Ion species discrimination method by linear energy transfer measurement in Fujifilm BAS-SR imaging plate.

We have developed a novel discrimination methodology to identify ions in multispecies beams with similar charge-to-mass ratios, but different atomic numbers. After an initial separation by charge-to-mass ratios using co-linear electric and magnetic fields, individual ions can be discriminated by considering the linear energy transfer of ions irradiating a stimulable phosphor plate (Fujifilm imaging plate) by comparison with the Monte Carlo calculation. We apply the method to energetic multispecies laser-driven ion beams and use it to identify silver ions produced by the interaction between a high contrast, high intensity laser pulse; and a sub-micrometer silver foil target. We also show that this method can be used to calibrate the imaging plate for arbitrary ion species in the range of Z ≥ 6 with dE/dx > 0.1 MeV/µm without requiring individual calibration.

Retrospective analysis of the survival benefit of chemotherapy for recurrent or advanced epithelial ovarian carcinoma in patients previously treated with paclitaxel plus platinum-based chemotherapy.

AIM: The outcomes of treatment for women with recurrent or advanced epithelial ovarian carcinoma previously treated with pacli- taxel plus platinum-based chemotherapy were analyzed. MATERIALS AND METHODS: Retrospective analysis was performed in a total of 65 series of treatments provided for 35 patients with a history of paclitaxel plus platinum-based chemotherapy. The chemotherapy regimens used were classified into the following four types for analysis: conventional paclitaxel plus carboplatin therapy (TC arm), pegylated liposomal doxorubicin-containing regimens (PLD arm), CPT-11-containing regimens (CPT-11 arm), and others. Disease-control rates (DCRs) were compared and subjected to univariate analysis. Progression-free survival (PFS) was determined from the date of the first cycle of each chemotherapy with the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: DCR was 80%, 71%, and 26% for the TC, PLD, and CPT-l arms, respectively. The median PFS was 286, 372, and 76 days for the TC, PLD, and CPT-11 arms, respectively. There was no discernible difference in PFS between the TC and the PLD arm. In contrast, PFS of the CPT- 11 arm was significantly shorter than that of the TC and PLD arms. In addition, three of seven (42.9%) treatments in the PLD arm maintained a progression-free period for longer than one year, while only one of 25 (4%) treatments in the TC arm maintained a progression-free period for more than one year. CONCLUSIONS: The PFS of PLD is similar to that of TC. PLD-containing regimens might have a potential benefit with a higher PFS over one year than the TC regimen.

Genetic correlation between the pre-adult developmental period and locomotor activity rhythm in Drosophila melanogaster.

Biological clocks regulate various behavioural and physiological traits; slower circadian clocks are expected to slow down the development, suggesting a potential genetic correlation between the developmental period and circadian rhythm. However, a correlation between natural genetic variations in the developmental period and circadian rhythm has only been found in Bactrocera cucurbitae. The number of genetic factors that contribute to this genetic correlation is largely unclear. In this study, to examine whether natural genetic variations in the developmental period and circadian rhythm are correlated in Drosophila melanogaster, we performed an artificial disruptive selection on the developmental periods using wild-type strains and evaluated the circadian rhythms of the selected lines. To investigate whether multiple genetic factors mediate the genetic correlation, we reanalyzed previously published genome-wide deficiency screening data based on DrosDel isogenic deficiency strains and evaluated the effect of 438 genomic deficiencies on the developmental periods. We then randomly selected 32 genomic deficiencies with significant effects on the developmental periods and tested their effects on circadian rhythms. As a result, we found a significant response to selection for longer developmental periods and their correlated effects on circadian rhythms of the selected lines. We also found that 18 genomic regions had significant effects on the developmental periods and circadian rhythms, indicating their potential for mediating the genetic correlation between the developmental period and circadian rhythm. The novel findings of our study might lead to a better understanding of how this correlation is regulated genetically in broader taxonomic groups.

