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Biomedical subjects

A Bergstrand

Publications and source records attributed to A Bergstrand.

At least 37 records · Page 2Linked to original sources
PubMed1989

IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients.

One hundred and seventy-six patients with mesangial IgA nephropathy have been studied retrospectively. Mean follow up from apparent onset of the disease was 9.3 years and with follow up from the diagnostic renal biopsy of 4.6 years. Our aim was to evaluate the prognostic significance of sex, age and type of symptoms at onset. The degree of proteinuria, presence of hypertension or decreased renal function, histological lesions and IFL pattern at the time of the diagnostic renal biopsy were recorded. 17 of the patients developed End Stage Renal Failure (ESRF) during the study. According to the Logrank test (renal survival) and Cox stepwise proportional hazard model, severity of glomerular mesangial lesions and degree of proteinuria are the most important indicators of a poor prognosis. The significance of all other parameters disappear after correction for histological lesions and degree of proteinuria. Our conclusion is that a semiquantitative light microscopical examination is an excellent prognostic index in IgA nephropathy, as is a simple determination of protein excretion in the urine.

Adult↗
PubMed1987

Preparation and characterization of subcellular fractions from the liver of C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase activities.

The present study was designed to prepare and characterize subcellular fractions from the liver of male C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase isozymes. The effects of different washing and pelleting procedures on the mitochondrial, microsomal and cytosolic fractions were studied. It was found that 133,000 gav for 60 min (i.e. more extensive force than the usual 105,000 gav for 60 min) was necessary to obtain a membrane-free cytosolic fraction, while one wash for microsomes and two washes for mitochondria yielded reasonably pure fractions. The purity of the different fractions obtained by differential centrifugation was then determined using established enzyme markers and morphological examination with the electron microscope. Several enzymes involved in drug metabolism were also measured in these fractions. The subcellular distributions obtained here for marker enzymes closely resemble those reported for rat liver. Starvation had no significant effect on the epoxide hydrolase activities nor did the addition of mouse bile or rat liver cytosol, which might contain inhibitors. The change in epoxide hydrolase activities with time after preparation of the subcellular fractions was studied, as well as the effect of freeze-thawing. The subfractions prepared here are suitable for the further characterization of the different forms of epoxide hydrolase present in mouse liver, as well as for other studies requiring well-characterized subfractions.

Animals↗
PubMed1987

Biochemical effects of gentamicin on rat kidney cortex. I. Analytical subfractionation of control tissue.

As a first step in studies of the molecular mechanism(s) underlying gentamicin toxicity, rat kidney cortex has been subfractionated using differential centrifugation. An analytical, rather than preparative approach was used. DNA was used as a marker for the nuclei, cytochrome oxidase for mitochondria, acid phosphatase for lysosomes, catalase for peroxisomes, NADPH-cytochrome c reductase for the endoplasmic reticulum, p-nitrophenyl-alpha-mannosidase (at pH 5.5) for the Golgi apparatus, AMPase for the plasma membrane in general, and alkaline phosphatase for the brush border, and lactate dehydrogenase for the cytosol. In addition, electron microscopy was performed on the subfractions obtained. The distributions of subcellular markers obtained here for the rat kidney cortex closely resemble the corresponding distributions reported for rat liver. This procedure can now be used to look for biochemical and/or toxic changes which might be reflected in an altered distribution pattern for marker enzymes.

Acetylglucosaminidase↗
PubMed1987

Biochemical effects of gentamicin on rat kidney cortex. II. Analytical subfractionation after short-term, high-dose treatment.

As a first step in studies on the molecular mechanism(s) underlying gentamicin toxicity, the effect of treating rats with this aminoglycoside antibiotic (100 mg/kg once or twice daily for 3 days) on the analytical subfractionation of the kidney cortex has been examined. DNA was used as a marker for the nuclei, cytochrome oxidase for mitochondria, acid phosphatase for lysosomes, catalase for peroxisomes (with reservations; see the companion paper), NADPH-cytochrome c reductase for the endoplasmic reticulum, p-nitrophenyl-alpha-mannosidase (at pH 5.5) for the Golgi apparatus, AMPase for the plasma membrane in general and alkaline phosphatase for the brush border, and lactate dehydrogenase for the cytosol. In addition, the presumptive lysosomal hydrolases N-acetyl-beta-D-glucosaminidase, p-nitrophenyl-alpha-mannosidase (at pH 4.5), cathepsin D, and DNase II were monitored. Electron microscopy was also performed on the subfractions obtained. The only significant biochemical changes brought about by gentamicin treatment were that N-acetyl-beta-D-glucosaminidase demonstrated both a greater total activity and a larger enrichment in the 104,000gav pellet, while p-nitrophenyl-alpha-mannosidase at pH 4.5 demonstrated the same total activity and a greater enrichment in the 104,000gav pellet. Since myeloid bodies were shown by electron microscopy to sediment primarily with the 500gav and 10,000gav pellets, the biochemical changes seen cannot be associated with these morphological structures. These findings suggest that selective changes in a certain subpopulation(s) of lysosomes or in certain lysosomal enzymes may be involved in the early stages of gentamicin toxicity. On the other hand, no lysosomal membrane damage was observed here, since both the latency of acid phosphatase and the recovery of this activity in the soluble cytosol were unchanged. The present investigation may also have relevance for the dosage and duration of gentamicin treatment chosen in clinical situations.

