Biomedical subjects
Publications and source records attributed to W Rapp.
Seven patients on long-term lithium treatment were given chlorothiazide for three days. The urinary concentrating capacity did not change during the study, but serum potassium decreased significantly. Thus, chlorothiazide does not seem to produce an effect on a moderately decreased concentrating capacity during long-term lithium treatment.
Specific cell markers were revealed on fixed and paraplast embedded human tissues by the indirect immunoperoxydase methode using immunoadsorbed antibodies. Immunenzymhistology proved to be a new field for image analysis.
Immunochemical homogeneous human pepsinogen I-group (PgI) was purified by solid immunoadsorbent and by DEAE-chromatography from gastric mucosa. PgI contained five electrophoretic distinct bands at pH 8.2 but only four bands at pH 5.6. After acid activation human pepsin (PI) was separated from the inhibitory peptide by affinity chromatography using poly-L-lysine. Purified PgI contained 9-16% of the inhibitory peptide. The yield of PI was 64 to 85%. A 65% increase of specific activity was observed. PI demonstrated three bands in agar gel electrophoresis at pH 5.6. The pH range of PI was rather wide, showing two maxima at pH 2.0 and pH 3.0 with hemoglobin as substrate. Irreverisble inactivation of PI was observed at pH 7.0 and at a temperature of 60 degrees C. The Km-value of PI was 0.170 mmol as determined with N-acetyl-L-phenyl-alanyl-L-3,5 diiodotyrosine. The specific activity was 9.6 IU/mg (hemoglobin substrate) and 0.032 IU/mg (dipeptide substrate). Porc pepsinogen (PPg) and its activated pepsin (PP) was used for comparison. PP showed indentical elution patterns in affinity chromatography. In AEE PPg and PP demonstrated both two components at pH 5.6 with different electrophoretic mobilities. The pH optimum of PP was observed at pH 2.0. PP was slightly more sensitive in alkali and heat inactivation than human P. A higher Km-value of PP of 0.082 mmol and higher specific activity as compared to human PI was observed.
Human pepsinogen II (PgII) was purified from human gastric mucosa by immunoadsorbents using anti-PgII antiserum. Contaminating pepsinogen I (PgI) was adsorbed by a subsequent anti-PgI immunoadsorbent. PgII was further purified on DEAE-Sphadex A50. By agar gel enzyme electrophoresis (AEE) at pH 8.2 PgII was separated into five proteolytic bands, demonstrated upon acidification and incubation with hemoglobin. PgII was converted to pepsin II (PII) by acidification at pH 2.0 and was immediately separated from its inhibitory peptide and from other substances by DEAE chromatography. Purified PII showed two bands in AEE at pH 5.6 and was immunochemically identical with PgII. The "gastricsin" and "pepsin" purified from acid gastric juice by classical procedures proved to be identical with PII and pepsin I (PI), respectively. PII showed a broad pH range with one maximum at pH 2.9. PII in contrast to PI did not hydrolize N-acetylphenylalanyl-3,5-diiodotyrosine and proved to be more alkali-stable than PI. A modified nomenclature is proposed for the human pepsinogen system.
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Goblet cell antigen (GOA) was purified from gastric signet ring cell carcinoma. It was immunogenic and was used to produced antisera which stained goblet cells of the small and large intestine and of intestinalized gastric mucosa by indirect immunological methods. Various types of gastric and colonic cancer contained GOA. These findings demonstrate a histiogenic relationship between intestinal goblet cells, various gastrointestinal cancers and associated premalignant conditions.
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Surface and foveolar gastric cells (SE) of 74 gastric resection specimens were studied by classical and indirect immunoenzyme histology. Immunoadsorbed CEA-antibodies reacting only with the specific determinant of of the CEA molecule were applied. The following SE types with different CEA distribution patterns were observed: Type SE-O, no CEA, normal neutral mucosubstances (MCS); type SE-A, CEA present in the lower half of the SE, important decrease of MCS, mild cell dysplasia by conventional criteria; type SE-B, CEA present in the total cell, absence of MCS, moderate until marked dysplasia; type SE-C, CEA present or decreased, absence of MCS, very important cell dysplasia resembling cancer cells. CEA proved to be useful as marker for the degree of SE dysplasia.
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An Alcian blue staining, perchloric acid-soluble, antigenic acidic mucosubstance (GOA) was purified from human gastric signet ring cell carcinoma with DEAE-cellulose chromatography, Seqhadex G-200 and preparative polycrylamide gel electrophoresis. Specific antisera were raised which reacted in indirect immunoenzyme histology with normal goblet cells of the small and large intestine and with goblet cells of intestinalized gastric mucosa. In surgical resection specimens of the stomach (n = 100) and of the colon (n = 19) 3 gastric signet ring cell carcinomas and 3 colonic colloidal adenocarcinomas stained for GOA, demonstrating an immunochemical relationship with normal intestinal goblet cells.
Two different fixatives were applied to human gastric mucosa for the study of antigenic marker substances. The first consists of 96% ethanol and 1% acetic acid (EA method), the second of 4% formaldehyde, 0.5% picric acid and 0.25% glutaraldehyde (FPG method). Samples of resected gastric specimens were fixed, dehydrated and cleared in benzene and embedded in paraplast. The morphology of gastric tissue was well preserved by both methods and permitted the simultaneous application of classical staining procedures and the immunoenzyme peroxidase technique for the demonstration of antigenic substances. The following marker substances could be demonstrated: Pepsinogen I and II group, surface epithelial antigen, parietal cell antigen, chief cell antigen, antral mucous cell antigen, carcinoembryonic antigen, goblet cell antigen and common site antigen of leucocytes. Various factors responsible for nonspecific reactions, such as endogeneous peroxidase activity and protein interactions were studied. The latter were circumvented by the use of highly purified antibodies or immunoglobulin fractions. The EA method proved to be the method of choice for future routine application of combined classical histology and immunoenzyme histology in gastric and intestinal diseases.