Immature performance linked with exaggeration of a sexually selected trait in an armed beetle.

Exaggerated traits can be costly and are often trade-off against other characters, such as life-history traits. Thus, the evolution of an exaggerated trait is predicted to affect male life-history strategies. However, there has been very little experimental evidence of the impact of the evolution of sexually selected traits on life-history traits. This study investigated whether increased investment in exaggerated traits can generate evolutionary changes in the life-history strategy for armed males. Male flour beetles, Gnatocerus cornutus, have enlarged mandibles that are used in male-male competition, but females lack this character exaggeration completely. We subjected these weapons to 11 generations of bidirectional selection and found a correlated response in pupal survival but not in larval survival or adult longevity in the male. That is, selecting for male mandibles negatively impacted survival during the production of mandibles. There is no correlated response in the life-history traits of the female.

Genetic basis of incidence and period length of circadian rhythm for locomotor activity in populations of a seed beetle.

Circadian rhythms are ubiquitous in a wide variety of organisms, although their genetic variation has been analyzed in only a few species. We found genetic differences in the circadian rhythm of adult locomotor activity among strains of the adzuki bean beetle, Callosobruchus chinensis, which differed in origin and have been maintained in isolation. All beetles in some strains clearly had free-running rhythms in constant darkness whereas most beetles in other strains were arrhythmic. The period of free-running rhythm varied from approximately 19 to 23 h between the strains. F(1) males from reciprocal crosses among strains with different periods of circadian rhythms had circadian periods that were intermediate between their parental strains. Segregation of the circadian rhythm appeared in the F(2) generation. These findings are consistent with the hypothesis that variation in the period length of circadian rhythm is explained by a major autosomal gene with additive effects and no dominance. This hypothesis was supported by the joint scaling test for the free-running period in the F(1) and F(2) generations. We discuss possible causes for genetic variation in circadian rhythm in the C. chinensis strains in terms of random factors and selection.

The clock gene cryptochrome of Bactrocera cucurbitae (Diptera: Tephritidae) in strains with different mating times.

Differences in mating time between populations can give rise to premating reproductive isolation. Tephritid fruit flies exhibit large variation in mating time among intra- or inter-specific populations. We previously cloned the clock gene period from two strains of melon fly, Bactrocera cucurbitae; in one the individuals mate early during the day, whereas in the other the individuals mate later. These strains were originally established by divergent artificial selection for developmental time, 'short' and 'long', with early and late mating times, respectively. The deduced amino acid sequences of PERIOD proteins for these two strains were reported to be identical. Here we cloned another clock gene cryptochrome (cry) from the two strains, and found two stable amino acid substitutions in the strains. In addition, the allele frequency at the two polymorphic sites of cry gene correlated with the circadian locomotor period (tau) across strains, whereas the expression pattern of cry mRNA in the heads of flies taken from the short strain significantly differed from that from the long strain. These findings suggest that variation in the cry gene is related to differences in the circadian behaviour in the two strains, thus implying that the cry gene may have an important role in reproductive isolation.

No genetic correlation between the sexes in mating frequency in the bean beetle, Callosobruchus chinensis.

Female multiple mating, which is common in animals, may have evolved not in response to fitness advantages to females but as a genetic corollary to selection on males to mate frequently. This nonadaptive hypothesis assumes a genetic correlation between females and males in mating frequency, which has received a few empirical investigations. We tested this hypothesis by observing the correlated response in male mating frequency in the adzuki bean beetle, Callosobruchus chinensis to artificial selection on female propensity to remate. Compared to control females, females from lines selected for increased or decreased female propensity to remate had, respectively, higher or lower mating frequency measured by the number of mating within a given period. This indicates that female receptivity to remating is genetically correlated with female mating frequency, and thus the artificial selection for female propensity to remate influenced female mating frequency. In contrast, males from the selected lines that diverged in female mating frequency did not vary significantly in their mating frequency. These results indicate that there is no genetic correlation between the sexes in mating frequency in C. chinensis. This study shows that the reason why females in C. chinensis remate despite suffering fitness costs cannot be explained by indirect selection resulting from selection on males to mate multiple times.

