[Morphologic and morphometric studies of the lung in shock of various etiologies].
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Biomedical subjects
Publications and source records attributed to G Köhler.
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Non-steroidal antirheumatic drugs (NSAIDs) have become essential in the treatment of chronic joint disease. The dosage has to be established individually for each patient because the resorption is independent from body size and body weight. After repeated administration NSAIDs are selectively concentrated in the inflamed tissue, which therefore has to be considered an independent compartment for the distribution of the drug. The concentration in this compartment is related to the basic disease and its degree of activity. With increasing activity of the disease the concentrations of NASIDs increase in the involved tissues.
Eight mutant hybridoma lines are described, which synthesize short immunoglobulin mu chains. Four internal deletions were mapped by Southern blot analysis. They are shown to remove DNA from either part or all of the first, and first and second, constant mu exons. The sizes of the deletions range between 0.6 and 5 kb, leaving an equal or unequal number of splice signals. Shorter mu RNA of one size was found irrespective of whether an exon was completely or only partially deleted. These results preclude exclusive 3' (constant region) to 5' (variable region) directional splicing of the mu RNA. No important signals seem to reside in the deleted DNA stretches affecting the transcription or the correct RNA splicing of the remaining exons. The internal mu protein deletions revealed unusual covalent light chain attachment demonstrating functional homology between the first (normally used) and fourth mu constant domain. The other mu protein deletions (10, 11, and 12 kd) involved neither gross DNA nor RNA lesions and are considered to be due to premature chain termination. Since secretion is found in most of the mutant IgM-producing lines, no single one of the four mu constant domains (including the C-terminal one which contains the so-called secretory piece) is necessary for secretion.
Between 1970 and 1979, 123 synovectomies of the ankle joint were performed on 99 patients. Sixty two of these patients (81 ankles) were followed up for an average period of four years. Using Steinbrocker's classification 10 ankles had Stage I disease, 34 had Stage II, 33 had Stage III and 4 had Stage IV. In more than 80% of the joints pain and swelling significantly decreased after operation, with improvement in the range of motion and of the gait pattern. However the procedure did not change the walking distance or dependency upon walking aids, probably because the ankle joint was rarely the only joint of the lower extremity affected by rheumatoid arthritis.
Patellar foci of any origin are very rare. Form 1955 to the end of 1979, 9 patients underwent patellar surgery in our hospital. 7 of these patients had tuberculosis, whereas in one case the patient had chronic nonspecific osteomyelitis, and in one case we were unable to clarify the underlying cause of the focus, neither from the histological nor from the bacteriological aspect. All tuberculous foci, one of which had penetrated into the knee joint, were situated in the corpus of the patellar. In a 10-year old girl, the entire patellar was infected with tuberculous foci. In the anterior-posterior x-ray film, the processes mainly presented a circular appearance. Their diameter different between 6 and 25 mm. In one of the foci, two sequesters were conspicuous, and one in another patient. 6 of the patients had an active organ tuberculosis at the same time, or reported on a specific disease during anamnesis. The period from the onset of complaints until diagnosis had been established, was on the average 14.4 months with the 7 patients under investigation (average age 29 years, 4 female/3 male). In view of the fact that all the patients reported here were late cases, the results of the combined drug and surgical removal of foci (filling of the surgical cavities with spongiosa) must be classified as good. One knee joint had to be stiffened by operation. There were no reactivations within an average followup period of 3 years.
Pseudothrombophlebitis secondary to rupture of a Baker's cyst had been described repeatedly in the literature of rheumatology. If this condition is mistaken for deep venous thrombosis and treated with anticoagulation, serious complication may result, like hematoma of the lower legs or retroperitoneal and gastrointestinal bleeding. The case demonstrated here shows that this condition is not limited to patients with chronic rheumatoid polyarthritis. Qur patient with an endoprosthesis of the knee suffered from marked reaction to metal (= metallosis) in addition to malacia patellae. The resulting severe synovitis was the cause for pseudothrombophlebitis. Therefore, in cases of suspected venous thrombosis in combination with gonarthritis, and arthrogram of the knee joint or a cystogram should be obtained in order to exclude the possibility of pseudothrombophlebitis.
The biological activities of mouse IgG1, IgG2a, IgG2b, and IgE monoclonal were investigated. As has been shown with conventional antibodies, monoclonal IgG1 and IgE are the two classes capable of sensitizing the mouse for anaphylactic reactions, IgE sensitizes the rat, and IgG2a sensitizes the guinea pig. What has not been seen with conventional antibodies is that large amounts of monoclonal IgG2a or IgG2b can sensitize the mouse, very large amounts of monoclonal IgE can sensitize the guinea pig, and very large amounts of IgG1 and IgG2a can sensitize the rat. One of the IgG1 monoclonal antibodies was capable of fixing complement by the classical pathway.
