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Biomedical subjects

B Hultberg

Publications and source records attributed to B Hultberg.

At least 73 records · Page 4Linked to original sources
PubMed1995

Beta-hexosaminidase in bile and plasma from patients with cholestasis.

beta-Hexosaminidase (Hex) activity was determined in bile from 18 patients with cholestasis, six patients without cholestasis and in ten normal liver biopsies. The difference in the mean activities in bile from patients with and without cholestasis was not significant. Only about 0.5 promille of total liver Hex activity was lost per day via the bile flow. Gel chromatography showed that enzyme forms present in bile had higher molecular weights than the forms present in liver tissue, indicating that the biliary enzyme was not routed through the lysosomes before release into the bile. In 32 patients with cholestasis, plasma Hex was increased compared to controls, and correlated to bilirubin. The activity was significantly higher in patients with severe cholestasis than in patients with less severe forms of cholestasis, but no significant difference in Hex activity was observed between patients with benign or malignant biliary obstruction. No significant difference was noted between patients with cholestasis for less than 1 week compared to those whose illness had lasted more than 1.5 weeks. The impact of biliary obstruction on plasma Hex is further illustrated by the observation that decompression lowered plasma Hex as well as bilirubin and alkaline phosphatase.

Aged↗
PubMed1995

Reduced, free and total fractions of homocysteine and other thiol compounds in plasma from patients with renal failure.

The levels of different fractions of homocysteine, cysteine and cysteinylglycine were investigated in 17 patients on chronic hemodialysis, 9 patients with reduced renal function and 4 patients with nephrotic syndrome and compared with 14 healthy subjects. Total plasma homocysteine, cysteine and cysteinylglycine were increased in the patients with reduced renal function and in those on chronic hemodialysis. The free (non-protein-bound) forms of plasma homocysteine and cysteine were significantly increased in all groups of patients. The reduced forms of plasma homocysteine and cysteine were, however, not increased in any of the patient groups; on the contrary, reduced plasma homocysteine was significantly decreased in the group of patients with reduced renal function. These findings indicate that the plasma levels of reduced forms of the thiol compounds are relatively normal and do not merely mirror the elevation of the disulfide forms. The possible relation between homocysteine and increased atherogenesis in patients with renal failure is discussed.

Adolescent↗
PubMed1995

Plasma homocysteine in the acute and convalescent phases after stroke.

BACKGROUND AND PURPOSE: Stroke patients frequently manifest moderate hyperhomocysteinemia. In most published studies, plasma homocysteine was measured at least 1 month after stroke (or the interval was not reported). To determine whether plasma homocysteine concentrations change in the acute phase, we compared acute-phase values with both convalescent-phase and control values. METHODS: Plasma homocysteine concentrations were measured in the acute phase (mean, 2 days after stroke onset) in 162 first-ever stroke patients aged 50 years or more (median, 75 years) and again at a median interval of 583 days (range, 460 to 645 days) after stroke onset in a subgroup of 17 patients, with values for 60 age-matched subjects serving as controls. Twenty of the control subjects were reexamined 2 to 3 years after their initial examination. RESULTS: The median plasma homocysteine concentration was 13.4 mumol/L in the patient group compared with 13.8 mumol/L for control subjects (NS, Mann-Whitney U test) and increased from 11.4 mumol/L in the acute phase to 14.5 mumol/L in the convalescent phase in the subgroup of patients examined twice (P < .01, Wilcoxon signed rank test). In the 20 reexamined control subjects, no significant change over time in plasma homocysteine concentration was found. CONCLUSIONS: The post-acute-phase increase in plasma homocysteine may explain why higher values were obtained for stroke patients than for control subjects in previous studies. Possible reasons for the variation in plasma homocysteine concentrations over time are (1) an acute-phase reduction secondary to a decrease in plasma albumin and (2) an increase in plasma homocysteine during the convalescent phase due to modified vitamin intake and/or lifestyle. The timing of plasma homocysteine measurements relative to stroke onset is a factor to be considered in the interpretation of results.

Aged↗
PubMed1995

Plasma beta-hexosaminidase isoenzymes A and B exhibit different relations to blood glucose levels in a population of Type 1 diabetic patients.

