Total respiratory system compliance after thoracoplasty.

Recent attention has been directed towards the deleterious effects of the sequelae of pulmonary tuberculosis on respiratory function. Thus, a study was undertaken to find out to what extent the deformity of thorax after thoracoplasty increases the mechanical work of breathing. Compliance of the total respiratory system (Crs) was measured with a pressure-type body plethysmograph in nine post-thoracoplasty tuberculosis patients, 15 patients with pulmonary tuberculosis and three patients with pleural diseases. Mean Crs in nine post-thoracoplasty tuberculosis patients was 0.0861 cmH2O-1, and that in six patients with moderately advanced pulmonary tuberculosis was 0.0841 cmH2O-1. Mean Crs (0.1301 cmH2O-1) in nine patients with a minimum lesion of tuberculosis was not different from the reference Crs values reported to date by several authors. Crs was significantly correlated with vital capacity, but not with functional residual capacity. There was no difference in specific Crs between post-thoracoplasty tuberculosis patients and patients with moderately advanced pulmonary tuberculosis. Crs of patients with a pleural disease was smaller than Crs of patients with a minimal lesion of pulmonary tuberculosis. The deformity of thorax after thoracoplasty caused a decrease of Crs. However, ventilation is not as severely impaired as anticipated from the degree of thorax deformity on chest X-ray film, providing that movement of the diaphragm is unrestricted.

Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.

[A case report of tuberculosis epidemic in a university].

Index case (S.K.) was a postgraduate in one institute of Tohoku University and was diagnosed as pulmonary tuberculosis by regular health check-up. Examinations of sputa indicated Gaffky 6 on smear and +3 in culture, respectively. Five months after the diagnosis of the index case, a professor (O.K.) who was teaching S.K. in the same institute was diagnosed as tuberculosis by the chest X-ray survey. One month later, another postgraduate (M.J.) studying in other institute was found to affected with tuberculosis by regular health check-up. Since two institutes were distant from each other, it seemed that neither S.K. nor O.K. had an opportunity to contact with M.J. It was revealed, however, that two postgraduates received some lecture in the same classroom twice a week. Considering all these facts, three cases presented here are regarded as tuberculosis outbreak in the university.

A novel human monoclonal antibody, TONO-1, reactive with T-lymphocytic leukemia cells.

Mononuclear cells from the peripheral blood of patients with systemic lupus erythematosus (SLE) were transformed with the Epstein-Barr virus (EBV) and the resultant polyclonal B-lymphoblastoid cell lines were tested for antibody activity to membrane antigens of certain T-cell lines. B lymphoblastoid cell lines secreting specific antibodies were fused with (mouse x human) heteromyeloma SHM-D33 cells. Among the large number of hybridomas generated, one which produced a human monoclonal antibody (MAb) TONO-1 (IgM, lambda) was selected. MAb TONO-1 proved to be reactive with 4 human T-cell lines, HPB-MLT, L-MAT, MOLT-3 and MOLT-4F, but not with B-leukemia, Burkitt's lymphoma, myelomonocytic leukemia, erythroleukemia or non-hematopoietic malignant cell lines. MAb TONO-1 reacted positively with fresh leukemia cells from 2 of 7 patients with acute T-lymphocytic leukemia, but no reaction was observed in non-T-cell leukemia cases. Normal lymphocytes, monocytes, granulocytes, red blood cells and platelets in the peripheral blood did not demonstrate remarkable binding. Neither thymocytes nor bone-marrow cells from healthy volunteers were reactive. The antigens defined by MAb TONO-1 were polypeptides of 57 kDa and 68 kDa. Immunohistological studies revealed no staining of thymocytes in the thymus of a 6-month-old child, but showed epithelial reticular cells and Hassall's corpuscles to stain positively. These results suggest that MAb TONO-1 is directed to T-leukemic cells and some components of thymus tissue.

Daily single-dose regimen and alternate-two-week triple-dose/day regimen of oral ofloxacin for the prophylaxis and control of exacerbations of chronic respiratory tract infections.

