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Biomedical subjects

W Bürgi

Publications and source records attributed to W Bürgi.

At least 37 records · Page 2Linked to original sources

Complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein and its homology to histocompatibility antigens.

In the present study the complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein was determined. This protein whose biological function is unknown consists of a single polypeptide chain of 276 amino acid residues including 8 tryptophan residues and has a pyroglutamyl residue at the amino terminus. The location of the two disulfide bonds in the polypeptide chain was also established. The three glycans, whose structure was elucidated with the aid of 500 MHz 1H NMR spectroscopy, were sialylated N-biantennas. The molecular weight calculated from the polypeptide and carbohydrate structure is 38,478, which is close to the reported value of approximately equal to 41,000 based on physicochemical measurements. The predicted secondary structure appeared to be comprised of 23% alpha-helix, 27% beta-sheet, and 22% beta-turns. The three N-glycans were found to be located in beta-turn regions. An unexpected finding was made by computer analysis of the sequence data; this revealed that Zn-alpha 2-glycoprotein is closely related to antigens of the major histocompatibility complex in amino acid sequence and in domain structure. There was an unusually high degree of sequence homology with the alpha chains of class I histocompatibility antigens. Moreover, this plasma protein was shown to be a member of the immunoglobulin gene superfamily. Zn-alpha 2-glycoprotein appears to be a truncated secretory major histocompatibility complex-related molecule, and it may have a role in the expression of the immune response.

Amino Acid Sequence↗

Human serum alpha 2HS-glycoprotein modulates in vitro bone resorption.

We previously isolated a family of bone-resorbing proteins from human cancer ascites fluid and established that the three purified bone-resorbing proteins were chemically and immunochemically related to each other and to alpha-2HS glycoprotein (alpha 2HS). After this finding we purified the normal human serum counterpart of these ascites proteins and studied its effects on bone resorption. The bone-resorbing properties of normal human serum alpha 2HS were examined in vitro over a wide dose range. This normal human serum glycoprotein had a biphasic effect on 45Ca2+ release from bone. More specifically, this protein stimulated bone resorption at the lower concentrations tested, with a maximum effect [treated over control ratio of 2.5 +/- 0.30 (+/- SE); P less than 0.01] at 40 micrograms/mL. In contrast, at doses above 40 micrograms/mL, a sharp decline in calcium mobilization occurred, with a return to baseline occurring above 80 micrograms/mL. These results suggest that serum alpha 2HS may participate in the regulation of bone metabolism in vivo.

Adult↗

Can automated haematology analysers discriminate thalassaemia from iron deficiency?

The use of automated analysers in population screening for beta-thalassaemia has been a matter of controversy. The new fully automated haematology analyser Sysmex E-5000 (Toa Medical Electronics Co. Ltd) facilitates the discrimination of heterozygous thalassaemia from iron deficiency anaemia. In addition to haemoglobin, mean corpuscular haemoglobin and mean corpuscular volume, the red cell size-distribution width is measured. In patients with hypochromic microcytic red cells, the Sysmex data have been evaluated and compared with the indices described by England and Fraser [Lancet i, pp. 449-452, 1973], Mentzer [Lancet i, p. 882, 1973] and by Shine and Lal [Lancet i, pp. 692-694, 1977]. For the detection of beta-thalassaemia trait, the size-distribution width is superior to the previously described indices. The sensitivity is 79%, the specificity 95% and the predictive value for a positive test 94%.

Diagnosis, Differential↗

Behavior of beta 2-microglobulin in patients with chronic renal failure undergoing hemodialysis, hemodiafiltration and continuous ambulatory peritoneal dialysis (CAPD).

