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.

Natural attenuation of Fukushima-derived radiocesium in soils due to its vertical and lateral migration.

Processes of vertical and lateral migration lead to gradual reduction in contamination of catchment soil, particularly its top layer. The reduction can be considered as natural attenuation. This, in turn, results in a gradual decrease of radiocesium activity concentrations in the surface runoff and river water, in both dissolved and particulate forms. The purpose of this research is to study the dynamics of Fukushima-derived radiocesium in undisturbed soils and floodplain deposits exposed to erosion and sedimentation during floods. Combined observations of radiocesium vertical distribution in soil and sediment deposition on artificial lawn-grass mats on the Niida River floodplain allowed us to estimate both annual mean sediment accumulation rates and maximum sedimentation rates corresponding to an extreme flood event during Tropical Storm Etau, 6-11 September 2015. Dose rates were reduced considerably for floodplain sections with high sedimentation because the top soil layer with high radionuclide contamination was eroded and/or buried under cleaner fresh sediments produced mostly due to bank erosion and sediments movements. Rate constants of natural attenuation on the sites of the Takase River and floodplain of Niida River was found to be in range 0.2-0.4 year-1. For the site in the lower reach of the Niida River, collimated shield dose readings from soil surfaces slightly increased during the period of observation from February to July 2016. Generally, due to more precipitation, steeper slopes, higher temperatures and increased biological activities in soils, self-purification of radioactive contamination in Fukushima associated with vertical and lateral radionuclide migration is faster than in Chernobyl. In many cases, monitored natural attenuation along with appropriate restrictions seems to be optimal option for water remediation in Fukushima contaminated areas.

Behavior of accidentally released radiocesium in soil-water environment: Looking at Fukushima from a Chernobyl perspective.

Quantitative characteristics of dissolved and particulate radiocesium wash-off from contaminated watersheds after the FDNPP accident are calculated based on published monitoring data. Comparative analysis is provided for radiocesium wash-off parameters and distribution coefficients, Kd, between suspended matter and water in rivers and surface runoff on Fukushima and Chernobyl contaminated areas for the first years after the accidents. It was found that radiocesium distribution coefficient in Fukushima rivers is essentially higher (1-2 orders of magnitude) than corresponding values for rivers and surface runoff within the Chernobyl zone. This can be associated with two factors: first, the high fraction of clays in the predominant soils and sediments of the Fukushima area and accordingly a higher value of the radiocesium Interception Potential, RIP, in general, and secondly the presence of water insoluble glassy particles containing radiocesium in the accidental fallout at Fukushima. It was found also that normalized dissolved wash-off coefficients for Fukushima catchments are 1-2 orders of magnitude lower than corresponding values for the Chernobyl zone. Normalized particulate wash-off coefficients are comparable for Fukushima and Chernobyl. Results of the investigation of radiocesium's ((134)Cs and (137)Cs) vertical distribution in soils of the close-in area of the Fukushima Dai-ichi NPP - Okuma town and floodplain of the Niida river are presented. The radiocesium migration in undisturbed forest and grassland soils at Fukushima contaminated area has been shown to be faster as compared to the Chernobyl 30-km zone during the first three years after the accidents. This may be associated with higher annual precipitation (by about 2.5 times) in Fukushima as compared to the Chernobyl zone, as well as the differences in the soil characteristics and temperature regime throughout a year. Investigation and analysis of Fukushima's radiocesium distribution in soils of Niida river catchment revealed accumulation zones of contaminated sediments on its floodplain. Average sediment deposition rates varied from 0.3 to 3.3 cm/year.

Molecular detection of p16 promoter methylation in the serum of patients with esophageal squamous cell carcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: Recent evidence shows that the presence of promoter hypermethylation of tumor suppressor genes has been demonstrated in the serum DNA of patients with various cancers such as lung, liver, and head and neck cancer. We have examined promoter hypermethylation of the p16 gene in esophageal squamous cell carcinoma (SCC) using methylation-specific PCR to detect tumor DNA in the serum. RESULTS: Aberrant promoter methylation of the p16 gene was detected in 31 of 38 (82%) esophageal SCCs. Subsequently, we tested for promoter methylation in the paired serum DNA of 31 patients with a p16 alteration in the primary tumor. We found that 7 of these 31 (23%) patients had the same methylation changes in the serum DNA. CONCLUSIONS: This result indicates that promoter methylation present in the tumors of esophageal SCC patients can be detected in the serum of the same patient and that this approach can potentially be used for the screening and monitoring of the disease.

