Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection

We describe an experience of a specific immune transfer treatment in a patient with chronic active EBV infection. The patient had low anti-EBV T cell-mediated cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may have been the primary cause of the disease. An EBV-specific cytotoxic T lymphocyte (CTL) line was established from PBMC obtained from the patient’s sister whose human leucocyte antigens (HLA) are identical to patient's. The patient received three courses of intravenously administered CTL at 3-week intervals. The number of the cells was increased with each course of treatment. After infusion of the T cell line, anti-EBV CTL activity was detected in the patient's PBMC. CTL activity increased markedly after the second course of immune transfer therapy. The amount of EBV DNA in the patient's plasma showed transient but repeated decreases. Serum levels of tumour necrosis factor-alpha (TNF-α), which had elevated before treatment, began to decrease after initiation of treatment. No adverse effects were directly associated with CTL infusions. Despite having previously received a pneumococcal vaccine and prophylactic antibodies, the patient died of infection caused by Streptococcus pneumoniae bacteraemia 27 days after the third infusion. Although the long-term efficacy and safety of this therapy remains to be established, our findings suggest that adoptive transfer of CTL specific for EBV obtained from an HLA-matched donor might be a promising treatment for patients with chronic active EBV infection.     

氧化锆种植体的体外细胞相容性研究

目的探讨成骨细胞对氧化钇稳定的四方相氧化锆材料的生物学反应,为氧化锆种植体用于临床提供基础参考。方法制备直径15mm,厚度1.5mm的氧化锆和纯钛样本,氧化铝水砂纸抛光,白光干涉测量仪测量材料表面三维形貌,接触角测量仪测量材料表面接触角,采用成骨细胞MC3T3-E1接种于材料表面,分别在第1天,4天,7天进行细胞计数,并测定细胞内m RNA含量;在第1天和3天时,采用FDA荧光染色观察细胞形态。采用独立样本t检验进行数据统计分析。结果纯钛表面的粗糙度大于氧化锆,但两种材料具有相似的接触角。细胞增殖试验显示两者具有相似的细胞附着和生长,以及细胞内m RNA含量,FDA荧光染色显示两种材料具有相似的细胞形态。结论氧化锆和纯钛材料相对成骨细胞具有相似的生物学作用。     

Skin Irritation to Glass Wool or Continuous Glass Filaments as Observed by a Patch Test among Human Japanese Volunteers

Glass wool and continuous glass filaments have been used in industry. We examined the irritability of those among Japanese. A patch test was performed on 43 volunteers for the followings: glass wool for non-residential use with and without a urea-modified phenolic resin binder, that for residential use with and without the binder, and continuous glass filaments with diameters of 4, 7, 9, and 13 µm. Materials were applied to an upper arm of each volunteer for 24 h. The skin was observed at 1 and 24 h after the removal. At 1 h after removal, slight erythema was observed on the skin of a woman after the exposure to glass wool for residential use without the binder. Erythema was observed on the skin of another woman at 1 h after a 24-h exposure to glass wool for non-residential use without the binder. There were no reactions at 24 h after the removal. The low reactions in the patch test suggested that the irritability caused by glass wool, irrespective of a resin component, could be induced mechanically, and that the irritability caused by continuous glass filaments with resin could be slight and either mechanical or chemical.     

Detection of Helicobacter pylori Gene by Means of Immunomagnetic Separation-Based Polymerase Chain Reaction in Feces

Background: Detection of Helicobacter pylori is usually performed by culture, polymerase chain reaction (PCR), histology, or urease test on gastric biopsy samples. Although methods based on feces are non-invasive, their sensitivity has been relatively low. In this study, to improve its sensitivity, immunomagnetic separation (IMS) was used as a pre-PCR step for direct detection of H. pylori in feces. Methods: Fresh fecal samples were taken from 72 patients attending for endoscopy. Of these, 57 patients had a positive H. pylori status according to the results of culture, histology, and PCR on gastric biopsy samples. Anti-H. pylori antibody-sensitized immunomagnetic beads were used to concentrate the bacteria. PCR was then performed to detect the H. pylori urease A-encoding gene. Results: Of the 57 H. pylori-positive patients, 35 (61.4%) had positive fecal samples by IMS-based PCR method. None of the 15 H. pylori-negative patients had positive fecal samples. The sensitivity of this method was 61.4%, and the specificity 100.0%. Conclusions: This study confirms that non-invasive diagnosis of H. pylori infection could be made from feces by using IMS-based PCR.     

Transcutaneous Bilirubinometry

ABSTRACT. A total of 576 transcutaneous bilirubin measurements were performed on 336 Japanese full-term breast-fed newborn infants during the first twelve days of life. Our present study revealed that transcutaneous bilirubin measurements obtained from the forehead, chest, and sternum correlated well with serum bilirubin concentrations measured by AO bilirubinometer (0.910–0.922, p <0.001, n =576). The 95% confidence lmits were ±3.04 mg/dl for the forehead, ±2.85 mg/dl for the chest, and ±2.84 mg/dl for the sternum readings. The overall mean of values from the forehead, chest and sternum, when compared with individual means, was found to correlate better with serum bilirubin concentrations ( r =0.930, p <0.001, n =576) and improve the 95% confidence limits to ±2.68 mg/dl. These results demonstrated that the accuracy and reliability of TcB measurement could be increased further with multiple site measurement. The study clearly indicates that transcutaneous bilirubinometry is useful for clinical screening of serum bilirubin levels in Japanese full-term newborn infants.     

Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L⁻¹ of urine (range: 0.17–546.31 pmol/L⁻¹. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary β 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.