beta 2-microglobulin (beta 2-m) is the major component of a new form of amyloid deposit found in carpal tunnel syndrome and dialysis arthropathy of long-term hemodialysis patients. In 52 patients on maintenance hemodialysis, serum beta 2-m concentration was elevated to 37.9 +/- 1.4 (normal 1.2 +/- 0.6) mg/l. It was correlated with the time on hemodialysis (r = 0.43, p less than 0.01) and was inversely correlated with residual renal function (r = 0.87, p less than 0.001). In 20 patients on CAPD, beta 2-m likewise was increased to 31.6 +/- 2.3 mg/l; daily elimination by dialysate was only 34 mg (normal 150 mg). Hemodialysis with a cuprophane membrane caused a rise in serum beta 2-m, whereas hemodiafiltration with a polysulfone membrane performed in 5 patients over 2 1/2 months was accompanied by a decrease in serum beta 2-m from 39.5 +/- 0.7 to 29.7 +/- 1.0 mg/l predialysis (19.1 +/- 1.1 postdialysis). On the other hand, beta 2-m elimination reached only approximately 100 mg per day in spite of markedly elevated serum levels. It is concluded that serum beta 2-m is massively elevated in long-term hemodialysis and CAPD patients; contrary to routine hemodialysis with cuprophane membranes, newer more permeable membranes will permit some elimination of beta 2-m. However, based on quantitative considerations it seems difficult to obtain beta 2-m concentrations in the high normal or moderately elevated range with present day techniques.

Humans↗

[Phagocytosis of blood cells in pleural effusions].

Macrophages can be found in pleural effusions in varying number according to etiology and duration of the underlying pleural disease. These phagocytes are able to ingest different particles and cells: morphologically intact white and red blood cells or degradation products (such as, for instance, specific granules of granulocytes) are detectable in up to 10% of pleural macrophages. Little is known about the significance and mechanisms of cytophagocytosis of blood cells by macrophages in pleural effusions. To learn more about it we studied the phenomenon of endocytosis in 105 patients with pleural effusions of various etiologies. Cytophagocytosis can be observed in all pleural effusions independently of underlying pleural processes. The nature of ingested cells in macrophages corresponds to free blood cells in effusions and a similar ratio can be shown. The results indicate that white and red blood cells which enter the pleural space may be eliminated by macrophages by a similar mechanism to the well known cytohemolysis of blood cells in the reticulo-endothelium of the body.

Blood Cells↗

The complete amino acid sequence of the A-chain of human plasma alpha 2HS-glycoprotein.

Normal human plasma alpha 2HS-glycoprotein has earlier been shown to be comprised of two polypeptide chains. Recently, the amino acid and carbohydrate sequences of the short chain were elucidated (Gejyo, F., Chang, J.-L., Bürgi, W., Schmid, K., Offner, G. D., Troxler, R.F., van Halbeck, H., Dorland, L., Gerwig, G. J., and Vliegenthart, J.F.G. (1983) J. Biol. Chem. 258, 4966-4971). In the present study, the amino acid sequence of the long chain of this protein, designated A-chain, was determined and found to consist of 282 amino acid residues. Twenty-four amino acid doublets were found; the most abundant of these are Pro-Pro and Ala-Ala which each occur five times. Of particular interest is the presence of three Gly-X-Pro and one Gly-Pro-X sequences that are characteristic of the repeating sequences of collagens. Chou-Fasman evaluation of the secondary structure suggested that the A-chain contains 29% alpha-helix, 24% beta-pleated sheet, and 26% reverse turns and, thus, approximately 80% of the polypeptide chain may display ordered structure. Four glycosylation sites were identified. The two N-glycosidic oligosaccharides were found in the center region (residues 138 and 158), whereas the two O-glycosidic heterosaccharides, both linked to threonine (residues 238 and 252), occur within the carboxyl-terminal region. The N-glycans are linked to Asn residues in beta-turns, while the O-glycans are located in short random segments. Comparison of the sequence of the amino- and carboxyl-terminal 30 residues with protein sequences in a data bank demonstrated that the A-chain is not significantly related to any known proteins. However, the proline-rich carboxyl-terminal region of the A-chain displays some sequence similarity to collagens and the collagen-like domains of complement subcomponent C1q.

Amino Acid Sequence↗

[Chronic fatal vitamin A poisoning with hemolytic anemia].

A case of chronic, lethal vitamin A intoxication is reported, the diagnosis of which was not established intra vitam. The patient presented with chronic mixed prehepatic and hepatic icterus and hypersplenism with hemolytic anemia. On post mortem histological examination, abundant deposits of neutral lipids in the reticuloendothelial cells of liver, spleen and bone marrow were found. Chemical analysis of the lipids extracted from these organs revealed esterified fatty acids. Triglycerides could be ruled out since the triglyceride content of the patient's liver was significantly lower than that of a normal control. By means of thinlayer chromatographic analysis it was possible to identify retinol, i.e. retinylester (vitamin A) in the deposits. Vitamin A was determined photometrically and found to be very elevated in the liver and, to a lesser degree, in the spleen of the patient. These findings lead to a definite diagnosis of chronic hypervitaminosis A. Unique features of the case presented are both hemolytic anemia and the lethal outcome of the chronic hypervitaminosis A.

