A case of hypereosinophilia with digital ischaemia successfully treated with intravenous prostaglandin E1.

In the therapeutic management of eosinophilic disorder, it is important to prevent hypereosinophilia (HE)-related organ damage even in the process of diagnosis. We describe here a unique clinical and histopathological findings of the patient with HE accompanied with digital ischaemia. Treatment with intravenous prostaglandin E1 was essential for digital ischaemia in our case while benralizumab, humanized monoclonal antibody against interleukin-5 receptorα, did not affect. Our case suggests an earlier intervention for digital ischaemia in the therapeutic management of eosiniphilic disorder.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Analysis of parameter variations in L-Q equations for river runoff processes from the viewpoint of spatial and temporal conditions.

This study aims to find out variation characteristics of the parameters of 'a' and 'b' in L = a x Q(b), an empirical equation for run-off loading (L) and flow rate (Q), by evaluating the effects of flow conditions and regional properties of the watersheds on the values. We selected the Kamo River basin (155 km2) as a study field, and conducted various kinds of investigations, such as 80 day high frequency observations, continuous monitoring for more than 2 years, storm event surveys, and simultaneous surveys of 39 stations. Then, we obtained 7-170 data in each of 39 sampling stations. The main results obtained are as follows: (1) L-Q equation with a range of 'a' can express L-Q relation in most of the WQIs (water quality indices); (2) 'a' receives temporal (flow condition) effects more in SS, VSS and Al, while it receives regional effect more in inorganic carbon, TN, Ca and Fe; (3) both of flow change in storm events, and base flow levels affect the L-Q relation, and their effects can classify the WQIs into several groups; (4) the effects of regional properties were obviously observed in 'a', and quantitatively evaluated, especially for density of population.

Expression of foreign type I ribulose-1,5-bisphosphate carboxylase/ oxygenase (EC 4.1.1.39) stimulates photosynthesis in cyanobacterium Synechococcus PCC7942 cells.

A reporter gene assay revealed that promoters derived from Synechococcus PCC7942 (S.7942) psbAI and Synechocystis PCC6803 (S.6803) psbAII were suitable for the expression of foreign ribulose-bisphosphate carboxylase (RuBisCO; EC 4.1.1.39) in S.7942 cells. Transformational vectors with a promoter and a foreign RuBisCO gene, cvrbc originated from Allochromatium vinosum, were constructed on a binary vector, pUC303, and introduced to S.7942 cells. When the cvrbc was expressed with the S.7942 psbAI promoter, the total RuBisCO activity increased 2.5- to 4-fold than that of the wild type cell. The S.6803 psbAII promoter increased the activity of the transformant 1.5-2 times of that of wild type cell. There was a significant increase in the rate of photosynthesis depending on the increase of RuBisCO activity. The maximum rate of photosynthesis of the transformant cell was 1.63 times higher than that of the wild type under the illumination of 400 micromol m(-2) s(-1), at 20 mM bicarbonate and at 30 degrees C. Although the photosynthesis of the higher plant is limited by the ability of photosystems under high irradiance and the high CO(2 )concentration, that of the S.7942 cell is limited by the RuBisCO activity, even at high CO(2) concentrations and under high irradiance.

Estimation of annual pollutant loadings in two small catchments and examination of their differences caused by regional properties.

A series of runoff surveys was conducted for more than one year in two small catchments of the Kamo River basin (75.4 km2) and the Takano River basin (66.8 km2) in Kyoto, Japan, which adjoin each other, and may have the same precipitation pattern. The investigation consisted of a high-frequency periodic survey, a long-term regular survey and a storm event survey. The survey results were compared with the regional properties of the basins, and the following results were obtained. (1) Pollutant loadings were successfully estimated as two portions of base discharge and storm events discharge from the survey results. (2) Estimated annual loading of the sites was 2.9-4.5, 1.3-1.8, 17-27, 1.3-2.2, 0.076-0.97 t/km2/y, respectively for COD(Mn), DOC, SS, TN and TP. (3) 52-53% of the whole flow, which was caused by rainfall events, conveyed 81-87, 68-73, 92-95, 64-67, 76-81% of the whole loading, respectively for COD(Mn), DOC, SS, TN and TP. (4) Differences of regional properties in two basins cause different runoff patterns, but the differences in runoff patterns also depend on the rainfall patterns. In general, a more urbanized basin receives early and strong influence of precipitation on the storm event runoff.