The activity of lysosomal enzymes, such as beta-hexosaminidase (Hex), is increased in the plasma and serum of diabetic patients. A positive association has been shown between enzyme activity and glycated proteins, indicating an association with the degree of metabolic control. Several isoenzymes of Hex exist. Studies have reported different proportions of the isoenzymes in plasma from diabetic patients, compared with healthy subjects. In the present study, Hex isoenzymes were examined in 76 Type 1 diabetic patients, of mean age 37.4 years (SD 12.9) compared with 38 age- and sex-matched healthy control subjects in an attempt to evaluate the influence of long- and short-term changes in blood glucose levels on these isoenzymes. The results show that Hex A activity (p<0.01), but not Hex B activity, was higher in the diabetic patients. Hex A activity was positively associated with both the actual blood glucose levels (r = 0.48, p<0.001) and haemoglobin A1c (HbA1c) (r = 0.43, p<0.001), while Hex B activity was associated with the level of HbA1c only (r = 0.42, p<0.001). Both Hex A and B activities were also positively associated with early signs of diabetic nephropathy (e.g. urinary excretion of Hex, fractional albumin excretion ratio and urinary albumin). There was no association between Hex A and B activities and different degrees of retinopathy. In conclusion, the present study demonstrates an association between Hex A and B and metabolic parameters in diabetes as well as with clinical signs of early diabetic nephropathy, but no association with the degree of retinopathy. Furthermore, Hex A seems to be more influenced than Hex B by short-term changes in blood glucose levels.

Adult↗
PubMed1995

Serum beta-hexosaminidase isoenzymes are precursor forms.

The lysosomal enzyme beta-hexosaminidase (Hex, EC 3.2.1.52) was purified from human serum and placental tissue. On gel chromatography, Hex isoenzymes (Hex A, B and P) from serum showed a molecular weight of about 150 kDa, i.e. higher than the 120 kDa found for the placental (tissue) isoenzymes (Hex A and B). Sodium dodecyl sulphate polyacrylamide gel electrophoresis of non-reduced serum Hex A revealed two different subunits, denoted alpha and beta, corresponding to apparent molecular weights of 70 and 67 kDa, respectively. Serum Hex B and Hex P were composed of beta-subunits only. In contrast, the apparent molecular weights of the alpha- and beta-subunits originating from tissue were both 55 kDa. Reduction of tissue Hex A and Hex B resulted in cleavage of the beta-subunit into several fragments, whereas the beta-subunit in serum forms was resistant to this treatment. These results are consistent with the serum forms never having entered the lysosome prior to their release to the extracellular environment and serum forms can therefore be classified as precursor molecules. No mature (tissue) forms were found in serum. Isoelectric focusing before and after neuraminidase treatment of the serum isoenzymes showed that they all contained sialic acid and that Hex B and Hex P had an identical focusing pattern after desialylation. Serum beta-hexosaminidase is frequently elevated in liver disease, alcoholism and pregnancy and the results of the present study indicate that this is due to an increased synthesis and secretion of hypersialylated beta-subunits, rather than to release of intralysosomally stored enzyme.

Antibodies, Monoclonal↗
PubMed1995

The use of iohexol clearance to determine GFR in patients with severe chronic renal failure--a comparison between different clearance techniques.

UNLABELLED: The nonionic low-osmolar contrast medium iohexol was used as marker of glomerular filtration rate (GFR) in 53 patients with stable renal function (group I: n = 32, group II: n = 21). All the patients had clearance values < or = 30 ml.min-1.1.73 m-2 body surface; 40 patients < 20 ml.min-1.1.73 m-2 body surface. Simultaneous determinations of renal clearance and plasma clearance, both as slope clearance and single sample clearance, were performed after intravenous injection of 10 ml iohexol 300 mg iodine/ml. In groups I and II plasma was sampled early (around 3 hours) and late (up to 24 hours) after the injection. In group I urine was collected during four 40-minute periods and in group II during one 3-hour period and in group II the residual urine was estimated by ultrasound. Plasma and urine iodine concentrations were analyzed with X-ray fluorescence technique (Reanalyzer PRX90, Provalid AB, Sweden). In group II S-creatinine and tubular function test were followed to detect any signs of nephrotoxicity. In 6 anuric patients (group III) 10 ml iohexol 300 mg I/ml was injected to assess its extrarenal clearance. In groups I and II the slope clearance correlated excellently with the single sample clearance (r = 0.99) when a late plasma sample was used in both techniques. In group II, where residual urine was estimated by ultrasound, renal clearance correlated better with slope clearance than in group I (r = 0.94 vs r = 0.89). There were no signs of nephrotoxicity in the parameters noted. In group III, extrarenal plasma clearance of iohexol did not exceed 2 ml.min-1.1.73 m-2. CONCLUSION: GFR < 20 ml/min can accurately and safely be determined as renal clearance or plasma clearance of iohexol after an intravenous dose of 10 ml 300 mg I/ml. Plasma clearance techniques, which have the practical clinical advantage of no urine sampling, do at low GFR require a late plasma sample taken, for instance, 24 hours after injection of iohexol, irrespective of whether slope technique or single sample technique or one-compartment or poly-compartment models are used.