Ultrasound-guided gradual reduction using flexion and abduction continuous traction for developmental dysplasia of the hip: a new method of treatment.

We describe our experience in the reduction of dislocation of the hip secondary to developmental dysplasia using ultrasound-guided gradual reduction using flexion and abduction continuous traction (FACT-R). During a period of 13 years we treated 208 Suzuki type B or C complete dislocations of the hip in 202 children with a mean age of four months (0 to 11). The mean follow-up was 9.1 years (five to 16). The rate of reduction was 99.0%. There were no recurrent dislocations, and the rate of avascular necrosis of the femoral head was 1.0%. The rate of secondary surgery for residual acetabular dysplasia was 19.2%, and this was significantly higher in those children in whom the initial treatment was delayed or if other previous treatments had failed (p = 0.00045). The duration of FACT-R was significantly longer in severe dislocations (p = 0.001) or if previous treatments had failed (p = 0.018). This new method of treatment is effective and safe in these difficult cases and offers outcomes comparable to or better than those of standard methods.

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina.

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.

Demonstration of somatomedin activity of "multiplication-stimulating activity" in rabbit costal chondrocytes in culture.

Multiplication-stimulating activity (MSA), a substance obtained from conditioned medium of Buffalo rat liver cells, stimulated replication of rabbit costal chondrocytes in culture and their DNA synthesis, sulfation of glycosaminoglycans, protein synthesis, and collagen synthesis. These stimulatory effects of MSA were dose-dependent in serum-free medium, indicating that MSA has intrinsic somatomedin activity. Even after several successive passages, cultured chondrocytes were more responsive to MSA than other organ- and cell-culture systems reported. Therefore, cultured rabbit costal chondrocytes proved a good in vitro system for analysis of somatomedin actions.

Radiation-related ophthalmological changes and aging among Hiroshima and Nagasaki A-bomb survivors: a reanalysis.

The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A-bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance.

Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki.

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.

Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detected as little as 0.05U/dl VII:Ag. Values for VII:Ag obtained for plasma samples from normal subjects (n = 20), patients with liver disease (n = 20), patients treated with warfarin (n = 20), and those congenitally deficient in factor VII (n = 7) correlated very well (r = 0.96) with data obtained in a radioimmunoassay using polyclonal rabbit antiserum to factor VII. This simple and sensitive monoclonal antibody based assay offers a convenient method for the detection of VII:Ag in various disease states.

Monoclonal antibodies to human factor VII: production of immunodepleted plasma for VII:C assays.

A high affinity monoclonal antibody to factor VII (RFF-VII/1), coupled to sepharose, was used to immunodeplete factor VII from normal plasma. The plasma could be used as a substrate in a one stage coagulation assay and performed as well as, or better than, commercially available factor VII deficient plasma or plasma from congenitally deficient factor VII patients. Plasma from normal donors (n = 20), patients with liver disease (n = 20), and patients receiving warfarin (n = 20), or congenitally factor VII deficient patients (n = 7) was assayed for VII:C concentration in a one stage coagulation assay. The concentration of VII:C detected with the immunodepleted plasma substrate was comparable in all cases with that seen with a commercially available substrate (r = 0.95).

Homozygous protein C deficiency with delayed onset of symptoms at 7 to 10 months.

We report an inbred family with two cases of homozygous protein C deficiency and review 11 other such cases. Both patients presented in the second half of their first year of life with recurrent rapidly disappearing ecchymotic skin lesions, disseminated intravascular coagulation, and venous thrombosis. Successful treatment has been achieved by frequent infusions of plasma or prothrombin complex then maintained with Warfarin. Homozygous recessive protein C deficiency usually presents in the neonatal period with purpura fulminans. Two cases have been described elsewhere which presented in the second decade of life with milder symptoms. The present cases appear to be intermediate in time of presentation and severity of symptoms. We also review the distinction that is now evident between recessive and dominant protein C deficiency.

Effect of ebselen on contractile responses in perfused rabbit basilar artery.

