Cl- -dependent) types. (1) Phospholipase A (2 mg/ml) caused no appreciable effects on either type of response. (2) Phospholipase C (2 mg/ml) markedly depressed both types of response. These suggested that the phosphoryl group of the phospholipid is an important site related to the binding of ACh, common to both types of ACh-receptors. (3) Carboxypeptidase A (10 mg/ml) caused no observable effects on either type of response. (4) Carboxypeptidase B (10 mg/ml) depressed the inhibitory type of response without affecting the excitatory one. (5) Pyridoxal-5'-phosphate (1 mM) also depressed the inhibitory response without affecting the excitatory one. These findings (4, 5) suggested that the Cl- -channel in the inhibitory ACh-receptor complex includes a C-terminal lysine which may play an active role in the movement of Cl- across the receptor membrane. (6) L-Leucine aminopeptidase (1 mg/ml) depressed the excitatory response without altering the inhibitory one. (7) p-Nitrothiophenol (1 mM)-also depressed the excitatory response without affecting the inhibitory one. These findings (6, 7) suggested the presence of a certain N-terminal amino acid near a glutamate or aspartate residue within a molecular moiety of Na+ -channel included in the excitatory ACh-receptor complex.

There are many cells in the abdominal ganglion which show a fast, Cl(-)-dependent hyperpolarizing response to gamma-aminobutyric acid (GABA). This response is characterized by an initial rapid increase in membrane conductance followed by an exponential decay to the original value despite a sustained application of GABA. The decay of the response was found to be largely due to the desensitization of the GABA receptor (binding site-ionophore complex) since the equilibrium potential for chloride remained unchanged when the conductance response was depressed. The apparent or measurable rate constant of desensitization (KD) increased when the concentration of GABA increased, showing a saturation in KD-[GABA] relationship at higher concentration of GABA. The rate of desensitization did not change significantly when the resting membrane was hyperpolarized from -40 to -80 mV, though the conductance response was markedly depressed due to a characteristic voltage-dependence in the receptor activation (Matsumoto, 1982). These observations are discussed in terms of an hypothesis in which the desensitization of GABA receptor is the result of an additional binding of a GABA molecule to the activated receptor.

This manuscript presents an unusual radiographic manifestation of multiple myeloma occurring in the mandible. A 40-year-old man, referred to our hospital, presented with a swelling of the right mandible. Microscopic examination and laboratory tests confirmed the diagnosis of multiple myeloma. Radiographic examination revealed a well-developed sun-ray appearance suspected in osteogenic sarcoma. This observation suggested the possibility of the periosteal reaction in this case of multiple myeloma.