Homologous recombination between p53 and its pseudogene in a radiation-induced mouse tumor

Genome recombination is essential for life; however, its dysfunction causes cancer. Here we report the formation of a chimera structure of the p53 gene due to homologous recombination with the p53 pseudogene in tumors produced by repeated local beta-irradiation of the backs of mice. The recombination occurred near the 5' end of exon 5. Because this tumor carried a 5-bp deletion in exon 6 of the expressed p53 allele, and the defect in p53 is reported to elevate the cellular recombination activity, this chimera formation is thought to be initiated by a radiation-induced DNA double strand break in the p53-mutated cell with enhanced recombination. The abundance of this chimera structure was estimated to be 8% of the total of tumor p53, and the functional p53 side of this chimera had no deletion in exon 6. The indication is that the recombination occurred before the loss of heterozygosity of the mutated p53 allele took place but after a few divisions of the original heterozygous p53-mutated cell toward monoclonal expansion. A novel mechanism of cancer induction is suggested.     

Transition of brain activation from frontal to parietal areas in visuomotor sequence learning

We studied the neural correlates of visuomotor sequence learning using functional magnetic resonance imaging (fMRI). In the test condition, subjects learned, by trial and error, the correct order of pressing two buttons consecutively for 10 pairs of buttons (2 x 10 task); in the control condition, they pressed buttons in any order. Comparison between the test condition and the control condition revealed four brain areas specifically related to learning: the dorsolateral prefrontal cortex (DLPFC), the presupplementary motor area (pre-SMA), the precuneus, and the intraparietal sulcus (IPS). We found that the time course of activation during learning was different between these areas. To normalize the individual differences in the speed of learning, we classified the performance of each subject into three learning stages: early, intermediate, and advanced stages. Both the relative increase of signal intensity and the number of activated pixels within the four areas showed significant changes across the learning stages, with different time courses. The two frontal areas, DLPFC and pre-SMA, were activated in the earlier stages of learning, whereas the two parietal areas, precuneus and IPS, were activated in the later stages. Specifically, DLPFC, pre-SMA, precuneus, and IPS were most highly activated in the early stage, in both the early and intermediate stages, in the intermediate stage, and in both the intermediate and advanced stages, respectively. The results suggest that the acquisition of visuomotor sequences requires frontal activation, whereas the retrieval of visuomotor sequences requires parietal activation, which might reflect the transition from the declarative stage to the procedural stage.     

An ultra-high-speed optoelectronic integrated receiver forfiber-optic communications

An ultra-high-speed optoelectronic integrated receiver consisting of a GaInAs p-i-n photodiode and a transimpedance AlInAs-GaInAs high-electron-mobility-transistor amplifier was successfully fabricated on an InP substrate. A 3-dB bandwidth of 6 GHz with a transimpedance of 50 dBΩ was achieved for the receiver with a feedback resistance of 750 Ω. Measured noise currents of the receiver were analyzed and found to be dominated by the low-frequency noise and the induced gate noise. A sensitivity of -21.2 dBm for 8.0-Gb/s NRZ signals was deduced from the noise current characteristics     

Predisposing factors for severe mitral regurgitation in idiopathic mitral valve prolapse

To elucidate predisposing factors for severe mitral regurgitation (MR) in idiopathic mitral valve prolapse (MVP), 124 MVP patients were classified into the following categories: 55 with isolated clicks (click group), 35 with a late-systolic murmur (late-SM group), and 34 with a holosystolic murmur (holo-SM group). Their clinical and echocardiographic findings were compared with those of 26 patients with spontaneous chordal rupture (rupture group). In 22 patients in the click group, 24 in the late-SM group, and 22 in the holo-SM group, follow-up studies were performed for a mean of 4.5 years (range 1 to 13.5). The mean age was youngest in the click group and oldest in the rupture group. The click and late-SM groups showed a female predominance, but the holo-SM and rupture groups showed a male predominance. There was no difference in the incidence of systemic hypertension among the 4 groups. Most patients in the click and late-SM groups had anterior leaflet prolapse. In the holo-SM and rupture groups, however, the incidence of posterior leaflet involvement was significantly increased. The incidence of thickened mitral valve increased in order of the click (8%), late-SM (21%), holo-SM (38%), and rupture (50%) groups. Six patients in the holo-SM group developed chordal rupture with severe MR during the follow-up period. In the click and late-SM groups, however, there were no complications and no development into a holo-SM. Thus, aging, male sex, posterior leaflet prolapse, thickened mitral valve, and holo-SM were found to be important predisposing factors for severe MR in idiopathic MVP.     

