Determination of the hyperfine coupling tensor in organic conductors κ-(BEDT-TTF)2X (X=Cu[N(CN)2]Br, Cu(NCS)2) on central ¹³C sites.

Although the organic superconductors κ-(BEDT-TTF)2X (X=Cu[N(CN)2]Br and Cu(NCS)2) have been studied by NMR spectroscopy, hyperfine coupling tensors are required to quantify NMR spectra. Angle dependences of NMR spectra were measured to determine hyperfine coupling tensors applicable to further NMR assessments of attractive physical phenomena on κ-salts. The tensors of κ-(BEDT-TTF)2X and ß(')-(BEDT-TTF)2ICl2 salts were compared to determine the hyperfine coupling mechanism in organic metals, with the results indicating that off-site dimer contribution should be considered. We also report the electron correlation of these salts and further application of the tensors.

Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.

BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth. CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.

Relationship between salivary antioxidant capacity and phases of the menstrual cycle.

BACKGROUND AND OBJECTIVE: Reactive oxygen species and free radicals are involved in the pathogenesis of periodontal disease. Previous studies have shown that the stage of the menstrual cycle is associated with the levels of gingival inflammation and discomfort. This study examined changes in salivary antioxidant activities, clinical parameters and bacterial levels during the menstrual cycle. MATERIAL AND METHODS: The study group consisted of 16 women with periodontitis and 12 healthy women. Clinical and bacterial measurements were performed for all subjects during the ovulatory and follicular phases. RESULTS: Salivary antioxidant activity during the ovulatory phase was significantly lower than during the follicular phase in the women with periodontitis. The antioxidant activity in all subjects during the ovulatory phase was negatively correlated with Prevotella intermedia (r = -0.430; p = 0.023) and total bacterial counts (r = -0.496; p = 0.007); however, these correlations were not significant for subjects in the follicular phase. CONCLUSION: This study showed that salivary antioxidant capacity decreased, while bleeding on probing and P. intermedia increased, over the course of the menstrual cycle in women with periodontitis. Antioxidant capacity could be involved in the pathogenesis of periodontitis.

Relationship between oral malodor and the menstrual cycle.

BACKGROUND AND OBJECTIVE: Sex hormones have been suggested to be important modifying factors that may influence the pathogenesis of periodontal disease. This study examined changes in volatile sulfur compounds (VSC) levels, clinical parameters and bacterial levels during the menstrual cycle. MATERIAL AND METHODS: The study group consisted of 10 female subjects with periodontitis and 12 periodontally healthy female subjects. Clinical and bacterial measurements were performed for all subjects during the ovulation and follicular phases of the menstrual cycle. RESULTS: Bleeding on probing (BOP) was significantly increased in the ovulation phase in periodontitis subjects but not in healthy subjects. The VSC levels in subjects with periodontitis increased 2.2-fold in the ovulation phase compared with the follicular phase. In the ovulation phase, VSC levels and BOP were significantly higher in subjects with periodontitis than in healthy subjects. The number, and salivary levels, of Prevotella intermedia in subjects with periodontitis were significantly higher in the ovulation phase than in the follicular phase. CONCLUSION: The present study indicated changes in VSC, BOP and P. intermedia during the menstrual cycles of women with periodontitis.

[False-negative cases of axillary ultrasonography: how much size?].

PURPOSE/AIM: 1. To review the sonographic criteria of axillary lymph node status in breast cancer patients. 2. To understand imaging pathologic correlations that the false-negative cases of axillary ultrasonography. CONTENT ORGANIZATION: The sonographic criteria, the accuracy of sonographic axillary ultrasonography, imaging pathologic correlations in false-negative cases, measurement of largest malignant focus size in lymph node, classification of ratio of malignant focus size, ratio of micro metastasis. SUMMARY: 1. Recently, lymph node evaluation that using serial section and immunohistochemical stains makes it difficult to detect imaging modalities. 2. Ultrasonography is limited how to detect the example of sentinel lymph node biopsy non-indications.

