Enhancement of the antineoplastic effect of anticarcinogens on benzo[a]pyrene-treated Wistar rats, in relation to their number and biological activity.

Naturally occurring anticarcinogens, such as vitamins C and E, and the microelement selenium were found to inhibit the induction of benzo[a]pyrene-induced malignant tumors in Wistar rats to various extends. The antineoplastic effect of the tested anticarcinogens is gradually increased according to the number of inhibitors selected. To date the maximum action against malignancy is manifested by use of the above three inhibitors. In the group of rats receiving vitamins C, E and selenium, the prolongation of life induced by adding more than one anticarcinogen to the treatment regime reached, and in some cases surpassed, the normal life expectancy of the rats. It is expected that by adding even more anticarcinogens, the antineoplastic potency (Ap) of the inhibitors will be further improved. These results encouraged us to conduct a clinical trial in terminal human cancer cases, in conjunction with the usual treatments of surgery or chemotherapy and irradiation.

Staining of surface antigens of Chlamydia trachomatis L2 in tissue culture.

Surface labeling of chlamydial elementary and reticulate bodies in L929 cells infected with Chlamydia trachomatis serotype L2 was monitored by using monoclonal antibodies (MAb) against the major outer membrane protein and lipopolysaccharide (LPS). Different staining and fixation procedures were used to detect these surface antigens during the developmental cycle. Anti-major outer membrane protein MAb yielded a clear staining pattern of exclusively chlamydial inclusions independent of the fixation or staining technique used. Anti-LPS MAb gave a faint staining pattern of reticulate bodies when methanol fixation was used and showed that LPS was released from chlamydiae into the host cell cytoplasm and into the surroundings of the infected host cell. However, when paraformaldehyde-glutardialdehyde fixation was used, extracellular LPS staining was not observed. The data show that chlamydial LPS is loosely bound in the bacterial outer membrane but suggest that shedding of LPS is a fixation artifact.

[Exogenous allergic asthma following pectin exposure--a new occupational allergen]. / Exogen-allergisches Asthma nach Pektin-Exposition--ein neues Berufsallergen.

In a 51-year-old male worker, workplace-related dyspnoea in the sense of bronchial asthma, was observed. On the basis of the medical history, the results of serology, inhalatory provocation and histamine release tests, despite a negative skin test, pectins were established to be the precipitating substances; in experiments on animals (Wistar rats), the instillation of pectins led to the development of bronchiolitis. An exogenous, allergic asthma following exposure to pectin may be considered to have been proven.

[Leu-M1, CEA and intermediate filament proteins in histochemical differential diagnosis of malignant pleural mesothelioma]. / LEU-M1, CEA und Intermediärfilamentproteine in der histochemischen Differentialdiagnose maligner Pleuramesotheliome.

The differential diagnosis "pleuramesothelioma" vs "metastatic adenocarcinoma" can mostly not be decided clearly by conventional histological methods in malignant pleuraneoplasias. Leu-M1 is employed in immunhistochemical diagnosis of lymphomas in Hodgkin's disease but it also reacts with adenocarcinoma cells. Pleuramesotheliomas are Leu-M1 negative. Intermediary filament proteins, CEA and Leu-M1 are important "markers" in the diagnosis of malignant pleuraneoplasias. 25 pleura biopsies of malignant pleura processes were subjected to immunhistochemical examination.

[Experimental and clinical data of the pulmonary toxicity of mitomycin C]. / Experimentelle und klinische Daten zur pulmonalen Toxizität von Mitomycin-C.

The pathological-anatomical development of injuries to the lung induced by mitomycin-C, begins with an irregular thickening of the endothelial cells of the capillaries and progresses to the liberation of surfactant and to the activation of alveolar macrophages. When the macrophages break down, the resulting liberation of mediators initiated the fibrotic process in the lungs. In animal experiments, it has been shown that simultaneous administration of steroids can completely prevent this development. Clinical investigations have shown that, with the aid of aggressive diagnostic procedures, as also thorough lung function studies and bronchoscopy with lavage, pulmonary damage can be detected early on, before clinical symptoms have occurred. In the clinical investigations, too, prophylactic administration of steroids has been shown--in a randomised comparison with urokinase and no accompanying treatment--to be able statistically significantly to reduce the occurrence of toxic injuries in the lungs.

Granulomatous pulmonary reactions after instillation of Mycobacterium gordonae. Light and electron microscopic investigations on the rat model.

