BackgroundIn the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients.MethodsWe immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer.ResultsPositive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs.ConclusionsB7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.

SUMMARY The anti‐manic, anti‐depressive and prophylactic effects of carbamazepine (CAZP, Tegretol‐Ciba Geigy) on the endogenous mani‐depressive psychosis (MDP) were investigated on 50 MDP cases. The dosage of the drug ranged from 200 to 1,200 mg daily (usually 400 to 600 mg). The effect of CAZP on 33 manic states was: “markedly effective” seven (23%), “effective” six (19%), “slightly effective” five (16%), “ineffective” 13 (42%), whereas the effect on six depressive states was: “markedly effective” one and “ineffective” five. No definite relationship was found between the kinds of drugs in combination use and the effect of CAZP. No significant difference of the CAZP effect was found in the four patient groups with different age of onset of the illness, nor among the “continuous,”“frequent” and “periodic” type cases. The prophylactic effect of CAZP on 27 cases in which the assessment of the effect on the manic episode was possible was: “markedly effective” 13 (48%), “effective” seven (26%) and “ineffective” seven (26%), whereas that for depressive episode was: 12 (45%), two (7%) and 13 (48%), and the result of the general assessment on each patient was 14 (43%), 10 (30%) and nine (27%), respectively. The kinds of drugs in combination use, age of onset and type of course of the illness did not have any influence on the prophylactic effect of CAZP. The prophylactic effect on MDP of CAZP did not parallel that of lithium salt, but CAZP may be effective on cases which did not respond to lithium and vice versa. Side‐effects such as ataxia, dizziness, exanthema, drowsiness and headache were observed in five of the cases, and the CAZP was discontinued in four of them. The mechanism of effectiveness of the CAZP on MDP was discussed.

Evaluation of the Effect of Heat Exposure on the Autonomic Nervous System by Heart RateVariability and Urinary Catecholamines: Shinji YAMAMOTO, et al. Department of Hygiene, Yamaguchi University Graduate School of Medicine-The aim of this study was to investigate the usefulness of heart rate variability (HRV) and urinary catecholamines (CA) as objective indices of heat stress effect. We examined physiological responses, subjective symptoms, HRV and urinary CA to evaluate the effect of heat exposure on the autonomic nervous system. Six healthy male students volunteered for this study. They were exposed on different days to either a thermoneutral condition at wet bulb globe temperature (WBGT) 21°C, or a heated condition at WBGT 35°C for 30 min, while seated on a chair. In the thermoneutral condition, differences of all parameters between the values before and after 30 min exposure were not statistically significant. In the heated condition, heart rate, body temperature and scores for subjective symptoms (feverishness, sweating, mood, and face flushing) significantly increased after 30 min exposure (p<0.05). Also, the high frequency component (HF%) of HRV significantly decreased and the low frequency/high frequency (LF/ HF) ratio of HRV significantly increased after 30 min exposure to the heated condition (p<0.05). There were no significant differences between the amounts of urinary CA before and after the 30 min exposures; however, the norepinephrine amount after 30 min exposure to the heated condition was significantly greater than that of the thermoneutral condition (p<0.05). The heat exposure (WBGT 35°C) induced activation of the sympathetic nervous system and a withdrawal of the parasympathetic nervous system. These findings coincide with observed changes of heart rate, body temperature and subjective symptoms. It is suggested that HRV (HF% and LF/HF ratio) and urinary norepinephrine may be useful objective indices of heat stress; HRV seems to be more sensitive to heat stress than urinary CA.

Cancer stem‐like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P‐CSLCs). A P‐CSLC‐enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2‐D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P‐CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P‐CSLCs and did not correlate with the levels of CD44v9, another P‐CSLC biomarker. Furthermore, the side population in the CRThigh/CD44v9low population was much higher than that in the CRTlow/CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P‐CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.

To determine whether noise conditions at the workplace are associated with hypertension in Japanese male blue-collar workers, the authors analyzed data obtained in an annual workplace health examination. Two hundred forty-two workers who used ear protectors at their jobs in a paper manufacturing plant served as a noisy workplace group, and 173 individuals who worked in a chemical plant comprised a nonnoisy workplace group. The prevalence of hypertension was 16.9% in the noisy workplace group and 34.7% in the nonnoisy workplace group (p < .01). A Mantel-Haenzel analysis showed the difference between the 2 groups to be significant. A logistic regression analysis with adjustment for confounding factors also showed a significant inverse association between hypertension and noise conditions at the workplace (odds ratio = 0.48; 95% confidence interval = 0.28-0.81). The implementation of guidelines for occupational noise management might have contributed to the workers' concern over the prevention of adverse health effects caused by workplace noise.

To assess the prevalence of cervical spondylosis and musculoskeletal symptoms among coolies a cross-sectional study was performed in Narayangonj City of Bangladesh on a random sample of 98 male coolies, using a questionnaire and the results of cervical spine X-rays. Statistical associations were investigated using the chi-square test. The results show a considerably higher prevalence of cervical spondylosis among the coolies (39.8%). More than half (51.3%) of the cases of cervical spondylosis were in subjects below the age of 40 yr, and a significant association was found between age group and prevalence of cervical spondylosis. The study also observed a significant association between duration of occupation and prevalence of cervical spondylosis. Coolies who had worked for 10 to 15 yr, or more than 15 yr, had higher rates of cervical spondylosis. In this study it was found that those who carried heavier loads suffered more from cervical spondylosis. Musculoskeletal symptoms in multiple body regions (two or more) were more prevalent (61.2%) than those in single body region (29.6%). Symptoms in the hands/fingers were the most frequent followed by the back and arms/forearms. In conclusion, the high prevalence of cervical spondylosis and musculoskeletal symptoms among professional coolies may be associated with the practice of carrying heavy loads on the head. Further study with a large sample of population is required to investigate this problem and to explore preventive measures.

Response in FBF due to grasping of vibrating handle was of different patterns from the baseline measurement under different room temperature conditions in both exposed and unexposed hands and it was influenced by room temperature. Overall, the influence was greater at lower test room temperature, inducing more significant increase in FBF.

UL16 binding protein 1 (ULBP1) expressed on the tumor cell surface binds to the natural killer group 2 member D (NKG2D) receptor presenting on natural killer (NK), cluster of differentiation (CD)8+ T, and γ δ T cells. However, the roles of ULBP1 and NKG2D expression and associated immune responses in gastric cancer are unclear. The present study investigated the associations between ULBP1 and NKG2D expression and clinical outcomes in patients with gastric cancer. The levels of ULBP1 and NKG2D expression were examined in human gastric cancer cell lines and gastric cancer tissues from 98 patients who underwent surgery from 2004 to 2008. MKN-74 cells expressed ULBP1 with ULBP2, −5, or −6. NKG2D was expressed at a higher level following activation of T cells and NK cells. Among the tissue sections positive for NKG2D expression, 6 patients were positive for CD8 and CD56. In all tissues, NKG2D-expressing cells were typically aCD8+ T cells. Patients with NKG2D expression in tumors exhibited significantly longer overall survival (OS) compared with patients without NKG2D expression in tumors (P=0.0217). The longest OS was observed in patients positive for ULBP1 and NKG2D, whereas the shortest OS was observed in patients negative for ULBP1 and NKG2D. The interaction between ULBP1 and NKG2D may improve OS in patients with gastric cancer, and may have applications in immunotherapy for the induction of adaptive immunity in patients with cancer. Additionally, ULBP1 and NKG2D may be useful as prognostic biomarkers in gastric cancer.