HMG-CoA reductase inhibitor mobilizes bone marrow--derived endothelial progenitor cells.

Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These circulating EPCs are derived from bone marrow and are mobilized endogenously in response to tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay of bone marrow mononuclear cells in vitro and EPC culture assay of peripheral blood from simvastatin-treated animals in vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments the circulating population of EPCs. Direct evidence that this increased pool of circulating EPCs originates from bone marrow and may enhance neovascularization was demonstrated in simvastatin-treated mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. The role of Akt signaling in mediating effects of statin on EPCs is suggested by the observation that simvastatin rapidly activates Akt protein kinase in EPCs, enhancing proliferative and migratory activities and cell survival. Furthermore, dominant negative Akt overexpression leads to functional blocking of EPC bioactivity. These findings establish that augmented mobilization of bone marrow-derived EPCs through stimulation of the Akt signaling pathway constitutes a novel function for HMG-CoA reductase inhibitors.

Evaluation and treatment for spinal cord tethering in patients with anorectal malformations.

BACKGROUND: It has recently been recognized that there is a close relationship between spinal cord tethering (SCT) and congenital anorectal malformation (ARM). PATIENTS AND METHODS: We evaluated spinal MRI examinations of 28 patients with ARM (14 boys and 14 girls) aged 5 months to 9 years. All patients diagnosed with SCT subsequently underwent operation. Patients were divided into high and low type ARM groups. We reviewed the relationship between SCT and ARM, and evaluated the untethering surgery. RESULTS: We evaluated 14 boys (high, 9; low, 5) and 14 girls (high, 4; low, 10). Of these 28 patients, 13 had SCT on MRI. Five out of 13 patients with high type ARM and 8 out of 15 patients with low type ARM had SCT. Seven out of 10 girls with low type ARM had SCT. Ten of these 13 patients with SCT experienced bowel/urological/orthopedic symptoms. SCT symptoms progressed prior to operation in the 2 patients who underwent untethering surgery a few years after their initial MRI examination. Postoperatively, orthopedic symptoms disappeared completely in all patients, but other symptoms did not. CONCLUSIONS: Based on the results of this study, we recommend routine MRI examination of patients with ARM and early untethering surgery in cases with SCT.

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.

Regenerative medicine legislation in Japan for fast provision of cell therapy products.

A new legal framework consisting of three laws for cell-based and tissue-based therapies went into effect in November 2014 in Japan. Among the provisions of the laws, the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) allows conditional and time-limited approval for regenerative medical products based on the ensured safety and estimated efficacy in small-scale clinical trials. The new legislation is expected to accelerate safe and fast provision of the innovative products to patients with intractable diseases.

Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.

BACKGROUND: We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. METHODS AND RESULTS: Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. CONCLUSIONS: Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.

Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure.

Does the average daily blood pressure correlate with hypertensive cerebrovascular disease better than the casual pressure, as has been reported in other target organ involvement? We investigated the associations of two abnormal findings on brain magnetic resonance imaging suggestive of a vascular etiology, low intense foci (lacunae), and periventricular hyperintense lesions on T1- and T2-weighted images, with both office and average daily blood pressure values in a population of 73 healthy normotensive and hypertensive elderly individuals (70 +/- 6 years old). Lacunae were detected in 34 subjects (47%); the number per subject ranged from 0 to 19 and was significantly correlated with advancing age. Furthermore, these changes were supposedly related to the average of noninvasive ambulatory (24-hour and during awake and asleep periods) pressure recordings but not to office pressures. The grade of periventricular hyperintensity was also significantly associated with advancing age and the average of ambulatory systolic pressure recordings, particularly during sleep, but not with office blood pressure. In comparisons of normotensive, "office hypertensive," and hypertensive subgroups, abnormalities on magnetic resonance imaging were appropriate to the level of the 24-hour blood pressure measurements but not to that of clinic pressure. In hypertensive patients, the presence of electrocardiographic evidence of left ventricular hypertrophy was also associated with greater abnormalities on magnetic resonance imaging. We conclude that ambulatory blood pressure monitoring is superior to casual pressure measurements in predicting latent cerebrovascular disease, which is unexpectedly common in apparently healthy elderly subjects.

