Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis

BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column-low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients' serum obtained before and just after SDSC-IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus. RESULTS: Both of the patients had an immediate decrease in anti-double-strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10) fractions. In addition, IgG3 was specifically removed from the patients' serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients' serum and the elimination of these fractions may have resulted in clinical improvement.     

Colonic pseudolipomatosis, microscopically classified into two groups

Background: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. Methods: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Results: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal‐looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal‐looking surface or non‐elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable‐sized vacuoles, and were related to lymph follicles. Conclusion: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.     

Dose-Related Effects of the Hepatocarcinogen, Wy-14,643, on Peroxisomes and Cell Replication

Dose-Related Effects of the Hepatocarcinogen, Wy-14,643, onPeroxisomes and Cell Replication. WADA, N., MARSMAN, D. S.,AND POPP, J. A. (1992). Fundam. Appl. Toxicol. 18, 149–154. The dose and time dependency of peroxisome proliferation andhepatocyte replication was evaluated in the liver of rats fedthe peroxisome proliferator and hepatocarcinogen, Wy-14,643.Male F344 rats were fed NIH07 diet blended with Wy-14,643 at0, 5, 10, 50, 100, or 1000 ppm for 1, 3, 6, or 13 weeks. Hepatomegalywas induced by Wy-14,643 at all doses and at all time points.Peroxisome proliferation was present in rats fed 5 ppm Wy-14,643as early as 1 week, as determined by the peroxisome-specificNAD⁺ reduction of palmitoyl CoA (PCO) and the peroxisome-associatedactivity of carnitine acetyltransferase (CAT) (5-and 11-foldover control, respectively). The elevations of PCO and CAT weredose-dependent from 5 to 50 ppm and then plateaued from 50 to1000 ppm throughout the treatment period. Hepatocellular replication,evaluated by nuclear histoautoradiography ([³H]thymidine labeling,6-day infusion), was increased in all Wy-14,643 dose groupsafter 1 week of treatment (5 ppm, 4-fold; 10 ppm, 5-fold; 50ppm, 13-fold; 100 ppm, 12-fold; and 1000 ppm, 13-fold over controls).However, in 5 and 10 ppm groups this cell replication returnedto control levels by 3 weeks. In contrast, 50, 100, and 1000ppm groups had sustained increases in cell replication up to13 weeks (13 weeks: 6-, 7-, and 9-fold over controls, respectively).We have demonstrated that Wy-14,643 can induce peroxisome proliferationat 5 ppm, a dose 200 times lower than the dose shown to be highlyhepatocarcinogenic in rats (100% incidence by 60 weeks). Incontrast, 50 ppm was identified as the minimal dose which inducedsustained cell replication in rat liver. These data show thatperoxisome proliferation can be dissected from sustained cellreplication for correlating either peroxisome induction or cellreplication with tumor formation. These results provide importantinformation that can be used to design carcinogenicity experimentsto test if peroxisome proliferation and/or chronic enhancementof cell replication predictive risk factors for hepatocarcinogenieity.     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Characteristics of juvenile dermatomyositis in Japan

Questionnaires were sent to 1290 hospitals in Japan asking for data on patients with juvenile dermatomyositis (JDM) diagnosed between June 1984 and May 1994. Of the 204 patients identified by these questionnaires, 102 met the criteria for JDM. JDM is categorized into three subtypes: Banker-type JDM , Brunsting-type and fulminant-type; patients with the latter exhibit markedly elevated serum levels of creatinine phosphokinase (> 10 000 U/mL) and appear to be at risk of renal failure. Cutaneous manifestations were present in 98% of patients and preceded the appearance of other symptoms. This tendency is one of the reasons for the difficulty in some cases in diagnosing the onset of JDM. Better criteria for early treatment of JDM are needed. The results of the present study suggest that itching and calcinosis are factors that indicate a poor prognosis in patients with JDM. Muscle enzyme levels do not always reflect disease activity, suggesting that methods other than measurement of muscle enzymes, such as measurement of the levels of neoprerin and von Willebrand factor antigen, as well as magnetic resonance imaging should be used to be evaluate disease severity. Patients with Brunsting-type JDM who exhibit dysphagia and antinuclear antibody positivity and patients with Banker-type JDM should be treated aggressively. Pulse therapy should be selected as the initial therapy in patients with fulminant-type JDM.     

The Economic Impact of Loss of Performance Due to Absenteeism and Presenteeism Caused by Depressive Symptoms and Comorbid Health Conditions among Japanese Workers

We aimed to determine the economic impact of absenteeism and presenteeism from five conditions potentially comorbid with depressive symptoms—back or neck disorders, depression, anxiety, or emotional disorders, chronic headaches, stomach or bowel disorders, and insomnia—among Japanese workers aged 18–59 yr. Participants from 19 workplaces anonymously completed Stanford Presenteeism Scale questionnaires. Participants identified one primary health condition and determined the resultant performance loss (0–100%) over the previous 4-wk period. We estimated the wage loss by gender, using 10-yr age bands. A total of 6,777 participants undertook the study. Of these, we extracted the data for those in the 18–59 yr age band who chose targeted primary health conditions (males, 2,535; females 2,465). The primary health condition identified was back or neck disorders. We found that wage loss due to presenteeism and absenteeism per 100 workers across all 10-yr age bands was high for back or neck disorders. Wage loss per person was relatively high among those identifying depression, anxiety, or emotional disorders. These findings offer insight into developing strategies for workplace interventions on increasing work performance.     

Infectious mononucleosis in Japan: Comparison with acute viral hepatitis type A

In order to clarify the characteristics of infectious mononucleosis hepatitis (IMH) in Japan, 20 cases with IMH treated at Kamo Hospital during the past 6 years (Group I) were analysed in comparison with cases of acute viral hepatitis, especially type A. The test for heterophil antibody was positive in only two cases. During the same period 209 cases were treated for acute viral hepatitis (type A: 77 cases = Group A; type B: 61 cases; type non-A, non-B: 71 cases). In Group I the common clinical symptoms and signs were headache, sore throat and lymph node swelling; jaundice was not as common as in Group A. GOT and GPT activities increased moderately in the acute stage, but they were significantly lower than those in Group A. LDH, AP, GGT and LAP activities were disproportionately higher to GPT activity in Group I. Liver biopsy in the convalescent stage showed that lipofuscin deposition and sinusoidal mononuclear cell infiltration were more prominent in Group I, while sinusoidal neutrocyte infiltration and focal necrosis at periportal areas were more common in Group A. Differential diagnosis of the two diseases could be made using these clinical features and histological findings. However, immunological differentiation is required for specific diagnosis because some features such as fever, prolonged elevation of thymol turbidity test, atypical lymphocytes in peripheral blod and predilection for young people were observed in both groups. Furthermore, the present study indicated that IMH is no longer rare and most cases do not demonstrate heterophil antibody in Japan.