Actinomyces denticolens colonisation identified in equine tonsillar crypts.

Recently, submandibular abscesses associated with Actinomyces denticolens have been reported in horses. The actinomycotic clumps have been observed in the tonsillar crypts. The aim of this study was to demonstrate colonisation of A denticolens in equine tonsils. Twelve equine tonsils obtained from a slaughterhouse were divided into two parts for histopathological examination and for isolation of A denticolens. When actinomycotic clumps were found in these tonsillar crypts, immunohistochemistry using hyperimmune serum against A denticolens (DMS 20671) was performed on the serial sections. To determine whether Actinomyces-like bacteria isolated using immunoantigenic separation technique were A denticolens, the isolates were analysed for the 16S rRNA gene sequence. Actinomycotic clumps were found in the tonsillar crypts of 11 (91.7 per cent) horses. The clumps were of the saprophytic type accompanied with the feedstuffs, but a few clumps were surrounded by inflammatory cells. A denticolens antigens were immunodetected not only in the clumps of 11 (100 per cent) tonsils, but also in the tonsillar parenchyma. Six isolates obtained from four tonsils showed 99.7-99.9 per cent similarity to A denticolens in the 16S rRNA gene sequence. In horses, the colonisation sites of A denticolens are the tonsils, thus the authors suggest that the tonsils provide the intrinsic infection site for A denticolens.

Relationship and factor structure in multisystem neurodegeneration in Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is a multisystem neurodegenerative disease. We aimed to identify the relationship and factor structure among its different features. MATERIALS & METHODS: Motor, olfactory and cognitive function, and cardiac sympathetic denervation were evaluated in 125 patients with PD using the Unified Parkinson's Disease Rating Scale (UPDRS) part III score, odor stick identification test for the Japanese (OSIT-J), Mini-Mental State Examination (MMSE), and [(123) I] meta-iodobenzylguanidine (MIBG) cardiac scintigraphy (heart-to-mediastinum (H/M) ratio). Pearson's correlation and multiple regression analysis were used to evaluate the association among the four measures with age, gender, and disease duration as the covariates. Exploratory factor analysis was used to identify the underlying factor structure among the measures and covariates. RESULTS: Pearson's correlation and multiple regression analysis showed correlations between OSIT-J score and MIBG H/M ratio, OSIT-J and MMSE scores, UPDRS part III score and MIBG H/M ratio, UPDRS part III score and disease duration, and MMSE score and age. Factor analysis identified three factors: (i) age and MMSE score; (ii) MIBG H/M ratio and OSIT-J score; and (iii) UPDRS part III score and disease duration. CONCLUSIONS: Our results suggest that aging, PD-related pathogenesis, and disease duration underlie the multisystem neurodegeneration present in PD. Moreover, age and disease duration are the major risk factors for cognitive impairment and motor symptoms, respectively. Olfactory impairment and cardiac sympathetic denervation are strongly associated in PD.

Heuristic optimization in penumbral image for high resolution reconstructed image.

Penumbral imaging is a technique which uses the fact that spatial information can be recovered from the shadow or penumbra that an unknown source casts through a simple large circular aperture. The size of the penumbral image on the detector can be mathematically determined as its aperture size, object size, and magnification. Conventional reconstruction methods are very sensitive to noise. On the other hand, the heuristic reconstruction method is very tolerant of noise. However, the aperture size influences the accuracy and resolution of the reconstructed image. In this article, we propose the optimization of the aperture size for the neutron penumbral imaging.

21Na(p,gamma)22Mg reaction and oxygen-neon novae.

The 21Na(p,gamma)22Mg reaction is expected to play an important role in the nucleosynthesis of 22Na in oxygen-neon novae. The decay of 22Na leads to the emission of a characteristic 1.275 MeV gamma-ray line. This report provides the first direct measurement of the rate of this reaction using a radioactive 21Na beam, and discusses its astrophysical implications. The energy of the important state was measured to be E(c.m.)=205.7+/-0.5 keV with a resonance strength omegagamma=1.03+/-0.16(stat)+/-0.14(sys) meV.

Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in humans.

