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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 163 records · Page 9Linked to original sources

Effects of the antisecretory factor in pigs.

The effect of the antisecretory factor (ASF) on experimental porcine enterotoxin-induced jejunal secretion was tested. The heat-labile enterotoxin (LT) from Escherichia coli and cholera toxin (CT) was used for challenge in ligated intestinal loops. Less than 10 units of ASF inhibited the LT-induced secretion, while that due to CT required more than 10 units of ASF. ASF was effective only when administered prior to toxin challenge, and could be given either intravenously or intra-intestinally. Mixing of ASF with specific anti-ASF antibodies prior to injection abolished its antisecretory effect. LT- and CT-induced secreted fluid contained equal concentrations of Na+, K+ and Cl-, and the ionic concentration was not affected by ASF. Less than 0.1 units of ASF per pituitary gland was present in 3- and 5-week old pigs, while it increased to 4.5 units in 28-week old animals, and to 12.2 units in pigs older than two years. However, after intra-intestinal vaccination with 2.0 mg CT, the pituitary ASF content in the 5-week old animals increased to 2.0 units within 24 h.

Administration, Topical↗

Purification and characterization of the antisecretory factor: a protein in the central nervous system and in the gut which inhibits intestinal hypersecretion induced by cholera toxin.

The antisecretory factors (ASF) are hormone-like proteins which inhibit cholera toxin-induced intestinal hypersecretion. Although ASF concentrations in young control rats were low, those in old control rats and toxin-treated rats were high. Toxin-treated rats had 200 ED50 units/g wet weight of ASF in the pituitary gland, while their intestinal mucosa, bile and milk contained 3, 0.5 and 0.5 units/g. In adult man and in 8-9-month-old pig the pituitary level was about 20 units/g. The isoelectric points of ASF from pig and rat were 4.8 and 5.0, respectively, while the molecular size as determined by gel filtration on Bio-Gel P-150 was the same in both cases (Kav 0.43). The molecular weight as determined by SDS-polyacrylamide gel electrophoresis was 60,000 for ASF from porcine pituitary gland. One ED50 unit of the purified porcine ASF corresponded to about 10(-13) mol (1-5 ng) of protein. There were two different ASF from human pituitary gland: pI 5.2, Kav 0.43; and pI 4.5, Kav 0.6. Since antibodies against porcine ASF failed to neutralize the latter protein, it may be unrelated to porcine ASF; the human pI 5.2-protein and rat ASF were both neutralized, but less effectively than was porcine ASF. All the ASF molecules attached to agarose gel, from which they dissociated again in methyl alpha-D-glucose: porcine and rat ASF were eluted at 0.3-0.9 M methyl alpha-D-glucose, human pI 5.2-ASF at 0.1-0.9 M, and human pI 4.5-ASF at 0.1-1.5 M methyl alpha-D-glucose.

Adult↗

Bile and milk from cholera toxin treated rats contain a hormone-like factor which inhibits diarrhea induced by the toxin.

Protection against intestinal secretion induced by cholera toxin (CT) was studied in adult and suckling rats. Peroral CT treatment of lactating females protected their suckling offspring against diarrhea. This milk contained a protective antisecretory factor (ASF) as shown by passive peroral or intravenous transfer of the milk to adult, nontreated recipients in which the cholera response was tested in ligated jejunal loops. Bile from CT-treated rats also contained ASF, which was still present 100 days after the last treatment. Although milk and bile from untreated rats contained no ASF, bile from very old untreated rats did. Chemical characterization showed that ASF in bile and milk both had isoelectric points of about 5.0 and molecular weights of about 25,000. These data are similar to those previously obtained for ASF isolated from porcine pituitary glands, and show that the antisecretory activity is unrelated to immunoglobulins.

Age Factors↗

[Anti-angina action and tolerance of isosorbide-5-mononitrate or nifedipine in retard form].

Twelve patients with stable angina and reproducible depression of the ST-segment during bicycle exercise of at least 0.15 mV were assessed in a double-blind randomized cross-over study. Patients were treated either with 50 mg isosorbide-5-mononitrate (IS-5-MN) daily or 2 X 20 mg nifedipine retard daily or the combination of both drugs for 2 weeks. The sum of ST-segment depression at maximal exercise was reduced by nifedipine and IS-5-MN to the same amount, while ST-segment reduction was highest during treatment with the combination of both drugs. The best exercise duration and maximal working capacity were also recorded during combination treatment. However, patient appreciation concerning efficacy and side-effects was best with nifedipine, slightly worse with IS-5-MN, and only one patient judged the combination of both drugs as good.