Pathogenicity of Mycobacterium gordonae in humans has so far been reported in the literature in the form of case reports only. Systematic experimental investigations have not been published. For this reason, the pathogenicity of two Mycobacterium gordonae strains isolated from human ivestigation material were tested in animal experiments. Measured amounts of in some cases live and in some cases heat-killed M. gordonae were instilled into the right lower lobe of the lung of anesthetized Wistar rats by means of a polyvinyl catheter. The tissue changes were investigated at graduated time intervals between 1 h and 24 weeks by light and electron microscopy. Small granulomas consisting of leukocytes and macrophages develop in the lung tissue 3 days after the instillation. Under the electron microscope, intracellular mycobacteria can be demonstrated. These do not proliferate. After 2 weeks, sarcoid granulomas have formed from epitheloid and giant cells. Casefying necroses are absent. Electron microscopically, it can be shown that the mycobacteria are broken down intracellularly in phagolysosomes, so that sarcoid granulomas free of bacteria are left behind.

Pulmonary metastasizing hemangiopericytoma.

Hemangiopericytomas are rare tumors, originating from pericytes of the small vessels, that can appear anywhere in the body. From the histological picture it is difficult to determine whether or not they are malignant. The metastasizing rate depends upon the tumor's location and varies from 50 to 80%. Local recurrences occur in roughly 50% of the cases. Hemangiopericytoma is normally surgically treated because radio- and chemotherapy are generally less effective. There is limited experience in treating metastasizing hemangiopericytomas with chemotherapy. We treated 2 patients with pulmonal metastasizing hemangiopericytoma: In 1, the tumor originated in the brain and in the other, the left knee. Both patients had chemotherapy over an extended period of time. By means of x-ray, histological, and electronmicroscopical examinations we report on the course of the diseases.

Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats.

Longitudinal light and electron microscopy investigations were previously carried out on Wistar rats to study the pathogenesis of pulmonary fibrosis due to asbestos. In the present study, the genesis of pulmonary carcinomas and pleural mesotheliomas have been investigated by light and electron microscopy on the same model after intrabronchial instillation of chrysotile B and benz(a)pyrene, as well as a combination of the two carcinogens. A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin by means of a polyvinyl catheter into the right lower lobe of the lung of 70 anesthetized 6-week-old Wistar rats caused pulmonary carcinomas or malignant pleural mesotheliomas in 18 animals (24%). The tumors occur at intervals between 12 and 31 months after the asbestos application. By electron microscopy, small asbestos fragments can be detected under the pleural mesothelium at the earliest 1 year after the intrabronchial application of chrysotile. A single combined instillation of 1 mg chrysotile and 0.5 mg benz(a)pyrene does not increase the tumor incidence. With simultaneous administration of these two substances, however, lung tumors arise very much earlier than in instillation of only one of the carcinogens. Thus, an adenocarcinoma was found in the lungs after 4.5 months, and a pleural mesothelioma was already found after 7.7 months. The intrabronchial instillation of benz(a)pyrene alone causes fewer lung tumors (tumor incidence 10%, interval between 13 and 33 months).

Isolation and characterization of coliphage omega 18A specific for Escherichia coli O18ac strains.

The bacteriophage omega 18A, specific for Escherichia coli O18ac strains, was isolated from sewage. The results of host range and conjugation experiments showed that the sensitivity of bacteria to the phage is associated with the presence of O18ac antigens. With some of the O18 strains the phage omega 18A produces clear lysis on bacterial lawns only when applied at a high multiplicity and moreover the phage does not multiply. With the help of the phage omega 18A, E. coli O18ac strains could be divided into two serologically distinct subgroups called O18A and O18A1. E. coli strains belonging to the subgroup O18A are sensitive to phage omega 18A whereas bacteria of subgroup A1 are resistant.

The simultaneous inoculation of Mycobacterium leprae and M. intracellulare into nude mice: development of cutaneous leproma and accelleration of foot pad swelling.

Organisms of the non-pathogenic Mycobacterium intracellulare serotype 19 Darden enhanced the pathogenicity of M. leprae when inoculated together into the foot pads of nude mice. This supporting effect could be demonstrated by an accelleration of foot pad swelling, beginning 4 months after inoculation and by the development of cutaneous leproma on dorsal and lateral body sites within 6 months after inoculation. These leproma increased in number and size during the 9 months they were under observation and demonstrated micromorphological characteristics similar to those of human leprosy.

[Pneumonitis with fatal pulmonary fibrosis (Hamman-Rich syndrome) due to parathion-(E-605-) poisoning]. / Pneumonitis mit letaler Lungenfibrose (Hamman-Rich-Syndrom) bei Parathion-(E-605-) Vergiftung.

