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Background Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. Methods We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from Findings We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0–5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91–0·98]) compared with those without type 2 diabetes (0·89 [0·87–0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Interpretation Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. Funding British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4?2 years (IQR 3?0?5?0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0?99 [95% CI 0?95?1?04] for ACEIs; 0?96 [0?92?1?01] for ARBs; 0?98 [0?89?1?07] for 13 blockers; 1?01 [0?95?1?07] for thiazides), with the exception of calcium channel blockers (1?06 [1?01?1?11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1?00 [95% CI 0?93?1?09] for ACEIs; 0?99 [0?92?1?06] for ARBs; 0?99 [0?89?1?11] for 13 blockers; 1?04 [0?96?1?13] for calcium channel blockers; 1?00 [0?90?1?10] for thiazides). Summary Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 13 blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4 & middot;2 years (IQR 3 & middot;0 & ndash;5 & middot;0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0 & middot;99 [95% CI 0 & middot;95 & ndash;1 & middot;04] for ACEIs; 0 & middot;96 [0 & middot;92 & ndash;1 & middot;01] for ARBs; 0 & middot;98 [0 & middot;89 & ndash;1 & middot;07] for 13 blockers; 1 & middot;01 [0 & middot;95 & ndash;1 & middot;07] for thiazides), with the exception of calcium channel blockers (1 & middot;06 [1 & middot;01 & ndash;1 & middot;11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1 & middot;00 [95% CI 0 & middot;93 & ndash;1 & middot;09] for ACEIs; 0 & middot;99 [0 & middot;92 & ndash;1 & middot;06] for ARBs; 0 & middot;99 [0 & middot;89 & ndash;1 & middot;11] for 13 blockers; 1 & middot;04 [0 & middot;96 & ndash;1 & middot;13] for calcium channel blockers; 1 & middot;00 [0 & middot;90 & ndash;1 & middot;10] for thiazides). Interpretation We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.

We present a measurement of the energy spectrum of ultra-high-energy cosmic rays performed by the Telescope Array experiment using monocular observations from its two new FADC-based fluorescence detectors. After a short description of the experiment, we describe the data analysis and event reconstruction procedures. Since the aperture of the experiment must be calculated by Monte Carlo simulation, we describe this calculation and the comparisons of simulated and real data used to verify the validity of the aperture calculation. Finally, we present the energy spectrum calculated from the merged monocular data sets of the two FADC-based detectors, and also the combination of this merged spectrum with an independent, previously published monocular spectrum measurement performed by Telescope Array’s third fluorescence detector [T. Abu-Zayyad et al., The energy spectrum of Telescope Array’s middle drum detector and the direct comparison to the high resolution fly’s eye experiment, Astroparticle Physics 39 (2012) 109-119, http://dx.doi.org/10.1016/j.astropartphys.2012.05.012 , Available from: ]. This combined spectrum corroborates the recently published Telescope Array surface detector spectrum [T. Abu-Zayyad, et al., The cosmic-ray energy spectrum observed with the surface detector of the Telescope Array experiment, ApJ 768 (2013) L1, http://dx.doi.org/10.1088/2041-8205/768/1/L1 , Available from: ] with independent systematic uncertainties.

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis., 10 pages, 9 figures

An antiphase boundary (APB)-like structure of the B19′ martensite in Ti–Ni alloy was investigated by transmission electron microscopy. The APB-like structure shows atomic shifts on both the (0 1 0)B19′ plane along the c-axis and the (0 0 1)B19′ plane along the b-axis; a kind of ledge-and-step structure on the b–c plane, in addition to a displacement along the a-axis. The displacement vector can be expressed as R = 〈−0.1648 1/2 0.4328〉 in terms of the conventional atomic coordinates of Ti and Ni in the B19′ martensite. The APB-like structure is not inherited from APB in the B2 parent phase. We conclude that the APB-like structure is developed by accidental impingement of differently nucleated martensitic domains during the transformation. This structure is defined as a kind of stacking fault with an APB-like contrast.

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 degrees C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 degrees C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.

