Clinical features and outcomes of Merkel cell carcinoma in 20 cats.

The biological behaviour and prognostic factors of Merkel cell carcinoma (MCC) in 20 cats were studied. The tumours were surgically removed and histopathologically examined. The animals were 8 to 20 years old (median age: 14 years), and the tumours were predominantly located in the neck and head. Follow-up data were available in 17 cases, and 12 cats died within a year of surgery. The overall median survival time after resection was 243 days (range 16-360 days). Recurrence occurred in 11 cases, although 6 of them (55%) were found to be margin-negative. Possible metastasis occurred after the surgery in 10 cases, although 6 of them (60%) were found to be margin-negative. The histopathological features of MCC included tumour necrosis in 16 cases (80%), vascular invasion in 6 cases (38%) and high mitotic counts (median: 28.5 per high-power field). Irregular acanthosis was noted adjacent to the tumours in 9 cases (60%). Immunohistochemically, the tumour cells were positive for cytokeratin (CK) 20 and p63 in all cases, synaptophysin in 19 (95%) cases, and CK18 in 16 cases (80%). The study shows that feline MCC is associated with a poor prognosis and exhibited a strong tendency towards local recurrence, regional lymph node metastasis and distant spread.

Changes in resting-state brain networks after cognitive-behavioral therapy for chronic pain.

BACKGROUND: Cognitive-behavioral therapy (CBT) is thought to be useful for chronic pain, with the pathology of the latter being closely associated with cognitive-emotional components. However, there are few resting-state functional magnetic resonance imaging (R-fMRI) studies. We used the independent component analysis method to examine neural changes after CBT and to assess whether brain regions predict treatment response. METHODS: We performed R-fMRI on a group of 29 chronic pain (somatoform pain disorder) patients and 30 age-matched healthy controls (T1). Patients were enrolled in a weekly 12-session group CBT (T2). We assessed selected regions of interest that exhibited differences in intrinsic connectivity network (ICN) connectivity strength between the patients and controls at T1, and compared T1 and T2. We also examined the correlations between treatment effects and rs-fMRI data. RESULTS: Abnormal ICN connectivity of the orbitofrontal cortex (OFC) and inferior parietal lobule within the dorsal attention network (DAN) and of the paracentral lobule within the sensorimotor network in patients with chronic pain normalized after CBT. Higher ICN connectivity strength in the OFC indicated greater improvements in pain intensity. Furthermore, ICN connectivity strength in the dorsal posterior cingulate cortex (PCC) within the DAN at T1 was negatively correlated with CBT-related clinical improvements. CONCLUSIONS: We conclude that the OFC is crucial for CBT-related improvement of pain intensity, and that the dorsal PCC activation at pretreatment also plays an important role in improvement of clinical symptoms via CBT.

Clinical porcine islet xenotransplantation under comprehensive regulation.

BACKGROUND: Xenotransplantation with porcine islets is a promising approach to overcome the shortage of human donors. This is the first report of phase 1/2a xenotransplantation study of encapsulated neonatal porcine islets under the current framework of regulations for xenotransplantation in New Zealand. METHODS: Newborn piglets were anesthetized and bled, and the pancreata were removed with the use of sterile technique and processed. Encapsulated neonatal porcine islets were implanted with the use of laparoscopy into the peritoneal cavity of 14 patients with unstable type 1 diabetes without any immunosuppressive drugs. The patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4; group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents per kg body weight. Outcome was determined from adverse event reports, HbA1c, total daily insulin dose, and frequency of unaware hypoglycemic events. To assess graft function, transplant estimated function (TEF) scores were calculated. Sufficient or marginal numbers of encapsulated neonatal porcine islets were transplanted into streptozotocin-induced diabetic B6 mice as an in vivo functional assay. RESULTS: There were 4 serious adverse events, of which 3 were considered to be possibly related to the procedure. Tests for porcine endogenous retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia events were reduced after transplantation in all groups. Four of 14 patients attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17, 0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study demonstrated that a sufficient number of the transplanted group reversed diabetes with positive porcine C-peptide. CONCLUSIONS: Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo assessment data demonstrated certain graft function.

Fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes rescue thrombocytopenic rabbits from non-compressible liver hemorrhage.