Risk factors for dysbaric osteonecrosis.

OBJECTIVES: Dysbaric osteonecrosis (DON) is a complication of ineffective decompression following exposure to high-pressure environments. This study was designed to determine risk factors for the occurrence of DON in divers. METHODS: Fifty-six male divers received skeletal examinations by radiography to assess the occurrence of DON. A questionnaire was used to obtain clinical and diving information, including diving experience and maximum diving depth. Blood samples were collected to analyse the levels of plasminogen activator inhibitor (PAI)-1, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, high-density lipoprotein, apolipoprotein A1 and apolipoprotein B. RESULTS: Lesions of DON were detected in 31 of the 56 (55%) divers. Multivariate logistic regression analysis showed that high levels of PAI-1, a coagulation marker (odds ratio 4.281; P=0.0296) and great maximum diving depth (odds ratio 5.627; P=0.0231) were independent predictors of DON. CONCLUSIONS: This study has shown the presence of coagulation abnormality in divers with DON. This result suggests that a pharmacological approach incorporating the use of an anticoagulant may represent a potential strategy for the prevention of DON.

Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry.

The cellular receptor for hepatitis B virus (HBV) infection has not yet been identified. The purpose of this study was to address the possibility of participation by desialylated HBV and the asialoglycoprotein receptor (ASGP-R) exclusively expressed on liver parenchymal cells, in infection. Assays for viral binding and entry were performed by culturing a hepatoblastoma cell line, HepG2, and HBV particles derived from the HBV carrier in the presence or absence of neuraminidase (NA). Viral binding and entry were clearly enhanced in the presence of NA, and the enhancement of the binding could be blocked by asialo-fetuin and ethylenediamine-tetraacetic acid (EDTA). In addition, covalently closed circular (CCC)-DNA, as a marker of infectivity, was detected in the presence of NA, but not in its absence. The optimal concentration of NA raised infectivity more than 1000 times. We concluded that this method makes it feasible to evaluate the infectivity of HBV in vitro and that ASGP-R may be a specific HBV receptor once viral particles are desialylated.

Preparation and characterization of spherical polymer packings from polybutadiene for size-exclusion chromatography.

Porous polymer spherical particles for column packings in nonaqueous size-exclusion chromatography (SEC) were prepared from 1,2-syndiotactic polybutadiene by suspension and evaporation method. The polymer microbeads obtained were crosslinked by radical reaction between 2-vinyl groups in polybutadiene with ultraviolet radiation, to render them insoluble. These microbeads have wider chromatographic separation width than polystyrene column packings. In addition, the polybutadiene microbeads did not show the excessive retention observed with commercial polystyrene columns for polycyclic aromatic compounds. Therefore, a close correlation between the elution volume and M, for polycyclic aromatic compounds was observed with polybutadiene microbeads columns.

Changes in remnant-like particle cholesterol level during treatment of hypertension with amlodipine and cilnidipine

This study was designed to determine the effect of antihypertensive agents (calcium channel blockers) on the levels of remnant-like particle (RLP) cholesterol; a major risk factor for coronary heart disease, during treatment of hypertension. Thirty six hypertensive patients of both sexes were selected into this study. Twenty-five of them were treated with amlodipine while eleven patients were treated with cilnidipine all for 3 months. At the beginning and after 3 months of treatment, serum RLP-cholesterol levels were measured in the two treatment groups. RLP-cholesterol level was significantly reduced after clinidipine treatment while the reduction in RLP-cholesterol level after amlodipine treatment was not statistically significant. Our findings show that calcium channel blockers may lower the risk of myocardial infarction, coronary atherosclerosis and/or coronary thrombus formation through reduction in RLP-cholesterol levels during antihypertensive pharmacotherapy

Activated protein C attenuates coagulation-associated over-expression of fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI-1.