In a current study of environmental information, it is important to detect the particular object from environmental images under various conditions for security such as navigation system of ships, bird-watching for the prevention of various damage, invaders check and human rescue in the marine casualty. This paper deals with the image processing techniques for the detection of the rescue target as a particular object from environmental images. When a marine casualty occurs the detection of the rescue target such as life rafts depends on the visual search of human eyes. It is predicted, however, that human eyes sometimes lose their sight and the ability of the detection falls owing to the long flight and a bad weather. For a practical purpose of the prompt rescue of human life, the development of the searching support system in place of human eyes is required. To realize a new type searching system for the detection of the rescue target, the development of new type image processing techniques in real time manner is important. At the first step of our study, we attempt to develop image processing techniques, in order to accurately detect the rescue target under various

We search for ultra-high energy photons by analyzing geometrical properties of shower fronts of events registered by the Telescope Array surface detector. By making use of an event-by-event statistical method, we derive upper limits on the absolute flux of primary photons with energies above ${10}^{19}$, ${10}^{19.5}$, and ${10}^{20}\text{ }\text{ }\mathrm{eV}$ based on the first three years of data taken.

We search for correlations between positions of extragalactic objects and arrival directions of Ultra-High Energy Cosmic Rays (UHECRs) with primary energy $E \ge 40$ EeV as observed by the surface detector array of the Telescope Array (TA) experiment during the first 40 months of operation. We examined several public astronomical object catalogs, including the Veron-Cetty and Veron catalog of active galactic nuclei. We counted the number of TA events correlated with objects in each catalog as a function of three parameters: the maximum angular separation between a TA event and an object, the minimum energy of the events, and the maximum redshift of the objects. We determine combinations of these parameters which maximize the correlations, and calculate the chance probabilities of having the same levels of correlations from an isotropic distribution of UHECR arrival directions. No statistically significant correlations are found when penalties for scanning over the above parameters and for searching in several catalogs are taken into account.

We conducted a cross-sectional study of elderly outpatients with hypertension to examine the relationship between quality of life (QOL) scores and social background factors. The subjects consisted of 516 outpatients (267 females), age of 60 or over, at nine clinics of major hospitals which participated in the National Cardiovascular Center Research Project. The perceived QOL was evaluated by the QOL scale originally based on Japanese patients with cardiovascular diseases. The scale consisted of the following 5 subscales; difficulty due to disease, psychological stability, independence, satisfaction in daily living and vitality. The background factors included family structure, socioeconomic factors and work status, and physical activity of daily living (ADL). After adjusting for age, sex, administered drugs and complicating conditions such as ischemic heart disease and/or apoplexy, a significant odds ratio of a low score of difficulty due to disease, psychological stability, satisfaction in daily living and vitality was found in the impaired physical ADL group with low socioeconomic class, and a significant odds ratio of low score of independence were found in the impaired physical ADL group who had lost jobs due to illness and had no children.

The Telescope Array (TA) experiment, located in the western desert of Utah, USA, is designed for the observation of extensive air showers from extremely high energy cosmic rays. The experiment has a surface detector array surrounded by three fluorescence detectors to enable simultaneous detection of shower particles at ground level and fluorescence photons along the shower track. The TA surface detectors and fluorescence detectors started full hybrid observation in March, 2008. In this article we describe the design and technical features of the TA surface detector. © 2012 Elsevier B.V., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

When hepatitis C virus antibody (anti-HCV) enzyme immunoassay (EIA1) testing became available in 1990, we tested samples from previously transfused blood units, traced the recipients of reactive units, and evaluated the recipients for HCV infection during the 12 months after transfusion. Ten of 42 recipients of EIA1-reactive blood were anti-HCV reactive on follow-up by EIA1 and 12 were reactive by a second- generation assay (EIA2). Reverse transcriptase-polymerase chain reaction (RT-PCR) detected HCV RNA in 5 seronegative recipients. In all, 17 of 42 recipients (40%) of EIA1-reactive blood had evidence of HCV infection. In comparison, 54 surgery patients, who received either no transfusion or autologous EIA1-nonreactive blood, remained EIA1 nonreactive and RT-PCR negative for 1 year; 1 patient (1.8%) became EIA2 reactive (P < or = .01). Of the recipients of anti-HVC reactive blood transfusions (reactive by both EIA1 and a supplemental 4-antigen strip immunoblot assay [RIBA2]), 14 (93%) of the recipients had evidence of HCV infection compared with only 3 of 27 recipients (11%) of EIA1-reactive, RIBA2-nonreactive blood (P < or = .01). Thus, blood components reactive for anti-HCV EIA1 may have transmitted HCV up to 40% of the time, but blood components found reactive by both EIA1 and RIBA2 may transmit HCV with a frequency of greater than 90%.

