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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 181 records · Page 10Linked to original sources

Urinary excretion of albumin and retinol-binding protein in lithium-treated patients.

Urinary excretion of albumin and retinol-binding protein was measured by means of sensitive and specific immunochemical methods in a transverse study of 20 lithium-treated patients and 24 apparently healthy individuals. Albumin creatinine clearance ratios were significantly higher in the lithium-treated patients, which may indicate glomerular lesions. Microalbuminuria correlated highly to duration of lithium therapy. No significant difference between the retinol-binding protein creatinine clearance ratios in the two groups could be shown. This suggests that the catabolism of low-molecular-mass proteins in the proximal tubules was normal.

Adult↗

Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro.

A significant fraction of the arterial smooth muscle cells in atherosclerotic plaques and injury-induced intimal thickenings express class II major histocompatibility complex (Ia) antigens. This might be the consequence of gamma-interferon secretion by T lymphocytes also present in these lesions. We have therefore analyzed the effects of gamma-interferon on cultured rat aortic smooth muscle cells. Recombinant gamma-interferon inhibited smooth muscle proliferation in vitro in a dose-response relation; inhibition was detectable down to a concentration of 1 unit/ml. In similar concentrations, gamma-interferon also induced Ia expression by the cells. This suggested that Ia antigens might be selectively expressed by nonproliferating smooth muscle cells. In vivo, there was a strong negative correlation between Ia expression and 3H-thymidine labeling of smooth muscle cells in intimal thickenings induced by balloon catheter injury. In rats receiving continuous infusions of 3H-thymidine for two weeks after injury, Ia-positive 3H-positive cells had undergone fewer rounds of replication than Ia-negative ones. This indicates that Ia-expression both in vivo and in vitro is associated with a reduced proliferative capacity. These results suggest that gamma-interferon, a secretory product of activated T lymphocytes, acts as a natural regulator of smooth muscle cell growth and Ia expression in injury-induced intimal thickenings and atherosclerotic plaques.

Animals↗

Smooth muscle cells express Ia antigens during arterial response to injury.

The atherosclerotic plaque is composed of vascular smooth muscle cells and of macrophages and lymphocytes derived from the blood. We have recently shown that smooth muscle cells express class II MHC (Ia) antigens in the atherosclerotic plaque but not in the normal vessel wall. In the present study, we have tested whether there is a relationship between arterial injury and smooth muscle Ia expression. Rat carotid arteries were deendothelialized with a balloon catheter, and the rat Ia antigens, I-A and I-E, were detected by immunocytochemistry. Leukocytes and smooth muscle cells were identified by monoclonal antibodies to cell type-specific antigens. Normal rat carotids were always I-A and I-E negative, but approximately 10% of the cells became I-A-positive and 5% I-E positive during the response to injury. Ia expression was limited to non-replicating smooth muscle cells, suggesting that Ia is expressed as part of an activation response in a nondividing subfraction of the cells. The frequency of Ia-positive smooth muscle cells was maximal at 2 weeks postinjury, which coincided with maximal leukocyte infiltration and with the appearance of T lymphocytes in the neointima. This suggests that T cells induce Ia expression in smooth muscle cells. This was confirmed in cell culture experiments, where conditioned media from activated T lymphocytes induced Ia antigens in arterial smooth muscle cells. A similar induction of Ia expression was induced by recombinant gamma interferon, suggesting that this lymphokine may be responsible for smooth muscle Ia expression also in vivo.

Animals↗

Selective conservative and routine early operative treatment in acute limb ischaemia.

Arterial thrombo-embolectomy is often unsuccessful in those patients with acute limb ischaemia that have peripheral arteriosclerosis. During this study, conservative heparin treatment and, when needed, delayed surgery was employed in acute limb ischaemia when the ischaemia was less severe as judged by assessment of distal motor and sensory functions, regardless of the presumed aetiology of the acute ischaemia. The results are compared with those during a preceding period, when the routine treatment was emergency thrombo-embolectomy. The emergency operation rate was reduced to 49 per cent. There were overall fewer deaths with gangrene (8 per cent versus 18 per cent). In acute arterial thrombosis, more good results were obtained (76 per cent versus 47 per cent), whereas results were unchanged in embolic cases despite the reduced emergency operation rate. This study suggests that the choice of initial treatment of patients with acute limb ischaemia may be based on the severity of the ischaemia, and that patients with less severe acute ischaemia benefit from initial conservative heparin treatment.

