Isotropy of Cosmic Rays beyond 10

We report an estimation of the injected mass composition of ultrahigh energy cosmic rays (UHECRs) at energies higher than 10 EeV. The composition is inferred from an energy-dependent sky distribution of UHECR events observed by the Telescope Array surface detector by comparing it to the Large Scale Structure of the local Universe. In the case of negligible extragalactic magnetic fields (EGMFs), the results are consistent with a relatively heavy injected composition at E∼10 EeV that becomes lighter up to E∼100 EeV, while the composition at E>100 EeV is very heavy. The latter is true even in the presence of highest experimentally allowed extragalactic magnetic fields, while the composition at lower energies can be light if a strong EGMF is present. The effect of the uncertainty in the galactic magnetic field on these results is subdominant.

The first report of the thyroid function of haemophilic patients with HIV/HCV co-infection in Japan.

INTRODUCTION: A high incidence of thyroid dysfunction is reported in patients with HIV or HCV mono-infection. We have conducted a periodic medical examination including the thyroid function for haemophilic patients with HIV/HCV co-infection due to contaminated blood products. METHODS: We examined the thyroid function (as assessed by the FT3, FT4 and TSH levels) in 45 haemophilic patients, including thyroglobulin and auto-antibody, antithyroglobulin antibody, antithyroid peroxidase antibody and anti-TSH receptor antibody in 28 patients. RESULTS: All the patients were males (median age: 42 years; range: 29-66). The median values of thyroid function were FT3 3.36 pg mL(-1) , FT4 1.125 ng mL(-1) and TSH 1.65 µIU mL(-1) . Five patients (11.1%) had high TSH levels. In 28 patients in whom the presence of auto-antibodies was examined, the median age was 47 years of age. The median value of thyroglobulin was 16 ng mL(-1) and two patients showed high levels of thyroglobulin. The presence of anti-TSH receptor antibody of all the patients was negative, but one patient (3.5%) was positive of antithyroid peroxidase antibody and antithyroglobulin antibody. CONCLUSIONS: Since 0.68-3.6% of the general healthy population is reported to show hypothyroidism, our data showed that the proportion of hypothyroidism in haemophilic patients with HIV/HCV co-infection was more frequent than that of the normal population.

Evaluation of the operative methods for Graves' disease.

AIM: In Japan, surgery for Graves' disease (GD), which is considered to be a radical therapy, has been restricted by various guidelines. Nevertheless, some patients benefit from surgery. We sought to identify a reasonable operative method for GD by comparing the efficacy and safety among patients undergoing different extents of thyroidectomy. METHODS: A total of 162 patients underwent thyroidectomy for GD between 2003 and 2012 in our department. We compared the clinical factors among those who underwent subtotal thyroidectomy (ST), near-total thyroidectomy (NTT), and total thyroidectomy (TT). RESULTS: The ST, NTT, and TT groups included 111, 21, and 30 patients, respectively. The patient sex, period between disease onset and surgery, and preoperative thyroidal function were not substantially different among the three groups. With regard to surgical variables, the duration of surgery, amount of blood loss, and postoperative length of hospitalization were not substantially different among the three groups. Postoperative recurrent laryngeal nerve (RLN) palsy was transient in all cases, but the rate was significantly higher in the TT group compared to the other two groups (P<0.001). The incidences of transient hypocalcemia and permanent hypoparathyroidism were not substantially different among the groups. The proportion of patients who required the postoperative administration of levothyroxine was significantly lower in the ST group compared to the TT and NTT groups. Hyperthyroidism recurrence was noted in eight patients in the ST group (7.2%). CONCLUSION: NTT for GD is thus considered to be a reasonable operative method regarding both efficacy and safety.

[Metabolic syndrome].

About 20 years ago, Reaven presented the concept that a series of related factors such as hyperinsulinemia, hypertension, low high-density lipoprotein (HDL)-cholesterol levels, and hypertriglyceridemia tended to co-occur in the same individual and that this risk-factor clustering and its association with insulin resistance might be of critical importance in the underlying cause of cardiovascular disease. This risk-factor clustering called as "syndrome X" has now become "metabolic syndrome" (METS). Nowadays, METS is becoming well known as a condition of high-risk for the subsequent development of ischemic cardiovascular disease in Western population as well as Japanese population and it is proved that the prevalence of METS is very common. There are several different diagnostic definitions for METS. In Japanese definition, waist circumference is essential for criterion of METS because visceral fat accumulation is believed to be associated with METS more closely than the body mass index (BMI) itself or the amount of subcutaneous fat. Therefore treatment strategy to reduce visceral fat seems to be crucial for management of patients with METS. Adipose tissue is not simply an energy storage organ, but also a secretary organ, producing a variety of bioactive substances, including adiponectin. Adiponectin is paradoxically reduced in obesity and elevated adiponectin concentration is associated with greater insulin sensitivity. Therefore hypoadiponectinemia can be considered a key factor of the development of METS. We believe that detection, prevention and treatment of METS are important clinical and public health challenges.