Acetylglucosaminidase↗
PubMed1985

Preparation and characterization of subcellular fractions from the head kidney of the Northern pike (Esox lucius), with particular emphasis on xenobiotic-metabolizing enzymes.

The present study was designed to prepare and characterize subcellular fractions from the head kidney of the Northern pike (Esox lucius), with special emphasis on the preparation of a microsomal fraction suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation as well as the recovery of different cell components was determined using both enzyme markers and morphological criteria. Finally, the subcellular distributions of several drug-metabolizing enzymes (NADPH-cytochrome c reductase, NADH-ferricyanide reductase, glutathione transferase, epoxide hydrolase) were determined. With the exception of NADPH-cytochrome c reductase, the subcellular distributions obtained here for drug-metabolizing and marker enzymes closely resembled those reported for rat liver. NADPH-cytochrome c reductase was apparently partially solubilized here from microsomal vesicles by an endogenous protease, which reduced its usefulness as a marker enzyme and raises questions concerning the measurement of activities catalyzed by the cytochrome P-450 system in these subfractions. In other respects the microsomal fraction prepared here from the pike head kidney seems well-suited for studies of drug metabolism.

Animals↗
PubMed1985

Are beta-haemolytic streptococci involved in the pathogenesis of mesangial IgA-nephropathy?

In retrospect we have found that 38 of 187 patients who fulfilled the criteria of mesangial IgA-nephropathy had possible acute glomerulonephritis at the onset of their disease. We have therefore studied anti-streptococcal antibodies (ASO and ADNAseB) prospectively. Forty-three per cent of the patients had ADNAseB greater than 800 units. Thirty-one per cent of the patients studied more than once had a fourfold or greater change in their ADNAseB titre. Thirty-three per cent of the patients had different groups of beta-haemolytic streptococci isolated from their throats. This indicates a possible role of beta-haemolytic streptococci in the pathogenesis of some cases of mesangial IgA-nephropathy.

Adult↗
PubMed1984

Preparation and characterization of subcellular fractions suitable for studies of drug metabolism from the trunk kidney of the Northern pike (Esox lucius) and assay of certain enzymes of xenobiotic metabolism in these subfractions.

The present study was designed to prepare and characterize subcellular fractions from the trunk kidney of the Northern pike (Esox lucius), with special emphasis on the preparation of a microsomal fraction suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Finally, the subcellular distributions of several drug-metabolizing enzymes (NADPH-cytochrome c reductase, NADH-ferricyanide reductase, glutathione transferase, epoxide hydrolase) were determined. With the exception of NADPH-cytochrome c reductase, the subcellular distributions obtained here for drug metabolizing and marker enzymes closely resembled those reported for rat liver. NADPH-cytochrome c reductase was apparently partially solubilized here from microsomal vesicles by an endogenous protease, which reduced its usefulness as a marker enzyme and raises questions concerning the measurement of activities catalyzed by the cytochrome P-450 system in these subfractions. In other respects the microsomes and supernatant fraction prepared here from the trunk kidney of the pike seem to be as well suited for investigations of drug metabolism as are the corresponding fractions from rat and pike liver.

Animals↗
PubMed1983

Renal function and biopsy changes during the course of Henoch-Schönlein glomerulonephritis.

