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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 145 records · Page 8Linked to original sources

Experimental Staphylococcus aureus arthritis in mice.

Staphylococcus aureus arthritis is usually caused by bacteremia and is highly destructive. Controlled studies on septic arthritis in humans are difficult to perform, because the time of onset of the infection is unknown. Animal models of bacterial arthritis make it possible to control important variables in experimental studies. We present a mouse model of S. aureus arthritis in which the intravenous administration of 10(7) cells of S. aureus LS-1 induced arthritis or osteitis or both within 3 weeks in 80 to 90% of the mice. Signs of arthritis emerged within the first few days after the injection. An interesting finding was that the S. aureus strain used in this study binds bone sialoprotein, a glycoprotein known to be specifically localized to bone tissue. This new model of S. aureus arthritis enables the study of the kinetics of joint destruction and the host-bacterium relationship as well as therapeutical approaches to septic arthritis and osteomyelitis.

Animals↗

Clostridium difficile toxin A induces a specific antisecretory factor which protects against intestinal mucosal damage.

Peroral challenge with toxin A from Clostridium difficile induced the formation of antisecretory factor in rats. The animals were given 100 micrograms of the toxin, which was followed by a pronounced diarrhoea and by the appearance of antisecretory factor in the pituitary gland. In electrofocusing, the induced antisecretory factor separated in two peaks (pI 5.4 and 5.0); both fractions showed a lectin-like binding to agarose. The pI 5.4 fraction inhibited cholera toxin as well as toxin A induced fluid secretion, while pI 5.0 inhibited toxin A induced secretion only. Immunohistochemistry showed that an antisecretory factor of pI 5.0 protected the mucosa from the cytotoxic effect of toxin A, but did not affect the binding of toxin A to the intestinal epithelium. Sodium dodecyl-sulphate-polyacrylamide gel electrophoresis of the pI 5.0 protein showed two major fractions to be present, one of molecular weight 60 kDa, the other of 30 kDa, the latter probably being a degradation product of the former.

Animals↗

Peripheral denervation suppresses the late phase of delayed-type hypersensitivity.

The impact of peripheral denervation on antigen-specific immune responses was analysed on the B and T cell levels. Delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC) or oxazolone was used in mice as a model system of in vivo T cell reactivity. Serum antibody levels to SRBC, measured by an enzyme-linked immunosorbent assay (ELISA), were evaluated to analyse the B cell response. The effect of peripheral denervation on immune responsiveness was studied both at the point of sensitization and elicitation. The results show that peripheral denervation significantly suppresses the local DTH response. The late, inflammatory phase but not the early phase of the DTH reaction was reduced after denervation (p less than 0.01). The DTH suppression by denervation was similar irrespective of whether the neurectomy was performed 1 or 4 weeks prior to sensitisation. Even in the contralateral limb, with intact innervation, the inflammatory DTH reactivity was decreased. We believe that this phenomenon might be due to abrogation of the reflex arch since the denervation procedure did not give rise to a significant systemic downregulation of DTH. Also, peripheral denervation significantly suppressed footpad swelling induced by local administration of cholera toxin, a potent phlogistic compound. The antibody response against the same immunogen was not influenced by denervation. Our results suggest that denervation of a mixed peripheral sensory/motor nerve abrogates the formation of both T cell-dependent and independent inflammatory responses.

Animals↗

Outbreak of spontaneous staphylococcal arthritis and osteitis in mice.

Staphylococcus aureus is the most common bacterial species found in association with nongonococcal bacterial arthritis in humans. We present here the first description of spontaneous bacterial arthritis and osteitis in mice. Clinically, the most obvious findings were swelling and/or ankylosis of hindpaws and nodose changes of the tail. The prevalence of arthritis and osteitis ranged from 0% to greater than 50% of the mice studied, depending on the mouse strain. The most prominent histopathologic feature of the arthritis was hypertrophy of the synovial tissue and destruction of cartilage and underlying bone. Most of the S aureus-infected mice displayed an identical phage type, which was also the only S aureus phage type found in skin isolates from clinically healthy mice. However, a few S aureus isolates were not typeable, indicating that an additional strain(s) might cause bacterial arthritis in mice.

Animals↗

Enterotoxins from Clostridium difficile; diarrhoeogenic potency and morphological effects in the rat intestine.

The action of toxins A, B, and C from Clostridium difficile was studied in the small intestine and colon of rats. All three caused fluid accumulation in the small intestine, maximal secretion being induced by 1 micrograms of toxin A, 20 micrograms of B, and 15 micrograms of C. Both toxins A and C caused shedding of epithelial cells from the villi without visible damage to crypt cells; toxin A caused further extensive necrosis and bleeding. Toxin B caused secretion without visible damage to the epithelial cells, though this activity was unstable and decreased significantly after one week of storage. In the colon, toxin A caused secretion and shedding of surface epithelial cells without damage to crypt cells, toxin C caused only a weak secretion, and toxin B had no effect at all. In terms of immunohistochemistry, it was found that toxin A bound to the enterocytes at the tips of the villi but not to goblet and crypt cells. The complex expression or interaction of the toxins produced by Cl difficile may explain the broad spectrum of disease (diarrhoea, colitis, and pseudomembranous colitis) associated with this micro-organism.

