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W Hofmann

Publications and source records attributed to W Hofmann.

At least 127 records · Page 7Linked to original sources

Modeling techniques for inhaled particle deposition: the state of the art.

Mathematical modeling of aerosol deposition in the human lung is based on idealized assumptions regarding the morphometry of the lung, the fluid dynamics behavior of the inspired air under defined breathing conditions, the transport of particles through the branching airway system, the physical mechanisms acting upon inhaled particles, and the deposition of particles within airways, airway bifurcations, and alveoli. Current models of particle deposition in the human lung, ranging from experimentally based semi empirical to rather sophisticated stochastic and numerical mathematical models, permit the prediction of particle deposition at different levels of complexity, ranging from total deposition in the whole lung to localized deposition patterns within single airway bifurcations. In this paper, the present state of the art in aerosol deposition modeling will be reviewed, focusing on the discussion of different conceptual ideas rather than on a complete listing of all published modeling efforts. The selection of specific contributions by various authors relevant to our present understanding of particle deposition in the human lung reflects the subjective view of the author. In addition, illustrations of salient features of different modeling approaches are based primarily on the author's own research.

Administration, Inhalation↗

Development and evaluation of a urine protein expert system.

Based on the quantitative determination of creatinine, total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin, and N-acetyl-beta, D-glucosaminidase in urine in combination with a test strip screening, the findings of hematuria, leukocyturia, and proteinuria can be assigned to prerenal, renal, or postrenal causes. Using this graded diagnostic strategy as a knowledge base, we developed a computerbased expert system for urine protein differentiation ("UPES") as a decision-supporting tool. The knowledge base was implemented as a combination of "if/then" rules and two-step bivariate distance classification of marker proteins. The knowledge for this form of pattern recognition was derived from the results for a set of 267 patients with clinically and histologically documented nephropathies. To determine the diagnostic value of UPES, we tested another set of data: results for 129 urine analyses from 94 patients. Using these data, the system reached 98% concordance with the clinical diagnoses for the patients and was superior to the diagnostic interpretations of four human experts. UPES has been successfully integrated into the laboratory routine process, including automated data import.

Acetylglucosaminidase↗

[Sonography as a tool in the diagnosis of displacement of the abomasum].

43 Holstein-Friesian cows were investigated by sonography for the occurrence of a displacement of the abomasum. 26 animals suffered from a displacement of the abomasum. The results of sonography of these diseased and of healthy animals are described. After sonography all animals were subjected to an exploratory laparotomy in order to check the validity of the sonographic diagnosis. The results and the diagnosis obtained by laparotomy were compared to the sonographic findings.

Abomasum↗

Chemical cross-linking leads to two high molecular mass aggregates of rat alpha 1 beta 1 integrin differing in their conformation but not in their composition.

In order to detect protein interactions of the collagen/laminin receptor alpha 1 beta 1 integrin, covalent chemical cross-linking was performed with the homo-bifunctional, amine reactive reagents DSS (disuccinimidylsuberate) and DSP (dithiobis(succinimidylpropionate)). After cross-linking of the 190 kDa rat alpha 1 integrin subunit, immunoblotting revealed two additional, immunoreactive, high molecular mass complexes (M(r) 240/290 k). Generation of the 240/290 kDa aggregates depended on the presence of the intact tertiary protein structure. As shown with immunoaffinity purified proteins, the 240/290 kDa aggregates consist exclusively of alpha 1 and beta 1 integrin subunits. No other cross-linked proteins associated with the alpha 1 or beta 1 subunit were detected. In contrast to the non-cross-linkable alpha 1 beta 1 integrin, the 240/290 kDa aggregates presumably represent active forms of the adhesion receptor, because both bound in vitro to collagen I and IV. This ability of alpha 1 beta 1 integrin to cross-link and produce two additional high molecular mass forms is shared by rat alpha 9 beta 1 integrin. Thus, the cross-linking approach directly indicates that beta 1 integrins occur in different conformations caused by variations in the folding and/or spatial arrangement of their subunits.

Animals↗

Characterization of molecular aggregates of alpha 1 beta 1-integrin and other rat liver membrane proteins by combination of size-exclusion chromatography and chemical cross-linking.