The specificities of four assays for hepatitis C virus (HCV) were compared by using units from volunteer blood donors. Upon Food and Drug Administration licensure of the first immunoassay for anti-HCV, EIA-1, units previously deemed acceptable for transfusion and all subsequent blood donations were screened. EIA-1 repeat-reactive (RR) units were tested for HCV by a second-generation enzyme-linked immunoassay (EIA-2) and by a four-antigen recombinant immunoblot assay (RIBA II) and for HCV RNA by reverse transcriptase polymerase chain reaction. All HCV RNA-positive samples were reactive by both RIBA II and EIA-2. All RIBA II-reactive sera were EIA-2 RR. In EIA-1, 0.45% of the prescreened units and 0.59% of the prospectively screened donors were RR. Of these, 52.5 and 54%, respectively, were EIA-2 RR, 71.4 and 69% of the EIA-2 RR units were reactive on RIBA II, and 93 and 88% of the RIBA II-reactive samples were HCV RNA positive. When the sample/cutoff ratio for EIA-2 was greater than 5, 91% of the samples were RIBA II reactive and 82% of the samples were HCV RNA positive. None of EIA-2 RR units with a sample/cutoff ratio of < 5 was RIBA II reactive or HCV RNA positive. In conclusion, RIBA II and RT PCR results are highly concordant. A sample/cutoff ratio of > 5 in EIA-2 is a good discriminator for the likelihood of a true HCV infection on the basis of RT PCR and RIBA II assays.

An enzyme-linked immunosorbent assay (ELISA) was developed by using a synthetic polypeptide (SP) whose sequence was derived from the structural region of hepatitis C virus (HCV). Results of several coded panels of sera obtained from volunteer blood donors and patients with apparent non-A, non-B hepatitis and/or hepatitis B virus used in this ELISA were compared with those of a commercially available first-generation C-100 ELISA (using nonstructural HCV antigens), an experimental second-generation C-200/C-22 ELISA (using both structural and nonstructural HCV antigens), and recombinant immunoblot assays RIBA-I and RIBA-II. In the majority of cases, the results obtained with the HCV-SP ELISA correlated well with those obtained by RIBA-II and C-200/C-22 ELISA. In contrast, many samples that were repeatedly reactive in the C-100 ELISA results were nonreactive with RIBA and HCV-SP ELISA. In addition, HCV-SP detected HCV-specific antibody that appeared within a month of infection and coincided with the earliest increase in alanine aminotransferase. In summary, we have developed an ELISA based on a structural HCV synthetic polypeptide, HCV-SP, that has high specificity and sensitivity and is capable of detecting specific antibodies in the acute phase of HCV infection.

A clinicopathological analysis of myocardial infarction with an onset of stroke-like symptoms was carried out on 30 autopsy cases at the Tokyo Metropolitan Geriatric Hospital. The cases were classified into four groups according to the types of brain lesions, I: embolism (n = 17), II: thrombosis (n = 9), III: bleeding (n = 2), and IV: no remarkable focal lesion (n = 2). Classification was made based on clinical findings, and pathological features. The characteristic clinical findings were conciousness disturbance, no elevation of blood pressure at the onset of stroke, hemiplegia and shock. However, the typical anginal chest pain was found in only 17% of cases. The underlying diseases and complications were hypertension, atrial fibrillation (Af), disseminated intravascular coagulation (DIC), renal failure, malignant neoplasma, and diabetes mellitus. The incidences of Af, DIC, mural thrombus, non-bacterial thrombotic endocarditis (NBTE) were significantly higher in the group with cerebral embolism than in the group with cerebral thrombosis. The coronary stenotic index was also smaller in the group with cerebral embolism. Therefore, the major etiology of cardio-cerebral apoplexy was a simultaneous embolism to the brain and heart due to Af, NBTE or, DIC.

