The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves' disease: the role of CD8+ cells

The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves' disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves' disease.     

Comparison of thermosensitivity in the preoptic/anterior hypothalamic area and the midbrain of the rabbit

Summary To characterize the role of the midbrain temperature-sensitive structure in thermoregulation, the relative importance of thermosensitivity in the hypothalamus and the midbrain was studied in terms of heat production and heat loss in the rabbit. It was found that altering the local temperature in the midbrain had no influence at all on heat loss from the ear surface and also on heat production, while cooling and warming of the preoptic/anterior hypothalamic area induced appropriate thermoregulatory responses.     

Long-term follow up studies of bronchial asthma in children. II. Prognosis and complications, treatment and allergic evaluations

A questionnaire on the prognosis of bronchial asthma was sent in 1988 to 1592 patients (1038 males, 554 females) averaging 20 years of age after 12 years' follow up. We reported on the prognosis and risk factors associated with asthmatic children in part I. The relation between prognosis and other allergic complications, treatment and laboratory data were investigated in this study. Eosinophil counts of more than 1000/mm3 and/or total serum IgE levels of more than 500 IU/ml (100 IU/ml in infants) indicated poor prognosis. However, the prognosis was not affected either by the allergens themselves or by the number of allergens determined by skin test and RAST. The prognosis was worse for patients with multiple allergic complications than for those without complications. Treatment may after the natural course of childhood asthma, but it has been difficult to evaluate the effect of each regimen over a long period. We compared the effect of hyposensitization (specific immunization) and non-bronchodilator antiasthmatic drugs (NBAAD), and found that hyposensitization alone gave better results than NBAAD and its combination. We had better results from hyposensitization over a period of 1 to 5 years than for less than 1 year or more than 5 years. We conclude that asthmatic children with risk factors should be kept under strict environmental control and given suitable therapeutic regimens to avoid the development of allergic diseases, the slow down of "allergic march", and to avoid intractable asthma.     

Thyroid function tests

About 80% of thyroid disease consists of thyroid-specific autoimmune diseases, Hashimoto's disease and Grave's disease. To diagnose thyroid diseases, testings for (1) thyroid function and (2) pathogenetic autoantibodies are indispensable. To assess thyroid function, serum hormone concentrations, such as TSH, FT4 and FT3 are measured. Among these hormones, serum TSH concentrations are the most reliable and informative regarding thyroid function, correcting indicating a hyperthyroid, euthyroid or hypothyroid state. Therefore, TSH measurement appears to be the first choice in selecting the hormone determination. Reference intervals for normal healthy subjects of TSH are around 0.4-5.0 microU/ml. The second choice for thyroid function assessment are FT4 which supersedes total T4(TT4). TT4 is affected by changes in serum thyroid hormone binding proteins(TBG, TTR, Albumin). For example, euthyroid pregnant women whose serum TBG are physiologically higher than those of non-pregnant women show augmentation of TT4. However, FT4 depicts within reference intervals, although measurement of FT4 alone is unable to detect any abnormality of thyroid hormone binding proteins. According to its plasma concentration and binding affinity, FT3 measurement deserves no more significance than T3. Another important test for thyroid diseases is to detect serum autoantibodies against thyroid tissues, such as TgAb, TPOAb. Much more important is TSH receptor antibody which differentiates Graves' disease from Hashimoto's thyroiditis. In patients who show hyperthyroidism and some very uncommon hypothyroidism, TSH receptor antibodies should be measured. Three indicators are available as routine tests; TRAb measured by radioreceptor assay; TSAb determined by bioassay using cultured porcine thyroid cells. Usually, TRAb activity clinically correlates well with TSAb. TSBAb was initially discovered in patients with severe hypothyroidism with atrophic thyroid gland. TSBAb blocks thyroid stimulating activity of TSH and consequently causes severe hypothyroidism. TRAb and TSAb are very useful to diagnose and follow patients with Grave's disease.     