[Surgical treatment for acute type A aortic dissection].

The purpose of this study was to assess the factors for clinical outcome of the surgical treatment of acute type A aortic dissection. From April 1996 to March 2006, 44 patients underwent emergency operation for acute type A dissection within 2 weeks from the onset. Resection of the intimal tear was performad with open distal anastomosis. The mean age was 63.4 (range 29-83) years, and 28 were female. As for their preoperative condition, 5 patients were in severe hemodynamic instability including cardiac arrest in 2, apnea in 1, and rupture in 4. Distal resection extended to ascending aorta in 24 patients (54.5%), hemiarch in 7 (15.9%), and total arch in 13 (29.5%). 30-day mortality was 4.5% and the incidence of stroke was 13.6%. Several methods were used including axillary artery cannulation and central repair with adventitial inversion technique. Patients with malperfusions caused by acute type A dissection should undergo immediate aortic reconstruction by adequate circulatory assisting methods.

Ca channel currents inhibited by serum from select patients with Guillain-Barré syndrome.

We performed an electrophysiological study demonstrating inhibition of spontaneous muscle action potentials within a coculture of rat muscle and spinal cord by exposure to serum, as well as purified IgG, from patients with the acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS). However, exposure to serum from two patients with the acute inflammatory demyelinating polyneuropathy (AIDP) form of GBS had no effect. Using a whole-cell recording technique, we then investigated the effects of serum and purified IgG from patients with GBS on voltage-dependent calcium channel (VDCC) currents in nerve growth factor-differentiated PC12 cells. Serum from patients with GBS (AMAN) inhibited VDCC currents in PC12 cells, which was fully reversible by washing with the bath solution. Similarly, purified IgG from the serum of two patients with GBS (AMAN) also inhibited VDCC currents in PC12 cells. In contrast, sera from patients with AIDP and healthy volunteers did not affect VDCC currents in PC12 cells. These results suggest that muscle weakness in some patients with GBS might be induced by inhibition of Ca2+ channel currents within motor nerve terminals.

[Overlapping ventriculoplasty for ischemic cardiomyopathy].

We have previously reported overlapping cardiac volume reduction operation (OLCVR) for dilated cardiomyopathy. Because of the acceptable clinical outcome and especially the excellent ellipsoidal shape of the left ventricle (LV) after surgery, we extended this indication for ischemic cardiomyopathy (ICM) with dilated LV. In such cases we combined OLCVR with mitral annuloplasty and papillary muscles approximation (PMA), called integrated overlapping ventriculoplasty (IOLVP). From March 2003 to July 2004, we performed IOLVP with coronary artery bypass grafting (CABG) for 8 patients who were diagnosed ICM. There is no operative mortality. Pre- and postoperative hemodynamics data are follows: LV ejection fraction (LVEF) improved from 22.4 +/- 11.9 to 33.4 +/- 10.5%, LV end-diastolic volume index (LVEDVI) decreased from 155.5 +/- 26.5 to 93.7 +/- 13.5 ml/m2 and LV end-diastolic diameter (LVDd) diminished from 66.0 +/- 8.9 to 60.5 +/- 8.4mm. Mitral regurgitation changed from 2.6 +/- 0.8 to 0.1 +/- 0.2 degree. New York Heart Association (NYHA) functional class improved from 3.3 +/- 0.5 to 1.3 +/- 0.5. LV shape became ellipsoidal without akinesis lesion. IOLVP is considered as a good option for ICM with dilated left ventricle.

[Primary pericardial malignant mesothelioma with incomplete endocardial cushion defect; report of a case].