Anemia, Hemolytic↗

[Pregnancy in a representative Swiss population (study of pregnancy and newborn infants in Aarau). 3. Diseases and drugs in pregnancy].

As part of an overall study, a cohort of 996 Swiss mothers was interviewed upon admission to the labour ward regarding illnesses, disorders and the use of drugs during pregnancy. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland, and with epidemiologic reviews of pregnancy events from other countries. Somatic illness, particularly the common cold, were reported by 55%, and complaints of a more psychosomatic character by 47%. Illness related to pregnancy was found in more than 40% of the women. Only 16% reported no illnesses or complaints during the course of pregnancy. On the other hand, 33% of the mothers had taken no medication during pregnancy. Compared with studies from other countries the use of medication in this group of women was lower, particularly self-medication for minor complaints. The women reported an average intake of 1.6 drugs. In the offspring of these mothers only a few minor somatic effects were demonstrable. The Brazelton behavioral assessment did, however, reveal some significant correlations.

Adult↗

[Benefits of routine automatic blood picture differentiation].

The benefits of automated blood smear differential cell counting as a supplementary laboratory examination have been studied. The investigations focussed on patients of whom hematology requisitions were limited to total leukocyte count and hemoglobin determination. The specimens were derived from patients of departments of surgery and obstetrics and gynecology. For specimen collection the vacutainer system was used. The blood smears were prepared in a Coulter Electronics slide spinner, stained with a Hematek II slide stainer and analyzed in the Coulter Electronics Diff 3-50 cell classifier. A total of 1700 blood smears were examined. Following processing of each sample, the classification of each cell was inspected. Corrections were performed, if necessary, and the number of classification changes performed for each smear was registered. Using the in-house normal ranges, 34.5% were pathological smears. Since this group included a large number of borderline cases, new discrimination limits for clinically relevant pathological findings were set empirically. According to these wider ranges, the fraction of pathological slides amounted to 15.2%. Among these, immature granulocytes, eosinophilia and lymphopenia were the most frequent pathological findings. Microscopic control proved in 57.6% of the total number of smears. This complemental procedure was not found to be time-consuming.

Automation↗

[The course of pregnancy in a representative Swiss sample (Aarau Pregnancy and Newborn Infant Study). II. Stimulants in pregnancy].

Within the framework of a study on the course of pregnancy, a cohort of 996 Swiss mothers was interviewed upon admission for delivery at Aarau Maternity Hospital regarding nicotine, alcohol, caffeine and narcotics consumption. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland and with epidemiologic reviews of pregnancy events from other countries. The relationship between these data and effects on the newborn is also discussed. This group of mothers aged 20-40 years had, even prior to pregnancy, below-average alcohol and nicotine consumption. During pregnancy nicotine use in the last trimester, though reduced, was still admitted by 18% of the gravidae despite the fact that about 3/4 of the mothers were well informed about detrimental effects on the offspring. Nicotine use by the mother had several somatic effects on the newborn, in contrast to consumption of caffeine and small amounts of alcohol. The behavioral assessment was altered by previous use of nicotine and caffeine.

Adult↗

[Automatic blood smear differentiation using the Coulter Electronics Diff 3-50 system].

The Coulter Electronics Diff 3-50 consists of a slide spinner, a slide stainer and a cell classifier. The cell analyzer is composed of an optical system with a microscope, microprocessor, video camera and printer. The system used in this laboratory is supplemented by a video monitor. The Diff 3-50 analyzes blood cells according to the classical criteria used in hematology. It classifies 11 types of nucleated blood cells and it processes an average of 45 blood smears per hour. It features a visual control of each cell classified with a built-in mechanism for change of classification by the operator if necessary. Moreover, the system estimates leukocyte and platelet count and generates a quantitative estimate of platelet number. Blood smears of 507 blood samples from patients admitted to the hospital were included in the present study. They were analyzed twice, first by the Diff 3-50, and secondly by visual checking of the automatic classification of each cell. The results of the two procedures were then compared. The findings indicate an overall false negative error of 1.4% and an overall false positive error of 4.3%. Major differences were found, though not consistently, only when the classification by the Diff 3-50 of the band neutrophils was compared with the visual classification performed by the operator. Lymphocytes and monocytes correlated well when both procedures were compared. Blasts present in 5 blood smears were recognized by the classifier. The Diff 3-50 identified immature granulocytes in 47 out of 48 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cell Count↗

