A clinical and serological study of linear IgA bullous dermatosis without linear immunoglobulin deposition other than IgA at the basement membrane zone using direct immunofluorescence.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports. OBJECTIVES: To reappraise the characteristic features of LABD with only IgA deposition at the basement membrane zone (BMZ) with direct immunofluorescence (DIF). METHODS: We retrospectively collected data from 101 patients from our archival records from 1 January 1996 to 31 December 2014 who had: (i) blisters on the skin and/or mucous membranes; (ii) subepidermal blisters in a biopsy specimen; and (iii) linear IgA deposition along the BMZ with/without linear C3 deposition at the BMZ with DIF. Most patients were referred for serological evaluation. Patients who showed concurrent linear IgG and/or IgM deposition at the BMZ under DIF were excluded. Clinical manifestations and serological findings were analysed. RESULTS: Heterogeneity of autoantigens in LABD was confirmed. Fifty-four of 101 patients (53%) had IgG antibodies detected either by indirect immunofluorescence, immunoblotting or enzyme-linked immunosorbent assays (ELISA). No statistical difference in clinical manifestations was found between patients in the IgG antibody-possessing group and patients in the other group. CONCLUSIONS: An association of IgG anti-BMZ antibodies with LABD may increase if new IgG immunoblotting or ELISA techniques become available. Consensus for diagnostic criteria for LABD is desired for prospective data storage, although it may be arbitrary.

Gate-Tunable Atomically Thin Lateral MoS2 Schottky Junction Patterned by Electron Beam.

Among atomically thin two-dimensional (2D) materials, molybdenum disulfide (MoS2) is attracting considerable attention because of its direct bandgap in the 2H-semiconducting phase. On the other hand, a 1T-metallic phase has been revealed, bringing complementary application. Recently, thanks to top-down fabrication using electron beam (EB) irradiation techniques, in-plane 1T-metal/2H-semiconductor lateral (Schottky) MoS2 junctions were demonstrated, opening a path toward the co-integration of active and passive two-dimensional devices. Here, we report the first transport measurements evidencing the formation of a MoS2 Schottky barrier (SB) junction with barrier height of 0.13-0.18 eV created at the interface between EB-irradiated (1T)/nonirradiated (2H) regions. Our experimental findings, supported by state-of-the-art simulation, reveal unique device fingerprint of SB-based field-effect transistors made from atom-thin 1T layers.

Summary of results of serological tests and diagnoses for 4774 cases of various autoimmune bullous diseases consulted to Kurume University.

BACKGROUND: Although many new disease entities of autoimmune bullous disease (AIBD) have recently been recognized, satisfactory immunological diagnostic methods and comprehensive classifications for various AIBDs have not been established. OBJECTIVES: To identify immunological diagnostics and comprehensive classifications for AIBDs. METHODS: We selected and examined 4774 patients with various AIBDs from our cohort of 5063 patients with difficult AIBDs, whose sera and information were sent for our diagnostic method from other institutes in either Japan or other countries over the last 19 years. We examined the sera by our immunological diagnostic methods including various immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay tests to make final diagnoses. RESULTS: By our immunological diagnostic methods, we successfully made final diagnoses for approximately three-quarters of the difficult cases of AIBD, although the remaining cases could not be diagnosed. Using the results, we suggest the most extensive and newest classification of AIBDs, and also propose the most efficient algorithm of immunological tests for the diagnosis of various AIBDs. CONCLUSIONS: The results in this study of 4774 patients with various AIBDs indicate that our immunological diagnostic method is useful for making diagnoses for most patients with AIBD. However, we need further improvements including new immunological techniques to establish more satisfactory methods.

Anti-desmocollin autoantibodies in nonclassical pemphigus.

BACKGROUND: Despite the established pathogenic role of anti-desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed. OBJECTIVES: The aim of this study was to develop reliable assays to detect anti-Dsc autoantibodies. METHODS: We expressed soluble recombinant proteins (RPs) of human Dsc1-3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme-linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs. RESULTS: Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16.5%, 36.7% and 59.5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc-positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre-absorption with Dsg RPs. CONCLUSIONS: The results of these novel ELISAs indicated that IgG anti-Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.

Clinical and immunological profiles of 25 patients with pemphigoid gestationis.