Systolic anterior motion of the anterior mitral leaflet and asymmetric septal hypertrophy (ASH) are characteristic features of hypertrophic obstructive cardiomyopathy (HOCM) on an echocardiogram. Among 9,670 patients over 60 years old examined by echocardiography from January, 1984 to October, 1990, 55 patients showed systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae (SAM). We investigated clinical features and morphological features of the left ventricle on an echocardiogram in the 55 patients with SAM. They were classified into three groups according to the degree of SAM. Thirty eight cases (group I) had no mitral and/or chordal-septal contact, 10 (group II) had brief contact (less than 30% on the echocardiographic systole) and 7 (group III) had prolonged contact (greater than or equal to 30%). Ages ranged from 60 to 99 with a mean age of 78.2 years. There were 19 males and 36 females and there was a predominance of females in each group. Thirty five cases had hypertension and 34 left ventricular hypertrophy on electrocardiograms. One case of group I, 3 of group II and 7 of group III had a clinical diagnosis of HOCM. In comparison with each group, the incidence of LVH (SV1 + RV5 greater than or equal to 35 mm) was 52% in group I, 90% in group II and 83% in group III and that of LVH (SV1 + RV5 greater than or equal to 70 mm) was 29%, 20% and 67%, respectively. On echocardiographic examination, the diastolic descent rate of the anterior mitral leaflet in the 3 groups was 36.1 +/- 13.1 mm/sec, 19.4 +/- 13.1 mm/sec and 10.7 +/- 11.8 mm/sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

This paper deals with the detection of the rescue target as a particular object from motion images under bad conditions. When shipwrecks occur, the search activities of rescue are done using an airplane. The detection of the rescue target such as a life raft depends on visual search of human eyes. To detect a small rescue target in the wide sea, the searcher man must monitor motion sights in nasty weather. In order to carry out the prompt rescue of human life, development of searching support system using image processing techniques in place of the human eye is required It is very difficult to process the motion images taken by the airplane, because these images are inferior due to shaking of the airplane, sunshine reflections and crest waves under bad conditions. We make a simulation experiment for detection of the rescue target from images. To get basic design data for development of the searching system in the case of a marine casualty, we propose motion image processing techniques using improved S/N ratio and dynamic range of the image data of the rescue target in the motion images under bad conditions

This paper deals with the detection of the rescue target as a particular object from motion images under bad weather conditions. When shipwrecks occur, the searching activities for rescue is done using an airplane. The detection of the rescue target such as life rafts depends on a visual search by human eyes. To detect a small rescue target in a wide sea area, the searching man must monitor motion sights under nasty weather. The human eyes sometimes loses its sight and the ability of detection fails owing to the long flight and the nasty weather. To support the searching activities in the case of a marine casualty, we propose motion image processing techniques using the improved S/N ratio and dynamic range of the image data of the rescue target in the motion images under bad conditions

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RT-PCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS.

This study was undertaken to investigate the endocrine changes that occur in male Tig:Wistar rats with Leydig cell tumors, with special reference to immunoreactive inhibin (ir-inhibin) and its dimeric forms. Adult male rats from 2 to 28 months of age were used. Blood samples were taken to measure plasma concentrations of ir-inhibin, inhibin-A, inhibin-B, 17beta-estradiol (E2), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Inhibin bioactivity in both peripheral plasma and testicular extracts was also measured. Rats aged 18 months and older had testicular Leydig cell tumor. Testicular tissue sections from 27-month-old rats examined immunohistochemically showed strong positive staining for all 3 inhibin subunits, in particular inhibin alpha and betaA subunits, in the tumor cells. Plasma concentrations of ir-inhibin began to rise significantly (P.05) at 18 months of age. High bioactivity of inhibin was detected not only in testicular extracts but also in peripheral plasma of aged rats. Thus, plasma concentrations of bioactive inhibin-A, but not inhibin-B, were significantly elevated with increasing age. The concentrations were significantly higher than those in normal male (P.01) or normal female (P.05) rats. Plasma concentrations of E2 were significantly (P.05) elevated only at 23-24 months of age. A marked reduction (P.05 to .001) in plasma LH and FSH concentrations was observed at 18 months of age and older. Plasma concentrations of testosterone were highest at 2 months of age and then decreased gradually and significantly (P.05 to .001) afterward. Significant (P.05 to .001) positive (testosterone vs LH) and negative (ir-inhibin vs FSH, ir-inhibin vs LH, and E2 vs FSH) correlations were observed. It is suggested that plasma inhibin-A levels are elevated in male Tig:Wistar rats with Leydig cell tumor, and thus inhibin-A may be used as a specific marker of testicular Leydig cell tumors. The present results also suggest that the age-related decline in plasma gonadotropins and thus testosterone levels in Tig:Wistar rats may be due to the development of tumors of the Leydig cells rather than to aging per se.