Adult↗
PubMed1995

Effect of thiol oxidation and thiol export from erythrocytes on determination of redox status of homocysteine and other thiols in plasma from healthy subjects and patients with cerebral infarction.

Changes in concentration of reduced and oxidized low-M(r) thiols were measured in blood and plasma before and after the separation of blood cells. If centrifugation of blood was postponed, the reduced form of homocysteine in plasma increased with time at 22 degrees C; in contrast, the concentrations of other reduced thiols (cysteine, glutathione, and cysteinylglycine) decreased. In plasma the reduced forms of all thiols disappeared at a rate that followed first-order kinetics. The rates of disappearance ("half-lives") were temperature-dependent; they were about the same for glutathione and homocysteine (11.7 and 14.3 min, respectively, at 22 degrees C) and somewhat higher for cysteinylglycine and cysteine. After establishing proper sampling conditions for reduced thiols, we measured this thiol fraction as well as free (non-protein-bound) and total thiols in 10 reference subjects and 19 patients with cerebral infarction. Mild but significant hyperhomocysteinemia involving total and free homocysteine (but not reduced homocysteine) was found in the patients.

Aged↗
PubMed1994

Serum beta-hexosaminidase isoenzymes are related to risk factors for atherosclerosis in a large population of postmenopausal women.

Lysosomes are involved in atherogenesis. Therefore we have studied the level of serum beta-hexosaminidase isoenzymes (Hex A and Hex B) in relation to risk factors for atherosclerosis in a homogeneous population of 886 post-menopausal women. We found a relation with several risk factors such as serum triglycerides, diastolic and systolic blood pressure, blood glucose, waist/hip ratio and body mass index but not with serum cholesterol. Also, the mean values for Hex A and Hex B were higher in smokers than in non-smokers but only the mean value for Hex A differed significantly. The relation of serum beta-hexosaminidase isoenzymes to risk factors might be due to lysosomal over-loading, which gives rise to increased enzyme synthesis and enhanced secretion of lysosomal enzymes to circulation. The subjects in the 95-100 percentile of Hex A showed significantly increased frequency of myocardial infarction of their fathers and of stroke in their mothers and the subjects in the 95-100 percentile of Hex B showed increased frequency of stroke in their mothers. Thus the findings of a relation between Hex isoenzymes and heredity for vascular disease further stress the significant relation between Hex isoenzymes and risk factors. Since Hex B is a sensitive marker for alcohol abuse, we also investigated its serum level in subjects that could be suspected of alcohol abuse. However, we did not find any differences in these subjects compared with the others, possibly due to the relatively short half-life of Hex B after alcohol withdrawal.

Alcoholism↗
PubMed1994

Plasma homocysteine in relation to serum cobalamin and blood folate in a psychogeriatric population.

Plasma homocysteine, serum cobalamin and blood folate were analysed in 296 consecutive patients referred to a psychogeriatric department for diagnosis of mental disease. Plasma homocysteine correlated with positive significance with age and serum creatinine, and with negative significance with serum cobalamin and blood folate. Approximately 35-40% of the patients with low serum cobalamin (< 150 pmol l-1) or low blood folates (< 150 nmol l-1) exhibited normal values of plasma homocysteine (< 19.9 mumol l-1). Possibly, these patients do not have a deficiency of the vitamins in the tissue. At least 7.5% of the patients with serum cobalamin levels (> 150 pmol l-1) showed an inexplicably increased level of plasma homocysteine. These patients might have a deficiency of tissue cobalamin despite the normal serum cobalamin levels. The effect of cobalamin supplementation for 7-10 days on plasma homocysteine was tested in 62 patients with different levels of serum cobalamins. We found the most pronounced decrease of plasma homocysteine in the patients with lowest serum cobalamin levels and in the patients with highest plasma homocysteine, indicating that the percentage decrease of the initial concentration of plasma homocysteine could reflect the degree of cobalamin deficiency. Folate supplementation for 7-10 days reduced plasma homocysteine not only in patients with folate deficiency but also in those with a normal folate status, and even in patients with cobalamin deficiency. The latter patients further reduced their plasma homocysteine after additional cobalamin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects.

