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Biomedical subjects

W Lange

Publications and source records attributed to W Lange.

At least 163 records · Page 9Linked to original sources

An enzyme-immunoassay for antibodies against hepatitis B core antigen: characteristics and clinical validation.

An enzyme-immunoassay (EIA) for antibodies to hepatitis B core antigen (anti-HBc) was developed. The new test uses undiluted samples, incubated directly into an HBcAg coated well. Three alternative test procedures are possible. The stability of reagents was studied and a preclinical evaluation was performed intramurally. An assay correlation study was organised. We report the results of the external evaluation performed at 4 centres. A mean analytical sensitivity of 1.1, 1.2 and 0.36 PEI units/ml anti-HBc was found for procedure I (1 h/1 h/30 min), procedure II (30 min/30 min/30 min) and procedure III (16-20 h/1 h/30 min), respectively. In total, 5288 determinations on serum or plasma from various patients and healthy individuals were performed: 10% with procedure I, 52% with procedure II and 38% with procedure III. The qualitative (positive or negative) results were compared with those found with tests used routinely at the centres--47% with Corzyme (Abbott) and 53% with Corab (Abbott)--in a first screening. A final evaluation was made taking into account the repeatability of the results. Based on all results together, the agreement between the new EIA for anti-HBc and the routine tests was 97.6% at the first screening and increased to 99.0% after further evaluation.

Blood Donors↗

Epidemiology and economic importance of hepatitis B in the Federal Republic of Germany.

Hepatitis is among the five most important notifiable infectious diseases in the Federal Republic of Germany where 15,000-20,000 new cases are reported annually. A total of 60,000 cases per year may actually occur when the presumed high incidence of unreported hepatitis is taken into consideration. Hepatitis B probably represents 35%-40% of these hepatitis cases. When considering the reported (7000/year) and unreported cases, 30,000 new infections may occur each year. Drug addicts with infection rates of over 80% and prison inmates with up to 72% of hepatitis B markers are the most important risk groups as well as patients from haemodialysis units (60%), haemophiliacs, and newborns of mothers who are HBV carriers. Medical personnel, with an infection rate of 15%-26%, are at significantly greater risk than the general public. Hepatitis B results in enormous annual health costs. Calculations based on 30,000 new cases per year indicate that the costs for therapy, rehabilitation, as well as loss of work-hours and income lie between 842 and 1113 million DM. The frequency of hepatitis B, its potential for temporary or prolonged health impairment, and the significant economic implications make it imperative to develop meaningful strategies for control.

Adolescent↗

Identification of endogenous sugar-binding proteins (lectins) in human placenta by histochemical localization and biochemical characterization.

Human placentas of different stages of development were histochemically analyzed for expression of endogenous sugar-binding proteins using a panel of biotin-conjugated, chemically glycosylated probes with specificity for beta-galactosides, alpha-galactosides, alpha-mannosides, alpha-fucosides and alpha-glucosides. Temporal differences in the expression of sugar-binding proteins and different patterns of staining of the component cell types of human placenta were discerned, especially pronounced for alpha-fucoside-specific binding in the trophoblast and alpha-glucoside-specific binding in fetal and maternal macrophages. Fractionation of salt and detergent extracts from human placentas by affinity chromatography on columns with immobilized carbohydrates or glycoproteins substantiated the histochemically detectable temporal changes on the basis of alterations in the pattern of individual sugar-binding proteins, as determined by gel electrophoresis under denaturing conditions. Analysis of the trophoblastic layer primarily disclosed the presence of several additional sugar-binding proteins (lectins) in comparison to full-term placenta. The presence and developmental changes of such endogenous sugar receptors may lead to specific carbohydrate-protein interactions of physiological significance with similarly developmentally regulated carbohydrated portions of glyco-conjugates, already detected in human placenta by plant lectins.

Carbohydrate Metabolism↗

Is motilin a cerebellar peptide in the rat? A radioimmunological, chromatographic and immunohistochemical study.

Motilin was demonstrated by the immunoperoxidase technique in endocrine cells of the gastrointestinal tract using several specific antisera. Motilin-like immunoreactivity could only be demonstrated with one of these antisera and was observed in Purkinje cells and dendrites of the cerebellum, in pyramidal cells and dendrites of the cerebral cortex and in dendrites of the CA 3 field of the hippocampus of the rat. Very low motilin-like immunoreactivity was found in cerebellum as well as in cerebral cortex using radioimmunoassay. However, using reverse phase liquid chromatography combined with UV-detection and radioimmunoassay, no peak of a peptide corresponding to synthetic motilin was detectable in rat cerebellar extracts, in contrast to findings in rat duodenum. The results do not suggest that motilin is an intrinsic neuroactive substance of the cerebellum.