1. TAS-103, a novel condensed quinoline derivative, has been developed as an anticancer drug targeting topoisomerases I and II. 2. The purpose of the present study was to characterize the metabolism and urinary excretion of TAS-103 after the intravenous infusion of a single dose to patients in Phase I clinical trials. 3. Five metabolites were detected using high-performance liquid chromatography (HPLC) photodiode array and a precursor scan by liquid chromatography mass spectrometry mass spectrometry (LC/MS/MS). 4. Structures of the five metabolites were determined using the results of enzymatic hydrolysis and the analysis of production mass spectra obtained by LC/MS/MS, and by comparing HPLC retention times and UV, mass and production mass spectra of authentic standards. 5. The metabolites were identified as demethyl-TAS-103 glucuronide (DM-TAS-103-G), TAS-103 glucuronide (TAS-103-G), TAS-103 glucuronide N-oxide (NO-TAS-103-G), demethyl-TAS-103 (DM-TAS-103) and TAS-103 N-oxide (NO-TAS-103). 6. The mean total amount of TAS-103 and TAS-103-G in urine was only 6.03% of the dose, suggesting that urine is not the main elimination route. TAS-103 was extensively metabolized, and a small percentage of the parent drug (0.41%) was found in urine.

Elastic alpha-12C scattering and the 12C(alpha,gamma)16O E2 S factor.

Angular distributions of 12C(alpha,alpha)12C have been measured for E(alpha) = 2.6-8.2 MeV, at angles from 24 to 166, yielding 12 864 data points. R-matrix analysis of the ratios of elastic scattering yields a reduced width amplitude of gamma12 = 0.47 +/- 0.06 MeV(1/2) for the Ex = 6.917 MeV (2+) state in 16O(a = 5.5 fm). The dependence of the chi2 surface on the interaction radius a has been investigated and a deep minimum is found at a = 5.42(+0.16)(-0.27) fm. Using this value of gamma12, radiative alpha capture and 16N beta-delayed alpha-decay data, the S factor is calculated at E(c.m.) = 300 keV to be S(E2)(300) = 53(+13)(-18) keV b for destructive interference between the subthreshold resonance tail and the ground state E2 direct capture.

First-pass of GTS-21 on canine gut wall and liver determined by portal-systemic concentration difference.

To clarify the cause of the canine individual variability of plasma concentration after oral administration of GTS-21 [(E)-3-(2,4-dimethoxybenzylidene)-3,4,5,6-tetra-hydro-2,3'-bipyridine dihydrochloride], we evaluated the absorption ratio (F(A)), intestinal availability (F(G)), and hepatic availability (F(H)). The bioavailability (F) was evaluated from the ratio of the area under the plasma concentration versus time curves after oral and intravenous administration. Three isoflurane anaesthetised dogs were fitted with an electromagnetic flow probe attached to the portal vein and cannulated through the portal and the femoral veins. After intraduodenal administration of GTS-21, both plasma concentrations were determined simultaneously. F(A) x F(G) was calculated from the portal-systemic concentration difference taking into consideration the blood-plasma partition ratio. F(A) was calculated from the residual drug contents of the small intestine. F(H) was calculated by dividing F by F(A) x F(G). The F values were 0.072, 0.021, and 0.037, indicating an individual variability of ca. threefold. The F(A) values were close to 1, and the F(G) values ranged from 0.449 to 0.461. Accordingly, the F(H) values were estimated at 0.170, 0.047, and 0.083. GTS-21 was completely absorbed but lost by first-pass effects of passage through the gut wall and liver. The first-pass effect of liver is larger than that of the gut wall, and dominates the individual variability in plasma concentration.

Reconfiguration of task-set: is it easier to switch to the weaker task?

Switching between two tasks afforded by the same stimuli results in slower reactions and more errors on the first stimulus after the task changes. This "switch cost" is reduced, but not usually eliminated, by the opportunity to prepare for a task switch. While there is agreement that this preparation effect indexes a control process performed before the stimulus, the "residual" cost has been attributed to several sources: to a control process essential for task-set reconfiguration that can be carried out only after the stimulus onset, to probabilistic failure to engage in preparation prior to the stimulus, and to two kinds of priming from previous trials: positive priming of the now-irrelevant task set and inhibition of the now-relevant task-set. The main evidence for the carry-over of inhibition is the observation that it is easier to switch from the stronger to the weaker of a pair of tasks afforded by the stimulus than vice versa. We survey available data on interactions between task switching and three manipulations of relative task strength: pre-experimental experience, stimulus-response compatibility, and intra-experimental practice. We conclude that it is far from universally true that it is easier to switch to the weaker task. Either inhibition of the stronger task-set is a strategy used only in the special case of extreme inequality in strength, or its consequences for later performance may be masked by slower post-stimulus control operations for more complex tasks. Inhibitory priming may also be stimulus specific.