Primary pericardial malignant mesothelioma is rare tumor and its prognosis is quite poor due to its late presentation and difficulty of complete resection. We describe a rare case of primary pericardial malignant mesothelioma in a 46-year-old female with incomplete endocardial cushion defect (ECD). Incidentally, we found 2 masses in the pericardial spaces after pericardiectomy. We have successfully removed these 2 masses en bloc and performed a total repair of incomplete ECD. Pathologically, these masses were a primary pericardial malignant mesothelioma. This patient is doing well 4 months after surgery without any evidence of recurrence despite reported poor prognosis of "primary pericardial malignant mesothelioma".

Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation.

BACKGROUND: CTLA4 immunoglobulin (CTLA4 Ig), which binds with high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting the costimulatory signal. CTLA4Ig has been used to achieve antigen-specific tolerance induction in cardiac allografts. On the other hand, we have shown that short-term administration of deoxyspergualin (DSG) and daily cyclosporine (CsA) induces long-term survival of cardiac xenotransplants. We hypothesized that the combination therapy of DSG and adenovirus-mediated CTLA4IgG might induce long-term, survival or tolerance in cardiac xenotransplantation. OBJECTIVES: Syrian hamster hearts were transplanted heterotopically into Lewis rats. We compared the survival time and immunopathology of the following five groups: (1) no treatment; (2) DSG (5 mg/kg per day intramuscularly [IM], days -1 to +7) alone; (3) CsA (15 mg/kg per day IM, day 0 to rejection) plus DSG; (4) AdexLacZ (LacZ-adenovirus 1 x 10(9) (PFU intravenously [IV], day -7) plus DSG; and (5) AdexCTLA4IgG (CTLA4IgG-adenovirus 1 x 10(9) PFU IV, day -7) plus DSG. RESULTS: The survival times were: (1) no treatment, 3.7 days; (2) DSG alone, 12.4 days; (3) CyA plus DSG, >100 days; (4) AdexLacZ plus DSG, 11.0 days; and (5) AdexCTLA4IgG plus DSG, 23.6 days. Adenovirus-mediated CTLA4IgG therapy with DSG prolonged survival time significantly compared with DSG alone or AdexLacZ plus DSG, but CTLA4IgG therapy was not as effective as CsA. Immunopathology showed the deposition of C3 and IgM on the endothelium in the AdexCTLA4IgG plus DSG group. CONCLUSIONS: We showed that the effectiveness of adenovirus-mediated CTLA4IgG gene therapy in cardiac xenotransplantation in less than that of CsA. Combination therapy with inhibition of the B7/CD28 constimulatory signal and DSG administration might not be sufficient for long-term survival or tolerance in cardiac xenotransplantation.

[Infected false aneurysm due to methicillin-resistant staphylococcus aureus after proximal aortic grafting].

A 70-year-old man developed meticillin-resistant staphylococcus aureus (MRSA) mediastinitis after prosthetic graft replacement of the ascending aorta. The sternal wound was reexplored and a single-stage procedure of irrigation, debridement, and omental transposition was performed. Ten months after the first operation, he suffered recurrence of pyrexia and the presence of false aneurysm originated from the distal suture line was diagnosed by the chest computed tomography (CT) scan. Re-replacement of the ascending aorta and proximal hemiarch with rifampicin soaked Gelseal was successfully performed. Hypothermic perfusion with circulatory arrest through peripheral cannulation and left ventricular venting via a left anterior thoracotomy was useful to obtain safe reentry in the operation of retrosternal false aneurysm.

A case of intraoperative acute aortic dissection caused by cannulation into an axillary artery.

