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Biomedical subjects

J Ingerslev

Publications and source records attributed to J Ingerslev.

At least 19 recordsLinked to original sources
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

Plasma levels of von Willebrand factor in non-insulin-dependent diabetes mellitus are influenced by dietary monounsaturated fatty acids.

We have previously demonstrated a lowering effect on von Willebrand Factor (vWF) of a diet rich in monounsaturated fatty acids (MUFA) as compared with a high-carbohydrate diet. In the present study 16 non-insulin dependent diabetic (NIDDM) subjects participated in a cross-over experiment on an out-patient basis comparing the effects on vWF of three weeks treatments with two diets similar in carbohydrate and protein content, one rich in MUFA (30 energy %) and one rich in polyunsaturated fatty acids (PUFA) (30 energy %). Before and on the last day of the two diets, the levels of vWF, fibrinogen, fibronectin and alpha 2-macroglobulin were measured. After 3 weeks diet intervention vWF levels were lower after the MUFA regimen compared with the PUFA diet (mean +/- SD) (1.15 +/- 0.36 vs 1.32 +/- 0.42 U/ml, p = 0.003). Similar and unchanged levels of fibrinogen, fibronectin and alpha 2-macroglobulin were seen. In conclusion, three weeks on a diet rich in MUFA lowers vWF as compared with a PUFA rich diet, suggesting a beneficial effect of MUFA on the endothelium in NIDDM patients.

Cross-Over Studies↗
PubMed1995

Detection of ten new mutations by screening the gene encoding factor IX of Danish hemophilia B patients.

Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.

Base Sequence↗
PubMed1994

[Coagulation factor VII--new physiopathological and therapeutic aspects].

Factor VII (FVII) is a vitamin K dependent coagulation factor that is synthesized in the liver, where clearance of the unactivated protein also takes place. It is a glycoprotein that following activation plays an important role in initiating coagulation after complex formation with tissue factor. A revised hypothesis of blood coagulation implicating the requirement of intact extrinsic and intrinsic pathways is presented. Increased activity of factor VII is associated with atherogenesis, and FVII deficiency may cause bleeding disorders. Recombinant FVIIa (rFVIIa) may be used in the treatment of haemophilic patients with antibodies against factor VIII or factor IX, utilizing its direct action in activation of factor X. Ongoing studies are investigating whether rFVIIa can shorten the bleeding time in patients with thrombocytopenia.

Blood Coagulation↗
PubMed1994

[Hemangiopericytoma. A rare vascular tumor with complicated operative and postoperative course].

Haemangiopericytoma (HPC) is a rare soft-tissue vascular neoplasm that may arise in almost all parts of the body. This report describes a 62-year-old man with one of the largest retroperitoneal HPC ever described weighing 950 grams. The surgical excision was followed by severe haemorrhages demanding several operations. The postoperative course was very complicated and prolonged. The geriatric rehabilitation was successful.

Hemangiopericytoma↗
PubMed1994

Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects.

High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Over Studies↗
PubMed1994

Mild haemophilia A in Iceland: clinical genetic studies of three families with the same mutation.

OBJECTIVES: The aim of the study was to define the phenotype in three families with mild haemophilia A and to determine restriction fragment length polymorphisms (RFLP), which could support a hypothesis of a common progenitor of the families. DESIGN: Family survey. SETTING: Index cases were identified in and outside hospital and a family survey for symptoms and signs of bleeding in family members and sampling for coagulation and RFLP studies were mostly carried out in the field. SUBJECT: Family members with and without symptoms of bleeding were selected for investigation and normal spouses and unrelated individuals were investigated for control. INTERVENTIONS: Medical advice regarding affected family members were given to the families and their physicians. MAIN OUTCOME MEASURES: Bleeding time, factor VIII activity, quantification of factor VIII:Ag, von Willebrand factor (vWF) Ag and vWF ristocetin assay. Typing of RFLP polymorphisms for genetic homogeneity. RESULTS: Bleeding manifestations are present in both sexes in the three families although more frequent and more severe in the males. The level of factor VIII activity is between 10 and 20% in most affected males whereas 35-60% is found approximately in 2/3 of female carriers and in 1/3 of them factor VIII activity is within the normal range. It is suggested that screening for this mild haemophilia A gene by a molecular genetic method would be of clinical value now, its mutation having been detected. CONCLUSIONS: Transmission of mild haemophilia A through six to seven generations is demonstrated by the study. The mild haemophilia A type described is the most prevalent of haemophilia A types in Iceland (population 260,000, 1992). The founder effect was confirmed by studies of RFLP polymorphisms.

