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H Thysell

Publications and source records attributed to H Thysell.

At least 73 records · Page 4Linked to original sources

Circulating anti-neutrophil cytoplasm antibodies in patients with rapidly progressive glomerulonephritis and extracapillary proliferation.

We investigated 39 patients with rapidly progressive glomerulonephritis and extracapillary proliferation for the presence of circulating anti-neutrophil cytoplasm antibodies (ANCA) by indirect immunofluorescence. Patients with antibodies against the glomerular basement membrane, systemic lupus erythematosus or with glomerulonephritis following infection and where renal disease could be ascribed to treatment with drugs were not included. IgG class ANCA producing diffuse cytoplasmic immunostaining were detected in 54% of the patients. With reservation for the difficulties involved in distinguishing between different forms of systemic vasculitis, these autoantibodies were present in patients with Wegener's granulomatosis (12 out of 17 patients), polyarteritis nodosa (4/6), idiopathic extracapillary glomerulonephritis (1/4), and with less distinct syndromes (4/10), but not in Henoch-Schönlein's purpura (0/2). Another 18% of the patients showed granulocyte-specific anti-nuclear antibodies' with perinuclear immunostaining. This pattern was recently reported to indicate the presence of antibody against myeloperoxidase of alcohol-fixed neutrophils. Autoimmune mechanisms, particularly those involving components of neutrophil granulocytes, could play a significant role in development of extracapillary glomerulonephritis.

Adult↗

Isolation and characterization of a tumor necrosis factor binding protein from urine.

Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF-BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF-BP was purified 1,000,000-fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF-Sepharose and reverse phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 30,000. The aminoterminal amino acid sequence D-S-V-X-P-Q-G-K-Y-I-H-P-Q-V-N-S-I-X-K-T revealed no significant homologies with previously described protein sequences. TNF-BP may act as a regulator of the bioactivities of TNF/cachectin.

Amino Acid Sequence↗

A tumor necrosis factor binding protein is present in human biological fluids.

Tumor necrosis factor (TNF) possesses both beneficial and toxic bioactivities. Mechanisms may operate to counteract harmful effects. We have identified a TNF binding protein (TNF-BP), which shows increased levels in serum and urine of patients on regular hemodialysis treatment (RDT). TNF-BP inhibited the specific binding of human recombinant TNF (rTNF) to its cell surface receptor. Results from gel chromatography demonstrated the presence in serum and urine of a macromolecule with an apparent molecular weight of 50,000, which formed a complex with rTNF. A 62-fold purification of TNF-BP from urine of patients on RDT was achieved by ion exchange chromatography and gel chromatography. Partially purified TNF-BP reduced the growth inhibitory effect of rTNF on a susceptible leukemia cell line. TNF-BP may act as a regulator of the biological activity of TNF and could have beneficial effects in certain inflammatory conditions.

Binding, Competitive↗

Visceral improvement following combined plasmapheresis and immunosuppressive drug therapy in progressive systemic sclerosis.

In a two-year prospective therapeutic trial, 15 patients with progressive systemic sclerosis (PSS) were treated with immunosuppressive drug therapy with or without long-term plasmapheresis. Before the trial all patients had severe involvement of either the esophagus, lungs or kidneys. One patient died of renal failure and another 2 patients withdrew unimproved. In the remaining 12 patients, objective improvement occurred in all but one. The degree and extent of skin involvement decreased significantly (p less than 0.01). Cineradiography revealed increased esophageal motility in 4 patients. Pulmonary function measured as total lung capacity and static lung compliance improved (p less than 0.01). In 4 patients the number of premature atrial or ventricular contractions at 24 h ECG monitoring decreased, as did the concentrations of immunoglobulins and ANA titres in serum. Although it could not be ascertained whether the clinical improvement was associated with combined therapy or immunosuppressive drug treatment alone, our results suggest that immunosuppressive therapy is beneficial in advanced PSS.

Adult↗

The prevalence of renal amyloidosis of the AA-type in a series of 1,158 consecutive autopsies.

To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent.

Aged↗

Demonstration and classification of amyloidosis in needle biopsies of the kidneys, with special reference to amyloidosis of the AA-type.

