Yuichi Ichinose

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia

A 31‐year‐old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon‐α since February 1995. After 16 months, he complained of low‐grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X‐ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Clinical evaluation of serum type IV collagen 7S in idiopathic pulmonary fibrosis

Abstract Type IV collagen is one of the major components of the basement membrane (BM). 7S domain (7S collagen) of type IV collagen is an N‐terminal peptide which is stable against protease and heat. We investigated serum concentration of 7S collagen in patients with idiopathic pulmonary fibrosis (IPF) and other pulmonary diseases. The aim of this study was to evaluate whether changes in the serum concentration of 7S collagen reflect the fibrotic process of IPF. We measured the concentration of serum 7S collagen with radioimmunoassay in patients with IPF, chronic pulmonary emphysema (CPE), sarcoidosis, infectious pulmonary diseases (IPD) and normal healthy controls. We also monitored 7S collagen during the clinical course in some patients with IPF and investigated the correlation between the serum 7S collagen, and lactate dehydrogenase (LDH) and erthrocyte sedimentation rate (ESR) in patients with IPF. Patients with IPF showed significantly higher serum concentration of 7S collagen than other pulmonary diseases and healthy controls. The serum concentration of 7S collagen significantly decreased in IPF patients who showed roentgenographic improvement after corticosteroid treatment. There was a correlation between the serum 7S collagen and LDH, and ESR. In conclusion, serum concentrations of 7S collagen increase in patients with IPE The measurement of 7S collagen is useful for the evaluation of fibrotic change in the lung.

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-α

Abstract We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor‐α (TNF‐α), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H‐7 and H‐8, a calmodulin antagonist W‐7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC‐9. H‐7, more potent in inhibiting PKC than H‐8, failed to attenuate the increase in permeability induced by TNF‐α. Neither PMA nor SC‐9 increased permeability. However, H‐8, which is a potent inhibitor of cyclic nucleotide‐dependent protein kinases, prevented the increase in permeability induced by TNF‐α. These results suggest that protein kinases other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF‐α. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF‐α.

A Study of Peripheral Airway Findings Using an Ultrathin Bronchofiberscope and Bronchoalveolar Lavage Fluid with Diffuse Panbronchiolitis

We investigated the peripheral airways using an ultrathin bronchofiberscope and analyzed bronchoalveolar lavage fluid (BALF) in 10 patients with diffuse panbronchiolitis (DPB; refractory and responsive to treatment with macrolide antibiotics) and 10 healthy volunteers. Refractory DPB patients had obstruction at the 11th or 12th level of bronchial branches and secretion from the 5th to 6th order bronchi to the 11th–12th level of bronchial branches. In responsive DPB patients, there was no obstruction of peripheral airways, but secretion in the bronchial lumens still remained in nearly all observed bronchial branches. Despite macrolide therapy, BALF from patients with refractory DPB contained a high percentage of neutrophils and had a lower CD4/CD8 ratio. Two-color analysis of T cell subsets in BALF revealed a high percentage and number of CD8+S6F1+ cells (activated cytotoxic T cells) in refractory DPB patients. Our findings suggest that obstruction around the terminal bronchioles may be correlated with BALF abnormalities and may be irreversible despite macrolide therapy in progressive DPB.

Simultaneous continuous 13C, 12C analysis of expired gas in the 13C breath test

The 13C breath test is a method of clarifying the metabolism of loaded substances by administering 13C‐labelled materials and calculating the 13CO2 and 12CO2 ratio (13C/12C isotope ratio) in the expired gas. The materials are metabolized and expelled in the expired gas. Because simultaneous continuous measurement of 13CO2 and 12CO2 in expired gas has been difficult up to the present, respective expired gases, including dead space before and after administration, have been sampled to separate sampling bags and 13C/12C has been measured in the bags and changed fraction of 13C/12C after administration (δ) has been used to judge the metabolic process. This method is affected by the contamination of the dead space gas. In the present study, in order to exclude the dead space effect, simultaneous continuous analysis of 12CO2 and 13CO2 of expired gas identifying alveolar gas was applied to the 13C‐urea breath test in addition to the conventional sampling bag method. Both isotope detectors were attached to a mass spectrometer. Fifty‐six cases receiving stomach health check‐ups for Helicobacter pylori were examined. δ was calculated in the bag or in phase III of continuous gas measurement. Because the bag contains dead space, δ was reduced and sensitivity and specificity with reference to gastric fluoroscopy or Helicobacter pylori IgG antibody were reduced. Decreasing the dead space contamination is important in reducing the measurement error in the 13C breath test and simultaneous continuous measurement is a good tool for this purpose.

Pulmonary tissue volume measured by acetylene rebreathing under artificial ventilation.

In order to evaluate the pulmonary congestive state of patients being mechanically ventilated, an acetylene rebreathing method was employed. Measurement of pulmonary tissue volume by the acetylene (C2H2) rebreathing method was performed in 15 patients under artificial ventilation including four congestive heart failure cases, one renal failure case, and 12 healthy controls.

Atypical Adenomatous Hyperplasia and Well Differentiated Adenocarcinoma: Analysis by Morphometry, DNA index and Immunohistochemistry.

高分化腺癌 (WDA) との異同が問題となる異型腺腫様過形成 (AAH) の形態学的特徴を検討した.1995年11月から2年間に手術された肺癌443例から, 癌病巣周囲あるいは孤立性にAAHが認められた41例を得, 135個の病巣を見出した.これらを細胞異型度によって高度 (H), 中等度 (M) および軽度 (L) に分類し, image cytometryを用いて核DNA ploidypatternを, 免疫組織化学的にp53, Ki-67, cyclin D1の発現を調べた.その結果, aneuploidyのものはWDA 81.82%であったのに対し, AAH-Hは66.67%, AAH-M 31.03%, AAHL24.32%であった.p53, Ki-67, cyclinD1の発現頻度は異型度と共に上昇した.癌周囲性AAH-L,-Mは孤立性AAH-L,-Mに比べてaneuploidyのものが多く, p53, Ki-67, cyclin D1の発現率も高かった.以上の結果はAAHがWDAの前駆病巣として矛盾しないものであり, 同時に同程度の異型度を示すAAHでも, 癌周囲AAHと孤立性AAHでは, 遺伝子レベルに相違があることを想定させた.

Screening of Helicobacter Pylori Infection in the Health Examination Detected by Urea Breath Test and Barium Meal Study

Screening of Helicobacter Pylori Infection in the Health Examination Detected by Urea Breath Test and Barium Meal Study: Fumihiro Yamasawa, et al. Marubeni Clinic

Lung Function for Normal Elderly Men and Women in General Health Examination.

従来高齢者が健康診断を受ける機会が少なかったため, 健常高齢者の肺活量や一秒量の正常値は一般成人健常者の値の年齢による回帰直線を高齢側に外挿して求めてきた。近年高齢者が健康診断を受ける機会が増加するに伴い, その正常値を別途に作成する必要性が生じてきた。そこで当センターにおいて健常例の基準を満たす60歳以上の例の努力肺活量, 一秒量, 一秒率, ピークフローの正常値を求めた。また加齢に基づく肺機能の低下が健常成人のように年齢と共に一次直線的に減少して行くものか否か検討したところ, 努力肺活量, 一秒量, 一秒率, ピークフローについて年齢が増加するに伴い, 経年変化が次第に不明瞭となる傾向を認めた。