Accuracy of a continuous blood pressure monitor based on arterial tonometry.

A validation study of the continuous noninvasive tonometric blood pressure monitor called JENTOW was performed in 20 normotensive subjects and 10 hypertensive patients. Tonometric and intra-arterial blood pressures were simultaneously recorded at supine rest and during a Valsalva maneuver and tilting test. The results of the strict evaluation of the instrument's capacity for reproducing intra-arterial blood pressure were as follows: 1) The overall frequency response of the transcutaneous blood pressure-monitoring system based on arterial tonometry was flat, with negligible delay to intra-arterial blood pressure in the range of 0-5 Hz. 2) The largest discrepancy between intra-arterial and tonometric pressure waveforms was found at the early systolic phase; except for this phase, the tonometric waveform was almost equal to the intra-arterial waveform. 3) The beat-to-beat variability of tonometric pressure corresponded to that of intra-arterial pressure almost perfectly in the physiologically significant frequency range of 0-0.5 Hz. 4) During resting conditions, the averages of the systolic and diastolic values measured tonometrically corresponded well to those measured intra-arterially. 5) The changes in the between-method discrepancy of blood pressure values during the Valsalva maneuver were statistically significant but small (< 5 mm Hg). 6) No significant effect of postural tilting was found on the between-method discrepancy. We conclude that this method is clinically acceptable and reliable except for its limited capacity for recording the higher frequency intra-arterial waveform and for responding to the relatively rapid and large transient changes in blood pressure.

Cardiovascular regulatory functions in elderly patients with hypertension.

To dissociate the effects of an elevated blood pressure on the cardiovascular regulatory functions from those of aging in the hypertensive elderly individual, resting hemodynamic measurements and circulatory autonomic functions in 30 elderly (mean age, 66 years) hypertensive (World Health Organization stages I and II) patients were compared with those in 30 healthy elderly (mean age, 65 years) normotensive volunteers. The elderly hypertensive group showed a significantly lower cardiac index and higher total peripheral resistance. beta-Receptor sensitivity, as determined by chronotropic dose of infused isoproterenol, and baroreceptor reflex sensitivity index, derived from phase II, but not phase IV, of Valsalva's maneuver, were only slightly but significantly reduced in the hypertensive group. The variability of heart rate at rest as an index of parasympathetic control of heart was similar between these two groups. Plasma norepinephrine level was significantly inversely related to resting mean blood pressure (r = -0.31, p less than 0.05) when analyzed as a whole group. Plasma renin activity, but not plasma aldosterone, was significantly decreased in the hypertensive group. To define the effects of age itself, these parameters in normotensive elderly subjects were also compared with those in 12 young normotensive subjects (mean age, 23 years). Although resting hemodynamic measurements did not differ, various circulatory autonomic functions were significantly different between these two age groups. The variability of heart rate in 24-hour ambulatory monitoring, beta-receptor responsiveness, resting vagal cardiac activity, and baroreceptor reflex sensitivity derived from phase IV of Valsalva's maneuver were significantly depressed in the elderly. Resting plasma norepinephrine level was elevated and renin-aldosterone system decreased in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension.