Many membrane proteins display their biological activity in molecular aggregates of interacting counterparts. The analysis of these aggregates remains difficult; especially intermolecular complexes of membrane proteins tend to dissociate or artificially aggregate during detergent extraction out of membranes. Thus, the existence of protein aggregates was investigated by two approaches. First, after modest detergent extraction, the presence of three well characterized rat liver membrane proteins, alpha 1 beta 1-integrin, dipeptidyl aminopeptidase IV (DPP IV) and cell-CAM 105 (CAM = cell adhesion molecule), in aggregates could be demonstrated when investigated by size-exclusion chromatography (SEC) under non-denaturating conditions. However, the applied detergents partially influenced the resolution of the separation reducing the ability to discriminate between native and artificial protein aggregates. To circumvent these problems, a second approach based on covalent cross-linking of native protein complexes by dithiobis(succinimidylpropionate) was combined with the performance of denaturating SEC. Under such optimized some high-molecular-mass complexes of all model proteins consisting of unknown components could also be detected. Taken together, non-denaturating SEC and chemical cross-linking in combination with denaturating SEC represent methodological approaches for the characterization of protein aggregates.

Adenosine Triphosphatases↗

[Acute liver failure as the initial manifestation of Wilson disease].

BACKGROUND: Establishing an early diagnosis is crucial to successfully treat mostly young patients with sudden onset acute hepatic failure as the initial symptom of Wilson's disease. Recognition of the entity of Wilsonian fulminant hepatitis is important, because liver transplantation improves survival if performed in a timely fashion. METHODS: Retrospective case analysis regarding characteristic profile of standard laboratory parameters and clinical course of acute Wilsonian hepatic failure. RESULTS: In two female patients (age 17 and 27 years) with non-autoimmune hemolysis serum AST and ALT levels were only moderately elevated with a conspicuously diminished ALT activity and relatively low serum alkaline phosphatase (AP) levels. Despite immediate application of D-Penicillamin one patient died from complications of multiorgan failure. CONCLUSION: In fulminant Wilsonian hepatic failure the AP/bilirubin ratio is usually below 2. Additionally calculation of free copper concentration in serum and renal excretion of ionic copper in combination with non-autoimmune hemolysis provide clues to establish an early diagnosis of Wilsonian hepatic failure.

Adolescent↗

Distribution and quantification of alpha 1-integrin subunit in rat organs.

The alpha 1 beta 1-integrin is known to be a receptor for collagen and laminin mediating cell-matrix interactions. A monoclonal antibody, 33.4, which specifically inhibits the alpha 1-integrin-mediated in vitro cell-collagen binding of rat hepatocytes and hepatoma-derived A-cells (Löster et al., 1994), was used to purify by immunoaffinity chromatography the alpha 1-integrin subunit from rat liver in large quantities for inducing a polyclonal antiserum. In immunoblot analysis on membrane extracts of several rat organs this polyclonal antiserum recognized only a 190 kDa-band, suggesting that it is highly specific for the alpha 1-integrin subunit. A sandwich-ELISA with monoclonal antibody 33.4 and the polyclonal antiserum against the alpha 1-integrin subunit, respectively, enabled the quantitative expression pattern of the alpha 1-integrin subunit to be studied in different rat organs. With the exceptions of brain (not detectable) and muscle (low concentration), the alpha 1-integrin subunit was detectable in almost all organs of the digestive, respiratory and urogenital system as well as in lymphatic organs. The highest relative concentrations of alpha 1-integrin subunit were found in uterus, lung and spleen, whereas in seminal vesicle, stomach, parotid gland, epididymis, kidney and liver only modest concentrations were evident. The organ distribution and localization of alpha 1-integrin subunit were studied by immunohistochemistry with monoclonal and polyclonal antibodies. Immunoreactivity was present in the plasma membranes of all smooth muscle cells, vascular endothelial cells of many organs and fibrocyte-fibroblast sheaths in the heart and kidney. Since these cells are in close contact with collagen-containing basal membranes as well as reticular fibrils, strong evidence exists that in rat tissues the alpha 1-integrin subunit is expressed at sites where collagen is present and might be involved in vivo in cell-collagen binding.

Animals↗

Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates.