BACKGROUND: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. OBJECTIVE: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. METHODS: Thrombocytopenia (platelets < 50 000 µL(-1)) was induced in rabbits by repeated blood withdrawal (100 mL kg(-1) in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. RESULTS: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24 h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25 000 platelets µL(-1)), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. CONCLUSIONS: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

Skin formation and bubble growth during drying process of polymer solution.

When a polymer solution with volatile solvent is dried, skins are often formed at the surface of the solution. It has been observed that after the skin is formed, bubbles often appear in the solution. We conducted experiments to clarify the relation between the skin formation and the bubble formation. We measured the time dependence of the thickness of the skin layer, the size of the bubbles, and the pressure in the solution. From our experiments, we concluded that i) the gas in the bubble is a mixture of solvent vapor and air dissolved in the solution, ii) the bubble nucleation is assisted by the pressure decrease in the solution covered by the skin layer, and iii) the growth of the bubbles is diffusion limited, mainly limited by the diffusion of air molecules dissolved in the solution.

Sporadic isolations of a multi-drug resistant Pseudomonas aeruginosa clone during a 14-month epidemic in a general hospital in Hiroshima.

BACKGROUND: During 2005-2007, we experienced sporadic isolations of multidrug-resistant (MDRP) Pseudomonas aeruginosa from wards in a general hospital in Hiroshima. The objective of this study was to analyze epidemiology relationships and the mode of spread of the strains. METHODS: Clonality was assessed using pulsed-field gel electrophoresis (PFGE) and serotyping. MICs were determined using the microdilution broth method. Investigations of the affected patients' movements and environmental sampling from the affected wards were conducted. RESULTS: An abrupt increase in MDRP isolations began at the end of 2005 and ended in February 2007. A total of 25 MDRP strains were sporadically isolated from nine wards. Fourteen strains were genotypically and serologically identical. Analysis of the patients' movements identified that six of the 14 MDRP-positive patients became positive for MDRP when they were in the intensive care unit (ICU), and two became positive after the patients moved from the ICU to another nursing unit. Four MDRP strains were isolated from patients who did not stay in the ICU and were in ward E6, which had the second highest number of isolations. In July 2006, environmental sampling of the hospital identified a toilet brush in ward E6 that was contaminated with MDRP that was genotypically and serologically identical to the clinical isolates. CONCLUSIONS: Our study suggests that the sporadic increase in MDRP isolates during 2005-2007 in the general hospital in Hiroshima was due to an epidemic of an MDRP clone. Continuity and spread of infection was probably due to cross infection and contamination in the hospital with the MDRP strain.

Altered immunoglobulin A and M levels associated with changes in BAFF and APRIL after administration of intravenous immunoglobulin to treat Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of unknown etiology. Immunoregulatory abnormalities have been thought to contribute to its pathogenesis. Although treatment with intravenous immunoglobulin (IVIG) effectively prevents significant cardiac morbidity, the mechanism by which IVIG produces an effect in KD has yet to be fully elucidated. OBJECTIVE: To investigate the effects of IVIG on the immune system of patients with KD. PATIENTS AND METHODS: Eleven patients with KD (mean [SD] age, 2.2 [1.5] years) were enrolled in this prospective study and treated with high-dose IVIG therapy (2 g/kg in 1 or 2 infusions) during the acute phase of the disease. We examined immunological changes, with special reference to Ig levels and 2 previously unassessed cytokines: B cell-activating factor belonging to the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL). RESULTS: Clinical symptoms disappeared quickly in all cases, with no coronary artery abnormalities. IgA and IgM levels responded more rapidly than previously reported and reached a peak between the 3rd and 10th day after the start of IVIG treatment. The mean (SD) BAFF level was high before IVIG treatment (3234 [1904] pg/mL) and decreased significantly (1085 [257] pg/mL) after IVIG treatment, whereas the mean (SD) APRIL level before IVIG treatment (18.0 [10.0] ng/mL) rose significantly (120.6 [41.2] ng/mL). A significant inverse correlation between BAFF and APRIL was observed in patients with KD. CONCLUSIONS: These results suggest that IVIG may affect the pathogenesis of KD through alteration of BAFF/APRIL.

Inter-comparison of absorbed dose rates for non-human biota.