We investigated the effect of long-term treatment with a calcium antagonist (nicardipine hydrochloride retard tablet) and a diuretic (trichlormethiazide) on quality of life (QOL) in elderly hypertensives in a multicenter, randomized, double-blind, comparative study (National Intervention Cooperative Study in Elderly Hypertensives Study Group). The percentage of patients who experienced side effects was 17.2% in the nicardipine group and 18.1% in the trichlormethiazide group and 2.9% and 4.3% of participants, respectively, withdrew due to those side effects. These results suggested that nicardipine was tolerated slightly better than trichlormethiazide. There were no significant differences between the two groups in terms of total QOL score or in degree of change (delta score) before and after calcium antagonist or diuretic administration. Lower score was seen in 3 categories (general symptoms, sleep scale, and sexual function) in the trichlormethiazide group (p0.05) and in one category (cognitive function) in the nicardipine group, but there was no significant difference in delta score in any of the individual items. In conclusion, the two anti-hypertensive agents had nearly equivalent effects on QOL in the long-term treatment of hypertension in the elderly and that neither resulted in a deterioration in QOL.

Vascular endothelial growth factor (VEGF) inhibits radiation-induced apoptosis in the leukemia cell line, CMK86 (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we attempted to identify a transcription factor involved in the cellular response to VEGF stimulation. We cloned the cDNA of a novel Kruppel-type zinc finger (ZNF) gene, ZK7, from a cDNA library constructed from the human leukemia cell line CMK86 after incubation with VEGF. This cDNA encoded a protein of 289 amino acids, which contained a Kruppel-associated box A-box domain at the NH2 terminus and seven ZNF motifs at the COOH terminus. These ZNF motifs were identical to those of HZF16 (M. Saleh et al., Am. J. Hum. Genet., 52: 192-203, 1993). ZK7 and HZF16 genes appear to be the splice variants transcribed from the same gene. Northern blotting and quantitative reverse transcription-PCR analysis revealed that expression of ZK7 mRNA in CMK86 cells and human hematopoietic progenitor cells was increased after VEGF stimulation, whereas that of HZF16 mRNA remained unchanged. To examine the function of ZK7 protein, we generated clones of a human monocytoid leukemia cell line, U937, which were stably transfected with ZK7 or HZF16 cDNA. Importantly, ZK7-overexpressing cells had lower sensitivity to ionizing radiation and the chemotherapeutic agent etoposide than U937 parent cells or HZF16-overexpressing cells. Therefore, ZK7 protein may be involved in the inhibitory effect of VEGF on apoptotic cell death in human hematopoietic cells.

We reported previously that vascular endothelial growth factor (VEGF) inhibits the apoptotic death of hematopoietic cells that is induced by exposure to ionizing radiation (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). In this study, we show that VEGF also inhibits apoptotic cell death that is induced by exposure to the chemotherapeutic drugs etoposide and doxorubicin. To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we examined expression levels of BCL2 family proteins in CMK86, a human leukemia cell line, after treatment with VEGF. Northern blotting and immunoblotting analyses revealed that the expression level of MCL1, a member of the BCL2 family, was increased by VEGF. Moreover, to examine the effects of MCL1 on apoptotic cell death induced by exposure to etoposide, we generated a clonal U937 myeloid leukemia cell line transfected with vectors that promoted the constitutive expression of MCL1. MCL1 decreased the caspase 3 activity induced by exposure to etoposide and increased the viability of the transfected cells after etoposide exposure. Therefore, MCL1 may be involved in the inhibitory effect of VEGF on apoptotic cell death.

When a marine casualty occurs, the detection of the rescue target such as life rafts depends on the visual search of human's eye. It is predicted, however, that human eye sometimes loses its sight and ability of detection falls down owing to the long flight and the nasty weather. For a practical purpose of the prompt rescue of human life, development of searching support system in place of human eye is surely required. To realize the detection of the small rescue target in the wide sea, we propose a new searching system using image processing techniques based on the color information. The searching system consists of a visual sensor, an equipment of image processing and a knowledge database. Integration of these parts enables us to detect the rescue target accurately no matter how bad the condition is. At the first step of our study, we attempt the development of image processing techniques to detect accurately the rescue target under the various weather conditions.