Two different oral ofloxacin regimens, a daily single-dose regimen with 200 mg (Regimen I) and an every-two-week multidose regimen with 3 x 200 mg/day (Regimen II) was compared as to the efficacy in controlling repeated acute exacerbations of chronic respiratory tract infections. Fifty-eight patients consisting of 19 patients each of bronchiectasis and pulmonary emphysema, 10 patients of chronic bronchitis, 5 patients of old pulmonary tuberculosis, 4 patients of diffuse panbronchiolitis and 1 patient of multiple pulmonary bullae were evaluated: 32 patients in Regimen I and 26 patients in Regimen II. The corrected mean incidence of exacerbations per case decreased from pre-study 2.47 to intra-study 0.59 in Regimen I, and from pre-study 2.66 to intra-study 0.95 in Regimen II, respectively, with a statistically significant difference (p < 0.05, respectively). Only one of 12 persistent isolates of Pseudomonas aeruginosa acquired a certain degree of resistance to ofloxacin. Adverse reactions were found in six of 66 patients. We conclude that long-term administration of an new-quinolone, especially a daily single-dose regimen with ofloxacin, is useful to control acute exacerbations of chronic respiratory tract infections.

Antibiotic susceptibility of the sputum pathogens and throat swab pathogens isolated from the patients undergoing treatment in twenty-one private clinics in Japan.

Bacteriology of the respiratory isolates from 2,539 patients with respiratory infections in 21 primary care clinics was documented. Of a total of 1,887 strains of potential pathogens recovered from 1,507 patients, 996 were gram-positive and 891 were gram-negative. Major pathogens were Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. The MIC's against microbial isolates of six antimicrobial agents were determined. Ciprofloxacin and ofloxacin were more active against S. aureus, Moraxella catarrhalis and Pseudomonas aeruginosa, and ampicillin and cefteram were more active against S. pnuemoniae and S. pyogenes than four other antimicrobials tested, respectively, in this experiment. New quinolones and new generation cephems were active against H. influenzae and Enterobacteriaceae. Only one strain of S. aureus was methicillin-resistant. As regards other pathogens, 6.5% of S. pneumoniae and 14.9% of H. influenzae were resistant to ampicillin, and 26.7% of H. influenzae were beta-lactamase-positive. MRSA was found infrequently. But ampicillin-resistant S. pneumoniae and H. influenzae were found in primary care clinics almost as frequently as in intensive-medication-oriented clinics.

Identification of Mycobacterium avium complex isolated in eastern and central Japan by using DNA probes.

An attempt was made to identify Mycobacterium avium and Mycobacterium intracellulare in the M. avium intracellulare complex (MAC) isolated in the Tohoku (38 strains) and Tokai (30 strains) districts of Japan by using DNA probes which are specific for M. avium, M. intracellulare and M. tuberculosis complex, respectively. The incidence of M. avium infection (82%) by far exceeded that of M. intracellulare infection in the Tohoku district of eastern Japan. In the Tokai district of central Japan, the incidence of M. avium infection (57%) were slightly larger than that of M. intracellulare infection. Five of 68 strains showed a positive reaction with two different DNA probes. Thus a possibility of mixed infection could not be ruled out, because reference strains showed a positive reaction with only one species-specific DNA probe.

A phase II study of vinorelbine, a new derivative of vinca alkaloid, for previously untreated advanced non-small cell lung cancer. Japan Vinorelbine Lung Cancer Study Group.