Animals↗

Immunobiological activities of nontoxic lipid A: enhancement of nonspecific resistance in combination with trehalose dimycolate against viral infection and adjuvant effects.

The ability of nontoxic monophosphoryl lipid A (MPL) to stimulate nonspecific resistance against viral infection was investigated. Mice pretreated intravenously with squalane-in-water emulsions of MPL, alone or in combination with other immunostimulants, were given an aerosol of influenza virus three weeks after the pretreatment. Complete protection against lethal influenza virus infection was conferred when MPL was combined with trehalose dimycolate (TDM). The protective activity of MPL plus TDM combination was corroborated by a significant reduction of the lung virus titers. Combination of lower doses of MPL with TDM extracted from Mycobacterium bovis, but not with that of M. phlei, induced significant resistance to influenza virus. Preparations containing MPL alone, or combined with mycobacterial cell wall skeleton or muramyl dipeptide, were not effective. The adjuvant activity of MPL on bivalent influenza subunit vaccine was also studied. The primary antibody responses to influenza A and influenza B antigens were enhanced by the addition of MPL and were higher than the vaccine associated with aluminum hydroxide. The adjuvant activity of MPL was confirmed by the elevated secondary response. High levels of circulating antibodies were still present in the MPL group when antibody titers in the controls were waning.

Adjuvants, Immunologic↗

Effects of muramyl dipeptide and trehalose dimycolate on resistance of mice to Toxoplasma gondii and Acanthamoeba culbertsoni infections.

The effects of synthetic muramyl dipeptide (MDP) and natural trehalose dimycolate (TDM) against parasitic infections by intracellular Toxoplasma gondii and free-living Acanthamoeba culbertsoni were studied. Significant resistance against oral T. gondii infection was induced by intraperitoneal pretreatment with TDM but not with MDP. The protective effect of TDM against T. gondii was corroborated by a significant reduction in the number of cysts in brains of pretreated animals and elevated serum antibody levels. Partial protection against lethal intranasal A. culbertsoni infection was conferred by specific immunization with viable trophozoites of nonpathogenic Acanthamoeba lugdunensis. The nonspecific resistance induced by intravenous pretreatment with MDP was similar to, whereas that stimulated by TDM was lesser than the protection conferred by A. lugdunensis. The Fc receptor-mediated phagocytosis of 51Cr-labeled sheep red blood cells by alveolar macrophages was enhanced by MDP. The phagocytic activity of peritoneal macrophages was increased by lower doses of TDM.

Acetylmuramyl-Alanyl-Isoglutamine↗

Enhancement of chemiluminescence and phagocytic activities by nontoxic and toxic forms of lipid A.

The effect on the respiratory burst of murine splenic cells after in vitro exposure to nontoxic monophosphoryl lipid A (MPL), toxic diphosphoryl lipid A (DPL), and refined standard endotoxin (RSE) was studied by luminol-dependent, zymosan-stimulated chemiluminescence (CL). CL was stimulated only to a minimum degree by 0.1 micrograms of MPL, DPL, or RSE, but this was clearly increased when 10-fold higher doses were used. CL activity generated by RSE, which contains only lipid A and ketodeoxyoctanate, remained at a moderate level, even when 100-fold higher doses were used. In contrast, ketodeoxyoctanate-free DPL elevated CL in a dose-dependent manner. Nontoxic MPL at a high dose significantly enhanced CL generation to levels that were comparable to those stimulated by DPL. In addition, phagocytosis of freshly prepared fluorescent beads by adherent peritoneal macrophages was enhanced seven- to 10-fold by toxic DPL and reference LPS, and fivefold by nontoxic MPL.

Animals↗

Lipophilic muramyl dipeptide-induced changes in electron microscopic morphology and phagocytic function of murine macrophages.

