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Biomedical subjects

M H Weber

Publications and source records attributed to M H Weber.

At least 19 recordsLinked to original sources

[Imaging and functional parameters in diagnosis of obstructive nephropathy].

Obstruction of the kidney leads to terminal kidney failure within a few years. Therefore, early recognition of such obstruction is of importance. Non-invasive diagnostic ultrasound examination now allows intrauterine visualization of a suspected obstruction. However, the implications of such a dilated ureteral pelvic system are obscure. Whether there is obstruction or dilatation can only be evaluated postnatally by a nuclear technique. The aim of our study was to measure the recovery of kidney function. We investigated 13 kidneys of 9 newborns or small infants (up to 2 years). The follow-up was continuous for up to 29 days. The parameters were: urine output (24-h clearance), glomerular filtration rate, fractional excretion of sodium and potassium, free water clearance, total protein excretion, albumin and alpha 1 microglobulin excretion. The urine output fell from 0.3 to 0.12 ml/min within 14 days after relief of obstruction. The glomerular filtration rate rose from nearly 30 ml/min to about 50 ml/min within a week. The fractional excretion of sodium and potassium indicated recovery of the proximal tubli. The fractional sodium excretion fell below 1% within 4 days. The free water clearance reflects the concentrating ability of the kidney, and in kidneys from newborns it had only positive values, while in kidneys of children older than 6 months there were also negative values. The protein excretion and the albuminuria showed recovery of the glomerular as well as the tubular system.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Globulins

Alpha 1-microglobulin (protein HC): features of a promising indicator of proximal tubular dysfunction.

alpha 1-Microglobulin (protein HC) is a stable urinary indicator protein which reflects acute and chronic dysfunctions of the proximal renal tubule. High urinary concentrations were found to be indicative of tubular drug toxicity, interstitial nephritis or chronic renal failure. The protein is synthesized by liver cells and readily associates with serum immunoglobulin A. Only the free form is filtered through the glomerulus and is reabsorbed by proximal tubular cells. The exact physiological function of this member of the new superfamily of lipocalins is still unknown, but there are indications that alpha 1-microglobulin (protein HC) may serve as an excretion vehicle for fluorescent, charge-heterogeneous substances of unknown nature. Additionally, it seems to be associated with the humoral and cellular immune response.

Alpha-Globulins

Rapid increases in the membrane expression of neutral endopeptidase (CD10), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD16) upon stimulation of human peripheral leukocytes with human C5a.

Rapid increases in the membrane expression of C3 receptors on granulocytes and monocytes in response to the anaphylatoxin C5a have previously been described. In this study we demonstrate increases in the membrane expression of neutral endopeptidase (NEP, CD10, CALLA), aminopeptidase N (APN, CD13), tyrosine phosphatase (CD45/CD45Ro) and the Fc R Fc gamma-RIII (CD16) on granulocytes within minutes of treatment with human C5a. Monocytes responded to C5a with increases in CD13 and CD45/CD45Ro. These membrane modulations could be prevented by preincubating the C5a preparations with anti-C5a mAb C17/5 but not by pretreating the cells with cycloheximide. Increases of CD10, CD13, and CD11b but not CD11a (LFA-1) were also observed in leukocytes from patients undergoing hemodialysis with cuprophan membranes. The increase of CD16 on granulocytes was dependent on the presence of plasma during in vitro activation with C5a indicating that plasma contains inhibitors which prevent the previously described loss of Fc gamma-RIII upon stimulation of the cells.

Aminopeptidases

Elevated plasma levels of the immunosuppressive complement fragment Ba in renal failure.

The complement fragment Ba is a 33 kD activation product of factor B which suppresses human B-lymphocyte functions in vitro. We report that plasma levels of Ba are highly elevated in patients with chronic renal failure (4.84 +/- 3.58 micrograms/ml) and in patients with end-stage renal disease undergoing regular hemodialysis (16.1 +/- 6.1 micrograms/ml) as compared to normals (1.01 +/- 0.30 micrograms/ml). Ba levels were strictly correlated with the creatinine clearance. The urinary excretion of Ba was 165-fold higher in patients with tubular proteinuria than in normals. These results indicate that the kidney is the major catabolic site for Ba. In addition, direct evidence was obtained for an enhanced turnover of the alternative pathway of complement in renal failure that, although it appears to be less important than the renal retention of Ba, contributes to elevated Ba plasma levels in these patients. Ba concentrations in dialysis patients who responded to hepatitis B vaccination were significantly lower than in non-responders. Furthermore, the in vitro IgM synthesis by purified mononuclear cells was negatively correlated with Ba concentrations determined in the plasma of these patients. These results suggest that the accumulation of Ba contributes to the defective immune response in patients with renal failure.

