A new temperature measurement procedure using phase mapping was developed that makes use of the temperature dependence of the water proton chemical shift. Highly accurate and fast measurements were obtained during phantom and in vivo experiments. In the pure water phantom experiments, an accuracy of more than +/- 0.5 degrees C was obtained within a few seconds/slice using a field echo pulse sequence (TR/TE = 115/13 ms, matrix = 128 x 128, number of slices = 5). The temperature dependence of the water proton chemical shift was found to be almost the same for different materials with a chemical composition similar to living tissues (water, glucide, protein). Using this method, the temperature change inside a cat's brain was obtained with an accuracy of more than +/- 1 degree C and an in-plane resolution of 0.6 x 0.6 mm. The temperature measurement error was affected by several factors in the living system (B0 shifts caused by position shifts of the sample, blood flow, etc.), the position shift effect being the most serious.

Hepatocyte growth factor (HGF) receptor, also known as Met, is a member of the receptor tyrosine kinase family. The Met–HGF interaction regulates various signalling pathways involving downstream kinases, such as Akt and Erk. Met activation is implicated in wound healing of tissues via multiple biological responses triggered by the above-mentioned signalling cascade. Here we report the development of artificial Met-activating dimeric macrocycles. We identify Met-binding monomeric macrocyclic peptides by means of the RaPID (random non-standard peptide integrated discovery) system, and dimerize the respective monomers through rational design. These dimeric macrocycles specifically and strongly activate Met signalling pathways through receptor dimerization and induce various HGF-like cellular responses, such as branching morphogenesis, in human cells. This work suggests our approach for generating dimeric macrocycles as non-protein ligands for cell surface receptors can be useful for developing potential therapeutics with a broad range of potential applications.

Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and functional recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes functional recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI.

Purpose -To assess the role of leader-member exchange (LMX) in affecting voluntary turnover in a high turnover work context. Design/methodology/approach -Following consideration of traditional predictors of employee turnover, how LMX is related to voluntary turnover is examined among 207 over-the-road truck drivers using a telephone survey. Findings -Leader member exchange is found to be nonlinearly related to turnover such that turnover is lowest when LMX is moderate (i.e. both "bad" and "good" LMX are associated with higher levels of turnover). Research limitations/implications -Findings indicate that LMX and other antecedents should be examined for nonlinear relationships to turnover. This research may help to bridge the gap between turnover research and that associated with supervision and leadership. Practical implications -These study results suggest that unrealistic expectations should not be formed regarding the power of any single factor (e.g. LMX) to reduce turnover. Originality/value -This paper suggests that nonlinear relationships between antecedents of turnover and turnover receive fuller consideration.The role of leader-member exchange in high turnover work environments Turnover experts, both academic and practitioner, have long asserted that supervision plays a meaningful role in voluntary employee turnover decisions. However, empirical investigation documenting these relations has lagged (Griffeth and Hom, 2001). Relatively few supervisory-linked antecedents of turnover beyond satisfaction with supervision have been explicitly studied (Griffeth et al., 2000). A more behaviorally-oriented specification of supervisory antecedents of turnover would be

This article discusses the applicability to a living animal of the temperature mapping method using the water proton chemical shift obtained with three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). There are several sources of error in obtaining the spectra with 3D-MRSI: signal noise, limitation in the frequency resolution due to the finite signal length, intravoxel inhomogeneity in the static magnetic field, and variation in the magnetic field due to the eddy current magnetic field. A spectral estimation method called phase deduction complex Lorentzian fitting (PD-CLF) was proposed. Numerical simulations demonstrated that this method reduces the error in the chemical shift to one third of that obtained with the simple frequency subtraction method that uses zero-padded first Fourier transformation (FFT). The temperature images obtained using 3D-MRSI with PD-CLF clearly visualized the changes and distribution of temperature in an anesthetized rat.