The effect of repeat administration of GTS-21 on mixed-function oxidase activities in rat.

The effect of repeat administration of GTS-21 on hepatic microsomal enzymes was determined in rats administered the drug at levels of 3, 60 and 300 mg/kg/day for 7 days. Liver weight and cytochrome P450 (CYP) contents were not changed. Cytochrome b5 contents were increased at the mid and high doses of GTS-21, as the contents increased with increasing dose, but were unchanged at the low dose. Five selective activities of CYP isoforms, acetanilide hydroxylase (CYP1A2), tolbutamide hydroxylase (CYP2C6), dextromethorphan O-demethylase (CYP2D1), p-nitrophenol hydroxylase (CYP2E1) and erythromycin N-demethylase (CYP3A) were examined. Enzyme activities were changed only at the highest dose; the activity of CYP1A2 was increased by 71% and the activities of CYP2C6 and CYP2D1 were decreased by 37 and 19%, respectively. At low and mid doses of GTS-21, all activities were unchanged. These data indicate that GTS-21 is not a strong modulator of the mixed-function oxidase system.

Experimental actinomycosis caused by Actinomyces-like bacteria in mice and a sow.

The present experiment was performed to test the pathogenicity of Actinomyces-like bacteria in experimental animals and swine. Two rough (R) strains of Actinomyces-like bacteria isolated from a site of arthritis and from the tonsil in pigs were used as inocula. To investigate their susceptibility to Actinomyces-like bacteria, BALB/c, SS and ddY mice and guinea-pigs were inoculated intraperitoneally with the strains of Actinomyces-like bacteria. The ddY mice were used for the long-term observation of Actinomyces-like bacteria lesions and the mammary tissue of a sow was inoculated with Actinomyces-like bacteria isolated from swine tonsil. Macroscopic observation revealed many abscesses on the surfaces of the abdominal and/or thoracic organs in the mice, but not on those of the guinea-pigs. The sow developed firm nodules at the inoculation site in the mammary glands. Histopathologically, the lesions in the mice were characterized as actinomycotic abscesses in the early stage and as pus-forming granuloma (PFG) in the advanced stage; the lesions were accompanied by crystalloid particles. Actinomyces-like bacteria induced granulomatous mastitis in the sow, and the lesion was characterized as PFG. The characteristic actinomycotic lesions in swine mammary glands were reproduced by experimental infection.

Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease.

1. GTS-21, a novel drug for Alzheimer's disease, is currently under clinical development. In the current study, the metabolism and disposition of GTS-21 have been evaluated in rat and dog after single oral and intravenous administration. 2. Following oral administration of [14C]GTS-21 to rat, radioactivity was primarily excreted in the faeces (67%) via the bile with possible enterohepatic circulation. Urinary excretion of radioactivity in rat and dog was 20 and 19% respectively. 3. GTS-21 was rapidly and extensively absorbed after oral administration and rapidly cleared from plasma. The maximum concentration ratio of GTS-21 to total radioactivity in plasma was low, indicating first-pass or pre-systemic biotransformation. 4. In rat, GTS-21 showed linear pharmacokinetics over doses ranging from 1 to 10 mg/kg with an absolute bioavailability of 23%. In dog, the absolute bioavailability was 27% at an oral dose of 3 mg/kg. 5. GTS-21 was O-demethylated to yield compounds that were then subject to glucuronidation. Three of the metabolites in rat urine were isolated and characterized as 4-OH-GTS-21, 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. The major urinary metabolites were 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. 6. In vitro chemical inhibition of cytochrome P450 in human liver microsomes indicated that CYPIA2 and CYP2E1 were the isoforms primarily responsible for the O-demethylation of GTS-21, with some contribution from CYP3A.

Effects of response type on coordinated responses during arm movement.

This paper reports some experimental results on the coordination of finger and vocal responses with passing through a target position in multijoint arm movement. In Experiment 1, we found that the difference in the timing of finger and vocal responses cannot be attributed entirely to efferent or representational effects. Instead, it appears to reflect the extent to which information about the internal stimuli generated by the arm movement are available to the centers controlling these different responses. That is, it is a compatibility effect. In Experiment 2, the case in which a finger response is made on the same side of the body as the moving arm was compared with the case in which it is made with the contralateral hand, which remains static. The interaction effect observed suggests that the pathways subserving coordinated responses are informationally encapsulated, so that information about arm movement is not shared between the neural centers controlling different coordinated responses.