Adult

[Localization and extent of tissue damage caused by extracorporeal lithotripsy (ESWL)].

Extracorporeal shock wave lithotripsy (ESWL) causes proteinuria. In our study we investigated the protein fractions and the electrolyte composition of the urine in patients who had been treated with ESWL. The aim was to obtain information on the degree and the localisation of the glomerular, tubular or vascular destruction caused by ESWL in humans. A total of 34 patients with stones had been treated with ESWL. As parameters we used: urine output, creatinine clearance, total protein, albumin, immunoglobulin G, N-acetyl-beta-D-glucosaminidase (beta-NAG), alpha-1-microglobulin, the fractional excretion of Na+ and apolipoprotein-A-1. After ESWL treatment proteinuria and albuminuria are found. Our parameters show no deterioration of the glomerula or the tubulus. The increase in apolipoprotein-A-1, a postglomerular parameter, however, is interpreted as a manifestation of vascular destruction after ESWL; this is normally temporary, leaving no permanent damage.

Acetylglucosaminidase

[Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases].

Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.

Arthritis, Rheumatoid

Urinary protein electrophoresis profile in normal and hypertensive pregnancies.

By using of modified urine preparation and a highly sensitive SDS-polyacrylamide gel electrophoresis (SDS-PAGE) we determined the urinary protein profile in 21 healthy males, 25 healthy females, 64 patients with uncomplicated pregnancy and 110 hypertensive pregnant women. The urinary protein patterns were similar in controls and in women with a normal pregnancy. There were no increase in the number of protein bands from the 1st trimester to term, and the electrophoresis pattern did not change in the postpartum period. In both groups, an intensively stained protein band with an apparent molecular weight of 105 kD was detected. The 105 kD band was significantly reduced or completely absent in 91 (83%) out of 110 hypertensive pregnant women. The urinary protein electrophoresis profile correlated significantly with the severity of the disease. The 105 kD band disappeared just before or simultaneously with the onset of clinical symptoms in 18 out of 32 hypertensive pregnant women followed throughout pregnancy. Postpartum the 105 kD in urine reappeared at 2 to 14 days after delivery in 49 of the 53 patients. Using a silver staining and Western blot, the 105 kD band was identified as Tamm-Horsfall protein, which is identical to the immunosuppressive glycoprotein uromodulin. The findings in the SDS-PAGE may reflect a transitory tubular dysfunction in cases of pre-eclampsia, which is usually reversible after delivery. The results of our study support the hypothesis of an immunological basis for this disorder.

Adolescent

Influence of CAPD and residual diuresis on the serum levels of alpha-1-microglobulin in end-stage renal disease.

The chronic retention of proteins of low molecular weight (LMWP) seems to be connected with some unsolved problems of end-stage renal disease (e.g. reduced immune function, AB amyloidosis, hormonal imbalances), irrespective of the type of renal replacement therapy. Therefore, several recently discovered LMWPs such as alpha 1-microglobulin have to be evaluated concerning their contribution to the uremic syndrome. Although we observed a considerable daily loss of total protein into the CAPD dialysate, no differences were found in the removal of small proteins (MW less than 68 kilodaltons) when compared to conventional hemodialysis. Maintenance of renal function (residual diuresis greater than 100 ml/day) seems to be more potent keeping the serum concentrations of LMWP low than CAPD or hemodialysis.

Adult

[Urine proteins in primates].