N-Alkylphthalimides: structural requirement of thalidomidal action on 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor alpha production by human leukemia HL-60 cells

Phthalimide analogs N-substituted with n-butyl, tert-butyl, hexyl and adamantyl groups were designed and prepared as simplified analogs of thalidomide and methylthalidomide. All the compounds prepared except N-n-butylphthalimide showed thalidomidal activity on 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor (TNF)-alpha production by human leukemia HL-60 cells. Among the investigated compounds, including thalidomide and methylthalidomide, N-adamantylphthalimide showed the most potent TNF-alpha production-enhancing activity.     

Naloxone and initial estrogen action to induce lordosis in ovariectomized rats: the effect of a cut between the septum and preoptic area

The objective of the study was to investigate the sociodemographic and psychological factors which are associated with choice or refusal of regional anesthesia for lower segment Caesarean section. A semi-structured questionnaire was administered preoperatively to consecutive women presenting for elective operation at two hospital sites in the same health authority. The questionnaires were administered to 39 pregnant women by two anesthetists, one at each site. Sociodemographic and past and present obstetric and anesthetic details were obtained. The Hospital Anxiety and Depression scale and the FEAR questionnaire were used with an additional visual analog scale to assess fearfulness associated with the proposed operation. A 'panic checklist' of ten items was also constructed to identify procedures associated with feelings of panic. Ten women requested general anesthesia. These women had a similar level of anxiety to the others, but were significantly more depressed, had had more pregnancies overall and more without live babies. There were also more aspects of the procedure at which they thought they might panic. Women who have suffered the loss of a conception with its associated grief and often obstetric intervention are more reluctant to be conscious during an operative delivery for a subsequent baby. Preventive measures should be considered at the time of fetal loss to avoid this. However, preoperatively a simple visual analog scale for fearfulness would identify these women so that any unresolved fears could receive full psychological assessment.     

One-dimensional drift-flux model for two-phase flow in a large diameter pipe

In view of the practical importance of the drift-flux model for two-phase-flow analysis in general and in the analysis of nuclear-reactor transients and accidents in particular, the distribution parameter and the drift velocity have been studied for vertical upward two-phase flow in a large diameter pipe. One of the important flow characteristics in a large diameter pipe is a liquid recirculation induced at low mixture volumetric flux. Since the liquid recirculation may affect the liquid velocity profile and promote the formation of cap or slug bubbles, the distribution parameter and the drift velocity in a large diameter pipe can be quite different from those in a small diameter pipe where the liquid recirculation may not be significant. A flow regime at a test section inlet may also affect the liquid recirculation pattern, resulting in the inlet-flow-regime dependent distribution parameter and drift velocity. Based on the above detailed discussions, two types of inlet-flow-regime dependent drift-flux correlations have been developed for two-phase flow in a large diameter pipe at low mixture volumetric flux. A comparison of the newly developed correlations with various data at low mixture volumetric flux shows a satisfactory agreement. As the drift-flux correlations in a large diameter pipe at high mixture volumetric flux, the drift-flux correlations developed by Kataoka-Ishii, and Ishii have been recommended for cap bubbly flow, and churn and annular flows, respectively, based on the comparisons of the correlations with existing experimental data.     

Comparison of the pattern of integrin expression between primary tumors and liver metastasis of gastric and colorectal cancers

To investigate the interrelationship between integrin VLA3 overexpression and liver metastasis, immunohistochemical studies of VLA3 were made in 73 cases of gastric cancer (66 cases without liver metastasis, 7 cases with liver metastasis) and 15 cases of colorectal cancer (3 cases without liver metastasis, 12 cases with liver metastasis). The rate of integrin VLA3 expression in 69 primary gastric and colorectal cancers without liver metastasis was 41%, that was higher than that (0%) in the 19 primary tumors of gastric and colorectal cancers with liver metastasis. In contrast, the positive rate for integrin VLA3 staining in 19 cases involving liver metastasis of gastric and colorectal cancers was 58% (11/19), which was higher than that (0%) in primary tumors. These findings suggest that VLA3 may play an important role in the process of liver metastasis of gastric and colorectal cancers.     

Absorption of methochlorpromazine in rat small intestinal everted sac

The absorption of methochlorpromazine in rat small intestinal everted sac was investigated. 0.22% of the drug added in mucosal fluid was transferred to serosal fluid for 30 min at 37 degrees C. The absorption of the drug was slightly inhibited by choline, and more markedly inhibited by more hydrophobic quaternary ammonium cations such as tetraethylammonium and cetyltrimethylammonium. Moderate inhibition was observed by a polyamine, spermine. The absorption rate of methochlorpromazine markedly depended on temperature. The Arrhenius plot of the apparent transfer rate constant revealed high activation energy (117 kJ/mol) for the transport. Uptake of methochlorpromazine to a small intestinal segment was also inhibited by other quaternary ammonium cations corresponding with their inhibitory effects on its transport. These results suggest that methochlorpromazine binds to the relatively hydrophobic region of small intestinal epithelial cells and transfers by passing through a high energy barrier.