Adolescent↗
PubMed1993

[Hereditary protein S deficiency and familial thrombosis. A review with description of a Danish family with protein S deficiency].

Protein S is approximately 69,000 Da polypeptide that acts as a co-factor in conjunction with activated protein C, in the natural anticoagulant system of protein C which irreversibly cleaves activated coagulation factors Va and VIIIa on the cell surface. Although synthesis of protein S takes place in several tissues, the hepatic production of protein S is presumably the most important. It has been established that heterozygous deficiency of protein S may be found in families with increased tendency to thrombosis (thrombophilia). The protein S gene, located on chromosome No. 3, consists of a translated gene, denoted PS alpha, and homologous untranslated region, designated PS beta. In inherited protein S deficiency deletions in PS alpha and PS beta have been detected. The present report deals with a Danish family with highly increased tendency to thrombosis, the propositus of which is a male who developed a large deep-vein thrombosis at the age of 18 months. In this family, nine cases with a plasma level of total protein S close to 50% of normal were identified, six of which had experienced one or more incidents of thrombosis in the past. We recommend that young patients who develop spontaneous arterial or venous thrombosis should be tested for the presence of inherited abnormalities of natural anticoagulants like antithrombin-III and proteins S and C.

Adolescent↗
PubMed1992

Tissue-specific expression in the salivary glands of transgenic mice.

Using a DNA construct, named Lama, derived from the murine parotid secretory protein (PSP) gene, we have obtained salivary gland specific gene expression in transgenic mice. Lama is a PSP minigene and allows analysis of the PSP gene 5' regulatory region by transgenesis. We show here that the regulatory region included in Lama with 4.6 kb of 5' flanking sequence is sufficient to direct expression specifically to the salivary glands. The expression level in the parotid gland is only about one percent of the PSP mRNA level, while that of the sublingual gland is near the PSP mRNA level. This suggests significant differences in the PSP gene regulation in the two glands. In addition, Lama is a secretory expression vector in which cDNAs or genomic fragments can be inserted. We demonstrate that the Lama construct can direct the expression of a heterologous cDNA encoding the C-terminal peptide of human factor VIII to salivary glands and that the corresponding peptide is secreted into saliva.

Amino Acid Sequence↗
PubMed1992

Expression of a cytomegalovirus IE-1-factor VIII cDNA hybrid gene in transgenic mice.

A construct containing the 5' end of the human cytomegalovirus major immediate early gene fused to the human coagulation factor VIII cDNA was used to produce transgenic mice. Two out of five transgenic lines transcribed the construct. The expression was consistently seen in a limited number of tissues and was highest in muscle tissues. This is in contrast to the almost ubiquitous activity demonstrated in earlier studies with the IE-1 enhancer/promoter. Human factor VIII protein was detected immunochemically in muscle tissues at levels several times higher than in human plasma.

Animals↗
PubMed1992

Fatal haemostatic complications due to thrombolytic therapy in patients falsely diagnosed as acute myocardial infarction.

This report describes the fate of two young men wrongly treated with thrombolysis for suspected myocardial infarction. Both had electrocardiographic changes upon admission. Correct diagnosis of aortic dissection and haemorrhagic pericarditis was obtained within a few hours, but due to the prolonged disturbance of haemostasis, appropriate therapy could not be instituted, and outcome was fatal for both patients. These cases underline the importance of rigid ST criteria, and procedures for neutralization of thrombolysis are proposed.