Using a hybridoma cell line which secretes hapten-specific immunoglobulin M (IgM), we have isolated a variety of mutants which produce abnormal immunoglobulin. Immunoglobulin was tested for the size and composition of the component heavy and light chains and for variable and constant region related functional and serological activities. Some mutants secrete IgM which seems to be defective in hapten binding; others make IgM which appears not to activate complement. Many of the mutants secrete monomeric as opposed to pentameric IgM. In some cases, the defect apparently correlates with structural alterations in the mu heavy chain: partial deletion, polypeptide addition, and abnormal glycosylation have been observed. These mutant cell lines provide a means of identifying the structural basis of IgM function and of studying the biochemistry of IgM synthesis and processing.
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A retrospective study has shown that postoperative infections could not be prevented from occurring after abdominal or vaginal hysterectomy by systematic post-operative antibiotic prophylaxis. The risk was not even substantially reduced. Prophylaxis against infection was found to be best achieved by proper surgical techniques, avoidance of long-time catheterisation, scrupulous observance of hygiene rules, and generous use of suction drainage.
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The role of specific structural elements in glycoprotein metabolism and secretion was studied using the IgM mu chains from normal and mutant hybridoma cell lines. Five classes of altered mu chains were studied, all of which lacked various portions of the normal protein sequence, and three of which had one and the others two fewer carbohydrate units than wild type mu. One mutant secreted mu chains more rapidly than wild type cells. Two of the mutant cell lines secreted very little IgM, and both of these degraded intracellular mu chains at an abnormally high rate. Tunicamycin largely blocked IgM secretion in wild type and three mutant cell lines, but caused less inhibition in the two other mutant lines. When glycosylation in the two low secreting mutants was blocked by tunicamycin, degradation of mu chains was substantially reduced in one but unaffected in the other. All of the above properties were retained by the altered mu chains when the mutants were further hybridized with cells producing wild type mu. Overall, the various carbohydrate units and polypeptide sequences seem to play different roles in a single protein's metabolism and expression. The carbohydrate moieties may exert independent effects on protein degradation and on secretion.
In 45 patients with rheumatoid arthritis 55 posterior capsulotomies with extension of the bicipital tendon were performed since 1973, using the method described by Wilson (1929), Herbert (1950) and Gschwend (1977). 35 patients with 45 operated knee joints could be followed up. The follow-up period was 6 months to 6 years. In more than 80% of the cases an improvement of extensibility over 20 degrees as well as of walking distance and security of gait could be achieved. Pain was relieved in the same proportion and, likewise, the patients' dependence on walking aids.
Necrotic areas of rheumatoid nodules were investigated electron microscopically. PMNs in different stages of disintegration were present in all cases. Granular material, sometimes in a fiberlike orientation, and small fibrils without periodicity were detected between the collagenous fibers. It is assumed that granular material and fibrillar remnants represent degraded collagen. Often these degradation products were present in the neighborhood of disintegrating PMNs. From this morphological relationship it is concluded that enzymes of PMNs may in part be responsible for the fibrinoid necrosis in rheumatoid nodules.
Glycerinated myocardial fibres treated with a detergent (Lubrol WX) and suspended in ATP salt solution produce half maximum isometric tension at pCa 6.2 (at pH 6.7). After addition of cyclic AMP (1-100 microM), the pCa required for half maximum activation is 5.9. c-AMP in concentrations of 1-100 microM induces a dose dependent inhibition (up to 40% at pCa6), and this effect can be amplified by the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine) 10(-4) M. The effect is similar in presence and absence of sodium fluoride 10 mM. Since in detergent treated skinned fibres the cell membrane and the sarcoplasmic reticulum are extracted and since the Ca2+ ion concentration was kept constant and buffered, we propose that c-AMP does not act via the cell membrane or the sarcoplasmic reticulum, but via phosphorylation of troponin I. The latter is the only component which becomes phosphorylated in skinned fibres during c-AMP induced relaxation, an effect which is also responsible for the inhibition of actomyosin ATPase at constant Ca2+ ion concentration (cf. Ray and England 1976).
Four methods employed in the diagnosis of experimental porcine trichinellosis (trichinoscopy, digestion method, immunofluorescence and enzyme linked immunosorbent assay (ELISA)) were compared by eleven laboratories in the countries of the European Economic Community and Sweden. The aim of this study was to test the reliability of ELISA during the onset of T. spiralis infection. Material from conventionally raised pigs infected with 1500 to 10000 larvae was compared to uninfected controls at Day 17 and Day 21 post infection. The serological techniques gave higher percentages of positive results than the direct techniques. Specific antibodies could be demonstrated with ELISA at an earlier stage and at higher percentages than with the other methods. ELISA micro-assay was the most sensitive procedure.
Eight lesions in the calcaneus have been treated surgically between 1955 and 1979; of these, six were due to tuberculosis, one to chronic osteomyelitis and the other was a cyst. The diagnosis was confirmed bacteriologically and histologically. In all cases (average age 49.1 years) the human bacillus was proved to be the cause of an haematogenous infection. The lesion was confined to the posterior part of the bone and there was no extension into the calcaneo-navicular joint. Two patients presented with fistulae. The interval from the onset of symptoms to confirmation of the diagnosis averaged 9.1 months. Three patients had previously been treated for tuberculosis (lung, pleura, kidney) and another patient, who had a simultaneous tuberculous infection of a sternoclavicular joint had suffered from tuberculosis cervical lymphadenitis at the age of nine years.U