Video-assisted subtotal or near-total thyroidectomy for Graves' disease.

BACKGROUND: Surgery remains the treatment of choice for patients with Graves' disease. The purpose of the present study was to assess the usefulness and efficacy of video-assisted subtotal or near-total thyroidectomy in patients with Graves' disease. METHODS: Between March 2000 and December 2004, 63 patients with Graves' disease underwent video-assisted subtotal, near-total or total thyroidectomy. Fifty-three patients (84 per cent) were considered for surgery after failure of antithyroid drug and radioiodine therapy, whereas the other ten patients were initially selected for surgical treatment based on their own preference. Treatment outcome was evaluated, including surgical complications, thyroid function, quality of life and patient satisfaction with the surgical result. RESULTS: All patients were operated on using a video-assisted technique, with some modifications depending on time and experience. There were no conversions to open surgery. Three patients (5 per cent) had temporary recurrent laryngeal nerve palsy that recovered spontaneously. Most patients were satisfied with the surgical results, particularly regarding the placement of the surgical scars. CONCLUSION: Video-assisted subtotal or near-total thyroidectomy is a safe and effective procedure for treatment of Graves' disease.

Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and corpus luteum.

In glucocorticoid target organs, local concentrations of active glucocorticoid are determined by the relative expression of two 11beta-hydroxysteroid dehydrogenases (HSDs): bi-directional 11beta-HSD type1 (11HSD1) that mainly activates cortisone to cortisol, and dehydrogenase 11beta-HSD type2 (11HSD2) that inactivates cortisol to cortisone. In this study, we examined the expression of mRNA encoding these two 11beta-HSDs in bovine granulosa cells harvested from preovulatory follicles and corpora lutea (CL). Ovaries were obtained from Holstein cows at a local slaughterhouse. Follicles larger than 10 mm in diameter and CL were dissected and follicular fluid and granulosa cells were taken. Corpora lutea were weighed and their stages were morphologically assessed (stage I, days 1-4; stage II, days 5-10; stage III, days 11-17; stage IV, days 8-20). Follicles were classified into four groups according to their hormonal status (oestradiol (E(2)): progesterone (P(4))>1: oestrogen active; E(2):P(4)<1: oestrogen inactive) and stage of the oestrous cycle (luteal or follicular phase). Total RNA was extracted with phenol-chloroform and subjected to a semi-quantitative RT-PCR for 11HSD1, 11HSD2 and beta-actin. Concentrations of steroids in follicular fluid were determined by an enzyme immunoassay. In granulosa cells, only 11HSD1 mRNA was detected. There was a negative correlation between the expression of 11HSD1 and the concentration of cortisol in follicular fluid (P<0.05), indicating 11HSD1 may act as a dehydrogenase in the bovine follicle. Both types of 11beta-HSDs were expressed in CL. The levels of mRNA for both isozymes were high in stage I and II, and were decreased in stage III CL. In stage IV CL, the expression of 11HSD2 but not 11HSD1 mRNA increased. These results indicate that the bovine granulosa cells and CL express 11HSD1 and 11HSD2, and they may play an important physiological role in the bovine ovary through modulating the local glucocorticoid environment.

Obstruction of St Jude medical valves in the aortic position: a consideration for pathogenic mechanism of prosthetic valve obstruction.

Between 1995 and 2000, 8 patients with St. Jude Medical (SJM) valves in the aortic position required 9 redo valve replacement for prosthetic valve obstruction. Obstruction of the prosthetic valve was diagnosed by simultaneous echocardiography and cineradiography, and process of restricted leaflet movement that progressed to hemodynamic impairment was observed by serial studies in three recent patients. An oral anticoagulation was considered to be adequate in all patients except one patient who had withdrawal of warfrain. Pannus was the sole cause of valve obstruction in seven events in 6 patients, and both thrombus and pannus in 2 patients. Pannus overgrowth was found on the inflow aspect of the SJM valve, and involved the ends of the straight edge of the leaflets over pivot guards. These results suggest that pannus might play the primary role in development of obstruction of aortic SJM valves in patients on adequate oral anticoagulation.