ABSTRACT

The discovery of a large array of tumor antigens has demonstrated that host lymphocytes can indeed recognize and destroy tumor cells as originally proposed in the cancer immunosurveillance hypothesis. Recent reports that led to the cancer immunoediting concept also strongly support the immunosurveillance hypothesis, and they further indicate that the host immune system plays a critical role not only in promoting host protection against cancer but also in selecting tumors that can better escape from immune attack. Thus, it is now clear that T cells have the ability to recognize and destroy spontaneously arising tumors. However, the generation of antitumor immunity is often difficult in the tumor-bearing host because of various negative regulatory mechanisms. Here, we review our recent work on tumor immunotherapy, which utilizes the activation of type-1 innate and/or acquired immunity as a potent strategy to overcome immunosuppression in the tumor-bearing host. We have established a variety of tumor therapeutic protocols that aim to activate type-1 immunity, such as tumor-vaccine therapy with CpG encapsulated in liposomes, cell therapy using tumor-specific Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG encapsulated in liposomes stimulated IL-12-producing DC and induced IFN-γ γ γ γ-producing NK cells, NKT cells, and tumorspecific CTL. Th1 cell therapy was also shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the DLN, which was critical for inducing tumor-specific CTL at the tumor site. Therefore, we conclude that the activation of type-1 innate and acquired immunity is crucial for tumor immunotherapy in order to overcome strong immunosuppression in the tumor-bearing host. (Cancer Sci 2004; 95: 697-703) ince the cancer immunosurveillance hypothesis was proposed by Ehrlich, Burnet, and Thomas, 1, 2) tumor immunologists have asked whether the host immune system can prevent tumor growth. Recent reports from several groups have re-addressed this issue and provided strong evidence for the existence of an effective cancer immunosurveillance process in mice.3-11) As summarized in Table 1, mice lacking specific cellular populations, such as T cells, natural killer T (NKT) cells, and/or natural killer (NK) cells, as well as specific molecules, such as interferon (IFN)-γ, interleukin (IL)-12, perforin, or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), unequivocally show higher incidences of tumor development. Moreover, administration of IL-12 or α-galactosylceramide (α-GalCer) that can stimulate T, NKT, and/or NK cells, reduces primary tumor incidence.Although it is much more difficult to address cancer immunosurveillance in humans, three lines of evidence suggest that cancer immunosurveillance indeed occurs in humans: (i) immunosuppressed transplant recipients display higher incidences of non-viral tumors, such as melanomas, colon, lung, pancreas, bladder, kidney, and endocrine system cancers, than agematched immunocompetent control populations, ...

In a pooled analysis of two prospective studies with 35 004 Japanese women, green-tea intake was not associated with a lower risk of breast cancer (222 cases), the multivariate relative risk for women drinking X5 cups compared with o1 cup per day being 0.84 (95% confidence interval 0.57 -1.24, Trend P ¼ 0.69). Although laboratory studies have suggested a protective effect of green tea on breast cancer risk, few epidemiological studies have examined the association. A case -control study of Asian Americans in the United States found a lower risk of breast cancer in association with green-tea intake (Wu et al, 2003), whereas a prospective cohort study in Japan found no association (Key et al, 1999). To further examine the association between green-tea consumption and the risk of breast cancer, we conducted a pooled analysis of two population-based prospective cohort studies among women in rural northern Japan. MATERIALS AND METHODSDetails of the design of the two cohort studies are described elsewhere (Tsubono et al, 2001;Nakaya et al, 2003). Briefly, Cohort 1 started in 1984 and included 17 353 women aged X40 years (94% response rate) (Tsubono et al, 2001); Cohort 2 started in 1990 and included 24 769 women aged 40 -64 years (93% response rate) (Nakaya et al, 2003). Self-administered questionnaires covered recent (Cohort 1) or usual (Cohort 2) consumption of green tea and used the same five frequency categories ranging from 'never' to 'X5 cups per day'. It had a reasonably high level of validity and reproducibility (Ogawa et al, 2003). After exclusion of those with missing responses or with a prior history of cancer, 14 409 subjects in Cohort 1 and 20 595 in Cohort 2 remained. We followed up vital and residential status of the study subjects by population registries. Through population-based cancer registries, 103 incident cases of breast cancer were identified in Cohort 1 (9 years follow-up with 111 267 person-years) and 119 in Cohort 2 (7 years follow-up with 151 882 person-years).We estimated relative risk (RR) and 95% confidence interval (CI) of breast cancer according to green-tea consumption, using Cox's proportional-hazards regression with the adjustment for age and potential confounders. To obtain a summary measure of results between Cohorts 1 and 2, the general variance-based method was used to pool each RR and 95% CI. We repeated all analysis after excluding breast cancer cases diagnosed in the first 3 years of follow-up (38 in Cohort 1 and 40 in Cohort 2). P-values for the test of linear trend were calculated by treating the green-tea consumption category as an ordinal variable. All reported P-values are two-tailed. Table 1 compares the characteristics of subjects in the highest and the lowest categories of green-tea consumption. Subjects in Cohort 1 with higher intake tended to be postmenopausal, while such women in Cohort 2 tended to be slightly older, postmenopausal and have a higher body mass index. Subjects in both cohorts with a lower intake tended to drink black tea less frequently and coffee mo...