Characterization of the B-chain of human plasma alpha 2HS-glycoprotein. The complete amino acid sequence and primary structure of its heteroglycan.

alpha 2HS-Glycoprotein, a normal human plasma protein, was recently shown to consist of two polypeptide chains. In the present study, we have separated these two chains from one another and have elucidated the complete primary structure of the B-chain. Employing automated Edman degradation, the polypeptide moiety of this chain was shown to consist of 27 amino acid residues with an unequal distribution of the neutral and charged amino acid residues. The first 20 residues are uncharged, whereas the carboxyl-terminal heptapeptide contains all charged residues. Utilizing 500-MHz 1H-NMR spectroscopy, the carbohydrate unit proved to be a trisaccharide consisting of sialic acid, galactose, and N-acetylgalactosamine O-glycosidically linked to serine (residue 6). The structure of the B-chain was found to be as follows. (formula; see text) Thus, the molecular weight of the B-chain is 3386. Evaluation of the polypeptide chain by the procedure of Chou and Fasman (Chou, P.Y., and Fasman, G.D. (1979) Adv. Enzymol. 47, 45-148) predicts that the B-chain has two beta-turns. Thereby, the carbohydrate unit which is linked to the Ser residue located in the first beta-turn appears to be directed away from the protein. The second beta-turn probably includes the Cys residue which links the B- to the A-chain. In agreement with the CD analysis, the B-chain lacks beta-conformation but possesses a short alpha-helical region.

Amino Acid Sequence↗

[Plasmapheresis treatment in multiple myeloma with kidney insufficiency].

Two patients with multiple myeloma and renal insufficiency are described. In both cases free lambda-chains were demonstrated in blood and urine. Plasmapheresis induced a marked reduction of lambda-chains in both patients. In one patient, a 63 year old man, oliguria ceased but renal function remained impaired and required treatment with longterm hemodialysis. The patient died after 6 1/2 months from sudden circulatory failure. In the second patient, a 68 year old woman, renal function was recovered sufficiently to enable hemodialysis to be stopped. Plasmapheresis may efficiently lower the paraprotein concentration in plasma and bring about improvement of renal function, at least in certain cases. However, treatment should be started before the terminal oliguric stage of renal insufficiency has been reached.

Aged↗

[Elimination of fluoride in urine during fluoridation of salt and drinking water].

From 552 ambulatory gynecological patients in different parts of Switzerland the urinary excretion of fluorine was measured. The patients were classified into 4 groups according to origin: (1) 84 women were from the Canton Basel-Stadt. In this city water has been fluoridated since 1962; (2) 139 women from Canton Glarus. In this area a pilot study was under way using table and baker's salt, to both of which 250 mg F/kg had been added; (3) 128 women from Canton Aargau who were using a low dose fluoridated salt (90 mg F/kg); (4) 201 patients from Cantons Aargau and Tessin respectively who were consuming neither fluoridated water or salt acted as controls. Quantitation of ionized fluorine in urine was performed by means of the fluoride ion sensitive electrode in afternoon urine samples, thus eliminating the influence of sex difference and diurnal rhythm in fluorine excretion. The molar urinary fluorine concentration was related to the corresponding urinary creatinine concentration and expressed as mumol F per mmol creatinine. The fluoridation of salt or water was considered ideal when the excretion factor amounted to 6.29 mumol X mmol-1. The most important finding was that the Glarus females excrete higher levels of fluorine than the patients from Basel, though the difference was no significant. The fluoridation of salt with 90 mg F/kg is followed by an increase of the excretion factor from 2.58 to 3.65 mumol X mmol-1. It could also be demonstrated that in Canton Glarus, where salt with higher fluorine content is used, the excretion coefficient remains below the level believed to be toxic in the long run. It is concluded that salt fluoridation with 250 gm F/kg is safe. Furthermore, the excretion of fluorine in the control group seems to confirm that fluorine is a trace element of ubiquitous occurrence even excreted in urine of individuals who deliberately avoid fluorine as an additive to table salt or water.

Creatinine↗