Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti‐BP180 C‐terminal domain antibodies associated with psoriasis and primary macroglobulinemia

A 61‐year‐old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl‐split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme‐linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M‐proteinemia of IgM‐κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C‐terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti‐BP180 C‐terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris.     

Neutrophil Phagocytosis of Platelets in the Early Phase of 2,4,6-trinitro-1-chlorobenzene (TNCB)-induced Dermatitis in Mice

Activated platelets form platelet–leukocyte aggregates in the circulation in inflammatory diseases. We investigated whether activated platelets in inflamed skin tissues are phagocytized and removed by neutrophils. To investigate the kinetics of platelets and neutrophils, we immunohistochemically examined the spatiotemporal distribution of them in a murine model of 2,4,6-trinitro-1-chlorobenzene (TNCB)-induced dermatitis by using confocal and structured illumination microscopy. Four hours after elicitation, aggregates of CD41-positive platelets were adhered to CD31-positive endothelial cells within the vessels, and CD62P and PF4, markers of activated platelets, were expressed on platelet aggregates. At 8 hour post-elicitation, fragmented CD41-positive platelets were located both inside and outside vessels. Twenty-four hours after elicitation, the number of Ly-6G-positive neutrophils ingesting fragmented CD41-positive platelets outside vessels was increased, and CD62P and PF4 expression on the phagocytosed platelets was no longer observed. Disc-shaped CD41-positive platelets were not found outside vessels at any time during the experiment. Our data revealed that aggregates of activated platelets inside vessels were ingested and removed by neutrophils in the early stage of TNCB-induced dermatitis, suggesting that the process of removal of activated platelets by neutrophils may play an important role not only in the early phase of skin inflammation but also in other types of acute inflammation.     

Interaction of Benzothiadiazides with Human Serum Albumin Studied by Dialysis and Spectroscopic Methods

The interaction of a series of benzothiadiazides with human serum albumin (HSA) was investigated by equilibrium dialysis (ED) and spectroscopic methods including circular dichroism (CD). The primary binding site of benzothiadiazides was designated site II, the diazepam site on the HSA molecule, as indicated by displacement experiments using different site-selective probes. Tyrosine and lysine amino acid residues were probably involved in the binding site of these compounds to HSA. Both electrostatic and hydrophobic interactions were found to play a role in the binding of these compounds to HSA. Among the compounds tested, chlorothiazide had the highest affinity (K₁ = 5.5 × 10⁴M^–1, K₂ = 5.8 × 10³ M^–1).The primary binding affinity of the compounds for HSA was of the order: chlorothiazide > cyclopenthiazide > polythiazide > ethiazide > trichlormethiazide = methyclothiazde > hydrochlorothiazide. Binding was insensitive to the N-B transition of HSA. The binding site is proposed to consist of a cationic site on the surface of the HSA molecule with a hydrophobic crevice to accommodate the aromatic ring of the compounds. Positions 3 and 7 of the benzothiadiazide molecule is thought to affect the binding affinity to HSA.     

Low control at work and the risk of suicide in Japanese men: a prospective cohort study

BACKGROUND: Although adverse psychosocial job characteristics are suspected predictors of suicide death, prospective studies based on established stress instruments are limited. METHODS: In a multicenter community-based Japanese cohort study, we prospectively investigated the association between psychosocial job characteristics and the risk of death from suicide among male workers. Baseline examination was conducted from 1992 to 1995 to determine the socioeconomic, behavioural and biological variables in addition to the psychosocial job characteristics of 3,125 male workers aged 65 and under and free from major illness. Low job control and high job demands were measured as adverse psychosocial job characteristics according to a job demand-control model questionnaire. Suicide deaths were identified using the Cause-of-Death Register. RESULTS: During the 9-year follow-up, 14 suicides were identified. The suicide death rate was 48.1 per 100,000 person years. Multivariate analysis revealed a more than fourfold increase in the risk of suicide among men with low control at work (relative risk: 4.10; 95% confidence interval: 1.31-12.83) compared with counterpart men after adjustment for age, marital status, educational attainment, occupation, smoking status, alcohol consumption, total cholesterol level, and study area. Job demands were not associated with risk of death from suicide. CONCLUSIONS: By using a job demand-control model questionnaire, low control at work was revealed as a predictor of suicide death among Japanese male workers. The finding implies that job redesign aimed at increased worker control could be a worthwhile strategy in preventing, or at least reducing, the risk of suicide death.     

Association between job stressors and heavy drinking: age differences in male Japanese workers

The objective of the present study is to investigate the association between various occupational stressors and heavy drinking among male Japanese workers in different age groups. Using the Generic Job Stress Questionnaire, 13 occupational stressors and 2 workplace support indicators were assessed. The questionnaire survey was conducted of 25,104 workers, and the present study analyzed the data from 17,501 male workers. Heavy drinking was defined as weekly alcohol consumption of >275 g, and a total of 1,131 men (6.5%) were classified as heavy drinkers. After adjusting for shift work, occupational class, marital status and smoking, heavy drinking was related to "support from supervisor" for the 18-29 and 50-72 yr-old groups. For the 30-39 yr-old group, heavy drinking was related to "intragroup conflict", "job control" and "cognitive demands." For the 40-49 yr-old group, heavy drinking was related to "physical environment", "quantitative workload" and "underutilization of abilities." The present study clarified that certain occupational stressors relate to heavy drinking, and that this association varies among different age groups.