The seminiferous epithelia of old mice (33 mo of age) are composed of spermatogonia and Sertoli cells. Histochemical examination using the anti-c-kit monoclonal antibody demonstrated that the number of differentiating type A spermatogonia decreases with age. To elucidate the differential activity of old mouse spermatogonia, we transplanted extremely thin seminiferous epithelia of old BDF, mice into W/Wv mouse testes and examined whether or not they could reinitiate differentiation. Artificially cryptorchid mice were used as the control. At 2 wk after transplantation, spermatocytes and round spermatids were detected in transplanted seminiferous tubules of the control, whereas the most advanced spermatogenic cells in those of old mice were spermatocytes. At 4 wk after transplantation, although elongated spermatids were detected in transplanted tubules of the control, haploid cells (spermatids) were still undetectable in those derived from old mice. Thus, meiosis was never restored, although spermatogonia of old mice can reinitiate differentiation into spermatocytes under suitable testicular conditions. Since it has been reported in several mammalian species that age-related changes in the testicular microenvironment lead to the gerontal cessation of spermatogenesis, the present results suggest that both a defective extratubular environment and a defective intratubular environment may cause the cessation of spermatogenesis in old BDF, mice.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Background There have been few studies on palliative care for patients with bone and soft tissue sarcoma due to its low prevalence. We report 19 cases of patients with bone and soft tissue sarcoma who were consulted to the palliative care team. Method We retrospectively reviewed all medical records of patients with bone and sot tissue sarcoma who were hospitalized for chemotherapy and consulted to the palliative care team from January 2010 to 15 October 2011. Results Nineteen patients (6 males and 13 females) were reviewed in this study. The median age was 50 years (23–87). The histological subtypes included leiomyosarcoma (n = 8), gastrointestinal stromal tumor (n = 3), Ewing sarcoma (n = 2), angiosarcoma (n = 2), osteosarcoma (n = 1), chondrosarcoma (n = 1), synovial sarcoma (n = 1), and malignant fibrous sarcoma (n = 1). The sites of metastases were lung (n = 11), pelvic viscera (n = 8), liver (n = 7), and bone (n = 7). The median number of chemotherapy regimens was 2 (0–5). The most common life-threatening complication was respiratory failure (n = 6), followed by bleeding of the tumor (n = 3), pulmonary embolism (n = 2), and bowel perforation (n = 1). Reasons of consultation were psychological support (n = 7), intractable pain (n = 6), and lymphedema (n = 6). Fifteen patients (79%) used opioids, including fentanyl patch 33%, fentanyl continuous infusion 20%, oral oxycodone 20%, oral morphine 13%, and morphine continuous infusion 13%. One patient used an antidepressant drug. Conclusions The patients with bone and soft tissue sarcoma tended to be highly distressed by the absence of enough information about their disease and standard chemotherapy in the early stage of therapy, therefore they needed psychological support. In the middle and the late stage of disease, they tended to have life-threatening complications that worsen the prognosis.

To evaluate the morphological and functional characteristics of the heart in elderly patients with white coat hypertension, we performed an echocardiographic study in 67 elderly individuals older than 60 years: 17 patients with white coat hypertension, 34 patients with true hypertension, and 16 normotensive control subjects. White coat hypertension was defined as a mean 24-hour ambulatory systolic blood pressure of less than 140 mm Hg associated with office hypertension. Cardiac responses to an isometric handgrip exercise test were used to evaluate left ventricular functional reserve. Left atrial dimension and left ventricular mass index were significantly greater in the white coat hypertension group than in the normotension group (P < .05) but were similar to values in the true hypertension group. Left ventricular diastolic function, expressed by peak late-early filling ratio of diastolic mitral flow, showed increasing impairment in the order of the normotension, white coat hypertension, and true hypertension groups (analysis of variance, P < .05); the ratio in the white coat hypertension group tended to be higher than that in the normotension group (unpaired t test, P = .054). The relation between fractional shortening and end-systolic stress did not shift downward after handgrip exercise in the white coat hypertension group, indicating that functional reserve in the left ventricle was maintained. Thus, patients with white coat hypertension had a moderately increased left atrial dimension and left ventricular mass in association with a tendency for disturbed diastolic function, although systolic functional reserve remained the same. These findings suggest that white coat hypertension in the elderly may not be innocent.