To examine whether sequence-specific antibodies directed against serum amyloid A were useful in the demonstration and classification of amyloidosis, needle biopsy specimens from the kidneys of 152 cases with renal disorders were investigated using the avidin-biotin-peroxidase complex technique of immunohistochemistry. A distinct immunoreactivity of protein AA was seen in biopsies from all 42 individuals who were clinically classified as having the AA-type of amyloidosis. The stained areas coincided with deposits stained by Congo red. Four of these cases demonstrated immunoreactivity of both protein AA and light immunoglobulin chains and all biopsies except one showed immunoreactivity for the amyloid P-component. After treatment with potassium permanganate, the amyloid deposits in the biopsies of all 42 cases lost their affinity for Congo red. Ten patients with clinical and laboratory findings compatible with the AL-type of amyloidosis were also investigated. All their biopsies demonstrated Congophilic amyloid deposits but none of them showed any immunoreactivity of protein AA. Amyloid deposits of lambda light immunoglobulin chains-but not kappa-were demonstrated in biopsies from four patients. The amyloid P-component was found in biopsies from six individuals and positive Congo red staining after treatment with potassium permanganate was seen in biopsies from four of the cases. Biopsies of 100 patients suffering from non-amyloid renal disorders were also examined. None of them displayed any immunoreactive deposits of protein AA. The investigation shows that amyloid deposits of the AA-type can be identified in needle biopsies when sequence-specific antibodies against serum amyloid A are used in the avidin-biotin-peroxidase complex technique. Both the diagnostic sensitivity (42 of 42) and specificity (110 of 110) of the assay were optimal (1.0). The method was found to be superior to other investigated techniques and useful for classifying amyloidosis in formalin-fixed renal biopsies.

Amyloidosis↗

Alkylating cytostatic treatment in renal amyloidosis secondary to rheumatic disease.

Fourteen consecutive patients with chronic inflammatory rheumatic disease and reactive renal amyloidosis were treated with alkylating cytostatics in 22 separate periods varying in duration between six and 30 months. Chlorambucil alone was given in 14 treatment periods, cyclophosphamide alone in six, and both alternately in two. The dosage was adjusted to attain a major suppression of the rheumatic inflammation and a blood lymphocyte level below 1.0 X 10(9)/l. Renal function improved in 12 treatment periods, renal deterioration was arrested in three periods, and in another four periods the rate of functional decline slowed down. In the remaining three treatment periods, associated with further deterioration in renal function, treatment was inadequate owing to blood dyscrasia and failure to control hypertension. Glomerular filtration rate (GFR) was followed more closely in 10 treatment periods, in all of which the falling trend was arrested or reduced. The survival rate at five years was 93%. Three patients who dropped out of the treatment programme are so far the only ones not still alive. Nine are still being followed up after 6-17 years, and the other two remaining live patients have had renal transplants for five years.

Adult↗

Reduced thermogenesis in muscle and disturbed lipoprotein metabolism in relation to thyroid function in haemodialysis patients.

Muscle thermogenesis, measured by direct calorimetry on resting biopsy samples, was studied in 28 haemodialysis patients and related to thyroid function variables, plasma lipoprotein concentrations and post-heparin lipase activities. The heat production was decreased in about 40% of the patients and significantly correlated with total thyroxine and free thyroxine index. In addition to a slight to moderate hypercholesterolaemia comparable to that found in subclinical hypothyroidism, the patients had also hypertriglyceridaemia in combination with low lipoprotein lipase activity and impaired fat tolerance. The latter abnormalities were related to the lowered muscle heat production values. The pattern of changes may represent a biological adaptation to the systemic illness for conservation of energy.

Adult↗

Production of an amino acid sequence-specific antiserum against human amyloid A (AA) and serum amyloid A (SAA) protein.

The hydrophilic nonapeptide Ser-Asp-Ala-Arg-Glu-Asn-Ile-Gln-Arg, identical with residues 59-67 of human amyloid protein A (AA) and serum amyloid protein A (SAA), was covalently bound via its carboxyl-terminal end to the carrier-protein keyhole limpet haemocyanin. The complex was injected subcutaneously into ten rabbits. All rabbits produced antisera which, unabsorbed, were specific for AA and SAA. The antisera and their isolated peptide specific antibodies were performance-tested and found to be excellent for demonstration of AA and SAA in immunoblotting and immunohistochemical techniques but unsuitable for immunoprecipitation. Since it is difficult to produce AA- and SAA-specific antisera by procedures earlier described and commercial supplies of good such reagents are unavailable, the easy production of sequence-specific such antisera will facilitate more extended studies of the corresponding antigens for diagnostic and scientific purposes.

Amino Acid Sequence↗

Systemic reactive amyloidosis caused by hepatocellular adenoma. A case report.

Systemic reactive amyloidosis caused by non-malignant tumors seems to be extremely rare. In the present paper a 39-year-old female with systemic reactive amyloidosis caused by a hepatocellular adenoma is described. The patient had a history of using contraceptive drugs. She had a pronounced nephrotic syndrome, a renal biopsy showing reactive (AA) amyloidosis, and a bone scintigraphy (99mTc methylene diphosphonate, TcMDP) showing an increased uptake in soft tissues. Removal of the adenoma was followed by a gradual resolution of the nephrotic syndrome and a normalization of the bone scintigraphy. The tumor was histologically a mixture of focal nodular hyperplasia and liver cell adenoma.

Adenoma↗

Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate.

