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Biomedical subjects

G Holm

Publications and source records attributed to G Holm.

At least 19 recordsLinked to original sources
PubMed1992

The morphology and metabolism of intraabdominal adipose tissue in men.

Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men.

Abdomen↗
PubMed1992

Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men.

A double-blind, placebo-controlled, cross-over study was carried out in 25 healthy, nonobese middle-aged men to test the effect of guar gum on glucose and lipid metabolism, blood pressure, and fibrinolysis. Ten grams guar or placebo granulate was given three times a day for 6 wk with a 2-wk run-in before and a wash-out period after. Decreases in fasting blood glucose (P < 0.001), cholesterol (P < 0.001), triglycerides (P < 0.05), plasminogen activator inhibitor-1 activity (P < 0.01), systolic blood pressure (P < 0.01), and diastolic blood pressure (P < 0.001) were seen during guar treatment when compared with placebo. Insulin sensitivity, measured with the euglycemic-clamp technique, increased (P < 0.01), adipose tissue-glucose uptake measured in vitro increased (P < 0.001), and 24-h urinary excretion of sodium and potassium increased (P < 0.001) during guar treatment. Fasting plasma insulin, renin, aldosterone, and fibrinogen concentrations as well as skeletal-muscle electrolytes, urinary catecholamines, and body weight remained unaltered. These findings support a role for guar in the treatment of the metabolic syndrome in which insulin resistance seems to play a pivotal role.

Adipose Tissue↗
PubMed1992

Increased serum CD8 soluble antigen level is associated with blood lymphocyte abnormalities and other established indicators of a poor prognosis in adult Hodgkin's disease.

Measurement of the soluble form of CD8 antigen (sCD8), a surface membrane component of suppressor/cytotoxic T cells, has yielded useful information relevant to prognosis in children with acute lymphoblastic leukaemia and Hodgkin's disease (HD). An ELISA technique was used to measure the amount of sCD8 in sera from 123 adults with untreated HD. Significantly higher mean sCD8 levels were found in patients with advanced disease (stage III-IV; P less than 0.001), B-symptoms (P less than 0.001), male sex (P less than 0.05) and increased spontaneous and decreased Concanavalin A induced blood lymphocyte DNA-synthesis (P less than 0.05). Actuarial survival of patients with high sCD8 levels was significantly worse than that of the remainder (P less than 0.05). However, the sCD8 level did not add prognostic information to that achieved by age, sex, lactate dehydrogenase (LDH) or clinical stage. A significant correlation between the sCD8 and LDH levels (r = 0.33; P less than 0.001) and inverse correlations between sCD8 levels and total blood CD4+ (r = -0.52; P less than 0.001) and CD3+ (r = -0.39; P less than 0.01) cell counts were found. Ten patients were also studied in complete remission, showing a significantly reduced sCD8 level in comparison to the pretreatment value (P less than 0.05). Increased sCD8 in HD may indicate enhanced suppressor T cell activity possibly compromising the host disease balance which could explain the association with prognosis.

Adult↗
PubMed1992

Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans.

Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition.

Adipose Tissue↗
PubMed1992

Induction of T-cell activation by oxidized low density lipoprotein.

Oxidation and scavenger receptor-mediated uptake of low density lipoprotein (LDL) in intimal macrophages are believed to be key events in the development of atherosclerosis. We report here that oxidized LDL increases DNA synthesis, expression of HLA-DR, and interleukin-2 receptors in T cells. The stimulatory effect of oxidized LDL was not due to a direct effect on T cells but required the presence of monocytes. Oxidized LDL also stimulated the release of interleukin-1 beta from monocytes. The maximal effect of oxidized LDL on T-cell activation and interleukin-1 beta release occurred at a concentration of 1 micrograms/ml. Native LDL also had the capacity to activate T cells, although only at higher concentrations. The stimulatory effect of both native and oxidized LDL was inhibited by superoxide dismutase. Monocytes as well as T cells were found to have the ability to oxidize LDL, suggesting that the stimulatory effect of native LDL may arise as a result of LDL oxidation during incubation with monocytes and T cells. The results suggest that oxidized LDL may activate T cells in atherosclerotic lesions.

Antigens, Surface↗
PubMed1992

The effects of testosterone treatment on body composition and metabolism in middle-aged obese men.

Twenty-three middle-aged abdominally obese men were treated for eight months with testosterone or with placebo. Testosterone treatment was followed by a decrease of visceral fat mass, measured by computerized tomography, without a change in body mass, subcutaneous fat mass or lean body mass. Insulin resistance, measured by the euglycemic/hyperinsulinemic glucose clamp method, improved and blood glucose, diastolic blood pressure and serum cholesterol decreased with testosterone treatment. A small increase in prostate volume was noted, but serum prostate specific antigen concentrations were unchanged and no adverse functional side-effects were found. Insulin sensitivity improved more in men with relatively low testosterone values at the outset. The mechanisms involved in these changes might act either via effects on visceral fat accumulation, followed by metabolic improvements, and/or via direct effects on muscle insulin sensitivity, as suggested by results of other recent studies. It is concluded that testosterone treatment of middle-aged abdominally obese men gives beneficial effects on well-being and the cardiovascular and diabetes risk profile, results similar to those observed after hormonal replacement therapy in postmenopausal women.