BACKGROUND: Systematic study of pemphigoid gestationis (PG) has not been performed owing to its rarity. OBJECTIVES: To perform clinical and immunological analyses of 25 patients with PG. METHODS: In addition to clinical and histopathological assessments, we performed immunofluorescence (IF), immunoblotting (IB) and enzyme-linked immunosorbent assays (ELISAs). RESULTS: PG developed preferentially during the second or third trimester of pregnancy, with a mean age at onset of 30·5 years. Histopathology showed subepidermal blisters less frequently. Direct IF showed C3 deposition in the basement membrane zone (BMZ) in all patients, with rare reactivity with keratinocyte cell surfaces. Ninety-two per cent of patients showed circulating IgG anti-BMZ autoantibodies during indirect IF of either normal or 1 mol L(-1) NaCl-split skin. Complement IF revealed linear C3 reactivity with the BMZ of normal skin in 68% of patients, and all patients had C3 reactivity on the epidermal side of 1 mol L(-1) NaCl-split skin. IB and ELISA of the NC16a domain of BP180 recombinant protein was positive in 96% and 92% of patients, respectively, while only four patients had a positive ELISA for BP230. In IB tests, 28% of patients reacted with the C-terminal domain of BP180 and 20% reacted with leucocyte adhesion deficiency-1 protein. Multigravidae developed PG during a significantly (P < 0·01) earlier stage (21·1 weeks) of pregnancy than primigravidae (31·3 weeks). CONCLUSIONS: IB and ELISA of the NC16a domain of BP180 were shown to be sensitive and diagnostic methods in PG. Patients with PG rarely reacted with BP230, suggesting a different pathogenesis between PG and bullous pemphigoid. Multigravidae developed PG skin lesions significantly earlier in pregnancy than primigravidae.

Clinical and immunological profiles in 17 Japanese patients with drug-induced pemphigus studied at Kurume University.

BACKGROUND: Drug-induced pemphigus (DIP) shows clinical, histopathological and immunological features of pemphigus. However, little is known about immunological profiles in DIP. OBJECTIVES: To characterize clinical and immunological profiles in patients with DIP. METHODS: We studied 17 Japanese patients with DIP who were treated at Kurume University Hospital or who consulted from other hospitals between 1997 and 2012. Complicated diseases, clinical and histopathological manifestations, responsible drugs and findings in immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were analysed. RESULTS: Eight of the 17 patients with DIP showed pemphigus foliaceus-like appearance, three showed pemphigus herpetiformis-like appearance, and six showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in 16 patients (bucillamine in nine cases, d-penicillamine in four cases, and cetapril, thiopronine and captopril in one patient each), and a nonthiol drug, sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four showed no specific reactivity. By IB of normal human epidermal extracts, in addition to positive reactivity with Dsg1, four patients with no detectable malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies without mucosal lesions. While 11 cases recovered after discontinuation of the causative drugs, six patients had a very protracted or intractable disease course, and might develop true pemphigus. CONCLUSIONS: The present study indicated that the majority of the patients with DIP studied showed a pemphigus foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol-containing drugs.

Plantar verrucous carcinoma: report of a case treated with Boyd amputation followed by reconstruction with a free forearm flap.

Verrucous carcinoma is a relatively rare, well-differentiated, squamous cell carcinoma. Although it is slow-growing and mimics benign skin lesions, it can cause extensive local destruction that necessitates amputation. It is often underdiagnosed as a benign tumor in its early course. We report a case of extensive verrucous carcinoma on a recalcitrant ulcer and a severe long-standing scar around it on the sole of the right forefoot, which had been treated as a benign tumor for more than two years. We treated it successfully with amputation of the foot and were able to spare the heel by using a free innervated forearm flap to cover the defect at the stump. The present case should remind clinicians that a verrucous lesion developing on a refractory ulcer may be a complex malignant neoplasm; an accurate diagnosis is difficult without a combination of clinical features and pathological findings from an adequately deep specimen.

Granuloma annulare in herpes zoster scars.

A 54-year-old Japanese female developed granuloma annulare twice in herpes zoster scars. Soon after the second event, she developed ulcerative colitis, which was well controlled by sulfonamides and corticosteroid suppository. She had no history of diabetes mellitus. There was no recurrence of granuloma annulare by June of 1999. Granuloma annulare might have contributed to the complications of ulcerative colitis, although this had not been noticed before.