Acute Disease↗

Rabbit antibodies against the low molecular weight folate binding protein from human milk. Use for immunological characterization of human folate binding proteins in an enzyme-linked immunosorbent assay (ELISA).

Antibodies to a low molecular weight folate binding protein isolated from human milk were raised in rabbits and used for development of a two-site enzyme-linked immunosorbent assay (ELISA) for immunological characterization of human folate binding proteins (FBPs). The high and low molecular weight FBPs from human milk were immunologically indistinguishable. Furthermore, the FBPs in human urine and cerebrospinal fluid showed a cross-reactivity of 70% and 30%, respectively. No cross-reactivity of the FBP from cow's milk was observed.

Antibodies↗

Increased urinary excretion of the retinol-binding protein in insulin-dependent diabetes mellitus in the absence of microalbuminuria.

Urinary excretion of the retinol-binding protein (RBP) was studied in 36 insulin-dependent diabetics with serum creatinine concentrations within the normal range and no microalbuminuria. The excretion was significantly (p less than 0.05) higher in the diabetics as compared to a group of apparently healthy persons. The diabetes control indices HbA1 and serum fructosamine showed no correlation to the rate of urinary RBP excretion. The present data support the idea that tubular dysfunction may be an early symptom of diabetic nephropathy.

Adolescent↗

Long-term results by epidural spinal electrical stimulation (ESES) in patients with inoperable severe lower limb ischaemia.

Arterial reconstruction is the treatment of choice for patients with severe lower limb ischaemia, but may at times be technically impossible. Thirty-two consecutive patients with impending (n = 24) or already established (n = 8) distal arteriosclerotic or diabetic lower limb gangrene, in whom vascular surgery was either technically impossible or had failed, were treated with epidural spinal electrical stimulation (ESES) for 27 +/- 16 (S.D.) months. All patients had severe rest pain, which was reduced by ESES in 91% of the cases. Improved ulcer healing was noted in 58% of the patients who had skin ulceration. Eighty-three percent of those patients who did not have established gangrene when ESES was started, retained their leg after 1 year, and 54% after 3 years. These results suggest that ESES often provides pain relief and improves skin healing in patients with impending arteriosclerotic or diabetic gangrene in whom vascular surgery is impossible or has failed. Epidural spinal electrical stimulation (ESES) does not affect the progression of established gangrene but may provide pain relief. The observed outcome of severe limb ischaemia in this study could be used to compare with those after arterial reconstruction performed in patients with poor run-off vessels, and may allow us to examine the natural history of this disease when adequate pain relief is provided. The results reported here and the previously reported enhancement of cutaneous blood flow in severely ischaemic extremities by ESES may suggest, that ESES enhances limb salvage by improving skin blood flow.

Aged↗

Improved survival in multiple myeloma with renal failure.

Forty-four myeloma patients with large tumour cell mass and impairment of renal function (S-creatinine greater than 2 mg/dl, stage III B) were studied. Seven patients, who received no active treatment, neither cytostatics nor plasmapheresis, survived for less than 1 month (median). Twenty-one patients who were treated with chemotherapy combination (M-2 protocol: melphalan, vincristine, BCNU, cyclophosphamide, prednisone) plus plasma exchanges for three days at the start of each 5-week cycle survived longer (median 17 months, p less than 0.01) than 16 patients who were treated with melphalan-prednisolone alone (median 2 months). However, better supportive care, dialysis, and improved antibiotic treatment may also have contributed to the improved results. It is concluded that intensive chemotherapy in full dosage, plasmapheresis, and active uremia treatment including dialysis should be considered in patients with advanced myeloma and renal failure.

Adult↗

Insulin sensitivity in patients with arterial insufficiency. Re-evaluation with the multilevel glucose clamp technique.