When hepatitis C virus antibody (anti-HCV) enzyme immunoassay (EIA1) testing became available in 1990, we tested samples from previously transfused blood units, traced the recipients of reactive units, and evaluated the recipients for HCV infection during the 12 months after transfusion. Ten of 42 recipients of EIA1-reactive blood were anti-HCV reactive on follow-up by EIA1 and 12 were reactive by a second-generation assay (EIA2). Reverse transcriptase-polymerase chain reaction (RT-PCR) detected HCV RNA in 5 seronegative recipients. In all, 17 of 42 recipients (40%) of EIA1-reactive blood had evidence of HCV infection. In comparison, 54 surgery patients, who received either no transfusion or autologous EIA1-nonreactive blood, remained EIA1 nonreactive and RT-PCR negative for 1 year; 1 patient (1.8%) became EIA2 reactive (Por = .01). Of the recipients of anti-HVC reactive blood transfusions (reactive by both EIA1 and a supplemental 4-antigen strip immunoblot assay [RIBA2]), 14 (93%) of the recipients had evidence of HCV infection compared with only 3 of 27 recipients (11%) of EIA1-reactive, RIBA2-nonreactive blood (Por = .01). Thus, blood components reactive for anti-HCV EIA1 may have transmitted HCV up to 40% of the time, but blood components found reactive by both EIA1 and RIBA2 may transmit HCV with a frequency of greater than 90%.

We studied the relationship between physical activity and ambulatory blood pressure (BP) in young and older shiftworkers by simultaneous recordings of activity, blood pressure and pulse rate (PR). Activity was assessed using Activetracer, a self-contained microcomputer with an acceleration sensor, attached to a waist belt. Ambulatory BP was monitored every 30 minutes for 48 hours with a TM2421. Three types of hemodynamic responses were noted in relation to the physical activity. The balance type, in which both BP and PR increase with physical activity, was observed in 5 of 10 young cases (50%) but only in 1 of 7 older cases (14.3%). The BP response type, in which the BP increases with no change in the PR, was observed in 6 of the 7 older (86%) but only in 3 cases in the young group (30%). The PR response type, in which only the PR increase correlated with activity, was observed in 2 cases in the young group (20%) and none in the older group. The difference in systolic BP between periods of activity and rest in the older shiftworker was significantly larger than that in the young group (15.9 +/- 6.4 vs. 5.9 +/- 6.6 mmHg, p.01), although no significant difference was observed in diastolic BP. In contrast, the increase in pulse rate after movement was significantly higher in the young group (4.4 +/- 4.0 vs. 9.0 +/- 4.8 bpm, p.05). Thus, the fluctuation of the systolic BP was more dependent on physical activity in the older group, whereas PR variations correlated with the physical activity in the young group.

Incidence of spontaneous tumors in C57BL/6 NCrj (CR), C5BL/6 CrSlc (SL) and B 6 Crj x DBA/2 NCrj F1 (BD) mice, which were reared under a barrier system and died natural death, were examined. Cohorts of mice in 200 to 300 each were purchased at 4 weeks of age and raised under SPF conditions. A large portion of the mice were used for various experiments between 3 and 30 months old while not a small number died before use and were autopsied. Median survival periods of the female and male were estimated at 697 and 680 days for CR, 764 and 806 days for SL and 866 and 929 days for BD, respectively. Incidence of spontaneous neoplastic lesions in the autopsied animals were 77.4% and 79.2% of 535 female and 590 male CR, 69.7% and 55.1% of 502 female and 463 male SL, and 75.8% and 78.0% of 298 female and 346 male BD, respectively. In CR, histiocytic sarcoma was the most predominant tumor, accounting for 72.1% of all tumors. In SL, malignant lymphoma was the most prevailing, forming 62.3%, and, in male BD, hepatocellular carcinoma was the most frequent, accounting for 41.8% of all tumors.

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.

