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Biomedical subjects

I Witt

Publications and source records attributed to I Witt.

18 recordsLinked to original sources
PubMed1991

Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices.

Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called beta A4-peptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since proteolytic cleavage of APP inside its beta A4 sequence was found to be part of APP processing the formation of the beta A4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP processing. After we had recently found that cultured human neuronal cells synthesize the most potent of the known human proteinase inhibitors, alpha-2-macroglobulin (alpha 2M), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether alpha 2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong alpha 2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear alpha 2M immunoreactivity in hippocampal CA1 neurons of Alzheimer's disease brains indicates that neuronal cells are the site of alpha 2M synthesis in AD brains. We did not detect elevated IL-6 or alpha 2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.

Acute-Phase Reaction↗
PubMed1991

Fibrinogen Kiel: a congenital dysfibrinogenaemia with (A alpha-16 Arg----His) substitution characterized by HPLC without prior isolation of fibrinogen.

A congenital fibrinogen variant in a German family is described which has been identified as a substitution of His in position 16 of the A alpha-chain for Arg, manifested over three generations in heterozygous form. The characterization is based on the reaction of the variant fibrinogen with thrombin and reptilase, on the HPLC-chromatographic properties and the amino acid composition of the abnormal fibrinopeptide A. Clinical observations in the affected family members (neither haemorrhagic nor thrombophilic tendencies), the results of routine coagulation tests (normal global clotting tests, prolonged thrombin and thrombin-coagulase time, decreased fibrinogen concentration in functional as opposed to immunological tests), and the autosomal co-dominant modus of inheritance of the fibrinogen variant are all in complete agreement with other reports in the literature concerning the same amino acid exchange. The results of our experiments with fibrinogen Kiel allow no definite conclusion regarding the question of whether it consists of pure homodimers or as of a mixture of homo- and heterodimers.

Amino Acids↗
PubMed1991

Test systems with synthetic peptide substrates in haemostaseology.

Since the early seventies, synthetic peptide substrates have been used in haemostaseology, enabling the introduction of photometry in coagulation analysis. Synthetic peptide substrates are short peptides (3-5 amino acid residues), with a chromogenic group coupled to the C-terminal end by an amide bond. The chromogenic group may be relatively specifically removed by proteases, and measured photometrically. By using the special properties of the many available substrates, test systems have been developed for procoagulant clotting factors, fibrinolytic factors, inhibitors of both systems and also for global tests of plasmatic coagulation. These tests can be performed manually or on automated analytical systems with high specificity, sensitivity and accuracy. The analytical advantages and new possibilities of the tests with chromogenic substrates have, in recent years, decisively stimulated not only haemostaseological basic research, but also clinical investigation and routine. Today, inhibitors of plasma coagulation (e.g. antithrombin III, protein C, C1-esterase inhibitor) as well as fibrinolytic parameters (e.g. tissue plasminogen activator, plasminogen activator inhibitor, alpha 2-antiplasmin) are nearly exclusively determined with chromogenic substrates. Further development will constitute the application of chromogenic substrates to "dry chemistry" methods.

Amino Acid Sequence↗
PubMed1990

Ischemic stroke due to protein C deficiency.

Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery.

Adult↗
PubMed1990

[Inhibitors of blood coagulation in vascular occlusion of the retina and optic nerve].

The influence of a disturbed hemostasis as one of the causes of retinal or ciliary vascular occlusions is still controversial. Antithrombin III, protein C and its cofactor protein S were investigated in 25 patients; 14 of them with a retinal vein occlusion, five showed an occlusion of retinal arteries and six of ciliary arteries. Patients with a preceding thromboembolic disease were excluded from the investigations. The mean values (+/- SEM) of antithrombin III (12.1 IU/ml +/- 0.4), protein C (116% +/- 4), total protein S (102% +/- 3) and free protein S (46% +/- 2) were equivalent to the mean values of a normal population. Neither does a defect or a lack of coagulation inhibitors have an essential influence on the development of an isolated retinal or ciliary vascular occlusion nor does the local occlusive vascular disorder influence the activity of systemic inhibitors.

Aged↗
PubMed1979

Primary structure of yeast proteinase B inhibitor 2.

The complete amino acid sequence of yeast proteinase B inhibitor 2 (IB2) was determined to be H3N+-Thr-Lys-Asn-Phe-Ile-Val-Thr-Leu-Lys-Lys-Asn-Thr-Pro-Asp-Val-Glu-Ala-Lys-Lys-Phe-Leu-Asp-Ser-Val-His-His-Ala-Gly-Gly-Ser-Ile-Leu-His-Glu-Phe-Asp-Ile-Ile-Lys-Gly-Tyr-Thr-Ile-Lys-Val-Pro-Asp-Val-Leu-His-Leu-Asn-Lys-Leu-Lys-Glu-Lys-His-Asn-Asp-Val-Ile-Glu-Asn-Val-Glu-Asp-Lys-Glu-Val-His-Thr-Asn-COO-. Elucidation of the primary structure was enabled by automated Edman degradation and COOH-terminal hydrolysis with carboxypeptidases A (bovine pancreas and Y (yeast). IB2 is the first proteinase inhibitor to be sequenced that possesses a structure devoid of disulfide bridges.

Amino Acid Sequence↗
PubMed1979

Flavanone synthase from Petroselinum hortense. Molecular weight, subunit composition, size of messenger RNA, and absence of pantetheinyl residue.