OBJECTIVE: To evaluate the possible role of the antioxidant ebselen in the treatment of cerebral vasospasm, we examined the effects of ebselen on the vasoactive mechanisms induced by endothelin (ET)-1, oxyhemoglobin, and oxygen-derived radicals. METHODS: Isolated rabbit basilar arteries with intact endothelium were fixed in a perfusion system and perfused intraluminally. Contraction of the artery was detected as an increase in perfusion pressure. RESULTS: Ebselen, in a certain concentration range (3 x 10(-6) and 10(-5) mol/L), significantly reduced the contractile response to ET-1 (10(-10) to 10(-8) mol/L) but not the contraction induced by 40 mmol/L potassium. It reduced the contraction induced by 10(-4) mol/L 1,2-dioctanoyl-sn-glycerol, a protein kinase C activator. Addition of 10(-5) mol/L dithiothreitol, a sulfhydryl-reducing agent, partially reversed the inhibitory effects of ebselen on ET-1- and 1,2-dioctanoyl-sn-glycerol-induced contractions. Ebselen (10(-5) mol/L) as well as a combination of catalase (1000 units/mL) and superoxide dismutase (150 units/mL) inhibited the potentiating effects of oxyhemoglobin (10(-5) mol/L) on ET-1-induced contraction. Both ebselen and catalase inhibited the contractile response to hydroxyl radical generated by ferrous ion (10(-3) mol/L) plus hydrogen peroxide (10(-2) mol/L). Ebselen reduced the response to potassium when a high dose (3 x 10(-5) mol/L) was applied and failed to preserve contractility of the preparation after exposure to hydroxyl radical. CONCLUSION: Ebselen suppressed ET-1-induced contraction and synergetic interaction between oxyhemoglobin and ET-1, where free radical formation was involved. These effects may result from modification of the intracellular regulatory system including protein kinase C, as well as from protection against free radicals.

Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries.

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.

Clinical evaluation of catheter-related fungemia and bacteremia.

Forty-four patients with catheter-related infection admitted to Hokusho Central Hospital between 1985 and 1991 were studied retrospectively. The rate of catheter-related fungemia or bacteremia to all corresponding cases of fungemia and bacteremia increased from 7.7% in 1985 to 28.8% in 1991. The isolated pathogens were Candida parapsilosis (8 strains), Candida tropicalis (6 strains), methicillin-resistant Staphylococcus aureus (MRSA) (6 strains), methicillin-sensitive S. aureus (MSSA) (5 strains) and Streptococcus epidermidis (3 strains). Bacteremia occurred after catheterization of the femoral vein for a mean duration of 37 days. The period was significantly shorter than that after catheterization of the subclavian vein (56 days). The major isolates from the subclavian vein were Candida spp. (14/17, 82.4%), followed by MRSA (1/17, 5.9%) and MSSA (1/17, 5.9%), while isolates from the femoral vein were Candida spp. (6/16, 37.5%), MRSA (5/16, 31.3%) and MSSA (3/16, 20.8%). Catheter removal alone did not improve the clinical condition, particularly in MRSA bacteremia; the combination of antimicrobial therapy and removal of the catheter was necessary for a better prognosis.

Predictability of internal carotid artery (ICA) dissectability in cases showing ICA involvement in parasellar meningioma.

The present study identified predictors for surgical internal carotid artery (ICA) dissection in cases showing ICA involvement in parasellar meningiomas. Twelve cases encountered over the past 4 years were reviewed. Based on MRI findings, patients were divided into two groups; six patients demonstrated complete ICA involvement (encasement) and the other six showed partial ICA involvement (engulfment). The ICA was dissected in all cases in the engulfment group and in four of six cases in the encasement group. The ICA can be dissected even if it is involved at the centre of the tumour if the tumour is soft and can be aspirated. Preservation of the perforating arteries is more important and more difficult. Angiographic finding showing encasement of a long segment of the ICA is unfavourable because of the high possibility that the perforating arteries are involved. Local stenosis of ICA is another unfavourable finding for surgical dissection because tumour invasion of the arterial wall would be suspected. Thus, ICA encasement by the tumour is the less favourable finding for surgery but it is not a decisive predictor. More important findings for ICA dissection in cases showing ICA encasement are involvement of a long segment of the ICA and local ICA stenosis on angiogram.

[Epidemic of Salmonella enteritidis infection of childhood in the northern area of Nagasaki].