The capacity of a lipophilic derivative of synthetic muramyl dipeptide (MDP), B30-MDP, to induce morphological changes and functional alterations in the activity of resident peritoneal macrophages was studied. Macrophages incubated in vitro for 24 h with B30-MDP, but not with MDP or medium, showed rounding and extensive ruffling of the cell surface when examined by scanning electron microscopy. Transmission electron microscopy of B30-MDP-treated macrophages revealed the development of large cytoplasmic vacuoles. These structural changes did not affect the viability of macrophages. The Fc receptor-mediated phagocytosis of 51Cr-labeled sheep red blood cells by adherent macrophages incubated with a high dose of MDP showed a modest response whereas even low doses of B30-MDP greatly enhanced the phagocytic activity. Adherent macrophages incubated with B30-MDP generated elevated levels of luminol-dependent chemiluminescence in response to stimulation by zymosan.

Acetylmuramyl-Alanyl-Isoglutamine↗

The morphology of lipopigment granules in oligodendrocytes of the cerebellum and spinal cord and in Schwann cells of the N. ischiadicus of the cat, Japanese waltzing mouse, and albino mouse.

In the oligodendrocytes of cerebellum and spinal cord and in the Schwann cells of peripheral nerves of cat, albino mouse, and Japanese waltzing mouse lipopigment bodies of different size and shape are deposited, which exhibit a characteristic internal structure. The following three subtypes can be distinguished: (1) Granules completely surrounded by a membrane and consisting regularly spaced lamellae, (2) granules consisting of a granular matrix with elucidations, and (3) granules with bifurcating stacks of lamellae. Thus, their structure is distinct from that found in nerve cells and other glial cells and allows the diagnosis of oligodendrocyte or Schwann cell. The significance of these granules in relation to function and aging is briefly discussed.

Animals↗

Depressed chemiluminescence response by influenza virus is enhanced after conjugation of viral subunits to muramyl dipeptide.

The effect on respiratory burst of murine spleen cells after in vitro exposure to influenza virus, subunits, or subunits conjugated to muramyl dipeptide (MDP) was studied by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. CL induced by infectious influenza A virus was depressed but could be elevated to normal levels when MDP was added together with a low, but not with a high, dose of the virus. Profound depression of CL was induced by high doses of influenza A/Brazil, A/Bangkok, and B/Singapore subunits. The same amounts of viral subunits conjugated to MDP restored or even enhanced the CL responses of spleen cells from BALB/c and C57BL/6 mice. Splenic cells from BALB/c mice generated higher levels of CL than did cells from C57BL/6 mice.

Acetylmuramyl-Alanyl-Isoglutamine↗

Trehalose dimycolate from various mycobacterial species induces differing anti-infectious activities in combination with muramyl dipeptide.

Significant resistance against influenza virus and Mycobacterium tuberculosis infections was induced when trehalose dimycolate from M. tuberculosis or M. bovis but not M. avium was combined with muramyl dipeptide. Trehalose dimycolate from M. tuberculosis, in contrast to that from M. avium, could confer resistance against Toxoplasma gondii infections.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Demonstration of hepatitis Be antigen and anti-hepatitis Be with enzyme immunoassay in a microtiter system].

A new microtitre enzyme-immunoassay (Organon Teknika ) to demonstrate HBe-antigen and anti-HBe was compared with a corresponding radioimmunoassay (RIA) of Abbott, on sera of patients with hepatitis-B and reference material. In a serial dilution of HBe-antigen reference preparation from the reference centre for hepatitis B in G ottingen , RIA was able to demonstrate HBe-antigen to a dilution of 1:1024, and the microtitre enzyme-immunoassay (Elisa) to 1:4096 (declaration of reference preparation: 1024 RIA units). In the anti-HBe reference preparation anti-HBe was demonstrated by Elisa to a dilution of 1:4096 and by RIA to 1:512. In tests on sera of patients with hepatitis B, Elisa was superior to RIA in demonstrating both HBe-antigen and anti-HBe. This advantage was particularly clear in the demonstration of anti-HBe. Using the Elisa system, either HBe-antigen or anti-HBe was demonstrated in the fourth week of illness in over 95% of patients. With RIA this result was achieved only in the eighth month after the onset of illness. According to the results obtained with the Elisa system, HBe-antigen is eliminated early and is quickly followed by anti-HBe, while according to results with RIA some time elapsed between the disappearance of HBe-antigen and the occurrence of anti-HBe. Elisa demonstrates high precision, both in a single test and also from test to test, and in this respect, too, it was not inferior to RIA. False-positive or non-reproducible positive reactions were very rare in both tests. These results indicate that Elisa is an alternative to RIA and, because of its higher sensitivity, is superior to RIA.

Enzyme-Linked Immunosorbent Assay↗