Several activated coagulation factors have been reported to enhance fibrinolysis by neutralizing plasminogen activator inhibitor type 1 (PAI-1) activity. We evaluated the physiological relevance of this mechanism using the euglobulin clot lysis time (ECLT) assay in the presence and absence of Ca2+, which is controlled by PAI-1 and mimics physiological thrombolysis. We found that the ECLT (18.5 +/- 0.6 h) was shortened by Ca2+ (5 mm) (6.6 +/- 0.1 h). A significant difference was observed in thrombin generation by the presence of Ca2+ in the euglobulin fraction. Prothrombin was almost fully converted to thrombin within 15 min in the presence of Ca2+, whereas essentially no conversion was observed without Ca2+. The presence of activated protein C (aPC) suppressed thrombin generation, and attenuated the shortening of ECLT in a dose-dependent manner, an effect enhanced by phospholipid and protein S. In the absence of Ca2+, aPC did not prolong the ECLT. After addition of biotin-labeled recombinant PAI-1 to the euglobulin fraction, PAI-1 was cleaved to lower molecular weight forms only in the presence of Ca2+. This cleavage did not occur in the presence of aPC, suggesting that thrombin was the catalyst for PAI-1 cleavage. The cleavage and inactivation of PAI-1 by generated thrombin is proposed to be responsible for the shortening of ECLT by Ca2+ and for coagulation-associated over-expression of fibrinolysis. Under such conditions, aPC appeared to suppress thrombin generation and to normalize highly activated fibrinolysis.

A cold-adapted endo-arabinanase from Penicillium chrysogenum.

Previously, three arabinan-degrading enzymes were isolated from Penicillium chrysogenum 31B. Here we describe another arabinan-degrading enzyme, termed Abnc, from the culture filtrate of the same organism. Analysis of the reaction products of debranched arabinan by high-performance anion-exchange chromatography (HPAEC) revealed that Abnc cleaved the substrate in an endo manner and that the final major product was arabinotriose. The molecular mass of Abnc was estimated to be 35 kDa by SDS-PAGE. Enzyme activity of Abnc was highest at pH 6.0 to 7.0. The enzyme was stable up to 30 degrees C and showed optimum activity at 30 to 40 degrees C. Compared with a mesophilic counterpart from Aspergillus niger, Abnc exhibited a lower thermal stability and optimum enzyme activity at lower temperatures. Production of Abnc in P. chrysogenum was found to be strongly induced by arabinose-containing polymers and required a longer culture time than did other arabinanase isozymes in this strain.

The association between negative and dysexecutive syndromes in schizophrenia: a cross-cultural study.

This paper examined the relationship between the 'negative syndrome' (NS) and the neuropsychological 'dysexecutive syndrome' (DES) in schizophrenia. The study also examined whether any relationship that exists between the NS and the DES holds equally for British and Japanese subjects. We compared 26 Japanese with 17 British schizophrenic patients, divided into 'mild' and 'severe' NS groups, on the basis of performance on neuropsychological tests, including the 'Behavioural Assessment of Dysexecutive Syndrome' (BADS). We found that patients with severe NS showed more everyday executive deficits than those with mild NS. The severity of NS was correlated with executive competence. The association between NS and the BADS performance was closer than that between NS and other conventional executive measures. These findings were not influenced by cultural differences between Japanese and British subjects, and, hence, suggested the existence of culture-neutral neurobehavioural processes.

Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice.