The structure, replicative properties, and sensitivity to neutralization by soluble CD4 and monoclonal antibodies were examined for molecularly cloned envelope glycoproteins derived from human immunodeficiency virus type 1 (HIV-1) viruses either isolated directly from patients or passaged in T-cell lines. Complementation of virus entry into peripheral blood mononuclear cell targets by primary patient envelope glycoproteins exhibited efficiencies ranging from that observed for the HXBc2 envelope glycoproteins, which are derived from a T-cell line-passaged virus, to approximately fivefold-lower values. The ability of the envelope glycoproteins to complement virus entry roughly correlated with sensitivity to neutralization by soluble CD4. Laboratory-adapted viruses were sensitive to neutralization by monoclonal antibodies directed against the CD4-binding site and the third variable (V3) loop of the gp120 glycoprotein. By comparison, viruses with envelope glycoproteins from primary patient isolates exhibited decreased sensitivity to neutralization by these monoclonal antibodies; for these viruses, neutralization sensitivity correlated with replicative ability. Subinhibitory concentrations of soluble CD4 and a CD4-binding site-directed antibody significantly enhanced the entry of viruses containing envelope glycoproteins from some primary patient isolates. The sensitivity of viruses containing the different envelope glycoproteins to neutralization by soluble CD4 or monoclonal antibodies could be predicted by assays dependent on the binding of the inhibitory molecule to the oligomeric envelope glycoprotein complex but less well by assays measuring binding to the monomeric gp120 glycoprotein. These results indicate that the intrinsic structure of the oligomeric envelope glycoprotein complex of primary HIV-1 isolates, while often less than optimal with respect to the mediation of early events in virus replication, allows a relative degree of resistance to neutralizing antibodies. The interplay of selective forces for higher virus replication efficiency and resistance to neutralizing antibodies could explain the temporal course described for the in vivo emergence of HIV-1 isolates with differing phenotypes.

Antibodies, Monoclonal↗

A mathematical equation to differentiate overload proteinuria from tubulo-interstitial involvement in glomerular diseases.

Determination of marker proteins like albumin and alpha 1-microglobulin allows to differentiate various types of proteinuria in kidney diseases. In the present communication we calculate the degree of tubulointerstitial involvement by quantitation of the tubular marker alpha 1-microglobulin in urine in relation to albuminuria. A mathematical relation between minimal tubular proteinuria with the degree of albumin excretion was observed. Cases forming this line did not exhibit interstitial fibrosis when analyzed histologically. In contrast most cases exhibiting higher excretion rates of the tubular marker showed various degrees of tubulointerstitial involvement. In order to differentiate interstitial contribution from overload tubular proteinuria in patients with an albumin excretion rate above 3000 mg/g creatinine alpha 1-microglobulin (measured) is suggested to be corrected by the "glomerular" component of alpha 1-microglobulin using the following equation: "tubulo-interstitial alpha 1-microglobulin" = alpha 1-microglobulin (measured) -4.7 exp (2.2 x 10(-4)) [albumin]. Alternatively the correction can be performed graphically. This procedure may be of considerable help in preventing misinterpretations of urinary protein patterns in patients with nephrotic proteinuria.

Albuminuria↗

[Longitudinal analysis of utilization of inpatient treatment based on insurance data of mandatory health insurance].

AIM: To investigate which of the routinely collected claims data from the German "Legal sickness funds" on hospital utilisation may be used, in addition to that prescribed by the legislator. DESIGN: We used claims data to study a cohort of sickness fund beneficiaries who were insured during the complete year 1992 (n = 81,309). Six utilisation parameters, using the number of cases and in hospital days overall as well as diseases specific (i.e. readmission rates, in-hospital days per person with [at least] one hospital stay) were calculated. RESULTS: There are 88 persons with (at least) one hospital stay, 116 hospital cases and a total of 1306 in-hospital days per 1000 insured persons in the study cohort. The average hospital days per person (14.8 days) are ca. 30% higher than the average length of stay (11.2 days). Hospital utilisation increases with age. Hospital stays associated with ICD-239 (neoplasms of unknown origin) resulted in a higher than average number of hospital days in total although the mean length of stay is not above the average. This is due to a high readmission rate. Hospital stays associated with elective surgical procedures have a high prevalence rate but a low readmission ratio and short length of stay. CONCLUSION: The parameters related to insured persons, cases and specifically personal parameters of hospital utilisation allow a detailed analysis of hospital care; different utilisation and user patterns can be investigated and possible determinants of utilisation can be identified. After technical transformation, routine data of the sickness funds can be used to obtain information relevant for health care planners as well as for quality management.

Adolescent↗

Cell-collagen adhesion is inhibited by monoclonal antibody 33.4 against the rat alpha 1-integrin subunit.

