Biomedical subjects
Publications and source records attributed to H Seyfried.
A family is described in which an apparent Ay phenotype was transmitted through 2 generations. We favor a mutation of the A allele as the most likely cause of the phenotype. Activities of the serum A-gene-specified transferase were not detected in any of the 3 family members with the Ay phenotypes.
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Antibody-dependent lymphocyte cytotoxicity was compared in two test procedures. Human erythrocytes (group O R1R1 or R2R2) and mouse lymphoma cells (line L1210) were used as target cells. Anti-Rh (anti-C + D) serum obtained from a hyperimmunized blood donor and serum obtained from rabbit immunized with L1210 cells were used as the source of antibody specific for target cells. In both tests, lymphocytes (PBL) or mononuclear cells (MNC) isolated from heparinized or defibrinated blood were used as effectors. In both tests comparable results were obtained.
Prostacyclin synthesis was studied by means of bioassay in histologically classified biopsy material derived from the human gastrointestinal tract. Tumour tissue generated significantly more prostacyclin than normal tissue. Whether this enhanced PGI2 formation is due to an increased number of endothelial cells in tumour tissue, or represents a characteristic property of the tumour cell itself is not yet clear. This property could be used in future for the detection and control follow-up of malignant disease by means of radioimmunological determination of stabile metabolites as a tumour marker.
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PGI2 synthesis was investigated in rectal mucosa of 8 patients with active ulcerative colitis, 4 in remission and 16 controls. Determinations were carried out using Moncada's bioassay. The results demonstrated enhanced PGI2 synthesis in rectal mucosa in active ulcerative colitis. Further clinical studies should clarify whether or not selective inhibiton of PGI2 synthetase might be a useful therapeutic approach in ulcerative colitis.
In the presence of cimetidine, pentagastrin and somatostatin prostacyclin formation does not differ significantly from the value obtained with the buffer control, whereas cimetidine alone is able to inhibit ADP-induced platelet aggregation in vitro to a small degree. It is concluded that the in vivo action of the drugs if not primarily mediated by prostacyclin.
Serum guanase activity was measured in 20 healthy adults and in 62 patients with acute viral hepatitis, chronic active hepatitis, chronic persistent hepatitis, liver cirrhosis and fatty liver. Guanase and gamma-GT in patients were elevated in 87 and 64%, respectively. Elevated guanase activities were found in most cases of acute viral hepatitis, as well as in chronic hepatopathies. In patients with acute viral hepatitis pathologic activities of guanase were found following partial or total normalization of other liver function tests.
The human gastric mucosa generates prostacyclin (22 +/- 6 ng PG I2/g). There is no age or sex difference in PG I2 formation by normal gastric mucosa. The properties of the substance are the same as reported in other tissues.
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1. PGI2 is synthetized in human gastrointestinal mucosa. 2. PGI2 seems to be responsible for pathophysiological conditions. 3. Disorders caused by an enhanced or diminished PGI2-synthesis could be treated in the future by inhibition of prostacyclin synthetase or exogenous synthetic PGI2 respectively. 4. In order to remove the problems with the unstable PGI2, synthetic analogs could be used for the treatment.
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Pathologically low serum total triiodothyronine (T3) concentrations are a characteristic finding in patients with severe non-thyroidal illnesses. No adequate explanation has yet been offered for this phenomenon. We have, therefore, investigated the serum concentrations of total thyroxine (T4), total T3 and total 3,3',5'-triiodothyronine (reverse T3)--the metabolically-inactive metabolite of thyroxine--and of TSH in 13 patients with acute myocardial infarction, in 12 patients with compensated liver cirrhosis, in 9 patients with decompensated liver cirrhosis and in 15 patients with chronic renal failure on chronic intermittent haemodialysis by radioimmunoassay. The values obtained were compared to corresponding values of a normal control group (n - 23). According to our results the decrease in serum T3 combined with normal T4 concentrations in severe non-thyroidal illnesses seems to be a consequence of an alteration in thyroxine degradation. Two different possibilities of alteration can be considered: 1. inhibition of the overall deiodinationof T4, leading to low total T3 serum concentrations with concomitant normal to low reverse T3 serum concentrations (chronic uraemia), 2. a shift in the monodeiodination of T4 towards enhanced reverse T3 production, leading also to low total T3 concentrations, but with a concomitant increase in reverse T3 serum concentrations (myocardial infarction, liver cirrhosis). The results obtained in our patients with liver cirrhosis show, moreover, that this alteration of T4 metabolism depends on the severity of the illness.