In the present study we trained tissue-plasminogen activator (tPA)-knockout (tPA -/-) and wild-type (tPA +/+) male mice in step-down inhibitory avoidance learning, a hippocampus-dependent task. tPA -/- displayed significantly shorter latencies to step down at 90 min, one, two and seven days after training indicating the learning deficit in these animals (P < 0.05 vs tPA +/+). The locomotor activity, the level of anxiety in an elevated-plus maze, as well as the pain threshold did not differ between the two strains of mice. The learning disability of tPA -/- was overcome by more intense training. The learning deficit was also partially restored by limited intrahippocampal delivery of tPA (infused for 2 h before training; P < 0.05 vs control), but not by the delivery of urokinase plasminogen activator, indicating the acute need for tPA in learning. The beneficial effect of tPA was abolished by co-infusion of its inhibitor tPA-STOP, indicating that the facilitatory effect of tPA on learning requires a proteolytic step. However, tPA activity in the hippocampus was not indispensable for effective memory retrieval in tPA-infused tPA -/- mice. Thus, rapid, specific and proteolytic action of tPA facilitates hippocampus-dependent learning, but not retrieval of previously acquired information.

Evidence for a multiple superconducting gap in MgB(2) from high-resolution photoemission spectroscopy.

We study the new binary intermetallic superconductor MgB(2) using high-resolution photoemission spectroscopy. The superconducting-state spectrum measured at 5.4 K shows a coherent peak with a shoulder structure, in sharp contrast to that expected from a simple isotropic-gap opening. The spectrum can be well reproduced using the weighted sum of two Dynes functions with the gap sizes of 1.7 and 5.6 meV. Temperature-dependent study shows that both gaps close at the bulk transition temperature. These results provide spectroscopic evidence for a multiple gap of MgB(2).

Successful treatment of low-flow priapism associated with phenothiazine therapy.

We present a case of low-flow priapism that was successfully treated. A 21-year-old man with a history of schizophrenia was admitted with a painful complete erection. He had taken propericiazine, phenothiazine derivatives, before hospitalization and was treated with a glandular-cavernosal shunt (El-Ghorab's procedure). Currently, he is able to have erections without any changes in his quality of life.

Is skeletal muscle damaged by the oxidative stress following anaerobic exercise?

We investigated whether the injury of skeletal muscle owing to the action of free radicals and the subsequent oxidative damage to tissues occurred during anaerobic exercise. To estimate injury to skeletal muscle, we determined certain indices of oxidative damage to skeletal muscle; i.e., leukocyte counts, concentrations of hypoxanthine, xanthine, urate, tissue- and serum-type CK-M isoforms, myoglobin, and total antioxidant capacity (TAC) of serum. Blood for these tests was collected at 3 min post-exercise. Post-anaerobic exercise concentrations of lactate were significantly increased from pre-exercise. The neutrophil and lymphocyte counts and alanine concentration were significantly increased by anaerobic exercise, even when the results were corrected for plasma volume changes; the plasma concentrations of hypoxanthine, urate, and TAC of serum were also significantly increased. The plasma concentration of xanthine was negatively correlated with TAC of serum. The activities of tissue- and serum-type CK-M were significantly increased post-exercise. When the hypoxanthine, urate, TAC of serum, myoglobin, and tissue- and serum-type CK-M were corrected for plasma volume changes, the post-exercise increases were no longer significantly different from the pre-exercise results. We suggest that these latter test results following anaerobic exercise exclude the presence of oxidative damage to skeletal muscle.

Comparison of the sensitivity of NAT using pooled donor samples for HBV and that of a serologic HBsAg assay.