OBJECTIVE: To examine the effect of diurnal blood pressure changes upon cerebrovascular damage in elderly patients with hypertension. DESIGN: Fifty-four asymptomatic hypertensive and 34 normotensive elderly subjects underwent both 24-h non-invasive ambulatory blood pressure monitoring and brain magnetic resonance imaging. METHODS. Diurnal variation was defined as a difference of greater than or equal to 10 mmHg between mean awake and asleep systolic blood pressure. Hypertensives were thus classified as dippers or non-dippers. Low intense foci (lacunae) and advanced periventricular hyperintensity were identified as silent cerebrovascular damage. RESULTS: In the hypertensive group, lacunae were correlated more closely with mean asleep systolic blood pressure than with mean awake systolic blood pressure. Age, awake blood pressure, predicted whole blood viscosity, lipid profiles or quantity of sleep did not differ between the hypertensive dippers or non-dippers. The non-dippers, however, showed significantly higher grades of cerebrovascular damage as well as cardiac hypertrophy by electrocardiography than the dippers, whose results were similar to those of normotensives in this regard. CONCLUSIONS: An absent or lower nocturnal blood pressure fall in elderly hypertensives is associated with silent cerebrovascular damage. In contrast, the presence of a nocturnal fall could prevent the development of hypertensive vascular damage.

Bone marrow as a source of endothelial cells for natural and iatrogenic vascular repair.

Postnatal neovascularization has previously been considered synonymous with angiogenesis, but the finding that circulating endothelial progenitor cells (EPCs) may home to sites of neovascularization and there differentiate into endothelial cells (ECs) is consistent with "vasculogenesis," through which the primordial vascular network is established in the embryo. Our findings suggest that growth and development of new blood vessels in the adult are not restricted to angiogenesis but encompass vasculogenesis as well, although the proportional contributions remain to be clarified. Likewise, augmented or retarded neovascularization probably involves enhancement or impariment of the vasculogenesis process.

Power spectral analysis of spontaneous blood pressure and heart rate variability in elderly hypertensives.

To examine the influence of hypertension on cardiovascular variability in elderly subjects, we measured spontaneous beat-to-beat blood pressure (BPV) and heart rate variability (HRV) in elderly subjects with or without hypertension at rest and during tilting. The study group consisted of 23 community-dwelling, male elderly subjects (aged 62-75 years) and was divided into two groups, i.e., a hypertensive group (HT group; n = 11) and normotensive group (NT group; n = 12). According to the modeling and decomposing algorithm of an autoregressive process, we estimated the component power of low-frequency (LF; 0.03-0.15 Hz) and high-frequency components (HF; respiratory frequency) of BPV and HRV by power spectral analysis. We also measured plasma norepinephrine (PNE) levels in the two groups at rest and during tilting. In the HT group, we found that the amplitude of LF-BPV was greater (p < 0.05) and its relative change by postural tilting was smaller (p < 0.05) than those in the NT group. We found no significant difference in the amplitude of LF-HRV and HF-HRV between the two groups, and found no significant response of the amplitude of LF-HRV and HF-HRV to postural tilting. We also found no difference in PNE level between the two groups at rest or during tilting. These results suggest that the regulatory function of sympathetic vasomotor activity assessed by power spectral analysis of BPV is altered in hypertensive elderly subjects, although the influence of hypertension on the autonomic control of the heart is less dominant in the elderly.

Effects of long-term treatment with low doses of carteolol on cardiovascular regulatory functions in elderly patients with mild hypertension.

Circulatory autonomic functions and resting and exercise hemodynamics were studied before and six months after daily administration of 5 mg of carteolol in seven elderly patients with mild hypertension. Blood pressure was reduced in all but one patient. In maximal exercise tests, blood pressure and heart rate responses were significantly attenuated after carteolol treatment, without reduction in exercise capacity. Cardiac index at rest was not affected. Cardiac parasympathetic activity, baroreflex function, and plasma catecholamine, renin, aldosterone, atrial natriuretic peptide, and vasopressin levels did not change during treatment. The results suggest that long-term use of low doses of carteolol may reduce blood pressure without affecting circulatory regulatory functions, even in elderly patients with mild hypertension.

Two-color fluorescence staining of lectin and anti-CD46 antibody to assess acrosomal status.