A study on the role of platelet function in patients with chronic pulmonary thromboembolism.

UNLABELLED: There has been no study on the platelet function in the patient with chronic pulmonary thromboembolism (CPTE). We speculate that the platelet function may be elevated in the patients. PURPOSE: 1. The platelet functions were compared among CPTE before surgery, deep vein thrombosis (DVT) and normal adult people. 2. The severity of CPTE in clinical grading to the platelet functions were compared. 3. The platelet function were compared before and after pulmonary thromboendarterectomy. METHODS: Pre-opetative CPTE group (n=16), post-operative CPTE group (n=11), DVT group (n=9) and control group (normal adult people: n=33) were investigated on the platelet functions defined as platelet adhesion (AD) and platelet aggregation (AG) test in this study. RESULTS: 1. No activation of platelet functions was observed in pre-operative CPTE patients. 2. There was no apparent relationship between the severity of disease and platelet functions. 3. Significant elevation of AG was obtained in the patients who received pulmonary thromboendarterectomy. CONCLUSION: In consideration to the finding in postoperative study, the administration of anti-platelet drug will help to prevent re-thrombosis of the pulmonary arteries after surgery.

Molecular cloning and heterologous expression of novel glucosyltransferases from tobacco cultured cells that have broad substrate specificity and are induced by salicylic acid and auxin.

Scopoletin is one of the phytoalexins in tobacco. Cells of the T-13 cell line (Nicotiana tabacum L. Bright Yellow) accumulate a large amount of scopoletin, also known as 7-hydroxy-6-methoxycoumarin, as a glucoconjugate, scopolin, in vacuoles. We report here the molecular cloning of glucosyltransferases that can catalyze the glucosylation of many kinds of secondary metabolites including scopoletin. Two cDNAs encoding glucosyltransferase (NtGT1a and NtGT1b) were isolated from a cDNA library derived from the tobacco T-13 cell line by screening with heterologous cDNAs as a probe. The deduced amino-acid sequences of NtGT1a and NtGT1b exhibited 92% identity with each other, approximately 20-50% identities with other reported glucosyltransferases. Heterologous expression of these genes in Escherichia coli showed that the recombinant enzymes had glucosylation activity against both flavonoids and coumarins. They also strongly reacted with 2-naphthol as a substrate. These recombinant enzymes can utilize UDP-glucose as the sugar donor, but they can also utilize UDP-xylose as a weak donor. RNA blot analysis showed that these genes are induced by salicylic acid and auxin, but the time course of the expression was different. This result is similar to the changes in scopoletin glucosylation activity in these tobacco cells after addition of these plant growth regulators. These results might suggest that one of the roles of the products of these genes is scopoletin glucosylation, in response to salicylic acid and/or auxin, together with the other glucosyltransferases in tobacco cells.

Analysis of Tag1-like elements in Arabidopsis thaliana and their distribution in other plants.

Analysis of genomic DNA of Arabidopsis Columbia (Col.) ecotype using a transposon Tag1-specific primer showed the presence of Tag1 homologues which was confirmed by Southern hybridization with a Tag1 probe. Further analysis showed that the homologue, 0.75 kb in length, had inverted repeats at both ends, 8-bp duplicated sequences at the site at which it is located and about 80% homology with Tag1, and was randomly distributed in the Arabidopsis genome. Based on these results, we concluded that these elements are non-autonomous variants of Tag1 and we termed this element sTag1. Using the polymerase chain reaction fragment hybridization technique, we found the distribution of such homologues in other plant species.

Repair of left ventricular rupture following mitral valve replacement concomitant with left atrial reduction procedure--intracardiac patch and extracardiac buttress suture.

Rupture of the posterior wall of the left ventricle after mitral valve replacement is a dire complication associated with a very high mortality. This study reports a successful repair of type I left ventricular rupture, which occurred after mitral valve replacement concomitant with a left atrial reduction procedure, by combination of an intracardiac patch and an extracardiac buttress suture. In a case such as this, in which hemostasis is quite difficult to establish, this combination technique is particularly effective.

Antiinflammatory effects of colforsin daropate hydrochloride, a novel water-soluble forskolin derivative.