[Suppressive effects of iodinated contrast media on human platelet aggregation].

Suppressive effects of several iodinated contrast media on stimulus-induced aggregation of human platelets were demonstrated. All contrast media, including ionic (iothalamate and ioxaglate) and non-ionic ones (iohexol, ioversol and iopamidol), suppressed the collagen- and thrombin-induced aggregation in a concentration-dependent manner. The effects of the former were much stronger than those of the latter. With ioxaglate, a similar inhibitory effect was also observed on PAF- and U46619-stimulated aggregation. The suppressive effect of ioxaglate on collagen-stimulated aggregation almost disappeared upon dilution of the medium with the platelet-poor plasma, suggesting that the effect is reversible.

Fastigial nucleus stimulation and excitatory spinal sympathetic activity in dog.

To locate the cerebellar-activated descending sympathetic pathways in the dog the fastigial nucleus (FN) was electrically stimulated in chloralose-anesthetized dogs while recording from sympathetic preganglionic neurons. Physiological interventions included lesions in the dorsolateral funiculus (DLF) of the spinal cord, myelotomy, arterial pressure changes, bilateral occlusion of the carotid arteries, and administration of clonidine. Multiunit activity at the T2 on T3 white ramus communicans was recorded on-line during rest and FN stimulation. Descending sympathetic activity (averaging 3.5 m/s) in the DLF was increased in response to FN stimulation but was significantly reduced by ipsilateral and eliminated by bilateral FN lesions. When testing for the effects of baroreceptor reflexes on the sympathetic pathway phenylephrine-induced hypertension decreased, but moderate hemorrhage increased the amount of preganglionic activity at rest and during FN stimulation. During hypertension and simultaneous carotid artery occlusion the amount of sympathetic activity that could be evoked was comparable to that evoked during normotensive states. Clonidine (IV) reduced the FN sympathoexcitation, but direct stimulation of the DLF indicated that clonidine had sympathoinhibitory activity at both medullary and spinal sites. In summary, rostral FN primarily excited ipsilateral descending sympathetic pathways in DLF, and this sympathoexcitation was partially inhibited by baroreceptor intervention.

Neural control of the heart during arrhythmias and exercise.

Involvement of neural activity during cardiovascular adjustments and during arrhythmias can be determined by comparing the results of cardiovascular changes after lesions are made in nuclei or pathways of the central nervous system or ablations of ganglia or nerves are made in the peripheral nervous system. The neural effects can be exaggerated if these systems are forced to perform at higher levels during a stressful situation. The purpose of this presentation is to discuss the responsiveness of the cardiovascular system after left or right stellate ganglionectomy and after lesions are made in the fastigial nucleus of the cerebellum in dogs stressed with submaximal exercise. These dogs are implanted with instruments that are designed to measure cardiovascular responses. Hypotheses for potential neural mechanisms are generated from the results of chronic animal studies, and these mechanisms are tested in anesthetized dogs and cats. Electrical stimulation of ascending and descending pathways in the central nervous system and stimulations such as coronary occlusion and mechanical probing are used to activate neural mechanisms in the anesthetized state. A general schema concerning the results of our studies provides further information about our approach to understanding the physiological role that the central nervous system may exert on the cardiovascular system during stress.

Effects of coronary artery occlusion on thoracic spinal neurons receiving viscerosomatic inputs.

Action potentials of single cells in the gray matter of the T2 to T4 spinal segments of chloralose-anesthetized cats were recorded during occlusion of the anterior descending branch of the left coronary artery. Only cells responding both to visceral and somatic afferent inputs were examined. In 53% of the cells the discharge frequency was unaffected by coronary artery occlusion (CAO). The remaining 47% could be classified by four response patterns: 1) in 18% frequency increased immediately following the onset of CAO; 2) in 22%, frequency increased 13.6 +/- 3.3 (SE) s after CAO and the increased frequency usually was associated with changes in the configuration of the electrocardiogram; 3) in 3%, frequency increased at the onset of CAO and then increased more approximately 11 s later; 4) in 4%, inhibition of spontaneous activity occurred during CAO. A noxious pinch applied to the somatic receptive field maximally excited 94% and inhibited 6% of the cells. Since viscerosomatic convergence provides a basis for referred pain, these cells could potentially be involved with transmission of nociceptive information to regions of the brain that integrate pain sensations.