A number of approaches have been proposed to estimate the exposure of non-human biota to ionizing radiation. This paper reports an inter-comparison of the unweighted absorbed dose rates for the whole organism (compared as dose conversion coefficients, or DCCs) for both internal and external exposure, estimated by 11 of these approaches for selected organisms from the Reference Animals and Plants geometries as proposed by the International Commission on Radiological Protection. Inter-comparison results indicate that DCCs for internal exposure compare well between the different approaches, whereas variation is greater for external exposure DCCs. Where variation among internal DCCs is greatest, it is generally due to different daughter products being included in the DCC of the parent. In the case of external exposures, particularly to low-energy beta-emitters, variations are most likely to be due to different media densities being assumed. On a radionuclide-by-radionuclide basis, the different approaches tend to compare least favourably for (3)H, (14)C and the alpha-emitters. This is consistent with models with different source/target geometry assumptions showing maximum variability in output for the types of radiation having the lowest range across matter. The intercomparison demonstrated that all participating approaches to biota dose calculation are reasonably comparable, despite a range of different assumptions being made.

Modeling on debonding dynamics of pressure-sensitive adhesives.

We propose a simple mechanical model describing viscoelasticity and cavitation during the debonding process in pressure-sensitive adhesives (PSA). Our calculation qualitatively reproduces typical stress-strain curves in the probe-tack test, such as the steep stress maxima and the following plateau region. It is shown that in the thin-film geometry the stress-strain curve is essentially determined by the cavities created by the large negative pressure. Effects of pre-existent air bubbles due to surface roughness are also discussed.

Debonding dynamics of pressure-sensitive adhesives: 3D block model.

We develop a 3-dimensional mechanical model which describes cavity expansions in a viscoelastic solid medium during the debonding phase of the probe-tack test. The stress-strain curves are in good agreement with experiments for the typical pressure-sensitive adhesives. We also show that the separation speed dependence can be explained by viscous dissipations due to large strain rates around the cavities.

The role of endoscopic endonasal approach to pituitary tumours: HUKM experience.

Surgery for pituitary tumours at our institution was performed by rhinosurgical route by combined procedure by otolaryngologist and neurosurgeons. A retrospective review of case records of patients who had endonasal endoscopic transphenoidal approach for pituitary tumours from September 1998 to December 2004 was performed. A total of 81 trans-sphenoidal surgeries were performed during this study period. Only 68 case records with adequate information were available for review, 56 patients were included in the study and 12 were excluded. There were 24 males (42%) and 32 females (58%). The ethnic distribution, were 29 Malays, 24 Chinese, 2 Indian and 1 others. The age ranged from 16 years to 76 years, with a mean of 46 years. The majority of our patients presented with visual symptoms (38), headache (28), menstrual cycle disturbance or impotence (14) and acromegalic features (16). Forty patients had macroadenoma (71%) and 16 had microadenomas (29%). Thirty-six patients out of 40 macro-adenomas had suprasellar extensions (90%). Only eleven patients had lumbar drain inserted prior to commencement of the surgery and the majority of these were macroadenomas. The common complications encountered were diabetes insipidus (4), cerebrospinal fluid leak (2), meningitis (3), epistaxis (2), septal perforation (2), intercavernous sinus haemorrhage (3) and anterior pituitary insufficiency (2). Our study reveals that endonasal trans-sphenoidal approach is a safe and effective method of management of pituitary adenomas.

Structure and property of self-assemble valinyl bolaform amides having different chirality.

Bolaform amides were designed from N,N'-bis(carboethoxy-L-valinyl)-diaminoethane (1) by linking t-butyloxycarbonyl-valine through ethylenediamine (EDA) to enable spectroscopic and X-ray diffraction analyses. N,N'-Bis(Boc-L-valinyl)-diaminoethane (2) and N,N'-bis(Boc-D-valinyl)-diaminoethane (3) were composed of L-Val and D-Val, respectively. N-(Boc-L-valinyl)-N'-(Boc-D-valinyl)-diaminoethane (4) was composed of both L-Val and D-Val, and was achiral (meso-peptide). Peptide 5 was a 1:1 mixture of 2 and 3, and was also achiral (racemate). These peptides mediated gelation of corn oil at a concentration of approximately 1%. Within crystals, the peptides formed beta-sheet ribbons, but differences were observed in hydrogen-bonding patterns and side-chain arrangements. These differences were also deduced from temperature dependence of amide protons. Force-field calculations based on the crystal structures indicated that association of beta-sheet ribbons had energy benefits, and it was assumed that molecular aggregation progressed spontaneously. These structural studies indicated the chirality of amino acids affected for the properties of bolaform amides.