Serum concentrations of creatinine and of the three low molecular weight (LMW) proteins cystatin C, factor D of the complement system and beta 2-microglobulin were measured in 135 consecutive patients, whose glomerular filtration rates (GFR) were determined by Cr-EDTA. In the total patient series, the reciprocals of S-creatinine and S-cystatin C were numerically and, in males, significantly more closely correlated to GFR than the reciprocals of S-factor D. The reciprocals of beta 2-microglobulin showed a weaker correlation to GFR than those of the other three substances. The calculated glomerular elimination rates of creatinine, cystatin C and factor D were normally distributed, in contrast to those of beta 2-microglobulin. According to data presented so far, cystatin C seems to be the LMW protein of first choice when GFR is to be estimated by measuring the plasma concentration of a LMW protein.

Adolescent↗

Temperature and vascular stability in hemodialysis.

The temperature of the blood returning from an extracorporeal circuit may influence the vascular stability. Mean arterial blood pressure, heart rate and the temperature in the in-and outlet lines for blood and dialysis fluid of the dialyzer (TBa, TBv, TDi and TDo) were continuously measured in 8 patients suffering from vascular instability during standard dialysis. The TBv was adjusted to 37, 36 and 35 degrees C at the start of dialysis by manipulating TDi. The patients were studied two times at each temperature level during a 4-hour dialysis. At the start of dialysis TBa was 35.7 +/- 0.3 degrees C. The patient's mean arterial blood pressure and heart rate decreased and increased, respectively, continuously during TBv 37 and 36 degrees C experiments, but were fairly stable at an TBv of 35 degrees C. The standard TDi of 37 degrees C should be abandoned for a temperature which is similar to TBa (35.7 degrees C) to avoid the vascular effects of heating or cooling the blood in the extracorporeal system.

Adult↗

Sarcoidosis with normocalcemic granulomatous nephritis. Five case reports and a review of 24 cases in the literature.

5 cases of sarcoidosis with normocalcemic granulomatous nephritis and renal impairment are described. 24 earlier reported cases with normocalcemic granulomatous nephritis of sarcoidosis were extracted from the literature and reviewed together with the present cases. GFR was normal (greater than 80 ml/min) in 2 of the patients, slightly to moderately decreased (80-20 ml/min) in 14 patients, and severely decreased (less than 20 ml/min) in 13 patients. The patients (19 males and 10 females) were 12-68 (median 45) years old. All patients with GFR less than 10 ml/min were more than 43 years old. 1 patient died in terminal uremia on admittance. All but 1 of the patients treated with corticosteroids improved (22 patients) or stabilized (5 patients) at least initially. 1 patient treated with a relatively low dose of a corticosteroid progressed to terminal uremia. 8 patients had a relapse when the corticosteroids were tapered or discontinued. 12 of the patients had residual renal impairment after initial successful treatment and in 4 cases the impairment worsened after a corticosteroid-sensitive relapse. It could be concluded from the study that an initial corticosteroid dosage of 1 mg prednisolone/kg BW or more should be used in granulomatous nephritis of sarcoidosis.

Aged↗

The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate.

The blood serum concentrations of creatinine and the low molecular weight proteins cystatin C, beta 2-microglobulin and retinol-binding protein were measured in 106 patients whose glomerular filtration rates were assessed by Cr-ethylenediaminetetraacetate (EDTA)-clearance determinations. The reciprocals of the serum concentrations of creatinine, cystatin C and beta 2-microglobulin were closely correlated to the Cr-EDTA-clearance (r = 0.73, 0.75 and 0.70, respectively) in contrast to the corresponding values for retinol-binding protein (r = 0.39). The calculated values of the glomerular elimination rate for creatinine and cystatin C were normally distributed in contrast to those for beta 2-microglobulin. The calculated glomerular elimination rate of cystatin C was not correlated to age, sex, type of disorder or disease activity. The results demonstrate that the serum level of cystatin C is a better measure of the glomerular filtration rate than the serum level of beta 2-microglobulin.

Adolescent↗

L-carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function.

Twenty-eight haemodialysis patients were randomized to L-carnitine, 2 g i.v. three times a week, and saline over a 6-week period. No obvious deficiency of carnitine was found in vastus lateralis with a median value of 12.9 mmol/kg dry weight; range 6.2-21.4. Female patients had lower total plasma carnitine compared to female controls, p less than 0.002, whereas no decrease was found in males. No relationship was found between muscle and total plasma carnitine. After carnitine administration the muscle carnitine level increased about 60%, p less than 0.01, and the total plasma carnitine level more than tenfold, whereas the initially high degree of acylation decreased, p less than 0.02. Maximum dynamic muscular strength was reduced with a mean value of 44% compared with healthy controls. Total metabolic activity of isolated skeletal muscle fibres, measured as heat production with a new technique using a perfusion microcalorimeter, showed a median value of 0.40 mW/g, 25% lower than normal, p less than 0.02. Carnitine administration had no effect on several different tests of muscular function. Neurophysiologically, discrete improvements in the temperature responses were recorded, but no changes in sensory and motor nerve conduction velocities or in vibration thresholds were noted. No symptomatic improvement was observed even in patients with the lowest carnitine levels prior to treatment. Our data do not support the hypothesis that carnitine deficiency contributes to muscle and nerve dysfunction in patients on chronic haemodialysis.

Adult↗