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Biomedical subjects

J Ingerslev

Publications and source records attributed to J Ingerslev.

At least 163 records · Page 9Linked to original sources

Enzyme-linked immunosorbent assay (ELISA) for the measurement of small quantities of alpha 2-macroglobulin.

A simple, sensitive and precise enzyme-linked immunosorbent assay for the quantitation of alpha 2-macroglobulin (alpha 2M) in supernatants of cell cultures was constructed. All reagents apart from the alpha 2M standard were commercially available. The assay range was 2.0-500 micrograms/l. The intra-assay coefficient of variation (CV%) was 4.6%, and the imprecision between runs was 8.9% at 10 micrograms/l and 9.0% at 110 micrograms/l. Recovery of alpha 2M, added to cell culture medium free of serum, was 97.5 +/- 7.2% (mean +/- SD) and the recovery of alpha 2M added to pooled human serum was 101 +/- 6.0%. There was no significant difference between the recovery of alpha 2M-standard and alpha 2M-trypsin complexes, whereas the dose response of a commercial alpha 2M-standard was lower than expected (81.1 +/- 7.5%), indicating a lower purity and/or conformational changes in the epitopes of this reagent. As expected, supernatants of mononuclear lymphocyte cultures enriched in monocytes contained significantly higher concentrations of alpha 2M than supernatants of cell cultures depleted in monocytes. Our results indicate that the ELISA method could be useful tool in the study of the alpha 2M turnover in all cell cultures in vitro.

Cells, Cultured↗

Factor VIII inhibitor treatment with high doses of F VIII.

A hemophilic patient with F VIII inhibitor was treated with intermittent F VIII infusions of 40 - 50 units per kg bodyweight per week. Although the inhibitor declined during treatment, an anamnestic response was recorded on two occasions. A continuous high dose F VIII regimen of 200 units per kg per day resulted in reduction of the inhibitor concentration to less than 1 unit per ml. No anamnestic response was seen after a later exposure to intensive F VIII therapy.

Antibodies↗

The origin of cerebrospinal fluid somatostatin: hypothalamic or disperse central nervous system secretion?

The present study deals with the origin of somatostatin in cerebrospinal fluid. Two groups of experiments were performed: (1) Diagnostic lumbar puncture was performed in 37 patients admitted for various neurological diseases. Immunological determination of albumin and gamma-globulin, and radioimmunological analysis of somatostatin in successive cerebrospinal fluid taps demonstrated that while the protein concentration was approximately 20% lower in the 11th ml compared to the 1st ml drawn, the somatostatin concentration was constant. (2) Intravenous arginine infusion (30 G/30 min) induced identical patterns of plasma growth hormone in 8 patients with multiple sclerosis in relapse, in 6 patients with multiple sclerosis in the stable phase, and in 7 patients in whom no neurological disease was eventually diagnosed. Cerebrospinal fluid somatostatin was significantly lower in the patients with multiple sclerosis in relapse than in the two other groups, while cerebrospinal fluid growth hormone concentration was identical. There was no correlation between basal or arginine provoked plasma growth hormone and the cerebrospinal fluid content of somatostatin. The results indicate that cerebrospinal fluid somatostatin is released dispersely from the central nervous system including the spinal cord - and that it offers no indication of the activity or tone of hypothalamic growth hormone release inhibiting control of the pituitary gland.

Adult↗

The excretion of C6-C10-dicarboxylic acids in the urine of newborn infants during starvation. Evidence for omega-oxidation of fatty acids in the newborn.

The excretion of C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, was measured during the three first days of life in 3 fasting newborns, 2 newborns fed with isocaloric glucose and 2 newborns given mothers'-milk. On the second and third day of life the starved children excreted 27-84 mmol adipic acid/mol creatinine, 6-22 mmol suberic acid/mol creatinine and 4-7 mmol sebacic acid/mol creatinine. The excretion of C6-C10-dicarboxylic acids in the neonates given glucose or mothers'-milk was, for the first three days of life, 0-9 mmol adipic acid/mol creatinine, 0-10 mmol suberic acid/mol creatinine and 0-4 mmol sebacic acid/mol creatinine. The latter amounts are equivalent to the excretion of dicarboxylic acids in older children. It is argued that the detected dicarboxylic acids are formed by omega-oxidation of long-chain monocarboxylic acids followed by beta-oxidation, and that the excreted amounts reflect omega-oxidation activity. It is speculated that the substantial omega-oxidation activity in the starving newborn serve to provide succinyl-CoA-substrate for the citric acid cycle and for gluconeogenesis.

Adipates↗

Low molecular weight organic acids in the urine of the newborn.

The urinary excretion of seven selected low molecular weight organic acids in normal neonates was measured by gas chromatography. First and third to fourth day of life excretion of the following compounds was significantly unchanged: 3-OH-butyric acid (less than 13 mumol/mmol creatinine), succinic acid (approx. 43 mumol/mmol creatinine), adipic acid (approx. 12 mumol/mmol creatinine), 2-OH-glutaric acid (approx. 23 mumol/mmol creatinine), 3-OH-3-Me-glutaric acid (approx. 25 mumol/mmol creatinine) and citric acid (approx. 115 mumol/mmol creatinine). The excretion of 4-OH-phenyl-acetic acid increased during the first four days of life (from less than 8 mumol/mmol creatinine to approx. 20 mumol/mmol creatinine). It is postulated that urinary orgainc acid excretion in the neonate, which is clearly different from the adult urinary pattern, is a reflection of the specific neonatal metabolic situation, including a high fatty acid utilisation and a low protein catabolism.