OBJECTIVE: To examine potential methods for distinguishing between the acrosome reaction and acrosomal loss. DESIGN: Prospective randomized study. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital, Suita, Japan. PATIENT(S): Five healthy volunteers and 34 patients with normozoospermia who were participating in an IVF program. INTERVENTION(S): Semen samples were collected from the volunteers before the hamster egg penetration assay and from the patients at the time of IVF. MAIN OUTCOME MEASURE(S): The numbers of oocytes penetrated and spermatozoa bound were determined with the hamster egg penetration assay. Acrosomal status was assessed with two-color fluorescence staining using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and MH61 (anti-CD46 monoclonal antibody) with Texas red-conjugated antimouse immunoglobulin G antiserum. RESULT(S): The MH61 monoclonal antibody inhibited the penetration of human spermatozoa into hamster oocytes but did not reduce the number of spermatozoa bound to the zona-free hamster oocytes. Two-color fluorescence staining revealed four staining patterns of the acrosomal region. The percentage of PSA-negative/CD46-positive spermatozoa increased to a greater extent than that of PSA-negative/CD46-negative spermatozoa with an increase in the incubation time. CONCLUSION(S): Two-color fluorescence staining with FITC-PSA and the anti-CD46 monoclonal antibody may be useful for distinguishing between the acrosome reaction and acrosomal loss.

Three year follow up study of national influenza vaccination practices in Japan.

STUDY OBJECTIVE: To evaluate new national influenza vaccination practices which were started in 1987 under a revised law in Japan. DESIGN: This was a three year, nonrandomised cohort study with information collected by questionnaire between 1989 and 1991. SETTING: Eight primary schools in the city of Yonago, Tottori, Japan. These schools were selected from 23 schools in the city. PARTICIPANTS: Altogether 4251 pupils (1355 boys and 2896 girls) in years 1-4 of the eight primary schools were included in this study, and followed up. Three years later, data for 1619 pupils (768 boys and 851 girls) were obtained and analysed. MAIN RESULTS: The one-winter seasonal incidence rates of influenza-like disease were 13.4%, 29.9%, and 10.3% in 1989, 1990, and 1991 respectively. The incidence rate of influenza-like disease in fully vaccinated pupils was significantly lower than that in unvaccinated pupils in 1990, but not in 1989 or 1991. Stepwise multiple regression analysis showed that the incidence of influenza-like disease had a statistical relationship with the frequency of vaccination and the school year (R2 was 0.0148). Standardised parameters of the frequency of vaccination and the school frequency of vaccination and the school year were -0.089 and -0.080 respectively. CONCLUSIONS: The preventive effects of influenza vaccine are not strong. There must be some unknown factors that affect the incidence of influenza. This vaccine is useful for pupils in the early school years who seem to have less resistance. All pupils should not be inoculated with the vaccine to reduce influenza transmission in the community or school.

Serum levels of VEGF and basic FGF in the subacute phase of myocardial infarction.

We examined serial changes in serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) measured by ELISAs in 45 patients with acute myocardial infarction (AMI) who received heparin intravenously for 3 to 5 days after the onset and in 30 control subjects with an old myocardial infarction. To evaluate the effect of heparin on these serum levels, heparin was administered intravenously in 10 patients with AMI on day 21. Blood samples were obtained from all AMI patients on days 1, 2, 3, 7, 14, 21, and 28 and from 10 AMI patients before and 1 h after heparin administration. Serum VEGF level was significantly reduced after heparin administration (P<0.001). Serum samples from day 1 to 3 were therefore excluded from the subsequent analysis. Serum VEGF level in AMI patients was significantly higher on day 7 than in the control subjects (P<0.0001), and then decreased over time (P<0.0001). The serum VEGF level on day 7 was independently associated with the peak serum CK level (P<0.05). The serum bFGF level did not differ significantly between the AMI patients and the control subjects. In conclusion, the serum VEGF level may be selectively elevated during the healing process after AMI.