Animals↗

Further studies on the effect of ASF factor on Cl- permeability across the Deiters' neurone plasma membrane.

Experiments have been performed in order to assess whether the antisecretory factor (ASF) can influence the permeation of Cl- ions across the Deiters' neurone plasma membrane in the outward direction. ASF is a naturally occurring, acidic protein with a molecular weight of about 60,000, which specifically inhibits enterotoxin-induced intestinal secretion. Both basal and "intracellular" GABA activated Cl- permeability was studied, and the result confirmed the existence of GABAA receptors on the Deiters' membrane cytoplasmic side. ASF completely abolished the effect of "intracellular" GABA on Cl- permeability in the outward direction. However, ASF did not influence the basal Cl- permeability in the outward direction.

Animals↗

[Radiologic diagnosis and therapy of pleural mesothelioma].

In Germany pleural mesothelioma occurs annually in 100-200 patients who had usually been working in the asbestos industry. In 100 mesotheliomas, evaluated radiologically, 61 presented pleural effusions and 82 a pleural tumour. This may result in retracting the hemithorax. Radiotherapy has a palliative goal. Applying 40 Gy may reduce pain and may inhibit fluid production. The irradiated volume should, if possible, spare lung tissue, which necessitates careful treatment planning.

Asbestosis↗

Prediction of outcome of decompression for carpal tunnel syndrome.

45 patients (55 hands) with carpal tunnel syndrome treated surgically have been studied. Painful nocturnal paraesthesiae occurred in patients with short histories and was a good prognostic feature. Electromyography proved of value in assessing motor lesions and the degree of the process. The first sign of muscle involvement was fibrillation potential. In longer histories, an increased amount of polyphasic potentials and reduced voluntary pattern was seen. The reduced pattern is reversible in cases of short duration and the absence of muscle wasting. In cases with marked alteration and signs of chronic muscle degeneration, the prognosis for pain is good, but not so for the neurological deficit. The nerve conduction velocity improved quickly after decompression of the median nerve in accordance with the complaints of the patient. Electrophysiological methods proved their value in staging and follow-up.

Adult↗

The antisecretory factors: inducible proteins which modulate secretion in the small intestine.

1. Cholera toxin and glucose induce the synthesis of antisecretory factors (ASF) of isoelectric points 5.0 and 4.3, respectively, and of a molecular mass of ca 60,000. 2. ASF, in nanogram amounts, inhibit intestinal secretion induced by cholera toxin, Campylobacter toxin, E. coli heat-stable toxin, C. difficile toxin A, and Dinophysis toxin. 3. Intraspinal injection of cholera toxin and glucose induces the synthesis of pituitary ASF much more effectively than does either peroral or intranasal administration. 4. Cholera toxin and glucose seem to act synergistically while inducing ASF. 5. Vagotomy abolishes both the intestinal effects of ASF and the peroral, but not the intraspinal induction of pituitary ASF. 6. ASF has no effect on ion transport across isolated intestinal mucosa from either pig or hen. 7. The results suggest that both the induction and the intestinal effects of ASF are mediated via the central and intestinal nervous system.

Animals↗

Toxic mussels and okadaic acid induce rapid hypersecretion in the rat small intestine.

The diarrheic activity of algal toxins in blue mussels (Mytilus edulis) has been quantitatively determined in ligated intestinal loops of the rat. Hepatopancreas from toxic mussels were disintegrated by freeze-pressing, and the homogenized tissue suspended in an equal amount (w/v) of buffer or in the liquid recovered after steaming. When such suspensions were injected into ligated loops of rat small intestine a rapid fluid secretion was observed. In contrast, the liquid from non-toxic mussel tissue homogenate was absorbed. Toxic tissue homogenates, liquid recovered after steaming of toxic mussels as well as purified okadaic acid produced maximum fluid accumulation in the loops within two hours. The maximum net fluid accumulation observed was ca 300 mg of weight increase per cm length of intestine. Within a range of 50-200 mg/cm the dose-response relationship was close to linear (r = 0.96, 0.99). In duplicate tests the average deviation from the mean was +/- 9 mg/cm (SD = +/- 4.9). Mussels yielding less than 100 mg/cm of weight increase per g hepatopancreas have been allowed for human consumption, a quantity agreeing with the allowed level of okadaic acid. The minimum quantity of okadaic acid which produced significant secretion in the rat intestinal ligated loop test was approx. 0.5 microgram. On a body weight basis, therefore, humans are estimated to be at least four times as sensitive as the rat to enteral challenge with okadaic acid.