OBJECTIVES: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. We explored possible determinants of plasma homocysteine and cysteine concentrations amongst middle-aged and elderly subjects. DESIGN AND SUBJECTS: Of 501 35-95-year-old randomly selected residents of Lund and Malmö, Sweden, 244 (49%; 131 men, 113 women) were investigated. RESULTS: Total plasma homocysteine concentrations were higher in men than in women (mean +/- SD: 13.9 +/- 4.1 and 12.3 +/- 4.1 mumol L-1; P < 0.001), increased markedly with age (Spearman's rho = 0.488; P < 0.001), and were correlated (P < 0.001) to concentrations of blood folate, serum vitamin B12, and serum creatine (rho = -0.366, -0.338, and 0.463). Users of multivitamins had lower homocysteine levels than nonusers [10.5 +/- 3.3 mumol L-1 (n = 31) and 13.5 +/- 4.2 mumol L-1 (n = 213), respectively; P < 0.001]. Total plasma cysteine concentrations also increased significantly with age and increasing serum creatinine, but were unrelated to gender, blood folate, serum vitamin B12 and use of multivitamins. CONCLUSIONS: Age, gender, folate, serum vitamin B12, serum creatinine and multivitamin usage are all important determinants of the plasma homocysteine concentration, whereas only age and serum creatinine are determinants of the plasma cysteine concentration. The age-related increase in homocysteine and cysteine may be linked to the age-related impairment of renal function, whereas the sex difference in plasma homocysteine may be because of the fact that more homocysteine is formed in men than in women in conjunction with creatine-creatinine synthesis.

Adult↗
PubMed1994

Lysosomes and human liver disease: a biochemical and immunohistochemical study of beta-hexosaminidase.

Liver biopsies from 88 patients with different liver diseases were studied for beta-hexosaminidase activity. Liver specimens with normal light microscopical morphology showed no immunohistochemical reactivity for beta-hexosaminidase. Increased reactions were noted, mainly in hepatocytes, in biopsies from the patients with different liver diseases. A very large interindividual variation of biochemical liver beta-hexosaminidase activity occurred even within the same diagnostic group, and no group of patients showed any significant increase of liver beta-hexosaminidase activity compared with the patients with normal liver histology. Livers with positive immunohistochemistry showed increased biochemical values for beta-hexosaminidase. In patients with cholestasis due to alcohol abuse, the immunohistochemical reaction was intense and the biochemical beta-hexosaminidase activity was significantly increased compared with non-alcoholic cholestatic cases. Furthermore, blood samples taken from 50 patients at the same time as the liver biopsies. These patients showed significantly increased serum beta-hexosaminidase activity compared with normal controls, but no correlation was found between beta-hexosaminidase activities in the liver and serum of these patients.

Adolescent↗
PubMed1994

Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine.

The total concentration of the atherogenic aminothiol acid homocysteine in plasma of healthy volunteers was decreased after oral administration of N-acetylcysteine (NAC), whereas the reduced and free (non-protein bound) fractions of homocysteine were increased. The decrease of the total fraction varied between 20 and 50% and was dose-related. Cysteinylglycine was also decreased after the administration of NAC, whereas cysteine did not change. Administration of high amounts of NAC probably displaces homocysteine and cysteinylglycine from their protein binding sites by disulfide interchange reactions. This leads to the formation of mixed low molecular-weight cysteine and NAC disulfides with high renal clearance and possibly also increased metabolic bio-availability, thereby eliminating homocysteine and cysteinylglycine from plasma. Since only a small amount of additional urinary homocysteine was recovered it is likely that this aminothiol acid is taken up by the tubular cells and further metabolized.

Acetylcysteine↗
PubMed1994

Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus.

