Changes of plasma concentration and elimination of various hormones by haemofiltration.
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Biomedical subjects
Publications and source records attributed to H Ludwig.
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The importance of genetically determined antigens of the HLA system in etiology and pathogenesis of juvenile onset diabetes (JOD) was studied in 93 JOD-patients and 68 blood relations. A close association was found between JOD and B-locus antigens B8 and Bw15, and C-locus antigen Cw3. Patients positive for one of these antigens have a 2-3 times -- and those positive for both B8 and Bw15 -- a 8.6 times greater chance of developing JOD, Evidence for a genetic heterogeneity between childhood type and later onset JOD could be obtained. B8 seems to play a particularly important role in childhood-type diabetes, whereas in the later onset JOD the antigens Cw3 and/or Bw15 might possibly represent an additional predisposing factor. Family studies have revealed a close correlation between glucose intolerance and those genes associated with JOD in blood relations below age 35. HLA-B7 which could be detected in that group of blood relations, and which was found statistically decreased in JODs might even exert some protective role. Incidence of haplotye identity in glucose intolerant siblings was almost three times higher than expected. These data provide evidence for the existence of a genetic basis which determines the susceptibility to develop JOD.
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The role of genetic factors in humoral anti-insulin-response was studied in 87 patients with juvenile onset diabetes. A significant insulin antibody formation was found in 76 (87%) juvenile diabetics. By dividing these patients in four groups according to different heights of insulin antibody levels (non-, low-, moderate- and high-responders) a positive or negative correlation between humoral anti-insulin response and certain HLA antigens could be found. Non-responders showed a close association with HLA-B7 positivity, whereas in the insulin high-responder patients, a considerable decrease of HLA-B8 and increase of HLA-Bw15 and HLA-Cw3 was found. These findings indicate that certain genetic constellations within the HLA complex might have an important part in determining humoral anti-insulin immunity.
HLA antigens and humoral antithyroid immunity have been studied in 97 thyrotoxic patients [48 without and 49 with endocrine ophthalmopathy (EOP)]. A statistical significant increase of HLA-B8 frequency could be observed only in the thyrotoxic patients with EOP, whereas in patients without EOP B8 frequency was similar as to the one in the controls. The C locus antigen Cw3 was significantly different between both groups of patients: increased in those with EOP and statistically significantly decreased in those without EOP. Thyroid microsomal antibodies were found to be associated with HLA-B8 positivity and were noted with highest incidence in B8 positive EOP patients. No such association was observed for thyroglobulin antibodies. These data show a genetic heterogeneity in thyrotoxicosis patients with and without EOP. HLA-Cw3 positivity represents and increased risk to develop EOP in thyrotoxicosis, as frequency of this antigen was significantly decreased in thyrotoxicosis patients without any signs of EOP. The increased frequency for microsomal antibodies in thyrotoxic patients with EOP, especially in B8 positives underlines the genetically influenced autoimmune reactivity in that disorder.
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Intravenous glucose tolerance test(taking the age dependent variabilities of the glucose assimilation into consideration) was performed in 68 blood relations (30 siblings, 19 parents, 19 children) of 19 patients with juvenile onset diabetes mellitus (JODM). In 29,4% of the first degree relatives (in 20% of the siblings, in 42% of the parents and in 31,6% of the children) an abnormal glucose tolerance was found. Four of the siblings presented with insulin dependent JODM. Glucose intolerance was detected more often (42%) in siblings and parents of patients with later onset (after age 25) JODM than in siblings and parents of JODM-patients with onset before age 25 (20%).
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In 19 patients with idiopathic adrenal insufficiency and in 19 controls, cellular (as measured by the migration inhibition test) and humoral (by means of immunoflourescence) immune reaction to adrenal antigens were investigated. Significant inhibition of migration was observed in 12 patients with adrenal microsomes; migration of mononuclear cells was however within normal range in 18 out of 19 controls. Adrenal antibodies could be detected in 11 (53%) of the patients. In a further series of investigations adrenal microsomes have been preincubated with specific antibody and used in migration inhibition tests. The migration indices observed with microsomes were compared to those obtained with microsomes preincubated with adrenal antibody. Migration inhibition with microsomes could be blocked by antibody in almost all antibody-positive patients. No uniform trend on the migration of mononuclear cells was found in the antibody-negative patients. A blocking of the cellular immune reaction by specific antibody seems likely. Possible mechanisms which could lead to such phenomena as well as the biologic significance of adrenal antibodies are discussed.
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In 19 families of juvenile diabetes patients intravenous glucose tolerance was tested and HLA antigens were determined. A total of 68 first degree blood relations (siblings, parents, children) was studied. Taking the age dependent variabilities of the glucose assimilation coefficient (k-value) into consideration, glucose intolerance was found in 35.5% of the blood relations. Particularly in blood relations (above all in siblings) aged under 35 and with glucose intolerance, a trend to increased frequencies of those HLA antigens (B8, BW15, CW3) associated with juvenile diabetes was found, but it is not yet clear whether this association will be of practical significance.
This report presents a review of recent developments in immunofluorescence and their resultant applications. After a short introduction to the basic principles of immunofluorescence, this study deals with newer developments in utilizable fluorochromes, new methods in the production of antisera and fluorochrome-labelled conjugates and recent improvements in the optical system. In particular, the necessity of suitable characterization and examination in regard to the quality of the conjugates is described in detail. A separate chapter has been devoted to the rapidly-developing quantitative immunofluorescence technique and its application.
Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphylococci was significantly lower compared to controls (p less than 0.001, p less than 0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls (p less than 0.05; p congruent to 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacteria antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.
MATERIALS: Human uteri were removed by vaginal hysterectomy on the first, second and sixth day of the menstrual cycle. METHOD: Washing, pinning, fixation in glutaraldehyde 2.5%, dehydration in ascending concentration of ethanol, critical point drying with carbon dioxide, sputter coating with gold. RESULTS: The re-epithelization of the endometrium starts immediatley after the onset of menstrual bleeding due to desquamation of the premenstrual endometrium. The remaining stumps of endometrial glands after the endometrial break-down, proliferate rapidly, forming marginal collars. Up to the sixth day the proliferative process has produced a continuous layer of fusiform cuboideal epithelial cells, which cover the entire endometrial surface of the uterine cavity. The dynamics of epithelial growth can be "seen" in following three subsequent stages of the process and in analyzing the arrangement of the cells around the openings of the endometrial glands. Accordingly ciliogenesis occurs in some surface endometrial cells. The paper gives an inconographic survey of the early proliferative phase, illustrating changes from glandular epithelium to the lining epithelial layer and ciliogenesis in the latter. The new formation of ciliae in endometrial epithelial cells is an unique phenomenon, being influenced by the cyclic endocrine regulation of the endometrial function in human reproduction.
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The pressure dependence of enzymatic dextran formation has been observed up to 1000 at for several substrate concentrations. First order denaturation effects could be separated from the thermodynamic effects, which lead to a volume of 30.4 to 44.0 ccm per mole for the formation and -13.6ccm per mole for the activation of the enzyme-substrate complex. Denaturation depends on the substrate concentration. This leads to the conslusion that only the free enzyme is denatured, wheras the ES complex is stable.