Salmonella Enteritidis infections were a local epidemic in the northern area of Nagasaki, Japan, during August to September in 1992. Out patients (142) visited our hospital because of diarrhea and-or abdominal pain and 96 patients had stool cultures and 51 patients were diagnosed as Salmonella infection. Of the 51 patients it was found that the Salmonella serogroups were 09, 07, 08 and the number of patients were 42, 8, 1, respectively. Phage type 1 was identified in all of the S. Enteritidis infected 38 patients who were examined. About 90% of the patients were under 10 years old. Namely, this Salmonella Enteritidis epidemic in childhood. The peak epidemic period was consistent with the local summer festival and the etiology of infection was thought to be caused by polluted handmade ice cream. S. enteritidis was identified from the ice cream which was also phage type 1. The latent period was 87 hrs.

[A case of Campylobacter fetus subspecies fetus meningitis].

A 40-year-old male with no history of underlying disease was admitted to Hokusho Central Hospital on May 25, 1991, complaining of high fever and headache. Physical examination on admission revealed a temperature of 38.5 degrees C, a pulse rate of 84 beat/min (relative bradycardia) and no abnormal findings for the chest or abdomen. Slight neck stiffness without Kernig's sign was observed at neurological examination. Laboratory data were: ESR 11 mm/lh, WBC 12000/mm3, C-reactive protein positive. Lumbar puncture showed an initial pressure of 230 mmH2O; CSF revealed a cell count of 2633/3 mm3 with mononuclear pleocytosis, total protein of 76 mg/dl and sugar of 54 mg/dl (CSF:blood glucose ratio 0.47). We initially suspected tuberculous or cryptococcal meningitis, but Campylobacter fetus subsp. fetus (C. fetus) was isolated from the CSF and venous blood on the 27th hospital day. IPM/CS 1 g/day, MINO 200 mg/day and FOM 4 g/day were intravenously administered. This antibiotic therapy was very effective: the patient was soon afebrile, and gradually all signs and symptoms were resolved. C. fetus was sensitive to IMP/CS, MINO, KM, GM, EM, OFLX, CP. The patient was discharged with no complication. He has eaten raw beef frequently before admission, but stool culture for C. fetus was negative.

[Yearly changes of isolated organisms from the respiratory tract in Hokusho Central Hospital].

Isolated organisms from the respiratory tract have been studied in our hospital from 1986 to 1993. The total number of samples were 18,345 and samples which showed 10(5) cfu/ml organisms were 8648 in our hospital for 8 years. Enterobacteriacae, Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, and glucose nonfermenting gram-negative rods were major isolates in 8 years. Haemophilus influenzae, which used to be the commonest isolate, decreased from 10.9% in 1993 while Enterobacteriacae increased from 8.9% in 1986 to 17.6% in 1993. S. pneumoniae and H. influenzae were major isolates from out-patients consisting of 50%, followed by Enterobacteriacae, P. aeruginosa and MSSA. Enterobacteriacae and P. aeruginosa were major isolates from in-patients, followed by MRSA and beta-Streptococcus. Streptococcus agalactiae, Serratia marcescens and Corynebacterium spp. prevailed especially in the geriatric ward. S. pneumoniae, H. influenzae and M. catarrhalis were major isolates from patients with pneumoconiosis, especially in winter.

[A study of respiratory infection and sepsis caused by MRSA at Hokusho Central Hospital].

At Hokusho Central Hospital, we studied the isolation rate of methicillin-resistant Staphylococcus aureus (MRSA) from 1985 to 1989; respiratory infection with MRSA, in 1989; and sepsis of MRSA, from 1988 to 1989. The isolation rate of MRSA from sputum increased from 0% in 1985 to 65.4% in 1989. MRSA was isolated mainly from elderly patients in a geriatric ward, with 55 of 67 strains (82%) being isolated from these patients in 1989. MIC80 of isolated MRSA strains was 0.01 microgram/ml to rifampicin, 0.02 microgram/ml to mynomycine, 3.13 micrograms/ml to vancomycin, 12.5 micrograms/ml to ofloxacin and 100 micrograms/ml to imipenem in 1989. One-third of the 60 isolated cases showed respiratory infections including 10 cases of pneumonia and 10 sepsis patients and 11 blood samples in 1988 and 1989, especially 92.9% of S. aureus isolated in 1989 was MRSA. Four of the 6 patients with respiratory infections of MRSA and 1 of the 3 patients with MRSA sepsis were treated successfully by a combination therapy of imipenem/cilastatin and cefazolin.