Protein excretion and protein fractions either according to their molecular mass or with immunological techniques were studied in the spontaneous morning urine of 17 primate species. The total protein concentration in most of the species ranges between 0.01 and 0.2 mg/ml. The pronounced proteinuria (4 mg/ml) in some south american species (Callithricidae) seems to be remarkable. By using immunoprecipitation (LC-Partigen plates), albumin could be detected in most species, alpha 1-microglobulin in some, and transferrin in few of the species. After electrophoretic separation on pre-cast 1D-micro- SDS-PAA gradient gels (8-25%, semi-automatic Phast-System) followed by CBB R-350 or silver stain respectively, in most species a protein pattern similar to human urine could be observed. As our results show, urine analysis is a suitable tool for noninvasive investigations in primates.

Albuminuria

Application of urinary indicator proteins in the non-invasive assessment of glomerulo-tubular lesions in patients with chronic glomerulonephritis and rheumatoid arthritis.

As the semiautomated electrophoretic analysis of proteinuria still needs technical experience, interest was focused on easy-to-perform methods of urinary protein measurement. SRID-tests for albumin, transferrin, IgG, alpha-1-microglobulin and a spectrophotometrical test for beta-NAG were carried out in 50 normal controls and compared to PCI/ECI-values of patients suffering from rheumatoid arthritis (n = 52) and various types of chronic glomerulonephritis (n = 41). Elevated levels of alpha-1-M and beta-NAG in chronic glomerulonephritis were interpreted as indicative for tubulointerstitial involvement in the chronic inflammatory process. PCI/ECI elevation in individual RA-samples may be caused by functional impairment of tubular protein handling due to chronic ingestion of non-steroid analgesics. The serum assays for transferrin (TF) and IgG based on SRID technique turned out to be too insensitive for the application on unconcentrated urine of normal control persons. In renal patients, however, TF-PCI values above 30 mg/g crea and IgG-PCI values above 50 mg/g crea have to be interpreted as pathologic indicating damage of the glomerular basement membrane. To elucidate TF- and IgG-values in urines with low protein content, highly sensitive nephelometric methods should be used. Concentration of urinary proteins using membrane filters may lead to protein losses, resulting in miscalculation of PC-indices.

Acetylglucosaminidase

[An abnormal course of the Th1-root of the brachial plexus in connection with a variety of the anterior scalenus muscle].

A scalenus anterior muscle with 2 insertions was found - one insertion at the Tuberculum m. scaleni anterioris, the other at the osteo-cartilaginous border of the 1st rib. In the thus formed opening, limited by the 2 insertions and the 1st rib, the Th1-root of the brachial plexus emerged. Its other roots passed between the scalenus anterior and medius muscles as usual. An aponeurotic membrane, attached to the inner margin of the 1st rib and narrowing the upper thoracic aperture prevented the Th1-root from crossing over the 1st rib behind the Tuberculum m. scaleni anterioris as it normally does.

Brachial Plexus

[Changes in Tamm-Horsfall protein excretion in the urine of patients with hypertension in pregnancy].

In previous studies we detected an intensively stained protein band with an apparent molecular weight of 105 kD in the urinary electrophoresis pattern of healthy control subjects and pregnant women; this protein band was identified as Tamm-Horsfall protein by using Western blot. The aim of the present study was to determine the changes of this THP band in 64 patients with an uncomplicated course of pregnancy and 135 hypertensive pregnant women by use of a special urine preparation and a modified SDS-PAGE. The number of protein bands did not change in the course of pregnancy and in the post partum period. The THP band was constantly found in all these patients independent of the gestational age. In 83% of the hypertensive pregnant women we observed a marked reduction in intensity or complete disappearance of the THP band. These changes correlated significantly with the severity of the disease. Follow-up analyses in 39 of these patients showed, that in 22 cases disappearance of the THP band occurred simultaneously with and in 11 women before clinical manifestation of the disease. In 81 of the 85 hypertensive pregnant women complete reappearance of the THP band was observed 2 to 14 days after delivery. Our findings may reflect a transitory tubular dysfunction in cases of preeclampsia and support the hypothesis of an immunological pathogenesis of the disease.

Electrophoresis, Polyacrylamide Gel

[Computer-assisted video processing of Phast gels with ELBA].