A patient with chronic Parathione (E 605) poisoning was observed over a period of 55 days. During that time he developed progressive changes, which were identical to those of progressive idiopathic pulmonary fibrosis. The rapid development of an alveolitis, followed by a lethal pulmonary fibrosis, differed in no way, macroscopically nor microscopically, from the lung changes in paraquat poisoning (paraquat lung). The radiological course has been correlated with the clinical and post mortem findings.

Pathogenesis of pulmonary fibrosis induced by chrysotile asbestos. Longitudinal light and electron microscopic studies on the rat model.

A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin was made via a polyvinyl catheter into the lower lobe of the right lung of 120 six-week-old Wistar rats under anesthesia. The animals were killed at intervals between five minutes and two years. The lower lobes of the right lung were investigated by light and electron microscopy. The process of pulmonary fibrosis induced by asbestos can be subdivided into four phases: these are the phase of phagocytosis (five to 15 min), the phase of granuloma formation (between one and two weeks), the phase of septal fibrosis (between two and six months) and finally the scar stage (after one year). After instillation of small asbestos fibers into the alveoli, a major proportion of these fibers is phagocytosed by alveolar macrophages after five minutes and leaves the lungs via the airways. A proportion of the fibers penetrates through the alveolar wall (mostly conveyed by type I pneumocytes) and reaches the interstitium of the lungs. There, the fibers are taken up by pulmonary tissue macrophages and giant cells. Within the phagolysosomes, the fibers are broken down into fragments less than 0.01 micron in length. Type II pneumocytes produce surfactant in excess. These cells become necrotic, tubular myelin and lamellar bodies pass into the alveoli and into the interstitium. Surfactant is phagocytosed by resident macrophages. These macrophages can break down. Besides asbestos and surfactant, mediators of fibrillogenesis are released. Macrophages following up from blood monocytes ingest surfactant and asbestos. This process is perpetuated up to complete scarring. After two years, small asbestos fibers less than 0.01 micron long are present in fibroblasts and pleural mesothelia.

Skeletal muscle antibodies in patients with a thymic tumour but without myasthenia gravis.

Sera from 9 patients with a primary thymic tumour but without myasthenia gravis (MG) at the time of thymectomy were examined for skeletal muscle antibodies. Antibodies to a citric acid extract (CA), associated with the presence of a thymic lymphoepithelioma in MG patients, were detected in 3 sera. AChR antibodies were detected in 5 sera, the concentration markedly elevated in 1 of them. Sarcolemmal and cross-striational antibodies were detected in 2 and 3 sera, respectively. Four of the 5 patients with thymic tumours other than a lymphoepithelioma had AChR antibodies, and 3 of them also had CA antibodies.

Functional morphology of phagocytosing alveolar macrophages. Long-term electron microscopic and X-ray microanalytical investigations on the rat model.

A single instillation of 1 ml iron dextran (containing 191.3 mg iron(III)hydroxide and 200 mg dextran) was administered under anaesthesia by a polyvinyl catheter into the lower lobe of the right lung in one hundred 4-week-old wistar rats. The animals were killed at intervals ranging between 1 min and 4 weeks. The lower lobe of the right lung was examined by light and electron (transmission and scanning) microscopy. In addition, X-ray microanalyses were performed on tissue sections in the transmission and scanning electron microscopes. The process of phagocytosis of iron dextran by alveolar macrophages can be subdivided into three stages, which we have termed the "phase of attachment" (from 1 to 5 min), followed by the "phase of phagocytosis" (from 5 to 20 min) and finally the "resident macrophage stage" (from 1 to 24 h). X-ray microanalysis shows a high phosphorus content even if iron dextran is concentrated on the surface of macrophages. Phagocytosis of particles between 15 and 40 A in size occurs within minutes, the particles being engulfed in phagosomes, which form as double-layered invaginations of the cell membrane into the interior of the cell. The fusion of phagosomes with lysosomes produces phagolysosomes (type 2 lysosomes) in which iron dextran is broken down into lamellar residual bodies. In these lamellar bodies X-ray microanalysis shows that in addition to abundant iron, there is a high phosphorus content, which may indicate the involvement of surfactant. Only 1 h after instillation, free particles of iron dextran can no longer be demonstrated in the alveoli, although a proportion of the iron dextran remains in resident macrophages (pulmonary tissue macrophages) and some is also found in splenic macrophages.