Amitriptyline-N-oxide and amitriptyline were compared double-blind in a material of out-patients with depressive syndromes, 21 and 22 patients respectively. Both drugs had a good antidepressant effect. The globally rated effect was equal. The effect upon the various depressive symptoms was equal. Definite reversal of depression occurred somewhat earlier on amitriptyline-N-oxide on which side effects were also less marked, but those of an anticholinergic and of a sedative nature. No orthostatic reaction, nor any effect upon blood status or liver function was observed. Amitriptyline-N-oxide appears to show a tendency to a somewhat more rapid onset of effect and less side effects.
A solid-phase sandwich radioimmunoassay was developed to quantitate human group-II pepsinogens in plasma. The test detected pepsinogen II in a concentration range of 0.25--64.0 ng/ml using sample volumes of 125 microliter. Purified group I pepsinogens showed no response up to concentrations of 100 microgram/ml. In apparently healthy donors, we observed mean plasma concentrations of 20.3 ng/ml (males) and of 15.5 ng/ml (females).
In a study of 28 schizophrenic in-patients treated with penfluridol or thiothixene, patients were followed with clinical ratings, EEG variables, the mean integrated amplitude (MIA) on both the left and right sides--both with filters with frequency ranges from 7.5 to 13.5 and 0.5 to 25 Hz--as well as its within-patient variance (WPV) on both sides and with both filters, and also with visual averaged evoked responses (V.AER). Moreover, determinations of plasma levels of the drugs were conducted in a search for possible objective measurements of the effects of the treatment, but also to try to find measurements that would make it possible to predict the outcome of treatment. MIA left/right and WPV left/right were found to be the most promising variables to follow the effect of treatment, which were correlated to factors 1 and 2 of the Mårten's S-scale. WPV left/right before treatment was correlated to changes in factor 4 of the S-scale during the trial.
When gastric cancer patients' leucocytes were exposed to a panel of tumour extracts, leucocyte migration reactivity was "positive" before operation (90% of cases), it declined after surgery and it reappeared in patients with local recurrence or metastases. In patients with non-malignant gastric diseases, "positive" reactivity against tumour extracts was associated almost exclusively with atrophic gastritis with and without intestinal metaplasia (24/43 cases). "Positive" patients also showed a pathological migration index with an extract of normal gastric mucosa.
The pepsinogen II group was prepared from gastric mucosal extract by a two-step procedure consisting of immunoadsorption to an anti-pepsinogen II column, followed by ion exchange chromatography on DEAE-Sephadex A-50. The final product was pure according to biochemical and immunochemical criteria. As determined by quantitative immunodiffusion, the enrichment factor of pepsinogen II was 34. A recovery of 55% was calculated. The effectiveness of this procedure was due to the use of purified anti-pepsinogen II antibodies for immunoadsorption. This was achieved by immunoadsorption to Sepharose bound crude pepsinogen and a further passage over an unrelated immunoadsorbent (human serum coupled to Sepharose). The immunoadsorbent prepared using purified anti-pepsinogen antibodies showed low non-biospecific binding of gastric extract proteins. Complete separation of pepsinogen II from pepsinogen I was observed in one single passage. Purified pepsinogen II showed two protein bands in polyacrylamide gel electrophoresis and four bands of proteolytic activity in agarose enzyme electrophoresis. In both methods, as well as in two-dimensional immunoelectrophoresis, components with the same electrophoretic mobility were detected in pure preparations of group and II pepsinogens. Consequently, only in pure preparations was it possible to define the exact number of bands belonging to each of the two groups and to assess the immunological specificity of every band. Upon hydroxyapatite chromatography purified pepsinogen II was further resolved into two fractions.
Human pepsinogen I group was purified by immunoadsorption techniques. Gastric mucosal extracts containing the pepsinogen I group and the pepsinogen II group and concentrated urine containing only pepsinogen I group were separated by DEAE-ion-exchange chromatography to remove the bulk of human serum protein. Fractions displaying proteolytic activity were further purified by adsorption on an anti-pepsinogen I group Sepharose immunoadsorbent column. After desorption, gastric pepsinogen I group was separated from pepsinogen II group. Trace amounts of contaminating protein were removed from preparations from gastric mucosal extracts and urine by passage over an anti-human serum immunoadsorbent column. The purity of pepsinogen I group from both sources was assessed by electrophoretic and immunological criteria. The isolated pepsinogen I group from gastric mucosal extracts and urine were by biochemical and immunochemical criteria identical with each other and with the pepsinogen I group in the unfractionated starting materials. By agarose enzyme electrophoresis four bands were detected and it was determined that the proteases of the pepsinogen I group express the same individual antigenic determinant.
In a controlled trial of penfluridol and thiothixene as maintenance drugs in patients with chronic schizophrenic syndromes, some improvement over previous neuroleptics was seen with both drugs. This improvement was mainly evident in variables concerned with participation in social activities as assessed with the S-scale and by ward behaviour. The drug dosages necessary were very low and gave few and easily manageable side-effects. There was no significant difference between penfluridol and thiothixene. Penfluridol has the clear practical advantage of being the only long-acting drug for oral administration so far available.