Animals↗

Seasonal, geographic and individual variation of okadaic acid content in cultivated mussels in Sweden.

In Western Europe the dinoflagellate toxin, okadaic acid (OA) has been the main cause of diarrheic shellfish poisoning (DSP). Chemical determination of OA in mussels by homogenization of the hepatopancreas, extraction, purification, reaction with 9-anthryldiazomethane (ADAM), HPLC-separation, and fluorometric quantification has been used for weekly monitoring of mussel growing farms and to control harvested mussels. Within a week, substantial rises (from 0.41 to 5.4 micrograms OA/g hepatopancreas) as well as great reductions (from 7.2 to 1.8 micrograms/g hepatopancreas) were recorded. The rapid rise implies that weekly sampling is not sufficient to ensure that mussels are free from toxic levels of OA. The rapid decrease reveals that efficient toxin clearance mechanisms exist in the mussels. Substantial OA clearance occurs also at low temperatures (1.4-3 degrees C). Within a mussel growing site the OA concentrations could differ considerably between adjacent mussels (0.63 and 4.2 micrograms OA/g hepatop.) and even more between mussels grown at different depths along the same rope (0.63 and 10 micrograms OA/g hepatop.). These data emphasize the importance of sampling in studies on DST in mussels. Great differences between the different mussel growing sites were also observed. These data have been discussed with respect to the spread of the toxin by the sea, and the possibilities of reducing the exposure of the mussels to the toxic algae.

Animals↗

[Radiologic control of therapy and after care in bronchial cancer].

All therapeutic modalities of lung cancer - surgery, radiotherapy and chemotherapy - may be controlled by radiological methods. During the week after surgery one x-ray examination of the thorax should be done every day, in order to rule out pneumonia, atelectasis, mediastinal shift etc. For radiotherapy, x-ray images can show the change in tumour volume and the occurrence of pneumonitis. For chemotherapy of oat-cell carcinoma, x-ray controls are important, because chemotherapy can be modified if the therapeutic effect is not satisfactory. For follow-up studies of treated lung cancer, x-ray examinations of the thorax are indicated every three to six months. Computed tomography bone scans and liver sonography should be employed whenever there are relevant clinical signs or symptoms.

Carcinoma, Bronchogenic↗

[Conventional roentgen diagnosis of bronchial cancer].

The incidence of lung cancer has increased tenfold since 1930. Early diagnosis using screening examinations have not been rewarding and even today lung cancer is usually diagnosed only at a late stage. Three manifestations-central lung cancer with endobronchial growth, central lung cancer with peribronchial growth and peripheral lung cancer-are the ones most frequently detected by x-ray examination. The staging of cancer, which determine the therapy, relies on x-ray findings to a great extent.

Carcinoma, Bronchogenic↗

Intake of monosaccharides or amino acids induces pituitary gland synthesis of proteins regulating intestinal fluid transport.

In cholera diarrhoea, the pituitary gland produces a 60-kDa protein known as antisecretory factor (ASF) which reverses intestinal secretion induced by the cholera toxin. We show here that ASF-like proteins are produced in the rat during intestinal secretion triggered by intake of a 500 mg dose of mannose, sorbitol, glycine or alanine. All the ASF-like proteins reversed cholera secretion, and all were of a similar size. However, they differed in charge: mannose and sorbitol induced a protein with an isoelectric point of 4.5; glycine induced two proteins, one with a pI of 6.3, the other of 7.7; and alanine induced two proteins, one with a pI of 6.3, the other of 9.4. Antibodies against naturally occurring ASF from porcine pituitary gland neutralized ASF induced by cholera toxin and two of the amino acid-induced proteins, while the sugar-induced protein(s) did not cross-react. All the proteins showed affinity to agarose and were dissociated again with methyl alpha-D-glucoside. A single peroral dose of cholera toxin or sorbitol induced antisecretory proteins which persisted in the pituitary gland for only 1-3 days. Seven treatments gave a sustained response, the protein induced by cholera toxin persisting for over 2 months, and that induced by sorbitol about 1 month.

Amino Acids↗

The effect of antisecretory factor on the permeability of nerve cell membrane to chloride ion.

The antisecretory factor (ASF) is a hormone-like protein (m.w. 60,000) that most effectively counteracts hypersecretion in vivo in the small intestine of pigs and rats. The present report demonstrate that 10(-13) moles of ASF inhibits significantly the 36Cl- permeation through the isolated neuronal plasma membrane of Deiters' cells in rabbits. This effect was enhanced by 0.2 mM gamma-aminobutyric acid (GABA), and quenched by the addition of anti-ASF immunoglobulins; pretreatment of the neuronal membrane with nipecotic acid (10(-6) M) or with bicuculline (10(-3) M) abolished the ASF action whilst picrotoxin (10(-4) M) pretreatment left the inhibitory effect of ASF unaffected. The results suggest that ASF blocks chloride channels in neuronal membranes, including those channels activated by GABA.

Animals↗