Renal function studies were performed in 18 subjects in different stages of Henoch-Schönlein glomerulonephritis (HS GN). Nine children were serially investigated, and nine adolescents or young adults, who were considered to have clinically recovered, were investigated only once, 10.5-14 years after the onset. Inulin and PAH clearance, as well as sodium excretion, were determined during hydropenia (HP) and 3% volume expansion (VE) with isotonic saline. In most patients in the former group a renal biopsy was performed during the first investigation and again one year later. The early disturbances in renal function resembled those we have found in other types of GN. The GFR was normal during HP or after VE in most cases one year after the onset. The natriuretic response to VE was decreased in most patients initially, and this was found to persist in half of the patients 2-3 years after the onset. Pathological urinalyses then indicated disturbances in the renal handling of sodium. A reduced capacity to excrete sodium, however, did not seem to be of prognostic significance since all patients, except one who developed renal insufficiency and hypertension, had normal urinalyses and blood pressure six years after the onset. This study provides no evidence that subjects with previous HS GN will later develop impaired renal function or be predisposed to hypertension.

Biopsy↗
PubMed1982

Preparation and characterization of subcellular fractions from the liver of the Northern Pike, Esox lucius.

The present study was designed to prepare and characterize subcellular fractions from the liver of the Northern pike (Esox lucius), with special emphasis on the preparation of microsomal fractions suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Attempts were also made to increase the recovery of fragments of the endoplasmic reticulum in the microsomal fraction. Finally, the subcellular distribution of several drug-metabolizing enzymes (cytochrome P-450, benzpyrene monoxygenase, epoxide hydrolase and glutathione transferases) were determined. With the exception of the subcellular distribution of epoxide hydrolase, the results obtained here resemble closely those reported fo rat liver and the microsomal fraction prepared is highly suitable for further studies of drug metabolism in pike liver.

Animals↗
PubMed1982

Course of renal function in IgA glomerulonephritis in children and adolescents.

The pathophysiology of IgA GN was investigated in different stages of the disease. Seventeen patients who were between 3.5 and 16.5 years of age at the onset were included in the study. Clearance studies were performed repeatedly in 6 patients (in 5 of them over a period extending from the onset to 5-9.5 years) and only once in 9 patients (10-23 years after the onset). Two patients (one with uremia) were only evaluated clinically. CIn, CPAH and UNaV were studied during hydropenia (HP) and 3% isotonic saline volume expansion (VE). Shortly after the onset CIn, CPAH and UNaV were depressed. Renal function was essentially normal and 1 and 2 years after the onset in spite of signs of active disease. A supernormal GFR was found in 7 patients after they had had the condition between 5 and 17 years. After a duration of IgA GN for greater than 9 years 3 of 12 patients had developed hypertension and uremia and 2 had hypertension or labile BP. Three of 10 patients had a normal GFR and BP, but had increased natriuresis during VE. Only 2 of 10 patients were normotensive and had normal renal function. Disturbances in the renal function are thus frequent in all stages of IgA GN and the changes seem to be related to the duration of the disease. Exaggerated natriuresis may indicate progressive disease.

Adolescent↗
PubMed1981

Immunosuppression by Cyclosporin A in human renal transplant recipients.

Nine renal transplant recipients were treated with Cyclosporin A (CyA). Seven of them were high risk patients (diabetics or above 55 years of age) receiving cadaveric grafts. Two were recipients of related grafts and azathioprine had been shown to give them severe GI symptoms. Secondary anuria developed presumably due to nephrotoxicity caused by CyA in 2 of the recipients of cadaveric kidneys. The patients were converted to conventional immunosuppressive drugs and after 2-3 weeks, renal function had recovered in both patients. Seven patients have been maintained on a combination of CyA and oral prednisolone. Four of these patients experienced one or more rejection episodes, all were reversible on treatment with methylprednisolone. Two patients had episodes of increased serum creatinine due to nephrotoxicity by CyA. Recovery occurred when the dose was reduced. Other side effects observed were: Hirsutism (3 patients), gingival hyperplasia (1), tremor (2) and leukopenia (1). Four patients had infectious complications and one died of cytomegalovirus pneumonia. Six patients are well having serum creatinine levels ranging from 89-181 mumol/1, 1 to 11 months after transplantation.

Adolescent↗
PubMed1980

Clinical trial of plasma exchange with a membrane filter in treatment of crescentic glomerulonephritis.

Four patients with rapidly progressive crescentic glomerulonephritis were treated with repeated plasma exchanges, using a disposable plasma filter (PLASMAFLO), combined with immunosuppression and anticoagulation. A definite improvement of renal function was observed in two patients and complete recovery of the severe lung changes of Goodpasture's syndrome was seen in one of them. In another patient rapid progression of renal insufficiency was arrested. One patient with anuria at the start of treatment remained anuric. The filter was capable of removing as large a molecule as IgM, and the plasma concentrations of immunoglobulins and complement factors declined successively after each treatment. Plasma exchange with the filter technique is readily accessible and safe in hands of the hemodialysis staff. Easy availability and simplicity are important advantages over the centrifuge methods, considering that prompt commencement of the treatment is a key issue in success.