Angina Pectoris↗

An inhibitory protein of intestinal fluid secretion reverses neuronal GABA transport.

Intestinal challenge with cholera toxin induces the synthesis of a hormone-like protein which counteracts intestinal hypersecretion. This study shows that the protein also inhibits GABA transport across the plasma membrane of Deiters' cells in rabbits. The inhibitory action of the protein was dose dependent, and 10(3) times more potent than met 5-enkephalin, hitherto the most effective known inhibitor of GABA transport in vitro. The influence of the protein on the plasma membrane was reversible, and did not affect either postsynaptic binding or uptake of GABA.

Animals↗

Morphine: continuous intravenous infusion versus intramuscular injections for postoperative pain relief.

Postoperative pain was controlled in 42 patients with either continuous intravenous (iv) or scheduled intramuscular morphine following surgery for gynecologic cancers. In this double-blind study, no statistical differences were found in pain control or rate of complications between the two methods of administration. Both routes were effective in controlling pain without producing major toxicity. Initial doses were based on the patient's weight and then adjusted every 4 hr. We conclude that both methods are safe and effective but that continuous iv infusion is the preferred route because of the ease of administration, elimination of multiple intramuscular injections, and possibly more even pain control.

Adult↗

Follow-up study of 100 malignant pleural mesotheliomas.

One hundred malignant pleural mesotheliomas have been treated in our hospital since 1955. Clinical and autopsy findings are analyzed and compared to X-ray changes. The most common symptoms were dyspnea (49%), pain (40%) and cough (36%). The main initial X-ray signs were pleural effusion (62%), pleural thickening (29%) and solitary nodules (6%). Prior to death a combination of effusion and pleural thickening was the usual finding. Histologically there were 49 biphasic, 32 mesenchymal and 18 epithelial malignant pleural mesotheliomas. At autopsy 82% of the cases had distant metastases, most of which had not been expected clinically. The median survival time was 7.3 months following the first clinical symptoms, and only 4 months after the first radiological signs.

Adult↗

Purification and characterization of a hormone-like factor which inhibits cholera secretion.

A factor which inhibits intestinal hypersecretion induced by cholera toxin was studied. The factor was extracted from intestinal mucosa or pituitary gland of pig. It has an isoelectric point of pH 4.7 +/- 0.1 at 10 degrees C and showed a weak affinity to dextran gel and a strong affinity to agarose gel. From agarose gel the factor was eluted with high concentrations of D-galactose or alpha-methyl-D-glucose, while D-glucose and lactose were less effective. After purification more than 2000 times by isoelectric focusing and gel chromatography, the factor was shown by SDS-polyacrylamide gel electrophoresis to be a protein consisting of subunits of molecular mass 30, 17 and possibly 15 kDa.

Animals↗

[Secondary arthrosis after surgical treatment of ankle fractures].

98 patients were clinically and radiographically examined 2 to 9 years following the osteosynthesis of ankle fractures. The rate of secondary osteoarthritis was 70% including 40% of minor, 17% of medium and 13% of serious changes. Depending on the injured structures and frequency of posttraumatic osteoarthritis varies. Medium and serious radiology changes cause obvious dysfunction in 56% and 62% respectively. Joints free of Osteoarthritis one year after the injury will not develop secondary osteoarthritis later.

Adolescent↗

[Lymphangitic carcinomatosis of the lung in metastatic breast carcinoma].

The lungs of 34 patients who had died of carcinoma of the breast and pulmonary lymphangitis carcinomatosa were prepared by air insufflation and then examined radiologically and histologically. The results were compared with x-ray examination performed just before death. The interstitial pattern of lymphangitis is due to tumour cell infiltration of septal, peri-vasal and peri-bronchial lymphatics, and to fibrosis. Pleural effusions developed in 17 patients and were twice as frequent on the side of the breast tumour. Hilar lymph node enlargement was found in only five cases, although histological involvement was proven in 19. Theories concerning the mode of propagation of pulmonary lymphangitis carcinomatosa are discussed.

Adult↗

[Malignant pleural mesotheliomas. Comparison of roentgenologic and autopsy findings].