Severe atherosclerotic disease of the ascending aorta is one of the risk factors of dissection of the ascending aorta and cerebral embolism during cardiac operations with cardiopulmonary bypass. Aortic dissection is rare, but once it happens, the mortality rate is high. For the patient with severely atherosclerotic or strongly calcified aorta, we should avoid cannulation into the aorta or clamping of it. In this case, we experienced aortic dissection although we chose the arterial cannulations into the axillary arteries because of the strong calcification of the ascending aorta and the abdominal aorta. The dissection was caused by the cannulation into the axillary artery. Transesophageal echocardiography (TEE) showed the dissection during the operation and the ascending aorta was replaced soon. Early diagnosis and treatment saved the patient. This case showed the following points: 1) cannulation into an axillary artery is not always safe; 2) TEE is very useful to detect the complicated dissection during operation; 3) replacement of the ascending aorta alone can be one of the choices for the treatment of aortic dissection caused by cannulation into an axillary artery.

Immunohistochemical detection of verotoxin receptors in nervous system.

Verotoxin receptor is a globotriaosylceramide (Gb3) present on vascular endothelial cells, in which the toxin causes hemolytic uremic syndrome. We established a sensitive method of immunohistochemical staining in serial sections using monoclonal antibodies (mAbs) against verotoxin and glycolipids that includes Gb3 and galactosylGb3 (GalGb3). With it, we showed co-localization of the verotoxin receptor and Gb3 in dorsal root ganglia (DRG) of humans, rabbits, rats and mice. We also used a very simple method to identify the presence of lipofuscin-like autofluorescence which complicates fluorescence microscopy observation of aged human nervous tissues.

Stereoselective effect of (R)- and (S)-1-methyl-1,2,3,4-tetrahydroisoquinolines on a mouse model of Parkinson's disease.

We carried out behavioral, pathological, and biochemical studies in order to determine whether the stereo-structure of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) affects the onset of Parkinson's disease-like symptoms, which are induced by 1,2,3,4-tetrahydroisoquinoline (TIQ) in mice. Pretreatment with (R)-1-MeTIQ or its racemate (RS)-1-MeTIQ prevented the TIQ-induced bradykinesia. Pretreatment with a combination of L-DOPA and carbidopa significantly prevented subsequent TIQ-induced bradykinesia. Furthermore, the pathological study demonstrated that either (R)-1-MeTIQ or its racemate protected against TIQ-induced loss of tyrosine hydroxylase-positive cells of the substantia nigra pars compacta. (R)-1-MeTIQ and its racemate also prevented the TIQ-induced reduction in the levels of dopamine and its metabolites in the striatum. Serotonin and its metabolite were not affected by repeated administration of (RS)-1-MeTIQ or its derivatives. On the other hand, (S)-1-MeTIQ induced moderate but significant bradykinesia, whereas (R)-1-MeTIQ did not induce this behavioral abnormality at all. In addition, (S)-enantiomer prevented the onset of TIQ-induced bradykinesia, though to a lesser extent than did either (R)-enantiomer or its racemate. However, (S)-enantiomer did not prevent the loss of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta. We concluded that (R)-1-MeTIQ, and not (S)-enantiomer, plays a crucial role in protection against TIQ-induced parkinsonism, a fact which suggests that enantiomeric biochemical events such as 1-MeTIQ biosynthesis may participate in the pathogenesis of Parkinson's disease.

[Grafting and concomitant left ventricular myotomy-myectomy in a patient with coronary artery disease associated with hypertrophic obstructive cardiomyopathy].

A 44-year-old man complained of chest oppression and systolic murmur. Echocardiography showed subaortic stenosis with outflow gradient of 135 mmHg, interventricular septal thickness of 21 mm, left ventricular posterior wall thickness of 11 mm, and 2/4 mitral regurgitation. Selective coronary angiography demonstrated 75% stenosis in left anterior desending branch. Coronary artery revasculization comcomitant with left ventricular myotomy-myectomy was performed. He had a good recovery from operation, and was discharged in 19th days in NYHA class I. Echocardiography one month after operation showed mild outflow pressure gradient, light systolic anterior motion of mitral anterior leaflet, and 1/4 mitral regurgitation. Careful operative management, including myocardial protection, avoiding perporation of ventricular septum, and postoperative medical care are mandatory to this group of patients. The use of cathecholamine and Ca-blocker will be attentioned because of the increasing the left ventricular pressure gradient.