Adipates↗

Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasectomy.

The possibility of autoantibodies--other than sperm antibodies--developing as a consequence of vasectomy has been investigated in 255 volunteers. During the first year after vasectomy no obvious increase was observed in the occurrence of any of these antibodies (rheumatoid factor, antinuclear antibodies and antibodies against smooth muscle, mitochondria, gastric parietal cell, thyroid microsomes and thyroglobulin). Ninety-nine of the patients were also examined for agglutinating and immunofluorescent antibodies to sperm to see if there was any relationship between the occurrence of anti-sperm antibodies and other autoantibodies. However, the prevalence of non-sperm autoantibodies did not differ in two nearly equal groups of patients with and without indications of autoimmune reactions to spermatozoa, respectively. Consequently the present results lend no support to the hypothesis that vasectomy could induce autoimmunity to other autoantigens than sperm-specific antigens.

Agglutinins↗

Diabetes-like alterations in hemostatic parameters after growth hormone administration for one week in normal man.

Excess production of growth hormone (GH) in poorly controlled diabetes is believed to be a causal factor in the development of diabetic angiopathy, the mechanism(s) of which is unknown. The present study was undertaken to determine whether exogenous growth hormone would specifically change some quantities and functional parameters known to often be abnormal in long-standing diabetes and thought to result from the development of vascular lesions in general. The authors studied capillary resistance, factor VIII coagulant antigen (F VIII:Ag), von Willebrand factor (vWf:Ag), fibronectin, fibrinogen, and tissue-type plasminogen activator (t-PA) before, during, and after 1 week's subcutaneous GH administration (6 IU per day divided into two doses). Capillary resistance decreased insignificantly, but returned to higher levels (p less than 0.05) 1 week after withdrawal. F VIII:Ag, vWf:Ag, fibronectin, and fibrinogen all increased significantly during GH treatment. Except for F VIII:Ag, these quantities returned to pre-medication levels 7 days after termination of GH administration. The present results may contribute to the clarification of the role of GH hypersecretion in diabetic microangiopathy and macroangiopathy.

Adult↗

Renal and glycemic determinants of glomerular hyperfiltration in normoalbuminuric diabetics.

Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).

Adolescent↗

Near normoglycemia for 1 year has no effect on platelet reactivity, factor VIII, and von Willebrand factor in insulin-dependent diabetes mellitus: a controlled trial.

The impact of prolonged near-normoglycemia on platelet reactivity (spontaneous and induced platelet aggregation), factor VIII, and von Willebrand factor in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated in a prospective, randomized, controlled clinical trial. Twenty IDDM patients with no or only minor clinical signs of microvascular disease were randomly assigned to 1 year of continuous subcutaneous insulin infusion (CSII) or unchanged conventional insulin treatment (CIT). Hemoglobin A1c declined during the 12 month observation period from 7.3 +/- 1.2% to 6.4 +/- 0.9% (2p less than 0.01) in the CSII group, while this measure of glycemic control was unchanged in the CIT group: 7.2 +/- 1.1% vs 8.0 +/- 1.6% (NS). Platelet reactivity, factor VIII, and von Willebrand factor concentrations were identical in the two groups at entry into the study, and no significant changes in these variables were seen in either group. Thus, the present results do not support the concept of increased platelet reactivity following CSII treatment.

Adult↗

Safety of plasma derivatives.

In clinical treatment practice of substitution therapy involving a plasma component, numerous aspects related to recipient's safety are relevant to the physician. Since viral contaminants may be present in the donor blood, safety begins in the institution collecting raw plasma where donors are inquired about any unusual behavior that may potentially threaten safety. Other measures that could lead to exclusion of a donation are positive serological tests for HIV and hepatitis B and C. In this context, meticulously accurate logistics are mandatory. During the course of manufacture of plasma products, viral inactivation procedures have been adopted based on chemical and physical principles. The distinct effects of these depend on methodology and the types of virus in question. An important safety measure relates to establishing that the label value of content corresponds to the in vivo recovery of the reconstituted plasma derivative and, by inference, the clinical efficacy of the product. In patients deficient in plasma coagulation factors, treatment may trigger the development of functionally inhibiting alloantibodies against the factor needed for substitution which is a significant clinical complication. The reported incidences of such inhibitors have varied greatly. No clear relationship between their frequency and the type of concentrate used have been established. However, recent experience has shown an unexpected increase in inhibitors in a regional subset of previously stable patients when shifted from a dry-heat-inactivated concentrate to a pasteurized version of the same concentrate. Hence, the possible introduction of neoantigens is important. In the early era of concentrate use, side effects to treatment were often observed like alloimmune hemolytic anemia and various degrees of anaphylactoid reactions. With the appearance of concentrates of increased purity that contain less unwarranted proteins, side effects of this kind have been rare. In conclusion, safety of plasma derivatives by today's standards is not a single entity, but a long chain of interdependent issues, each of which needs full attention to protect patients from mild and serious treatment complications.

Blood Coagulation Factors↗