In 100 pleural mesotheliomas follow up x-ray studies were compared to autopsy findings. Initially x-ray examinations show effusions in 62%, diffuse pleural thickening in 29% and solitary pleural nodules in 6%, prior to death effusions and pleural thickening are usually combined. In 17 tumor nodules doubling times ranged from 0.5 to 3 months. The epithelial type of mesotheliomas is predominantly combined with pleural effusions, while pleural thickening is more often found in the mesenchymal type of the tumor.

Humans↗

Intestinal adaptation to cyclic AMP-mediated hypersecretion induced by the heat-labile enterotoxin of Vibrio cholerae and Escherichia coli.

Adaptation to cholera toxin (CT) and the heat-labile enterotoxin (LT) from E. coli is studied in vivo in the rat small intestine. Repeated peroral pretreatment with CT or LT induces protracted inhibition of the intestinal fluid response to these toxins. The CT-induced mucus release from intestinal goblet cells is not influenced by CT pretreatment and the binding of CT to the epithelium remains intact. However, the adenylate cyclase activity, which mediates CT and LT action, is repressed--as judged from the response of this enzyme to both CT, LT and prostaglandin E1. The results suggests that protection against CT and LT acquired in the gut is achieved by desensitization of the adenylate cyclase system.

Adenylyl Cyclases↗

Cytoskeletal disarrangement in rat intestinal epithelium after in vivo exposure to secretagogues.

Cholera toxin (CT) and E. coli heat-labile enterotoxin (LT) induced hypersecretion in the small intestine, as did cytochalasin B and dibutyryl-cyclic AMP (DB-cAMP). The cytoskeleton in the apical part of the intestinal epithelial cells was disorganized after challenge with either of the four secretagogues, but not cholera B-subunit toxoid, as revealed by immunofluorescence microscopy using actin and the intermediate filament keratin as markers. Electron microscopic analysis confirmed the re-engagement of the terminal web and the appearance of short microvilli lacking most of their normally observed central core of actin filaments. Pretreatment with chloroquine prevented cytoskeletal disorganization as well as hypersecretion by CT, but not by cytochalasin B. A similar effect was achieved with chloroquine on CT-induced fluid secretion, while chlorpromazine inhibited the fluid response to cytochalasin B as well as to CT. The observed cytoskeletal re-engagement might be one of the reactions behind enterotoxic diarrhoea.

Animals↗

Internalization in vivo of cholera toxin in the small intestinal epithelium of the rat.

The binding and internalization of cholera toxin (CT) into the intestinal epithelium were studied in vivo in rats. The distribution of CT was ascertained using immunofluorescence and by immunoenzyme-electron microscopy, with horse-radish peroxidase anti-CT antibodies as the conjugate. The toxin was rapidly bound and internalized into both epithelial and goblet cells; CT was evenly distributed on the microvilli at the bases of which it appeared in invaginations (coated pits). Though not found in nuclei, CT appeared intracellularly in coated vesicles, and dissolved in the cytoplasm where it was enriched at the terminal web. The basolateral membrane, except for the tight junctions, was outlined with CT; some staining also appeared in the basement membrane, in fibroblasts, macrophages and in the blood-vessel walls in the submucosa. The lysosomatotrophic agent chloroquine simultaneously inhibited CT-induced fluid secretion and intracellular distribution of CT in the cytoplasmic matrix, but not in the vesicles. The inhibitor of CT-action on adenylate cyclase, chlorpromazine, did not affect the cellular distribution of CT. Our results suggest that CT mainly is internalized by endocytosis into the intestinal epithelium. The toxin is probably released from vesicles into the cytoplasm via secondary lysosomes.

Animals↗

Intestinal resistance to cholera toxin in mouse. Antitoxic antibodies and desensitization of adenylate cyclase.

Mice were immunized perorally with cholera toxin (CT), cholera B-subunit (CB), or buffer as control. The response of anti-CT antibodies of the IgG, IgA and IgM class in bile, IgA being predominating, were similar in both immunized groups. The same number of anti-CT containing plasma cells (ACC) were determined in the intestinal lamina propria of CT - as well as of CB-immunized mice 20 days after the last immunization, while ACC at day 4 in the CB group were 50% higher than in the CT group. In contrast to the vigorous antibody response to CT in both groups of immunized mice, only animals immunized with CT displayed resistance to CT-induced intestinal hypersecretion and to CT stimulation of adenylate cyclase. The CB-treated group responded to CT with fluid accumulation and enzyme activation similar to controls. The results suggest that intestinal resistance to CT in mouse is due to desensitization of adenylate cyclase rather than to CT-neutralizing antibodies.

Adenylyl Cyclases↗