Flavanone synthase from irradiated cell suspension cultures of parsley was purified to apparent homogeneity. Molecular weights of about 77 000 for the enzyme and about 42 000 for the subunits were determined respectively by sedimentation-equilibrium measurements and disc-gel electrophoresis in the presence of dodecyl sulfate. A specific antiserum was prepared for the enzyme and was used in an assay for flavanone synthase mRNA activity in partially purified RNA preparations. The apparent molecular size of flavanone synthase mRNA was estimated by sucrose gradient centrifugation and gel electrophoresis under partially denaturing conditions. Values of about 17 S and Mr = 0.62 X 10(6) were obtained. The fractionation patterns suggested that flavanone synthase mRNA was homogeneous in size. All together, the results support the idea that the enzyme is composed of two subunits which are probably identical. Amino acid analysis and a microbial assay were carried out to test the possible occurrence of cysteamine, beta-alanine, and pantothenate in the enzyme. The results were negative, indicating the absence of pantetheine or a similar residue. The possible similarity in mechanism between flavanone synthase and 3-oxoacyl-(acyl carrier protein) synthase is discussed.

Acyltransferases↗
PubMed1978

[Liver disease in homozygous alpha1-antitrypsin deficiency (author's transl)].

Among twelve patients with homozygous alpha1-antitrypsin deficiency (Pi-type Z), five cases of infantile liver disease were diagnosed. The course of the disease was extremely variable; only one patient died of liver cirrhosis at the age of fourteen. In four cases the clinical, biochemical and histological (2 cases) findings became normal over a follow-up period of one to fifteen years. The results of these observations demonstrate that in alpha1-antitrypsin deficiency even when associated with proven liver disease the prognosis need not be unfavorable.

Adolescent↗
PubMed1977

[New methods of coagulation analysis using chromogenic substrates].

The available assay systems for the determination of coagulation factors based on clotting methods are unsatisfactory, despite efforts to stabilize and to standardize them. Analysis by means of chromogenic peptide substrates offers new possiblities for routine diagnostics, and for fundamental research. The development of these new methods, however, is at an early stage.

Blood Coagulation Factors↗
PubMed1976

[LP-X in newborns: increased incidence of positive tests without cholestasis (author's transl)].

The investigation of 194 newborns has shown that during the first weeks of life the abnormal lipoprotein-X (LP-X) was present in the serum of nearly 50% of the infants, with no clinical chemical evidence of cholestasis. The percentage of LP-X positive tests was even higher in the group of immature newborns (65%). There was no correlation between the bilirubin concentration and the detection of LP-X. The activities of leucine arylamidase (EC 3.4.1.1) and gamma-glutamyltransferase (EC 2.3.2.2) as well as the concentrations of total and free cholesterol did not differ in the LP-X positive and negative infants. Except in one case, LP-X was never detectable on the first day of life. The earliest date of appearance was the second day. In the serum of some infants, who were LP-X positive shortly after birth, the lipoprotein could still be found at the age of 2--3 months. The incidence of LP-X was not higher in newborns with blood group incompatibility than in newborns with unspecific hyperbilirubinaemia. After exchange transfusions LP-X disappeared in most cases, but it could later often be detected again. In some newborns, who were LP-X negative a few days after birth LP-X was first detected at the age of 2-3 months. The LP-X test is of no use for th diagnosis of cholestasis in newborn infants. The test is specific for cholestasis only after the first year of life. The increased incidence of positive LP-X tests in newborns is discussed as a consequence of immature liver function.

Bilirubin↗
PubMed1975

[Hypophosphataemia as early sign of septicaemia in childhood (author's transl)].

The early diagnosis of septicaemia in children is difficult because the clinical and laboratory findings can be inconclusive. Results of blood cultures are usually available after two days only. Especially in the neonate, delayed or uncritical use of wide spectrum antibiotics can have negative consequences. We tested whether inorganic serum phosphate determinations could be helpful for diagnosing septicaemia in children. As in adults hypophosphataemia is a frequently occurring symptom in children with septicaemia. Hypophosphataemic values below 4.3 mg/100 ml in the neonate and below 3.2 mg/100 ml in an older child support the diagnosis of septicaemia. The possiblity of quick evaluation has some diagnostic importance.

Adolescent↗
PubMedDate not supplied

[Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols].

1. Treatment according to the ALL/NHL-BFM 90 protocol I (induction phase) caused multiple and severe coagulation changes in all 14 patients of our study. Glucocorticoids alone made Fibrinogen drop to 148 mg/dl, AT III and Protein C rise to 136% or even 179% respectively. After day 12, immediately following the start of therapy with Coli-Asparaginase (ASP), fibrinogen continued to drop to reach its lowest average value of 46 mg/dl on day 24. Anticoagulant factors like plasminogen (lowest average value: 36%), AT III (47%) and Protein C (93%) dropped abruptly. These alterations were reversed after discontinuation of Glucocorticoids and ASP. During consolidation (protocol II) similar alterations are observed as in protocol I when Glucocorticoids are applied alone. However, after Erwinia-ASP there is no fall in AT III, plasminogen, and Protein C as is observed in protocol I with Coli-ASP. 2. Severe hemorrhages or thromboses are uncommon as compared to the degree of coagulation changes which can be regularly observed. Complications occur more often in girls. Most of them are seen during the 2nd or 3rd week of simultaneous ASP-Glucocorticoid therapy. 3. To avoid twofold alteration of hemostasis it should be considered to apply Glucocorticoids and ASP separately and to replace Coli-ASP by Erwinia-ASP. The efficacy of prophylactic replacement of decreased coagulation factors has not yet been confirmed. Immunologic and infectious side effects have to be taken into consideration. 4. More definite recommendations can be given when each suspected bleeding and/or thrombosis is confirmed by imaging procedures, when it is documented and registered, and when coagulation studies are performed during the critical phase.

Antineoplastic Combined Chemotherapy Protocols↗