BACKGROUND: To evaluate the effects of colforsin daropate hydrochloride (colforsin), a water-soluble forskolin derivative, on hemodynamics and systemic inflammatory response after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Twenty-nine patients undergoing coronary artery bypass grafting were randomized to receive either colforsin treatment (colforsin; n = 14) or no colforsin treatment (control; n = 15). Administration of colforsin (0.5 microg.kg(-1).min(-1)) was started after induction of anesthesia and was continued for 6 hours. Perioperative cytokine and cyclic adenosine monophosphate levels, hemodynamics, and respiratory function were measured serially. RESULTS: Marked positive inotropic and vasodilatory effects were observed in patients receiving colforsin. Interleukin 1beta, interleukin 6, and interleukin 8 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the colforsin group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) in the colforsin group, and the levels correlated inversely (r = -0.56, p = 0.002) with the respiratory index after cardiopulmonary bypass. CONCLUSIONS: Intraoperative administration of colforsin daropate hydrochloride had potent inotropic and vasodilatory activity and attenuated cytokine production and respiratory dysfunction after cardiopulmonary bypass. The results indicate that the technique can be a novel therapeutic strategy for the systemic inflammatory response associated with cardiopulmonary bypass.

[Effects of colforsin daropate hydrochloride in patients undergoing coronary artery bypass surgery].

The effects of Adehl, colforsin daropate hydrochloride, on hemodynamics were studied in patients undergoing cardiac surgery. Twenty-six patients who underwent coronary artery bypass grafting were divided into two groups according to the intraoperative administration of Adehl. The control group (n = 14) received no Adehl treatment and the Adehl group (n = 12) received Adehl infusion immediately after anesthesia induction (0.5 microgram.kg-1.min-1) for 6 hours. Hemodynamic measurements and clinical results were accessed perioperatively. The Adehl group resulted in significantly (p < 0.05) lower pulmonary capillary wedge pressure and systemic vascular resistance, and significantly (p < 0.05) greater cardiac indices and left ventricular stroke work indices than those in the control group. No significant difference was found in the rate pressure product between the groups. The Adehl group resulted in significantly shorter duration of intubation and ICU stay. Adehl was not associated with a significant increase in the prevalence of adverse effects. The results suggest that Adehl has positive inotropic and vasodilator effects without increasing myocardial oxygen consumption. Thus, it is suggested that Adehl can be a useful agent for the perioperative management in patients undergoing cardiac surgery.

Differences in management and outcomes of acute myocardial infarction among four general hospitals in Japan.

OBJECTIVE: To ascertain the differences among hospitals in Japan in the management patterns and outcomes of patients with acute myocardial infarction (AMI). DESIGN: Retrospective cohort study by means of patient chart review. SETTING: Four tertiary-care teaching hospitals in Japan observed over a 1-year period. STUDY PARTICIPANTS: Consecutive patients (N=482) admitted for AMI. MAIN OUTCOME MEASURES: Clinical characteristics, rates of diagnostic and therapeutic procedures performed, cardiac complications, and length of stay. RESULTS: Patients' clinical characteristics differed significantly among the four hospitals in terms of age, gender, and prior cardiac history, but not in terms of comorbidity or infarct location. The frequency and type of diagnostic and therapeutic procedures were different, and in-hospital mortality varied (4-14%, P=0.022). Average length of hospital stay ranged from 15.8+/-12.6 days to 41.0+/-19.4 days (P=0.0001). After adjustment for the clinical characteristics, these differences remained significant among hospitals. CONCLUSION: Considerable differences in the management and outcomes of patients with AMI exist in Japan.

Surgical treatment of prosthetic valve endocarditis with left ventricular-aortic discontinuity: reconstruction of the left ventricular outflow tract with a xenopericardial conduit.

BACKGROUND AND AIM OF THE STUDY: Aortic prosthetic valve endocarditis (PVE) with annular destruction presents a challenge that requires techniques to eradicate the infection and correct the hemodynamic abnormality. METHODS: Between July 1, 1996 and March 31, 2000, six patients with native or PVE of the aortic valve and aortic annular destruction underwent surgical treatment. Of these patients, three (two men, one woman; mean age 71.0 years) had circumferential annular destruction of the aortic annulus, and formed the basis of this study. The microorganisms responsible for the infection were Streptococcus spp. in two patients and Staphylococcus aureus in one patient. In addition to aggressive debridement of the infected tissue, repair was achieved by reconstruction of the left ventricular outflow tract with a xenopericardial conduit and fixation of the new prosthetic valve to the conduit. RESULTS: One patient with ventricular septal perforation, multiple systemic embolism and sepsis died of low cardiac output syndrome soon after surgery. Two operative survivors were followed up for 9 and 51 months, with no late deaths. No patient has experienced recurrent infection, pericardial patch aneurysm, or prosthetic valve detachment. CONCLUSION: These operative procedures provide easy and secure fixation of the pericardial patch to the healthy tissue under excellent operative view, as well as a sturdy structure for the fixation of the new prosthesis, and complete exclusion of the abscess cavity from the blood stream.