Adolescent↗
PubMed1979

Renal functional changes in acute glomerulonephritis in children. A one-year follow-up.

Renal function was studied in three patients with post-streptococcal, four patients with IgA and one patient with non-streptococcal proliferative glomerulonephritis (GN) at the onset of the disease and two, six and 12 months later. Renal biopsies were performed at the onset of the disease and 12 months later. Standard clearance techniques were used for the functional studies. The latter were performed during hydropenia and continuous isotonic saline infusion. During hydropenia, the GFR was uniformly depressed shortly after the onset of the disease, but it normalized during the following two months. The filtration fraction was depressed in poststreptococcal GN at the onset and it normalized with the GFR. In IgA GN, the filtration fraction remained within normal limits during the entire course of the illness. The natriuretic response to isotonic saline volume expansion was low in all patients at the onset of the disease, but normalized in post-streptococcal and IgA GN during the one-year follow-up. In spite of normalized renal function, biopsy findings in IgA GN were unchanged 12 months later. An episode of macroscopic hematuria in one patient with IgA GN at the six-month investigation had no apparent effect on renal function.

Acute Disease↗
PubMed1979

Oxidative biotransformation of benzo(a)pyrene by human lung microsomal fractions prepared from surgical specimens.

1. Microsomal fractions were prepared from 15--50 g specimens of human lung tissue (mostly alveolar) obtained at surgical resections of 13 middle-aged male patients suffering from different pulmonary tumours. Marker enzyme assays indicated that the frations contained about 25% of the endoplasmic reticulum of the homogenate and about 10% of its mitochondrial membranes. 2. The content of cytochrome b5 corresponded to that of rodent lung microsomes, whereas the apparent content of cytochrom P-450 was much lower. 3. The extent of benzo(a)pyrene metabolism varied 13-fold between individuals in the group and was not detectable in about 40% of the cases. 4. The dihydrodiols as % of total metabolites formed was higher than in laboratory animals, the 7,8-dihydrodiol in most cases amounting to more than 40% of total dihydrodiols. 5. The apparent rate of hydroxylation was stimulated by 1 mM 2-diethylaminothyl 2,2-diphenylvalerate and by 1 mM 1,2-oxy-3,3,3-trichloropropane, but inhibited moderately by 0.1 mM metyrapone and extensively by 0.05 mM 7,8-benzoflavone. 6. Ethoxyresorufin deethylation qualitatively paralleled benzo(a)pyrene hydroxylation among individuals.

Benzopyrene Hydroxylase↗
PubMed1977

Lateral enzyme topology in the rough endoplasmic reticulum of rat liver.

Rough microsomes were subfractionated on the basis of different properties in order to investigate the nature and extent of the enzyme heterogeneity of these vesicles. A discontinuous gradient, containing monovalent cations allowed the separation of a ribosome-poor membrane fraction which was enriched in electron transport enzymes and relatively poor in phosphatases. Zonal centrifugation on a stabilizing gradient separated 3 fractions characterized by enrichment of electron transport enzymes, glucose-6-phosphatase and adenosinetriphosphatase, respectively. An essentially similar pattern was seen when ribosomes were removed with EDTA and the denuded vesicles subfractionated on a sucrose gradient. Rough microsomes from phenobarbital-treated rats exhibited the same pattern both qualitatively and quantitatively. It appears that electron transport enzymes and two types of phosphatases are heterogeneously distributed among rough microsomal vesicles.

Animals↗
PubMed1977

Preparation and characterization of total, rough and smooth microsomes from the lung of control and methylcholanthrene-treated rats.

Optimal conditions for the preparation of relatively pure microsomes and microsomal subfractions from rat lung have been determined. The most importnat of these conditions is homogenization of a 20% (w/v) suspension of lung tissue in 0.44 M sucrose/1% (w/v) bovine serum albumin with four up-and-down strokes at 440 rev./min in a Potter-Elvehjem homogenizer. The 10000 X g supernatant prepared from this homogenate can be centrifuged at 105000 X g to obtain total microsomes or subfractionated into rough and smooth microsomes on a Cs+-containing discontinuous sucrose gradient. The total, rough and smooth microsomes have been characterized in terms of their chemical composition, enzymatic activity, and morphology. These preparations should prove useful in studies of various enzymes in lung (e.g. benzpyrene monooxygenase, epoxide hydrase, enzymes of phospholipid and ascorbic acid synthesis) and in subfractionations designed to reveal heterogeneites in the lateral plane of the lung endoplasmic reticulum.

Animals↗