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.

Adult↗
PubMed1993

Release of beta-hexosaminidase isoenzymes in cultured human fibroblasts.

We have used enzyme immunoassay methods to study the intra- and extracellular isoenzyme pattern of beta-hexosaminidase (Hex) in human fibroblast cultures. The released activity into the medium during 24 h was about 10% of the intracellular activity. Intra- and extracellular ratio of Hex B to total Hex (Hex A plus Hex B) was about one-third. Estimation of the molecular weight of the released activity showed that it corresponded to 150 kDa, which is equal to the high molecular mass precursor forms of the enzyme. NH4Cl is known to disturb the intracellular transport of lysosomal enzymes and increase the secretion of newly synthesized precursor forms. Addition of NH4Cl even at 3 mM resulted in an increased release of total Hex, which was already noted within 24 h. We speculate that the increased concentration of plasma NH4+ in patients with liver disease interferes with the intracellular distribution pathway of the lysosomal enzymes and this could contribute to the increased content of lysosomal enzymes present in plasma from these patients. Tunicamycin (0.3-3.0 micrograms/l) increased the percentage of Hex B in the medium, whereas an increased release of Hex was noted only after 48 h. Tunicamycin is known to enhance the secretion of N-linked oligosaccharide-free forms of lysosomal enzymes. Thus the oligosaccharide chains on alpha- and beta-subunits seem to be important for the normal formation process of the Hex A isoenzyme.

Ammonium Chloride↗
PubMed1993

Trichloroethylene exposure in vapour degreasing and the urinary excretion of N-acetyl-beta-D-glucosaminidase.

In order to elucidate the potential nephrotoxicity of low level occupational exposure to trichloroethylene (TRI), urine analysis of the tubular enzyme N-acetyl-beta-D-glucosaminidase (U-NAG) was included in a cross-sectional study of metal degreasers in central Sweden. Eighty-six percent of 8-h TRI in air measurements were well below 50 mg/m3. Normal levels of NAG were found in morning urine samples from 29 workers compared to a historical reference group. A weak positive correlation (r = 0.48; P < 0.01) was observed between U-NAG activity and the concentration of the TRI metabolite trichloroacetic acid in urine but not with other estimates of recent or long-term exposure. In conclusion, TRI does not seem to be nephrotoxic at low exposure levels.

Acetylglucosaminidase↗
PubMed1993

Determination of urinary N-acetyl-beta-glucosaminidase in patients with hypertension and renal artery stenosis.

The purpose of the study was to measure the urinary excretion of N-acetyl-beta-glucosaminidase (U-NAG) in patients suspected of having renovascular hypertension and to compare the enzyme excretion before and after active intervention with operation or percutaneous transluminal renal angioplasty (PTRA). Eighty-one patients with severe, therapy-resistant hypertension were examined with regard to renal artery stenosis (RAS). At least one significant renal artery stenosis was found in 61 patients, whilst the remaining 20 patients were classified as having essential hypertension. Enzyme levels were found to be significantly higher in RAS patients as compared with patients with severe hypertension lacking significant renal artery stenosis, 0.66 (0.41-0.91, median value, 1st and 3rd quartiles) versus 0.35 (0.27-0.54); P < 0.01. Both groups of patients had significantly higher U-NAG values than a healthy reference population (0.2, 0.13-0.27; P < 0.01). Forty of the RAS patients were randomized to surgery or PTRA and followed prospectively for 2 years. After either renal vascular surgery or PTRA a significant rise in U-NAG excretion was observed 7-10 days after treatment. Urinary NAG excretion remained elevated during long-term follow-up. It is suggested that U-NAG should be determined in patients with therapy-resistant hypertension with suspicion of renal artery stenosis.

Acetylglucosaminidase↗
PubMed1993

Elevated plasma homocysteine in alcoholics.

A significantly higher concentration of plasma homocysteine compared with controls was noted in a group of alcoholics (n = 42) hospitalized for detoxication. Normal concentrations of plasma homocysteine were reached within 1 or 2 weeks after admission to the hospital. In another group of abstinent alcoholics (n = 16) plasma homocysteine did not deviate from that of controls. Since hyperhomocysteinemia has been associated with premature vascular disease, we speculate that the increased plasma homocysteine in alcoholics might cause the increased incidence of stroke found in these patients.

Adult↗