BACKGROUND: Studies were conducted using samples from early and late-stage HBV-infected persons to determine the pool size at which PCR had better sensitivity than a sensitive HBsAg chemoluminescence immunoassay (CLIA-HBsAg). STUDY DESIGN AND METHODS: HBV seroconversion panels were tested for HBsAg by CLIA and for HBV DNA by nested PCR (95% hit rate: 100 copies/mL); PCR was carried out at various dilutions. HBV serologically positive samples that were detected from the simultaneous screening of 540,161 routine whole-blood donations using CLIA-HBsAg and agglutination assays were also characterized for additional markers of HBV infection. RESULTS: In 9 of 10 HBV seroconversion panels, PCR had better sensitivity than CLIA-HBsAg at dilutions of 1-in-25 or lower. Of 65 CLIA-only confirmed-positive donor samples (agglutination assay-negative), 8 represented early infection, 2 of which were PCR positive at a 1-in-50 dilution but negative at a 1-in-100 dilution. Only 2 of 47 samples from probable late-stage HBV infection that were positive on CLIA only were PCR positive with 0.1-mL sample volume and the S-region primer; the remaining 45 samples required a 1.0-mL sample input and C-region primer for increased PCR positivity. The remaining 10 CLIA-only confirmed-positive donor samples were from HBV vaccine recipients. None of the 12 CLIA- and HBsAg-negative donor samples that were strongly anti-HBc reactive could be detected by PCR at any dilution; all 12 were PCR positive when undiluted, but 4 required a 1.0-mL input volume for PCR positivity. CONCLUSION: For the detection of samples representing early-stage HBV infection, PCR at dilutions of 1-in-25 or lower (equivalent to a pool of < or =25 members) had greater sensitivity than CLIA-HBsAg. In contrast, samples from late-stage HBV infection were detected by PCR only with undiluted samples (0.1-mL or 1.0-mL input volumes), regardless of CLIA-HBsAg reactivity. Therefore, although NAT using minipools of 25 donations or less may be effective for the detection of early-stage HBV infection, it may not be effective for the detection of persistent HBV infection.

Tissue-type plasminogen activator is involved in the process of neuronal death induced by oxygen-glucose deprivation in culture.

Effect of tissue-type plasminogen activator (tPA) on oxygen-glucose deprivation (OGD) was studied in cultured cortical neurons prepared from tPA gene knockout (tPA-KO) and wild-type (Wt) mice. Three hours of OGD induced 45% and 23% of neuronal death in Wt and tPA-KO mice, respectively. Neuronal death in tPA-KO mice was increased to 42% by additional tPA. Six hours of OGD induced 80% and 40% of neuronal death in Wt and tPA-KO mice, respectively, whereas the addition of tPA increased to 62% in tPA-KO mice. These results suggest that tPA is directly involved in the process of neuronal death induced by ischemia-mimic stress without involving vascular or circulatory components.

Down-regulation of the alpha-Gal epitope expression in N-glycans of swine endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene. Modulation of the biosynthesis of terminal structures by a bisecting GlcNAc.

The down-regulation of the alpha-Gal epitope (Galalpha1,3Galbeta-R) in swine tissues would be highly desirable, in terms of preventing hyperacute rejection in pig-to-human xenotransplantation. In an earlier study, we reported that the introduction of the beta1,4-N-acetylglucosaminyltransferase (GnT) III gene into swine endothelial cells resulted in a substantial reduction in the expression of the alpha-Gal epitope. In this study, we report on the mechanism for this down-regulation of the alpha-Gal epitope by means of structural and kinetic analyses. The structural analyses revealed that the amount of N-linked oligosaccharides bearing the alpha-Gal epitopes in the GnT-III-transfected cells was less than 10% that in parental cells, due to the alteration of the terminal structures as well as a decrease in branch formation. In addition, it appeared that the addition of a bisecting GlcNAc, which is catalyzed by GnT-III, leads to a more efficient sialylation rather than alpha-galactosylation. In vitro kinetic analyses showed that the bisecting GlcNAc has an inhibitory effect on alpha-galactosylation, but does not significantly affect the sialylation. These results suggest that the bisecting GlcNAc in the core is capable of modifying the biosynthesis of the terminal structures via its differential effects on the capping glycosyltransferase reactions. The findings may contribute to the development of a novel strategy to eliminate carbohydrate xenoantigens.

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.