To evaluate the effectiveness of vinorelbine (NVB) in patients with non-small cell lung cancer (NSCLC), a late Phase II study was conducted. A total of 80 patients with Stage III or IV NSCLC who had no previous therapy were entered into the study. Seventy-nine patients were eligible for response and toxicity. NVB was administered weekly by intravenous injection at a dose of 25 mg/m2 in 20 ml of saline and was generally administered in four cycles or more, unless patients had disease progression. Of the 79 eligible patients, 23 (29.1%) showed a partial response (95% confidence interval, 19.1-40.4%). The median duration of partial responses was 14.7+ weeks. The median survival time for all patients was 40.1+ weeks. The major toxicity was leukopenia. Grade 3 and 4 leukopenia occurred in 48 patients (60.8%). Other toxicities of grade 3 or more included anemia (6.3%), local cutaneous reaction (3.8%), pneumonitis (1.3%), nausea and vomiting (1.3%), mucositis (1.3%) and constipation (1.3%). The absolute dose-intensity of NVB was 22.33 mg/m2/week. A weekly schedule of intravenous administration of 25 mg/m2/week of NVB was reasonable for maintenance of activity, and acceptable for toxicity in the chemotherapy of advanced NSCLC.

[Late phase II clinical study of KW-2307 in previously untreated patients with non-small cell lung cancer. KW-2307 Study Group (Lung Cancer Group)].

A late Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in previously untreated patients with non-small cell lung cancer was jointly carried out in 26 medical institutions. Of 80 enrolled cases, 75 cases were eligible, and PR was attained in 23 cases (30.7%). The main adverse effect of this drug, leukopenia (neutropenia), was observed in 62.7% (83.3%) of Grade 3 and 4 cases, but they recovered rapidly. In addition to decreased hemoglobin in 67% (Grade 3 in 5.7%) of the cases, adverse effects included slight disorder of hepatic function, anorexia, nausea and vomiting, fever, general fatigue, phlebitis, paresthesia and interstitial pneumonia. Peripheral neuropathy such as paresthesia occurred rarely and was slight, if any.

Application of an air-filled tube for measuring intraesophageal pressure.

We devised a new method for measuring esophageal pressure (Pes) with use of a flexible tube without a balloon at a constant rate of airflow through the tube into the esophagus (balloonless method). A study with 133Xe showed that the air that accumulated in the esophagus did not interfere with the measurement of Pes. We measured dynamic compliance (Cdyn) and pulmonary resistance (RL) with the balloonless method in 19 subjects and obtained a static deflation pressure-volume curve (P-V curve) in 10 other subjects. Cdyn was 0.243 +/- 0.099 l/cmH2O and RL was 1.52 +/- 0.42 cmH2O.l-1.s. In 6 of the 10 subjects, a P-V curve was also obtained with the balloon tube (balloon method). K, the index of compliance in the exponential function V = V0(1-e-KP) where V0 is volume at infinite pressure, was 0.136 +/- 0.040 cmH2O-1 with the balloonless method and 0.153 +/- 0.023 cmH2O-1 with the balloon method. No statistically significant difference was found between these two values. In conclusion, Cdyn, RL, and the P-V curve can be obtained precisely with the balloonless method.

Restriction fragment length polymorphism of the human CYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure.

Polymorphic metabolism of certain chemical carcinogens may result in differences in susceptibility to cancers. Human CYP2E1 (cytochrome P450IIE1) is an enzyme involved in the metabolic activation of precarcinogens such as nitrosamines. We detected a restriction fragment length polymorphism (RFLP) of the human CYP2E1 gene for the restriction endonuclease Dra I. The distribution of this polymorphism was examined among lung cancer patients (n = 91), patients with cancer of the digestive tract (n = 45) and controls (n = 76). A significant difference in the distribution was observed between lung cancer patients and controls (chi 2 = 11.4 with 2 df; p < 0.005). On the other hand, there was no significant difference between patients between cancer of the digestive tract and controls (chi 2 = 4.87 with 2 df; NS). This finding suggests that the Dra I polymorphism of the CYP2E1 gene is associated with susceptibility to lung cancer. In addition, an association was found between the amount of lifelong smoking exposure and the distribution of the genotypes of the RFLP among lung cancer patients. The distribution pattern seemed deviated from that of controls especially in the population of low smoking exposure. Our Northern blot analysis data using RNA from human liver autopsy samples suggest that the Dra I polymorphism might be associated with the gene expression of CYP2E1 at mRNA level.

Variety of laminin expressions in murine neoplastic cell-lines - neuroblastoma na cells produce only laminin-b2 chain.