Previous studies have claimed that changes in insulin and glucose metabolism in patients with peripheral arterial insufficiency indicate an increased sensitivity to insulin for glucose uptake. We have re-evaluated this concept in 11 patients with intermittent claudication and 11 matched controls with a multilevel euglycaemic glucose clamp technique. The groups were matched for age, sex and body composition but not completely for smoking habits and physical fitness. Although the control group had a normal physical fitness the patients had 40% lower maximal exercising capacity. The patients' maximal walking capacity was 186 +/- 27 m evaluated on a treadmill. No patient with ischaemic ulcers or rest pain were included. The euglycaemic glucose clamp was performed at five insulin plateau levels (70, 110, 190, 590 and 1440 mU/l) of one h duration each and whole body glucose uptake during the last 20 min was calculated. No differences in maximal glucose uptake (Vmax) or insulin level for half maximal glucose uptake (Km) between the groups were observed. The concentration or the magnitude of the decrease in arterial FFA levels did not differ significantly between the groups at any physiological insulin level. This study can not confirm previously described changes in insulin sensitivity in patients with arterial insufficiency. Although the discrepancy between present and previous results remains unclear it may reflect the combined effects of different methods used, including the selection of reference patients, rather than an increased insulin sensitivity in patients with arterial insufficiency. This study suggests that previous conclusions based on glucose tolerance tests should be interpreted with caution.

Biological Transport, Active↗

Plasma fibronectin levels during daily plasmapheresis.

Plasma fibronectin concentrations were studied in 10 patients with multiple myeloma. After plasma exchange for 3 d (2.5-3 l plasma daily) the plasma fibronectin decreased to about 50% of the initial level. Resynthesis of fibronectin seemed to increase during 3 d of plasmapheresis, and was sufficient to normalize plasma fibronectin concentration. The plasma fibronectin concentration reached the initial level within 2 d after interrupting plasmapheresis in spite of concurrent cytotoxic treatment. The patients studied showed no signs of infection.

Fibronectins↗

Salivary glands in long-term alloxan-diabetic rats. A quantitative light and electron-microscopic study.

Fifty untreated diabetic animals were compared with 58 age-matched non-diabetic controls. Reduced salivary gland weight was evident after one month's diabetes and this was unchanged after 12 months of diabetes. Submandibular/sublingual gland weight was proportional to the reduced body weight in the diabetic rats. Parotid gland weight, however, was proportionally more reduced. Only diabetic rats had lipid inclusions in the acinar cells of their submandibular glands and the morphometrically estimated amount of inclusions was positively correlated to the blood glucose level. Acinar cell size was significantly increased in long-term diabetic rats as compared with short-term diabetic rats and controls. Capillary basement membrane width was significantly increased in long-term diabetic rats compared with age-matched controls and with short-term diabetic rats. Thus, both the degree and duration of diabetes have a major effect on salivary gland morphology in alloxan diabetic rats.

Animals↗

Enzyme resistant starch fractions and dietary fibre.

Starch fractions that are more or less enzyme resistant may behave like dietary fibre, both physiologically and analytically. Ungelatinized granules from potatoes, high amylose maize and green bananas are poorly digested. Starch made resistant to amylase due to new covalent bindings, formed at heat treatment or present in starch derivatives used as food additives, may also be more or less undigestible. "Resistant starch" present in bread and corn flakes is probably retrograded amylose. It is undigestible in the small intestine, but readily degraded by the large bowel microflora. Amylose-lipid complexes seem to be completely absorbed in spite of their resistance to amylase degradation in vitro. Since undigestible starch fractions behave physiologically like non-starch polysaccharides, they should be included in the dietary fibre concept. "Resistant starch" is analysed as glucose based fibre with all current methods except one, which includes an initial DMSO solubilization step.

Amylases↗

Immobilized purified folate-binding protein: binding characteristics and use for quantifying folate in erythrocytes.