Adipose Tissue↗
PubMed1991

Anti-idiotypic immunity as a potential regulator in myeloma and related diseases.

In this paper some recent and partly preliminary results on anti-idiotypic immunity against clonal B cells in human monoclonal gammopathies are summarized. B cell lines producing antibodies to idiotypic determinants on autologous monoclonal immunoglobulin could be propagated after activation with Epstein-Barr virus of peripheral blood lymphocytes from patients with MGUS and MM clinical stage I but not from untreated persons with advanced MM. Blood T lymphocytes from patients with MGUS and Waldenström's macroglobulinemia were activated to DNA synthesis and production of interleukins by the autologous M protein. In another series of experiments T cell clones raised from patients with MM clinical stage I and MGUS bound F(ab')2 fragments of the autologous M protein and were stimulated to DNA synthesis by the idiotope-bearing protein. Control experiments demonstrated the specificity for idiotypic determinants. Ten of eleven clones were CD4-/CD8+. Finally, using a panel of 8 mAbs to alpha/beta V region epitopes, we noted a clonal expansion of CD4+ and CD8+ T cells in MGUS and MM patients.

Animals↗
PubMed1991

Establishment of idiotype bearing B-lymphocyte clones from a patient with monoclonal gammopathy.

B-lymphocyte clones bearing an idiotypic Ig structure, which could also be found on the serum M-component, have been isolated from peripheral blood of a patient with monoclonal gammopathy (MG) using an immune-rosetting technique and limiting dilution. The majority of the cells had the surface phenotype id+/CD19+/CD20+/CD21+ or id+/CD19+/CD20+/CD21-. Some of the clones originated from spontaneous outgrowth of lymphocytes and some were derived from in vitro Epstein-Barr virus-infected lymphocytes. Three of the B-lymphocyte clones and the patient's bone marrow plasma cells appeared to have clonal identity as shown by the same Ig heavy chain gene rearrangements in Southern blot analysis using a JH probe. The study further supports the notion that the peripheral blood of patients with MG contains B lymphocytes that belong to the tumor clone.

Antibodies, Monoclonal↗
PubMed1991

Lymphocyte abnormalities predicting a poor prognosis in Hodgkin's disease. A long-term follow-up.

Two hundred sixty-two adult patients with Hodgkin's disease (HD) were studied. Incorporation of carbon-14-thymidine was measured in unstimulated monocyte-depleted lymphocyte cultures, and in cultures activated by concanavalin A (Con-A) before institution of therapy in all patients. Total blood lymphocytes and T-cell subsets were enumerated in the last 108 patients. Patients had significantly decreased total (CD3+, CD4+, CD8+) and relative (CD3+, CD4+) T-cell counts compared with healthy controls. Stage IV patients tended to have lower total lymphocyte and subset counts than remaining patients. However, significantly reduced total lymphocyte and CD8+ counts were only observed in comparison to patients in clinical stage II. Thirty-three percent of patients had an increased spontaneous and a decreased Con-A-induced blood lymphocyte DNA synthesis. Functional lymphocyte abnormalities were related to advanced clinical stage, high age, mixed cellularity, and lymphocyte depletion histopathology and presence of B symptoms. The 10-year survival of patients in this group was 36%, compared with 62% for the remainder. In a multivariate analysis of the whole series lymphocyte DNA synthesis was besides age the strongest predictor of prognosis. In univariate analyses of the second patient series total lymphocyte, T-cell and subset counts were related to prognosis. These relatively simple lymphocyte functional tests may help to identify young HD patients for whom intensive cytoreductive therapy with or without autologous stem cell support may be the best therapeutic option.

Actuarial Analysis↗
PubMed1991

Generation of T cell clones binding F(ab')2 fragments of the idiotypic immunoglobulin in patients with monoclonal gammopathy.

Lymphocytes from two patients with multiple myeloma stage I and one patient with monoclonal gammopathy of undetermined significance were found to proliferate specifically in response to low concentrations of F(ab')2 fragments of the autologous M component. T cell clones isolated from repeatedly stimulated cultures bound specifically the autologous idiotype and proliferated after addition of soluble idiotype and exogenous interleukin-2. The majority of clones were CD8+ and showed negligible staining for CD4. Idiotype-binding clones could not be isolated from cultures of lymphocytes from a healthy control stimulated under the same conditions. The study provides support for the existence of idiotype-reactive T cells in monoclonal gammopathies. Such cells might have a regulatory role on the tumor cell clone and may be important for a future therapeutic approach.

Cell Division↗
PubMed1991

Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension.

A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension.

