IgG2 Deficiency Associated with Defects in Production of Interferon-Gamma; Comparison with Common Variable Immunodeficiency

We report a novel mechanism of IgG2 deficiency. Several investigators have reported patients with IgG subclass deficiencies due to homozygous deletion of immunoglobulin heavy chain constant region genes. However, it is unclear what mechanism is responsible for IgG subclass deficiency in cases where no gene deletions have been detected and which are accompanied by recurrent infections due to aberrant immunoregulation. In the present study, we have focused our attention on production by peripheral blood mononuclear cells ( PBMCs ) of interferon-gamma (IFN-γ), which is known to induce IgG2 expression. PBMCs from four patients with IgG2 deficiency and their families were studied. Mitogen-induced IFN-γ production by PBMCs was decreased in all of the patients, although the proliferative responses of PBMCs and the percentages of CD3, CD4 , and CD8 T cell subsets were not decreased. IgG2 production by PBMCs was restored upon addition of IFN-γ and mitogen to the PBMCs of the patients with IgG2 deficiency though it was not restored in the patients with common variable immunodeficiency. We conclude that defects in production of IFN-γ play an important role in IgG2 deficiency.     

Defective Calcium-Dependent Signal Transduction in T Lymphocytes of Ataxia-Telangiectasia

T-cell functions of two patients with ataxia-telangiectasia were investigated. Patients with ataxia-telangiectasia had reduced percentages of circulating CD3⁺ cells and CD4⁺ cells, although neither patient had a reduced percentage of circulating CD8⁺ cells. The proliferative responses and interleukin-2 production of peripheral blood mononuclear cells to T-cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4⁺ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4⁺ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca²⁺-dependent signal transduction through the CD3 complex of the surface in T cells of ataxia-telangiectasia.     

Long-term Follow-up Results after Flow Diverter Therapy Using the Pipeline Embolization Device for Large or Giant Unruptured Internal Carotid Artery Aneurysms: Single-center Retrospective Analysis in the Japanese Population

Flow diverter (FD) therapy using Pipeline embolization device (PED) has become an important alternative to treat internal carotid artery (ICA) aneurysms. Herein, we report the long-term outcome for 3 years after FD therapy using PED for ICA aneurysms in Japan. The patients who underwent angiographical and/or clinical follow-up for 3 years after the FD therapy using PED of large or giant unruptured ICA aneurysms from December 2012 at our university hospital are the subjects of this study. We retrospectively reviewed the in- and outpatients’ medical charts, and written operative and radiological records. There were 84 patients with 90 aneurysms who could be clinically and/or angiographically followed up for 3 years. Of these, 7 aneurysms were only available for clinical follow-up. Of the remaining 83 aneurysms, 6 aneurysms had vessel occlusion due to stent thrombosis or parent artery occlusion, and 60 of the remaining 77 (77.9%) had complete occlusion. In multivariate analysis, older age (>70 years), wide neck, and non-adjunctive coiling contributed statistically significantly to incomplete occlusion. Of the 84 patients, 2 patients (2.4%) had delayed complications between 6 months and 3 years after the initial FD placement. Three patients (3.6%) had poor outcome due to postoperative major stroke complications, 2 of which were acute complications. The long-term results after FD therapy are good both angiographically and clinically. Endothelialization of the aneurysmal neck and intra-aneurysmal thrombosis contribute to complete occlusion. The primary reason for the somewhat low complete occlusion in Japan may be the patients are generally older.     

Plasma disappearance of homologous and heterologous pancreatic enzymes in dogs

Homologous and heterologous (human) pure pancreatic juice was infused into dogs to compare the behaviour of pancreatic enzymes in the circulation. This was achieved by estimating the magnitude of elevation and speed of disappearance of pancreatic enzymes in plasma. The half-lives of the plasma enzymes did not differ significantly between dogs and humans. However the half-lives of other enzymes (longest for amylase and shortest for trypsinogen) did differ. The magnitude of elevation expressed as a ratio of peak (5 min) to basal level was greatest for trypsinogen (28 times) and least for amylase (1.4 times). However, 289% and 410% of the initial lipase enzyme activity was recovered 5 min after infusion of dog and human pure pancreatic juice, respectively (44% when measured by immunoreactive human lipase activity). The excess recovery requires re-evaluation of diagnostic value of turbidimetric activity of plasma pancreatic lipase.     

Gastric Cancer Developing in a Patient with Chronic Lymphocytic Leukemia with Massive Gastrointestinal Involvement

Massive infiltration of neoplastic lymphocytes caused a variety of gross gastrointestinal manifestations in a 71-year-old patient with chronic lymphocytic leukemia (CLL). These included plaque-like elevations in the esophagus, convoluted gyrus-like folds in the stomach, and many polypoid lesions in the stomach and duodenum. No gross lesions were noted in the large intestine. Four years later, systemic chemotherapy reduced the gastrointestinal involvement, but a papillary elevation grew at the gastric angle, which was shown to be an early cancer on histological examination. Gastrointestinal involvement in CLL and second cancers associated with CLL are reviewed, with special reference to the possible relationship between CLL and gastric cancer.     

Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co-administration of erythromycin

Abstract A case of repetitive hallucinations during treatment with a therapeutic dosage of triazolam (0.25 mg/day) and nitrazepam (5 mg/day) is presented. The patient suffered from acute pneumonia and chronic renal failure. Such non-psychotic symptoms as anxiety, tremor and depressed feeling were observed initially. However, after co-administration of erythromycin (600 mg/day), visual hallucinations and abnormal bodily sensations developed repeatedly after each administration of triazolam or nitrazepam. This report suggests that benzodiazepine hypnotics even at a therapeutic dosage with co-administration of erythromycin causes serious psychotic symptoms in vulnerable patients with physical complications.     

Inhibition of proliferative responses of lymphocytes to food antigens by an anti-allergic drug, N(3'',4''-dimethoxycinnamoyl) anthranilic acid (Tranilast) in children with atopic dermatitis

Experimental studies have shown that N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) inhibits reaginic antibody-mediated hypersensitivity reactions, and it has been demonstrated to be an effective drug for patients with bronchial asthma. On the other hand, from the nature of the cellular infiltrate seen in eczematous lesions, it appears that some form of cell-mediated immunity may be involved in addition to IgE-mediated immunity in the pathogenesis of atopic dermatitis (AD). Moreover, we have previously reported that the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) or bovine serum albumin (BSA) in children with AD who are sensitive to hen's egg or cow's milk were significantly higher than those of healthy children and hen's egg or cow's milk sensitive children with immediate symptoms. In this study, we have showed that the proliferative responses of PBMCs to OA were dose-dependently inhibited by Tranilast on patients with AD. The responding cells to OA were shown, through separation experiments, to be T cells, and the proliferative responses of T cells to OA were also dose-dependently inhibited by Tranilast. Moreover, the inhibition was thought to occur at the initial stage of the proliferative reactions. These results suggest that Tranilast can be clinically applied to patients with AD.