In the present study, we investigated the expression of laminin in three murine neoplastic cell lines; 3LL-SA (Lewis lung carcinoma), NA (neuroblastoma) and F9 (teratocarcinoma). Both Western and Northern blot analyses demonstrated that parietal endoderm-like F9 expressed three laminin chains A, B1 and B2. On the other hand, 3LL-SA cells synthesized two laminin chains B1 and B2, and NA cells only B2 chain. The analyses of the restriction fragment length polymorphism indicated that the genes for coding regions of all chains were present and grossly intact both in 3LL-SA and in NA just as in F9. These findings suggest that expression of laminin seems to be transcriptionally regulated in each neoplastic cell line specifically. Since these cell lines produce different forms of laminin, they can be used for investigation of the multifunctions of laminin molecule.

Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study.

In order to study whether hyperplasia or hypertrophy of cells is responsible for the thickening of airway muscles, 3-D morphometry of airway muscle cells was performed on resin-embedded semithin serial sections of autopsied lungs from 10 asthmatics and five control subjects. There were five Type I and five Type II asthmatic lungs, as defined in an earlier study, thickened muscles being found only in the central bronchi in Type I and distributed over the whole airway tree in Type II. The analysis was based on "unbiased" 3-D morphometry to obtain the numerical density NV of muscle cells using a "disector," a spatial probe introduced by Sterio in 1984, which we modified into a stack of serial sections. The mean number NL of cells per unit airway length and the mean volume Vc of a single muscle cell were also determined. In Type I asthmatics, the number of cells increased in the larger bronchi unaccompanied by cellular hypertrophy at any level of the airway tree. In contrast, in Type II asthmatics, hypertrophy was shown to prevail over the whole airway, but it was most remarkable in the bronchioles, whereas hyperplasia was mild and localized only in the bronchi. The two types of asthmatic lungs may therefore result from different pathogeneses.

Effects of catechins on the mouse lung carcinoma cell adhesion to the endothelial cells.

We studied the effects of 5 kinds of catechins on the adhesion of mouse lung carcinoma 3LL cells to the monolayer of bovine lung endothelial cells. (-)-Epicatechin gallate and (-)-epigallocatechin gallate were active in inhibiting the 3LL cell adhesion, while (+)-catechin and (-)-epicatechin were inactive. (-)-Epigallocatechin showed a considerable cytotoxicity. These data suggest that the specific chemical structure is required to exert the inhibitory activity of catechins and the search for the cellular binding protein(s) bound to these inhibitory catechins would provide a clue to clarify the mechanism of interactions between tumor cells and endothelial cells.

Difference in laminin expression between high and low metastatic cell clones derived from murine Lewis lung carcinoma.

We investigated the expression of laminin in two cell lines with different metastatic potentials established from murine Lewis lung carcinoma. Immunostaining of the cells with anti-laminin antibody and Northern blot analysis of laminin mRNA demonstrated that the high metastatic clone expressed less laminin than the low metastatic one. In contrast, expressions of 67 kDa-laminin receptor were at similar levels between these two lines. These findings show the possibility that endogenous laminin may contribute to the difference in metastatic properties in the murine Lewis lung carcinoma cell lines examined.

[Identification of Mycobacterium tuberculosis complex and Mycobacterium avium-intracellulare complex by using nonisotopic DNA probes].

A total of 31 clinical isolates of mycobacteria consisting of 21 strains of M. avium-intracellulare complex (ten strains each of M. avium and M. intracellulare identified by specific 125I-labeled DNA probes and one strain of M. avium-intracellulare complex identified by conventional biochemical tests) and 10 strains of M. tuberculosis (identified by a specific 125I-labeled DNA probe) were subjected to identification by hybridization protection assay (HPA) with an acridinium-ester (AE) labeled DNA probe. The results thus obtained were in complete agreement with those obtained by 125I-labeled DNA probes (30 strains) or by conventional biochemical tests (one strain). HPA by the AE-labeled DNA probe is safe, simple and rapid, and can be done with ease in any clinical laboratory.