Adult↗
PubMed1991

A small dose of soluble alginate-fiber affects postprandial glycemia and gastric emptying in humans with diabetes.

Seven men with well-controlled, noninsulin-dependent (type 2) diabetes ingested on two different mornings, in random order, meals with or without a 5.0-g sodium alginate supplement (algae-isolate, 75% soluble fiber). The meals contained similar amounts of digestible carbohydrates, fat and protein. The gastric emptying rate of the meal containing sodium alginate, measured by detection of 51Cr mixed into the meals, was significantly slower than that of the fiber-free meal. Sodium alginate also induced significantly lower postprandial rises in blood glucose, serum insulin and plasma C-peptide. The diminished glucose response after the addition of sodium alginate could be correlated to the delayed gastric emptying rate induced by the fiber (rs = 0.92, P less than 0.01).

Adult↗
PubMed1991

Anti-idiotypic antibodies in patients with monoclonal gammopathies: relation to the tumour load.

The production of anti-idiotypic antibodies from Epstein-Barr virus transformed peripheral blood lymphocytes was analysed in 12 patients with multiple myeloma and monoclonal gammopathy of undetermined significance. A low anti-idiotype production was found in patients with advanced disease (multiple myeloma stage III), whereas the production was high in patients with multiple myeloma stage I and monoclonal gammopathy of undetermined significance (MGUS) (P less than 0.01). The study supports the existence of an immunological network response in patients with monoclonal gammopathies.

Aged↗
PubMed1991

Increased luminol-enhanced chemiluminescence of blood monocytes and granulocytes in Hodgkin's disease.

The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin's disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients' monocytes and PMN was higher than that of controls (P less than 0.01 and P less than 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P less than 0.05). Furthermore, patients with lymphocytic depletion or mixed cellularity subtype demonstrated an increased CL of PMN as compared with the remainder. Enhanced CL of phagocytes has been observed in chronic inflammatory disease and can be induced by various serum factors such as monokines and immune complexes. The present study demonstrates an increased CL of blood-borne phagocytic cells in untreated HD. Furthermore, CL of blood monocytes and PMN correlated to tumour burden and histologic subtype, respectively.

Adolescent↗
PubMed1991

Peripheral blood T lymphocytes in patients with monoclonal gammopathies: expanded subsets as depicted by capacity to bind to autologous monoclonal immunoglobulins or reactivity with anti-V gene-restricted antibodies.

The presence of T cells binding F(ab')2 fragments of the idiotypic immunoglobulin was examined by immunofluorescence in peripheral blood of patients with monoclonal gammopathy. In 3 out of 11 tested patients, 1-15% idiotype-binding T cells of either CD4 or CD8 phenotype were found. In 1 patient both a CD4+ and a CD8+ idiotype-binding T-cell fraction were present. In 1 patient the idiotype-binding T cells also reacted with a mAb directed against the variable parts of the TCR alpha or beta chains, further indicating a clonal origin at the alpha/beta level. 3 patients had an expanded predominant T-cell receptor V gene usage based on the reactivity with the limited panel of TCR mAb, but these "clonal" T cells did not bind the idiotype. The study supports the existence of idiotype-specific T cells in peripheral blood of patients with monoclonal gammopathy. Such cells might have a regulatory role on the monoclonal B-cell clone and may be an important target for immunotherapy.

Aged↗
PubMed1991

In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds.

Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOC1) in the matrices tested. In some test systems, the specimens with a higher EOC1 concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOC1 content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus analagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOC1 concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOC1 content, were of low toxicity, and the observed effects need to be verified in future studies.

Animals↗
PubMed1991

Platelet aggregating activity in serum from patients with HLA-B27 associated rheumatic and cardiac disorders: a possible link to the proliferative vascular changes.

OBJECTIVE: To search for possible serum factors (immunochemical abnormalities) that reflect HLA-B27 associated inflammatory process with the proliferative endarteritis, which is an important cause of severe bradycardia and aortic valve regurgitation. PATIENTS AND METHODS: Seventy four men with pacemakers were studied: 24 were HLA-B27 positive and had associated rheumatic and cardiac disorders, 13 were B27 positive but had no clinical or radiographic signs of a related rheumatic condition, and 37 were B27 negative controls. Randomly obtained serum samples were examined for a series of serum factors. RESULTS: Thirteen (57%) of the 23 patients with HLA-B27 and associated rheumatic and cardiac conditions had platelet aggregating activity in their serum. No such activity was found in sera from patients in the other groups. None the less, immunochemical abnormalities were common among patients of all groups; 30 (41%) had antinuclear antibodies or rheumatoid factor or both. CONCLUSION: The platelet aggregating activity found in patients with HLA-B27 and associated rheumatic and cardiac conditions may reflect serum factors that increase the stickiness of platelets and increase their adhesion to the vessel wall. This suggests a link via release of platelet derived growth factor(s) with the characteristic histopathological feature of proliferative endarteritis. Immunochemical abnormalities were common in serum from all men with pacemakers.

Adult↗