A monoclonal antibody (mAb 33.4) is described which inhibits the adhesion and spreading of an adherent cell line (A-cells), established from Morris hepatoma 7777 and isolated hepatocytes on collagen IV but not on laminin, fibronectin, and vitronectin. mAb 33.4 retains its immunological activity after immobilization and covalent cross-linking to Protein G-Sepharose and is therefore a suitable tool for the preparative equimolar purification of two proteins with M(r) of 130 and 190 kDa from detergent-solubilized membrane fractions by immunoaffinity chromatography. The 190-kDa protein was identified as rat alpha 1-integrin subunit by N-terminal amino acid sequencing, while the 130-kDa protein was specifically stained by a beta 1-integrin subunit-specific antiserum. In immunoblot analysis mAb 33.4 recognized the 190-kDa band, suggesting that it is specific for the rat alpha 1-integrin subunit. The epitope recognized by mAb 33.4 is conformation-dependent because the staining in immunoblots was very strong if the SDS-PAGE was performed in the absence of reducing agents. The expression of alpha 1 beta 1-integrin in sinusoidal hepatocyte membrane domains of liver sections is shown by mAb 33.4 and antisera raised against the rat alpha 1- and beta 1-integrin subunits.

Animals↗

Electrically evoked potentials in the rat hippocampus slice in the presence of aminophylline alone and in combination with quinolones.

The excitability of brain matter was tested bt electrically evoked field potentials in the CA1 region of the rat hippocampus in vitro. In contrast to the quinolones which only increased the amplitudes of electrically evoked potentials, aminophylline induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of aminophylline (0.5 microM) to different degrees, ranging from 135.3% for ciprofloxacin to 223.8% for nalidixic acid. The rank order of potency of CNS side effects reported in the literature correlates very well with the increase of the population spike amplitude in the hippocampus slice preparation. This feature could be important during the development of new chemical analogues of quinolones.

Aminophylline↗

Diagnostic strategies in urinalysis.

The traditional methods in urinalysis (visual microscopy, qualitative test strip screening) were compared with automated microscopy (UA-1000, TOA-medicals, Japan) and quantitative single protein analysis in 562 fresh morning urine samples. Albumin served as "glomerular" and alpha 1-microglobulin as "tubular" markers measured by turbidimetry. The test strip delivered at least one positive result in 60% of the urine for blood (21%), leukocytes (27%), or protein (34%). In only 4% casts or renal cells were found by traditional microscopy, whereas automated microscopy was positive for these findings in 28% of the urine. Quantitative urine protein analysis alone exhibited results outside the reference interval in 52% of the urine. Combination of the test strip procedure for blood and leukocytes with urine protein analysis increased the number of positives to 73%. Thirteen percent of these additional findings were classified as glomerular (64%) and tubular (72%) proteinurias. In 7% of the urine a false positive protein test strip result was confirmed by quantitative albumin determination. Of 157 urine samples, positive in mechanized video recorded screening, 60 (38%) were normal in single protein analysis. The results allow for the conclusion that the advanced techniques are superior to traditional screening procedures in detecting abnormal urine composition. It is suggested that traditional urinalysis should be supported or replaced by quantitative determination of albumin and alpha 1-microglobulin. This recommended strategy is able to exclude or detect tubulo-interstitial nephropathies or microalbuminuria in earlier phases of renal complications, such as in diabetes mellitus, hypertension or in nephrotoxic injury. A fully mechanized version is suggested to meet appropriate quality criteria and economic needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Differentiation of proteinuria and haematuria by single protein analysis in urine.

Single proteins and tubular enzymes have been proposed as markers to detect and differentiate prerenal, glomerular, tubular, and postrenal forms of proteinuria and haematuria. By quantitation of total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin, and N-acetyl-beta, D-glucosaminidase (beta-NAG) activity it has become possible to clearly separate these forms by analysis of a single sample of second morning urine. When this program was applied to screening of hospital patients, albumin, total protein, and NAG proved to be sufficient to exclude clinically relevant disturbances. alpha 1-Microglobulin was useful to separate primary glomerulopathies from tubulo-interstitial diseases. Glomerular and postrenal haematuria could be clearly separated by their different excretion rates of alpha 2-macroglobulin, when urine albumin concentration exceeds 100 mg/L. The results imply that wider application of these techniques can help to detect renal abnormalities at an earlier stage and differentiate the various forms by less invasive techniques.

Albuminuria↗