Recent studies on the roles of antiglycosphingolipids in the pathogenesis of neurological disorders.

Evidence is mounting to suggest a causal role of humoral immunity arising from antiglycosphingolipid (GSL) antibodies in a variety of neurological disorders. These disorders include the demyelinating and axonal forms of Guillain-Barre syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and IgM paraproteinemia. Many claims have been made regarding other neurological disorders, which should be carefully scrutinized for their validity, based on several criteria proposed in this review. These criteria include 1) characterization of the causative antigens and immunoglobulins, 2) correlation of the pathological lesions and clinical manifestation of the antigens, 3) establishment of animal models using pure GSLs as the antigens, 4) immunopathogenic mechanisms of the neurodenerative process, 5) mechanisms for the malfunctioning of blood-nerve barrier and the ensuing leakage of circulating antibodies into peripheral nerve parenchyma, and 6) the roles of anti-GSL antibodies that may cause humorally mediated nerve dysfunction and injury as well as interference with ion channel function at the node of Ranvier, where carbohydrate epitopes are located. Finally, the origin of the anti-GSL antibodies is discussed in light of the recent circumstantial evidence pointing to a molecular mimicry mechanism with infectious agents. With a better understanding of the immunopathogenic mechanisms, it will then be possible to devise rational and effective diagnostic and therapeutic strategies for the treatment of these neurological disorders.

GM2 ganglioside regulates the function of ciliary neurotrophic factor receptor in murine immortalized motor neuron-like cells (NSC-34).

We previously reported that ciliary neurotrophic factor (CNTF) increased the serum-free cell survival of immortalized motor neuron-like cells (NSC-34), and addition of the exogenous ganglioside GalNAc beta4(Neu5Ac alpha3)Gal beta4GlcCer (GM2) facilitated cell survival together with CNTF. Moreover beta 1,4 N-acetylgalactosaminyltransferase (GM2 synthase) activity increased in NSC-34 cells cultured with CNTF. We now have examined whether CNTF-induced cell survival is associated with the collaboration between GM2 and the CNTF receptor (CNTF-R). Despite the presence of CNTF (50 ng/ml), anti-CNTF-R antibody caused cell death and prevented the up-regulation of GM2 synthase expression. The addition of GM2 (1 to 20 microM) abrogated the anti-CNTF-R antibody effect which shortened cell survival and blocked GM2 synthase activation. Use of [125I]CNTF showed the specificity of CNTF binding in NSC-34 cells in situ. GM2 produced a 5-fold increase in the CNTF binding affinity per cell but did not change the binding site number. The study by metabolic labeling with [1-(14)C]N-acetyl-D-galactosamine ([14C]GalNAc) showed that biosynthesized GM2 was involved in the immunoprecipitation of CNTF-R. These findings indicate that up-regulated GM2 synthesis induces functional conversion of CNTF-R to the activated state, in which it has affinity for CNTF. We conclude that GM2 is a bio-regulating molecule of CNTF-R in motor neurons.

Biochemical and pathological study of endogenous 1-benzyl-1,2,3,4-tetrahydroisoquinoline-induced parkinsonism in the mouse.

We administered 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ; 80 mg/kg, i.p.), an endogenous neurotoxin known to cause bradykinesia, the Parkinson's disease-like symptom, in order to obtain biochemical and pathological evidence of behavioral abnormalities. Immunohistochemical analysis demonstrated that 1-BnTIQ did not decrease the number of tyrosine hydroxylase-positive cells in the substantia nigra. Biochemical analysis demonstrated significantly increased striatal dopamine (DA) content, while DA metabolites in the striatum remained at control levels. We concluded that the 1-BnTIQ-induced bradykinesia has a different mechanism of action than that underlying the MPTP-induced depletion of striatal DA neurons.