Recurrent isolation of an uncommon yeast, Candida pararugosa, from a sarcoma patient.

A yeast was repeatedly isolated from the saliva of a sarcoma patient. A relatively uncommon species, Candida maris, was identified based on the API 20C profile. The yeast species most frequently obtained from the patient's mother and from clinic staff was Candida albicans. A comparison of the yeast obtained from the patient with the type strain of C. maris strongly suggested that the former was not representative of C. maris. Analysis of partial ribosomal DNA sequences of the patient strain and from the type strain of C. maris showed that the two are phylogenetically not closely related. The patient strain was very close to Candida pararugosa, a relatively uncommon asporogenous yeast. DNA reassociation studies among C. pararugosa and patient isolates showed that they were conspecific. We could not determine the source of the yeast infection. This case will alert hospital staff to be aware of the possibility of unexpected environmental microorganisms as causes of infections, colonizations and persistent environmental contamination events in immunocompromised patients.

A case study of radon-222 transport from continental North-East Asia to the Japanese islands in winter by numerical analysis.

A case study of the regional transport ( approximately 3000 km) of radon-222 ((222)Rn) from continental North-East Asia to the Japanese islands was performed by numerical analysis using five separate source areas (South, Middle and North China, Russia and Korea), while a seasonal northwest wind blew over the Japan Sea. The results for three periods (Term I: 16-18, Term II: 22-25 and Term III: 27-28 in December 1990) were compared with concentrations measured at the Kanazawa site (near the coast of the Japan Sea facing the seasonal wind) and the Nagoya site (overland and downwind on the shores of the Pacific Ocean). Most of the (222)Rn at the Kanazawa site was calculated to come from North China and Korea in Term I, Middle China, North China, and Korea in Term II, and Russia and Korea in Term III. The considerable differences in the origins of (222)Rn emanated from the continent were estimated between Terms I, II and III, even though the similar northwest wind was dominant over the Japan Sea. A contour line analysis indicated movement of (222)Rn emanated from Middle China in a northerly direction first and then a southeasterly direction, resulting from low pressure. The results suggest that the low-pressure systems play an important role in the transport of (222)Rn in North-East Asia.

Gamma-irradiation effect: variation of photosynthetic activity of Euglena.

OBJECTIVE: To study the effects of gamma-ray irradiation on carbon fixation (Specific production rate: SPR), CO2 utilization efficiency (CUE) and electron transfer rate (ETR) in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response dependent manner. METHODS: Euglena cells were cultured in an inorganic nutrient medium containing ammonium chloride or proteose peptone. Cells were exposed to gamma-ray at 5 doses (0, 100, 250, 350, 500 Gy for water). Five days after irradiation, three photosynthetic activities were measured. SPR, which is a carbon uptake rate per unit carbon mass, was determined by 13C tracer methodology. CUE was evaluated using a relation of carbon isotope fractionation in Calvin cycle. ETR in photosystem II (PS II) was measured by a chlorophyll fluorescence analysis. RESULTS: Even at a dose of 500 Gy, 80% of ETR of the non-irradiated control (0 Gy) was sustained, while SPR and CUE were about half the level in the non-irradiated control at 500 Gy. Furthermore, the dose response of ETR was considerably different from the others. CONCLUSION: Our findings suggest that not only PS II but also the Calvin cycle in the photosynthetic system is affected by gamma ray irradiation.

High-energy carbon ion irradiation and the inhibition of negative gravitaxis in Euglena gracilis Z.

PURPOSE: To study the effects of high-energy carbon ion irradiation on negative gravitaxis in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response-dependent manner. MATERIALS AND METHODS: Cells were exposed to 290 MeV amu(-1) carbon ion from the Heavy Ion Medical Accelerator in Chiba (HIMAC) at 12 doses (0, 1, 5, 7.5, 10, 15, 20, 50, 75, 100, 150, 200 Gy for water). r was used to quantify negative gravitaxis observed in a recently developed biomonitoring system. RESULTS: Negative gravitaxis of Euglena was significantly affected by irradiation at a dose >7.5 Gy, 28 h after irradiation. Negative gravitaxis recovered after a few days. The rising phase of r during the first 30 s of orientation was independent of irradiation dose. The recovery mechanism itself was damaged by 290 MeV amu(-1) carbon ions at a dose >50 Gy. CONCLUSIONS: The results indicate that negative gravitaxis in Euglena may be affected by the radiation experienced during a space experiment especially during the occurrence of solar flares. The analyses of time needed to reorient to the gravitational vector suggest that the steering control of the flagellar apparatus is affected by exposure to the 290 MeV amu(-1) carbon ion irradiation, resulting in an altered beating pattern of a flagellum and/or changes of the cell form during reorientation.

Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels, and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients.

AIMS: Recent studies have stressed the roles of genetic factors on the plasma levels of hemostatic markers and on cardiovascular complications. We investigated the association of DNA polymorphisms for beta-fibrinogen, factor VII, and PAI-1 with plasma levels of these factors and with ischemic heart disease (IHD) and cerebral infarction (CI) in patients undergoing hemodialysis (HD). METHODS: beta-fibrinogen G/A-455, factor VII R353Q and PAI-1 4G/5G polymorphisms were determined by PCR-RFLP in 149 HD patients and in 100 controls. The plasma levels of fibrinogen, factor VII and PAI-1 were also measured. RESULTS: The allele frequencies and the genotype frequencies of these 3 polymorphisms were not different between HD patients and controls. In HD patients, plasma fibrinogen levels were significantly lower in the GG genotype than in the GA genotype, and plasma factor VII activity was significantly higher in the RR genotype than in the RQ genotype. Multiple regression analysis disclosed that CRP and beta-fibrinogen polymorphism were the significant determinants of fibrinogen levels. Plasma PAI-1 levels were not different among the 3 genotypes. The frequency of the A-455 allele was significantly higher in HD patients with CI than in those without CI, and the genotype distribution for beta-fibrinogen differed significantly between the 2 groups. Between the same 2 groups, however, significant differences were found neither in the frequency of the 353Q or 4G allele nor in the genotype distribution for factor VII and PAI-1. No significant differences in the frequency of the G-455, 353Q or 4G alleles, or in the genotype distribution for beta-fibrinogen, factor VII and PAI-1 were observed between patients with IHD and those without IHD. Multiple logistic regression analysis demonstrated that neither polymorphism was associated with CI or IHD. CONCLUSIONS: In HD patients, beta-fibrinogen and factor VII polymorphisms affected plasma levels of fibrinogen and factor VII, respectively. Beta-fibrinogen polymorphism was not an independent but a possible risk factor for CI in HD patients. Further study will be needed to confirm the precise role of 5-fibrinogen polymorphisms in the pathogenesis of CI in HD patients.

Effect of asymmetric modification on the conformation of ascidiacyclamide analogs.

Ascidiacyclamide (ASC), cyclo(-Ile1-Oxz2-d-Val3-Thz4-)2 (Oxz=oxazoline and Thz=thiazole) has a C2-symmetric sequence, and the relationships between its conformation and symmetry have been studied. In a previous study, we performed asymmetric modifications in which an Ile residue was replaced by Gly, Leu or Phe to disturb the symmetry [Doi et al. (1999) Biopolymers49, 459-469]. In this study, the modifications were extended. The Ile1 residue was replaced by Gly, Ala, aminoisobutyric acid (Aib), Val, Leu, Phe or d-Ile, and the d-Val3 residue was replaced by Val. The structures of these analogs were analyzed by X-ray diffraction, 1H NMR and CD techniques. X-Ray diffraction analyses revealed that the [Ala1], [Aib1] and [Phe1]ASC analogs are folded, whereas [Val1]ASC has a square form. These structures are the first examples of folded structures for ASC analogs in the crystal state and are similar to the previously reported structures of [Gly1] and [Phe1]ASC in solution. The resonances of amide NH and Thz CH protons linearly shift with temperature changes; in particular, those of [Aib1], [d-Ile1] and [Val3]ASCs exhibited a large temperature dependence. DMSO titration caused nonlinear shifts of proton resonances for all analogs and largely affected [d-Ile1] and [Val3]ASCs. A similar tendency was observed upon the addition of acetone to peptide solutions. Regarding peptide concentration changes, amide NH and Thz CH protons of [Gly1]ASC showed a relatively large dependence. CD spectra of these analogs indicated approximately two patterns in MeCN solution, which were related to the crystal structures. However, all spectra showed a similar positive Cotton effect in TFE solution, except that of [Val3]ASC. In the cytotoxicity test using P388 cells, [Val1]ASC exhibited the strongest activity, whereas the epimers of ASC ([d-Ile1] and [Val3]ASCs), showed fairly moderate activities.