Adult↗
PubMed1992

Influence of dry heat treatment and anticoagulant on coupling of fibrinogen and fibronectin to von Willebrand factor in normal plasma.

In plasma from healthy subjects a coupling was identified between von Willebrand factor (vWf), fibrinogen (fg), and fibronectin (fn) that was dependent of anticoagulants heparin, EDTA, and citrate. Binding was quantitated by ELISA methodologies, based on polyclonal antibodies directed against the proteins studied, in order to express the percentage of moles of fg or fn bound to moles vWf, C[fg/vWf] or C[fn/vWf] (mol/mol)%. The intra-assay coefficients of variation (CV%) for fg and fn bound to vWf were 10.6% and 7.4% (n = 10) respectively, and the inter-assay coefficients of variation were 24.4% and 22.2% (n = 10). The largest degree of coupling was found in heat-treated lyophilized heparin plasma, where C[fg/vWf] and C[fn/vWf] were 12.9 +/- 1.4 (mol/mol)% and 2.4 +/- 0.1 (mol/mol)% (mean +/- SD). Binding was further qualitatively demonstrated through experiments using gel filtration chromatography and agarose gel electrophoresis followed by immunoblotting. In all instances coupling of vWf with fg was higher than with fn. Lyophilisates of normal plasma that were subjected to dry heating (60 degrees C in 72 h) showed considerably increased coupling. Previous investigators, studying reconstituted factor VIII concentrates by means of gel filtration, pointed out that an association between vWf, fg and fn was present in such therapeutic material. This investigation signifies that a coupling between these proteins may be present even in the source plasma, and that 'dry heating' increases binding. Implications of these results are discussed.

Anticoagulants↗
PubMed1992

The Glostrup Population Studies, 1964-1992.

The Glostrup Population Studies, 1964-92, comprise descriptive and analytical, clinical epidemiological studies. Since 1964, different birth cohorts have been examined. More than 20,000 persons, randomly selected from the background population of 300,000 inhabitants (Copenhagen County), have been invited to participate. The project started in 1964 with a survey of the 1914 population on risk factors for coronary heart disease. As the 1914 population has been followed and new cohorts added, a time-sequential design, suited for studies of aging, has been constructed. The staff has been kept in the unit for up to 28 years. Doctoral candidates in medical science and Ph.D candidates have defended their analyses of Glostrup data in several fields and continue to belong to the group of representatives, supporting the board of leaders. The head of Medical Department C serves as chairman, thus maintaining a close connection with clinical medicine.

Adult↗
PubMed1992

85-year-olds in Denmark. The socio-psychological conditions and general health and disorders in a representative group of 85-year-old Danes.

A population of persons born in 1897 and resident in Glostrup and eight surrounding municipalities was investigated when these persons were 70, 80 and 85 years old. Some of the results are mentioned from the cross-sectional, epidemiological survey on the socio-psychological conditions and general health and disorders in this representative population which includes almost 2% of the Danish 85-year-olds. The examination programme was extensive, and of data rather comprehensive. The aim of this article is to make known some of the information, observations and results of several tests performed, including 56 different laboratory tests and nutritional analyses. It is worth mentioning that about three fourths of the 85-year-olds were self-reliant and contended with their actual life and lifestyle. Nevertheless suggestions or recommendations for interventions were given to 85% of the participants as well as the general practitioners. The data have already formed the basis of several frames of references.

Aged↗
PubMed1991

[Standardized prothrombin time determinations and optimal anticoagulant therapy].

WHO and other international organizations have recommended the introduction of a standardized prothrombin time determination. This would allow a universal scale for the intensity of oral anticoagulation therapy to be used. A prerequisite is the use of thromboplastin, calibrated against the international reference thromboplastin, standardized methodology etc. This permits every prothrombin time determination to be expressed as International Normalized Ratio (INR). The introduction of INR facilitates the implementation of optimal oral anticoagulation as defined by larged international studies.

Anticoagulants↗