Referring to one-dimensional micro electrophoresis-gels, produced at the division of nephrology (Klinikum Göttingen) by using the Phast-System (Pharmacia, Freiburg), the ELBA-program for image evaluation of electrophoretic gels (interactive systems, Heidelberg) was investigated. The digital image, obtained with a computer-controlled video-camera, can be stored up in a personal computer. Independend of time, the digitized data may be retrieved and utilized for evaluation of specific urinary protein patterns. Changes in intensity and constellation of the protein patterns, which may occur during the progress of a disease, can be figured directly in one graphical plot. Therefore, any urinary protein pattern of one or a number of gels can be exactly compared to each other in a short time.

Blood Proteins

[Urinary proteins as indicators of diabetic nephropathy].

During the last ten years, several studies proved the applicability of urinary albumin quantification in the early diagnosis of diabetic nephropathy. Owing to its high accuracy and its comparable low methodological effort, only the albumin determination was emphasised. Parallel studies of urinary protein patterns, however, using sodium dodecylsulfate-polyacrylamide gel-electrophoresis demonstrated the increased excretion of other high- and low-molecular mass proteins in different stages of diabetic nephropathy. Consequently an extension of the mere albumin assay including a macromolecular (e.g. transferrin) and a micromolecular (e.g. alpha-1-microglobulin) protein seems meaningful. According to this study, both methodological lines (combined quantitative and qualitative analysis, respectively) are useful tools in the early detection and the follow up of diabetic nephropathy.

Adolescent

Urinary protein analysis.

The differentiation and analysis of urinary proteins has substantially contributed to our knowledge of physiological and pathophysiological processes during glomerular filtration and tubular catabolism of plasma constituents. By use of high-resolution biochemical separation techniques, several urinary polypeptides could be identified as plasma proteins, tissue antigens, tubular enzymes and protein breakdown products. With regard to clinical application, the separation results of conventional gel chromatography and agarose electrophoresis were surpassed by fast protein liquid chromatography and polyacrylamide electrophoresis in one- and two-dimensional systems. In contrast to early one-dimensional polyacrylamide gel electrophoresis (PAGE) methods using homogeneous gels on a macro scale, modern gradient slab gels achieve better resolution over the entire relative molecular mass range of urinary proteins. For clinical demands, the use of micro-scale gradient gels, either laboratory-made or pre-cast, together with an improved Coomassie Brillant Blue staining, offers several advantages, including rapidity, sensitivity and economy. Isoelectric focusing and two-dimensional PAGE, combined with sensitive silver staining and immunoblotting methods, have proved to be valuable tools for the identification and characterization of urinary proteins in defined renal and extra-renal diseases. The quantitative determination of urinary indicator proteins such as albumin and alpha 1- and beta 2-microglobulin can be regarded as a reasonable complement to the pattern diagnosis, especially in the long-term course of renal diseases.

Animals

[Changes in the urinary protein pattern in SDS polyacrylamide gel electrophoresis in normal and hypertensive pregnancies].

The urinary protein pattern was determined in 46 healthy male and female subjects, 64 patients with an uncomplicated course of pregnancy and 88 hypertensive pregnant women by use of a special urine preparation and a modified SDS-polyacrylamide gel electrophoresis (SDS-PAGE). There were no differences in the protein electrophoresis pattern between the control subjects, independent of sex and age, and the pregnant women. The number of protein bands did not change in the course of pregnancy and in the post partum period. In both groups, an intensively stained protein band with an apparent molecular weight of 105 kD was detected. In 71 of the 88 hypertensive pregnant women we found a marked reduction in intensity or complete disappearance of the 105 kD protein band. Follow-up analysis in 30 of these pregnant women showed, that in 24 cases disappearance of the 105 kD band occurred simultaneously with and in 6 women before clinical manifestation of the disease. There were no differences in the protein electrophoresis pattern between patients with preexisting renal or hypertensive disease and hypertensive women without a complicated history. In 49 of the 52 hypertensive pregnant women complete reappearance of the 105 kD band was observed 2 to 14 days after delivery. By using silver staining and Western blot, the 105 kD band was identified as Tamm-Horsfall protein. Our findings may reflect a transitory tubular dysfunction in cases of preeclampsia and support the hypothesis of an immunological pathogenesis of the disease.

Adolescent