The dot immunobinding assay (DIA), a modified enzyme immunoassay (EIA), has been demonstrated to be a highly sensitive and specific assay for the detection of antibody to a number of viruses. Different laboratory procedures are available for detecting antibody to the immunodeficiency viruses; however, these procedures require a certain amount of sophisticated equipment and trained personnel. Further, commercial kits for detecting antibody to human immunodeficiency virus, as now available, are not easy to use in the nonlaboratory setting. The DIA, as described herein, may be formatted to test up to 30 serum samples and is designed to be used in the absence of laboratory equipment. To determine the effectiveness of the DIA as a test kit for the detection of HIV and human T-cell leukemia virus type I (HTLV-I) antibodies, the kit was compared with commercial EIA and Western blot (WB; immunoblot) kits. Testing approximately 1,000 human serum samples for HIV antibody by DIA and EIA revealed a total agreement of 98.1%, a specificity of 99.0%, and a sensitivity of 95.9%. For 804 serum samples tested (200 were tested independently in two laboratories), eight results were discrepant: four DIA negatives which were EIA borderline positive and four DIA positives which were EIA negative. Testing the eight discrepant sera by immunofluorescence assay and WB resulted in their being either negative or indeterminate. The four DIA positives were indeterminate by WB. Close agreement was obtained when the remaining sera were compared by DIA, EIA, and WB. Of interest was finding that the DIA results compared favorably with those obtained by WB. Twenty-six suspect HTLV-I-positive serum samples tested by DIA also gave results comparable to those obtained by EIA and WB.

Intravenous drug users are frequently exposed to parenterally transmitted viral infections, and these infections can spread to the general population through sexual activity. We investigated the prevalence of serologic markers for human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type I/II (HTLV-I/II), hepatitis B virus (HBV), and hepatitis C virus (HCV) in intravenous drug users and their sexual contacts. Of 585 drug users from northern California tested for these serologic markers, 72% were reactive for the antibody to HCV, 71% for the antibody to hepatitis B core antigen, 12% for HTLV-I/II antibodies, and 1% for the HIV-1 antibody. The prevalence of serologic markers for these four viruses correlated with the duration of intravenous drug use, the ethnic group, and the drug of choice. More than 85% of subjects infected with either HCV or HBV were coinfected with the other virus. All persons reactive to HTLV-I/II antibodies had antibodies for either HBV or HCV. Of 81 sexual contacts tested, 17% had evidence of HBV infection while only 6% were reactive for HTLV-I/II antibodies and 4% for the antibody to HCV. None of this group was infected with HIV-1. We conclude that HTLV-I/II and HCV are inefficiently transmitted to sexual contacts while HBV is spread more readily. Programs designed to discourage the sharing of drug paraphernalia, such as needle and syringe exchanges, should decrease the risk of parenterally spread viral infections in intravenous drug users and thus slow the spread of these infections to the general population.

By studying 3,408 consecutive autopsied elderly patients, we found that two thirds of the 132 massive cerebral infarctions (86) were embolic, of cardiac origin. Embolic infarction associated with nonvalvular atrial fibrillation was seen in 48 cases (36%), half due to the first stroke. Embolic infarction associated with heart disease other than nonvalvular atrial fibrillation was seen in 23 cases (17%), and that from nonbacterial thrombotic endocarditis was seen in 15 cases (11%). Thrombotic infarction or infarction of nonembolic cardiac origin was found in only 39 cases (30%). Of 56 patients with fatal massive cerebral infarction who died less than or equal to 2 weeks after their stroke, 25 (45%) had embolic strokes associated with nonvalvular atrial fibrillation. Our study shows that nonvalvular atrial fibrillation is a very important cause of fatal massive cerebral infarction in the elderly.

The antihypertensive effect and possible adverse effects of bisoprolol were assessed in 96 Japanese patients with mild to moderate hypertension. After a 2- to 4-week placebo period, bisoprolol was administered to 68 outpatients at a daily dose of 5 mg to 20 mg for 6 to 8 weeks, and to 28 inpatients with the same dose range up to a maximum of 4 weeks. For outpatients, blood pressure and heart rate were recorded every 2 weeks, while for inpatients, in addition to daily measurements, the effect of bisoprolol on diurnal variation of blood pressure was also studied. Bisoprolol lowered blood pressure and heart rate significantly in both groups of patients. The most common adverse effect was bradycardia. It is expected that bisoprolol will be a very effective and useful antihypertensive drug.

Complete drainage of the pulmonary veins into the right heart is one of the rarest and most severe congenital cardiac anomalies. The X-ray studies may suggest this diagnosis if pulmonary veins enter either coronary sinus or inferior vena cava. In the case reported, right heart catheterization and angiocardiography were used and the diagnosis of persisent left superior vena cava and partial direct drainage of the pulmonary veins into right auricle was made.