Purified folate-binding protein from cow's milk was immobilized on monodisperse polymer particles (Dynospheres) activated by rho-toluenesulfonyl chloride. Leakage from the spheres was less than 0.1%, and the binding properties were similar to those of the soluble protein with regard to dissociation, pH optimum for binding pteroylglutamic acid, and specificity for binding various folate derivatives. We used the immobilized folate-binding protein as binding protein in an isotope-dilution assay for quantifying folate in erythrocytes. The detection limit was 50 nmol/L and the CV over a six-month period was 2.3% (means = 1.25 mumol/L, n = 15). The reference interval, for folate measured in erythrocytes of 43 blood donors, was 0.4-1.5 mumol/L.

Carrier Proteins↗

Diagnostic value of microalbuminuria in pre-eclampsia.

Microalbuminuria, (relative albumin clearance) detected by means of a sensitive, specific immunochemical method was a more discriminatory diagnostic test in pre-eclampsia than the customary test strip reaction for clinical proteinuria. Furthermore, relative albumin clearance may serve as a valuable quantitative and objective measurement for monitoring therapy or control of pre-eclampsia.

Albumins↗

Rabbit antibodies against the folate binding protein from cow's milk. Production, characterization and use for development of an enzyme-linked immunosorbent assay (ELISA).

Rabbit antibodies to purified folate binding protein from cow's milk whey were used for development of a two-site enzyme-linked immunosorbent assay (ELISA) for quantitation of bovine folate binding proteins. The folate binding proteins in human milk and serum showed no cross-reactivity. A partial saturation of purified bovine folate binder with folate gave rise to an increased antigenicity probably due to a ligand (folate)-induced exposure of antigenic sites on the protein.

Animals↗

Accuracy of dynamic ultrasonography in the diagnosis of malignant liver lesions.

In order to assess the diagnostic accuracy of dynamic ultrasonography of malignant liver processes, 350 patients suspected of having malignant liver disease who had been examined sonographically were retrospectively classified as to the true diagnosis at the time of scanning. The true diagnosis was obtained in 218 cases. The prevalence of malignant lesions was 38 per cent. Comparison with the ultrasonographic findings yielded two false positive, five false negative, and eight inconclusive answers. The predictive diagnostic values were 97 and 96 per cent for positive and negative findings, respectively. It is concluded that in hospitals with an experienced ultrasound staff and modern dynamic gray-scale equipment, ultrasonography is the examination of choice in cases of suspected liver processes.

Aged↗

Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant gamma chain.

Class II antigens of the major histocompatibility complex (MHC) are normally expressed only by cells of the immune system. They may, however, also appear on other cells, both in vivo and in vitro. We have studied class II MHC antigen expression on human arterial smooth muscle cells using immunocytochemical analysis of surgical biopsies. The class II antigens, HLA-DQ and HLA-DR are virtually absent from cells of normal arteries, but appear in atherosclerotically transformed tissue, where the majority of cells express HLA-DR, and one-third of the cells express HLA-DQ. These atherosclerotic plaques are composed of a heterogeneous population of cells, which includes smooth muscle cells, macrophages, and T cells. Among smooth muscle cells containing the muscle-specific intermediate filament protein desmin, one-third of the cells express HLA-DR and almost as many express HLA-DQ. These cells also contain the invariant gamma chain, which is associated with class II antigens during intracellular transport. Plaque macrophages, in contrast, are usually of the DQ-DR+ phenotype. The patterns of class II antigen expression are discussed in relation to cell differentiation and pathogenesis of disease.

Antigens, Differentiation, B-Lymphocyte↗

The outcome in arterial thrombosis misdiagnosed as arterial embolism.

In an analysis of 236 consecutive patients with acute limb ischemia treated as embolic event, using only the Fogarty catheter, 30 cases of arterial thrombosis were identified. This group was compared with 92 patients with true embolism. Surgical failure was significantly more common in the thrombosis than in the embolism group (50% vs. 13%). The rate of hospital deaths was high (27%) among the patients with thrombosis, and there was close correlation (r = +0.76) between early postoperative gangrene and early death in these patients, but not in those with embolism. Severe ischemia, advanced age and surgical failure were significant risk factors for mortality in the patients with thrombosis. The authors conclude that early identification of these patients is important, that risk factors should be evaluated and that operations should be done by surgeons accustomed to procedures for adequate revascularization, since simple thrombectomy is associated with high rates of failure and mortality.

Diagnostic Errors↗