The AutoAnalyser Technicon II system was adapted for screening red cells for the presence of warm-type autoantibodies. A significant decrease in optical density was recorded when the red cells of 38 patients with autoimmune haemolytic anaemia were tested using the bromelin-methylcellulose method. This was never seen with the red cells of 226 patients with other diseases or of healthy blood donors. The method is very simple and more sensitive than the manual direct antiglobulin test.
The principle of detecting red cell antibodies by automated technique using the two-channel Technicon Auto-Analyser with some modification is described. The sensitivity of automated methods in detecting antibodies of different specificities was determined. The study was carried out with 76 diagnostic human sera produced by the Institute of Hematology, Transfusion Centers and commercial firms: anti-RhD, -C, -E, -CW, -c, -e, anti-K, -k, Kpa, anti-Fya, -Fyb, anti-Jka, -Jkb, anti-M, -S, -s, anti-P1, anti-Lua, anti-Lea, -Leb, anti-H, -A1, anti-I, anti-Lua and anti-Vel. A majority of the antibodies were detected by both automated methods with greater sensitivity than by manual methods. Greatest sensitivity was observed in the detection of anti-S, -Vel and antibodies of the Rh system. Anti-Leb and anti A1 antibodies were not detected. The studies are the basis for introduction of the automated technique into routine use for antibodies in blood donors and recipients.
The degradation of haemoglobin haeme of senescent red blood cells - involving NADPH-dependent haeme oxygenase and biliverdin reductase - in the reticuloendothelial cells of the spleen, bone marrow and liver accounts for 80 to 90% of the 250 to 300 mg of bilirubin formed in 24 hours. The remaining 10 to 20% derive from catabolism of other haemoproteins and from the destruction of maturing red blood cells in the marrow. In studies with isotopically-labelled metabolic precursors of haeme this fraction can be found in the early-labelled peak. In plasma virtually all the bilirubin is tightly bound to plasma proteins, largely albumin, because it is only sparingly soluble in aqueous solutions at physiological pH. In the sinusoids unconjugated bilirubin dissocates from albumin, enters the liver cells across the cell membrane through non-ionic diffusion and is bound by the two cytoplasmic proteins Y (or ligandin) and Z. Little is known about the transfer of unconjugated bilirubin from these binding proteins to the smooth endoplasmatic reticulum, where it is converted to a water-soluble ester glucuronide by bilirubin UDP-glucuronyl transferase. The physiological significance of non-glucoronide conjugates (sulphate, disaccharides) is only of minor importance. Following conjugation, bilirubin is transferred rapidly across the canalicular membrane into the bile canaliculi. This process is energy-dependent and occurs against a concentration gradient. The epithelial lining of the intestine and of the gall bladder, which can easily reabsorb lipid-soluble unconjugated bilirubin, is virtually impermeable to organic anions of the size and charge of conjugated bilirubin, thereby ensuring efficient excretion of this pigment. In the intestinal tract bilirubin is reduced to urobilinogen, which is subsequently reabsorbed to some extent into the enterohepatic circulation, removed from plasma by the liver and excreted unchanged in the bile. This rapid bacterial reduction of bilirubin makes it unlikely that unconjugated bilirubin is formed and absorbed to an appreciable degree. The residual part of urobilinogen is further reduced to urobilin, stercobilin and dipyrrolmethenes and excreted in the faeces.