High prevalence of hepatitis C virus infection in schistosomiasis japonica patients associated with hepatocellular carcinoma

Schistosomiasis japonica (SCJ) patients frequently develop hepatocellular carcinoma (HCC). This study investigated relationship between SCJ infection, hepatitis virus infection, and incidence of HCC, in 25 patients with chronic SCJ infection and HCC (SCJ with HCC group), 51 patients with chronic SCJ infection without HCC (SCJ group) and 65 HCC patients without SCJ (HCC group). Number of patients who were positive to HBsAg or hepatitis B virus DNA were 4 (16.0%) in the SCJ with HCC group, none (0%) in the SCJ group, and 5 (7.9%) in the HCC group; while number of patients who were positive to anti-hepatitis C virus antibody were 21 (87.5%) in the SCJ with HCC group, 3 (5.9%) in the SCJ group, and 58 (84.6%) in the HCC group. Biopsy was performed for all patients, and background histological features of each specimen were evaluated based on the histological activity index scoring system. Mean scores of inflammatory changes in both the portal area and parenchyma in the SCJ with HCC group were significantly higher than those in the SCJ group. Nodular formation which is common in post-viral hepatitis was frequently observed in the SCJ with HCC group, and histological changes in non-cancerous area of the SCJ with HCC group showed the characteristics of chronic viral hepatitis. We conclude that infection of hepatitis virus, particularly hepatitis C virus, affects synergistically on the hepatocarcinogenesis in patients having SCJ infection.     

Microwave tumour coagulation plus in situ treatment with cytokine-microparticles: induction of potent anti-residual tumour immunity.

After local microwave coagulation and subsequent intra-tumoural injection of microparticles encapsulating interleukin-2 and granulocyte-macrophage colony-stimulating factor, the anti-tumour efficacy against subcutaneous Lewis lung carcinoma in syngeneic mice was evaluated. This treatment elicited a potent systemic anti-tumour immunity that protected treated mice from re-challenge with the same tumour cells and caused the distal tumours in a bilateral tumour model to be rejected. Cytotoxicity assay indicated that both T- and natural killer cells acted as the effector cells in the anti-tumour immunity. These data highlight the feasibility of microwave-pre-treated in situ cancer vaccination for clinical use.     

Molecular investigation of pathogenic factors of suspected-diarrheogenic Escherichia coli isolates from patients feces

One hundred fifty-one O serotypable Escherichia coli strains which were assumed diarrheogenic E. coli among 2,240 strains of E. coli isolated from the in- and outpatients stools with or without gastrointestinal symptoms at Kyorin University Hospital from February 1994 to September 1996 were examined for the relationship between the possession of eight pathogenic factor-related genes and gastrointestinal symptoms of the patients using the polymerase chain reaction (PCR) for these strains. The rate of possession of pathogenic factor-related genes in the E. coli examined was 20.5% (31 strains) and gastrointestinal symptoms were found in all the patients with these strains except one. In the patients without gastrointestinal symptoms, E. coli isolates that possesses these genes was detected in only one case during 61 cases. The respective genes detected were eaeA and astA in each 14 strains, VT1 in 6, VT2 in 5, ST1b in 4, aggR in 3 and LT in 2, ST1a and invE gene was not detected. In particular, the O157 strains were found in 55.6% (5/9 strains) for these genes, and individual strains had VT1, VT2, eaeA and astA genes simultaneously. In contrast, none of these related genes was found in 9 strains of enteroinvasive serotype but enteropathogenic E. coli-related genes were found in 3 strains. The rate of possession of the genes related to enterotoxigenic E. coli, O159 which was most frequently isolated was low as 2.3% (1/43 strains, astA gene) and there were strains showing low correlation to the state of possession of the genes with the O serotype. Since the prevalence of the gastrointestinal symptoms is clearly high for the case which possesses the strain of which the pathogenic factor-related gene was detected, it was suggested that detection of pathogenic factor-related genes in E. coli isolates from feces using the PCR could be an effective means to decide whether the bacteria concerned was a causal bacteria or not in clinical practice.     

结核感染若干年后特异性γ-干扰素应答减弱

假设：随着时间的流逝，结核感染者记忆性T细胞对特异性抗原的应答减弱。背景：很多证据表明特异性全血γ-干扰素（IFN-γ）检测试验Quanti—FERON～TB Gold（QFT—G）能够检测出近期结核感染者，并具有较高的灵敏度和特异性。目的：我们应用此项技术检测日本一个社区的成人群体以确定其流行病学应用价值。方法：1559例参加定期体检的健康志愿者入选本研究。结果：40～49岁人群QFT—G的阳性率为3．1％，50～59岁人群的阳性率为5．9％，60～69岁人群的阳性率为9．8％。作者根据一系列研究估计40～49岁、50～59岁、60～69岁的预期结核感染率分别为11．1％、29．6％、53．1％。预期阳性率与实际阳性率之间存在的巨大差异提示结核感染后随着时间的延长IFN-γ应答减弱。那些经胸部X线证实存在陈旧性结核病灶者阳性率大大低于100％。结论：特异性IFN—γ应答可能在结核感染后随着时间的推移大大地减弱。需要在感染者中长期地纵向研究细胞介导的免疫动力学。