Plant hormone regulation on scopoletin metabolism from culture medium into tobacco cells.

Tobacco (Nicotiana tabacum L. Bright Yellow) T-13 cell line has an ability for production of scopoletin. In this cell culture, scopoletin is taken up from culture medium and accumulated in vacuoles after conversion to scopolin when cells are treated with 2,4-dichlorophenoxyacetic acid (2,4-D) (Taguchi et al. (2000)). To clarify the effect of 2,4-D on tobacco cells, its interaction with several other plant hormones was investigated. Other auxins also stimulated the uptake in the same manner as 2,4-D did, although higher concentrations were required than that of 2,4-D. When p-chlorophenoxyisobutyric acid (PCIB), an antiauxin, was added to the cell culture before 2,4-D, it inhibited 2,4-D-stimulated scopoletin uptake. This result suggests that the stimulation of scopoletin uptake was one of the auxin effects on tobacco cells. Among other classes of plant hormones that were tested, only salicylic acid stimulated the uptake. When these hormones were added to the cell cultures before 2,4-D, methyl jasmonate and kinetin reduced scopoletin uptake. These results suggest that this scopoletin uptake by tobacco cells is regulated by the interaction between different plant hormones.

Triple valve replacement with bileaflet mechanical valves: is the mechanical valve the proper choice for the tricuspid position?

A more durable mechanical valve may be a better choice for the tricuspid position than a bioprosthesis when the patient already has mechanical prosthesis in the left side of the heart. Eleven cases of triple valve replacement (total follow-up period, 49.5 patient years), all with mechanical valves, are reviewed to assess optimal valve selection. Nine patients had undergone a total of 12 previous cardiac surgeries. Three patients died in hospital (27.3%), but there were no late deaths among the survivors. Two cases of valve thrombosis in the tricuspid position occurred (linearized incidence: 4.04%/patient years) and 1 of these required reoperation. Because of this high incidence of valve thrombosis, the bileaflet mechanical valve is not considered to be the best choice. Even if mechanical valves are implanted in the left side of the heart, a bioprosthesis may be a better choice at the tricuspid position.

Coronary artery bypass grafting in patients with mild renal insufficiency.

UNLABELLED: It is well known that dialysis-dependent renal failure increases the likelihood of a poor outcome following cardiac surgery. However, it is not known whether non-dialysis-dependent mild renal insufficiency also influences clinical outcome. Fifty-five patients with non-dialysis-dependent renal insufficiency undergoing coronary artery bypass grafting (CABG) (Renal group: serum creatinine level >1.5 mg/dl) were enrolled. These patients were then matched on prognostic variables to 148 patients with normal renal function ( CONTROL GROUP: serum creatinine level <1.5 mg/dl). The early postoperative clinical results showed that patients in the Renal group were more likely to develop postoperative renal failure (18% vs 1%: p=0.0002) and hemorrhage requiring re-exploration (11% vs 2%; p=0.01). Total morbidity was significantly higher in the Renal group (40% vs 22%; p=0.01). Multivariate analysis revealed that the Renal group was the second most important predictor of morbidity (odds ratio (OR) =2.2) behind left ventricular dysfunction (OR=2.9). The Renal group was also the second most important predictor of postoperative renal failure (OR=12.5). Therefore, non-dialysis-dependent mild renal insufficiency also increases the risk of morbidity following CABG.

High-dose cimetidine reduces proinflammatory reaction after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cimetidine, which is usually used for gastric ulcer, enhances cellular immunity. The effect of cimetidine on perioperative proinflammatory response after cardiac surgery with cardiopulmonary bypass was investigated. METHODS: Elective coronary artery bypass graft cases in which CPB was performed were placed randomly in a cimetidine (C) group (n = 20) or a no-treatment (N) group (n = 20). The time course of plasma levels of neutrophil elastase, interleukin (IL)-6 and IL-8, leukocyte counts, lymphocyte recovery ratio, C-reactive protein, creatine-kinase-MB, and oxygenation index were analyzed. RESULTS: The plasma levels of neutrophil elastase and IL-8 were inhibited in the C groups at 2 hours after CPB termination. In a comparison of the two groups, the C group demonstrated higher lymphocyte recovery ratio and lower C-reactive protein on postoperative day 5 and shorter intubation time. No intergroup differences were observed in IL-6, leukocyte counts, creatine-kinase-MB levels, or oxygenation index. CONCLUSIONS: Cimetidine may reduce surgical stress and augment the immune system after cardiac surgery with cardiopulmonary bypass.